MANAGEMENT OF THYROID CANCER

By

Salah Mabruok Khalaf

South Egypt Cancer Institute2012

Local seminar Medical Oncology department

Epidemiology

bull Thyroid Cancer accounts for 15 of all cancers

bull The most common endocrine malignancy (95 of all

endocrine cancers)

bull Sex Female to Male Ratio 251 except anaplastic

carcinoma

bull Age most common after age 30

Risk Factors for Thyroid Cancer1 Neck irradiation

The only well-established risk factor for differentiated thyroid cancer

2 Genetic factors1 Papillary thyroid carcinoma may occur in several rare inherited

syndromes including iFamilial adenomatous polyposis

iiGardners syndrome

iiiCowdens disease

2 Medullary carcinoma in MEN syndrome

3 Other risk factors i History of goiter

ii family history of thyroid disease

iii Female gender

iv Asian race

Clinical Manifestation

bull Thyroid enlargement bull Most patients are euthyroid and present with a thyroid nodule

bull Symptoms such as dysphagia dyspnea and hoarseness usually indicate advanced disease

bull Cervical lymph node enlargement

Investigations

bull Serum TSHbull Fine Needle Aspiration Cytology (FNA)bull High Resolution Thyroid US- helpful in

detecting non palpable nodule and solid versus

cystic lesionbull Thyroid Isotope Scanning- to assess functional activity of

a nodule

bull FNAC indicationsISonar-based criteria

Solid nodule

1 More than 1 cm if associated with sonographic suspious features

2 More than 15 cm in absence of sonographic suspicion

Mixed solid and cystic 1 More than 15 cm if associated with sonographic suspicious features

2 More than 2 cm in absence of sonographic suspicion

Spongiform nodule (microcystic component gt 50 of nodules

IHigh risk Clinical feature

RT exposure

Genetic predisposition

Sonographic suspicious features (hypoechoic microcalcification increased central vascularity infiltrative margin or taller than wide in transverse plan)

Fine Needle AspirationbullProcedure of Choice ndash Fast minimally invasive and few riskbullIncidence of False positive 1bullIncidence of False negative 5bullFNA is not a tissue diagnosisbullLimitation of FNA

bull Cannot distinguish a benign follicular from a malignant lesion (cancer invade capsule)

FNA Results of Thyroid Nodulebull Benign(70) --gt FU 6-12 monthsbull Indeterminate(10) --gt repeat FNA I123 scan bull Follicular neoplasm(5) --gt I123 scan or surgerybull Suspicious (10) --gt surgerybull Carcinoma (5) --gt surgery

Classification and Incidence ofThyroid Cancer

Tumors of Follicular Cell Origin1048708 Differentiated Papillary 75 Follicular 10 Hurthle Cell 51048708 Undifferentiated Anaplastic 5 1-Small cell carcinoma 2-Giant cell carcinoma

Tumors of Parafollicular cells Medullary 5

Other 1 1-sarcomas 2-lymphomas 3-epidermoid carcinomas 4-Teratomas 5-metastasis from other cancers

Papillary Cancer The most common malignant thyroid tumor (70-80 of all cancers) Women predominance Age 38-45 Accounts for 90 of radiation induced thyroid cancer Prognosis directly related to tumor size

bull Papillary Cancer

1Histologic1 Psammoma bodies

2 Orphan Ann nucleus

2Multicentric 30-50

3Spread via Lymphatics- propensity for cervical node involvement

4Invasion of adjacent structures and distant mets uncommon

FOLLICULAR THYROID CANCER1Usually Encapsulated2More Common Among Older Patients3Woman gt Man4More Aggressive amp Less Curable Than Papillary5Vascular Invasion (veins and arteries) within the thyroid gland is common6Blood Spread (lung and bone)7Types

1 Follicular carcinoma 2 Follicular carcinoma variant Minimally Invasive Hurthle Cell

8Rarely associated with radiation exposure

Huumlrthle Cell Neoplasms

1More aggressive than other differentiated thyroid carcinomas (higher metslower survival rates)

2Less affinity for I131

3Need to differentiate from benignmalignant

4Metastasis may be more sensitive to I131 than primary

Medullary Thyroid Cancer 1 Usually present as a mass plusmn lymphadenopathy

2 It can also be diagnosed by fine-needle aspiration biopsy

microscopically typically

3 Family members should be screened for calcitonin

elevation andor for the RET proto-oncogene mutation

4 Not associated with radiation exposure

5 Residual disease (following surgery) or recurrence can be

detected by measuring calcitonin

Medullary Thyroid Cancer Occurs in Four Clinical Settings

I- Sporadic

180 of all cases of medullary thyroid cancer

2Typically unilateral

3No associated endocrinopathies

4Peak onset 40 - 60

5Females predominance 32 ratio

6One third will present with intractable diarrhea

Diarrhea is caused by increased gastrointestinal secretion and hypermotility due to

the hormones secreted by the tumor (calcitonin prostaglandins serotonin or VIP)

II-MEN II-A (Sipple Syndrome)

(Multiple Endocrine Neoplasia II A)

1Sipple syndrome has

[1] bilateral medullary carcinoma

[2] pheochromocytoma

[3] hyperparathyroidism

2This syndrome is inherited in an autosomal dominant fashion

Because of this males and females are equally affected

3Peak incidence of medullary carcinoma in these patients is in the

30s

III-MEN II B

1This syndrome has

[1] medullary carcinoma

[2] Pheochromocytoma

[3] mucosal ganglioneuromas and Marfanoid habitus

2Inheritance is autosomal dominant as in MEN IIA (m=f)

3Pheochromocytomas must be detected prior to any operation

4The idea here is to remove the pheochromocytoma first to remove

the risk of severe hypertensive episodes while the thyroid or

parathyroid is being operated on

IV-Inherited medullary carcinoma without associated endocrinopathies

This form of medullary carcinoma is the least aggressive Like other types of thyroid cancers the peak incidence is

between the ages of 40 and 50

Anaplastic cancer

1)Peak onset age 65 and older

Very rare in young patients

2)Males more common than females by 2 to 1 ratio

3)Undifferentiated

4)May arise many years (gt20) following radiation

exposure

5)Neck mass usually large diffuse and very hard

6)Rapidly growing often inoperable highly recurrent

7) Invade locally metastasize both locally and distantly

(to lungs or bones)

8) Cervical metastasis are present in the vast majority

(over 90) of cases at the time of diagnosis

9) Mean survival 6 months

10) Often requires the patient to get a tracheostomy to

maintain their airway

STAGING OF THYROID CANCER

In differentiated thyroid carcinoma several classification and

staging systems have been introduced However no clear

consensus has emerged favoring any one method over another

bull AMES systemAGES SystemGAMES system

bull TNM system

bull MACIS system

bull University of Chicago system

bull Ohio State University system

bull National Thyroid Cancer Treatment Cooperative Study

(NTCTCS)

TNM Staging bull Primary tumor (T) (All categories may be subdivided into (a)

solitary tumor or (b) multifocal tumor)

TX Primary tumor cannot be assessed

T0 No evidence of primary tumor

T1 Tumor le 2 cm limited to the thyroid

T2 Tumor gt 2 cm but le4 cm limited to the thyroid

T3 Tumor gt 4 cm limited to the thyroid or any tumor with

minimal extrathyroid extension (eg extension to

sternothyroid muscle or perithyroid soft tissues)

bull T4a Tumor of any size extending beyond the thyroid capsule to invade subcutaneous soft tissues larynx trachea esophagus or recurrent laryngeal nerve

bull T4b Tumor invades prevertebral fascia or encases carotid artery or mediastinal vessels

All anaplastic carcinomas are considered T4 tumorsbull T4a Intrathyroidal anaplastic carcinomamdashsurgically resectable bull T4b Extrathyroidal anaplastic carcinomamdashsurgically

unresectable

bull Regional lymph nodes (N) (Regional lymph nodes are the central compartment lateral cervical and upper

mediastinal lNs)

bull NX Regional lymph nodes cannot be assessed bull N0 No regional lymph node metastasis bull N1 Regional lymph node metastasis

bull N1a Metastasis to level VI (pretracheal paratracheal and prelaryngealDelphian on the cricothyroid membrane (precricoid) lymph nodes)

bull N1b Metastasis to unilateral or bilateral cervical or superior mediastinal lymph nodes

bull Distant metastases (M) bull MX Distant metastasis cannot be assessed bull M0 No distant metastasis bull M1 Distant metastasis

AJCC Stage Groupings Papillary or follicular thyroid cancer

bull Younger than 45 yearsbull Stage I

bull Any T any N M0 bull Stage II

bull Any T any N M1

bull Age 45 years and olderbull Stage I

bull T1 N0 M0bull Stage II

bull T2 N0 M0 bull Stage III

bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0

Papillary or follicular thyroid cancer

Age 45 years and older

Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T3 N1b M0 T2 N1b M0 T4a N1b M0

Stage IVB T4b any N M0

Stage IVC Any T any N M1

Stage I

T1 N0 M0

Stage II

T2 N0 M0

Stage III

T3 N0 M0

T1 N1a M0

T2 N1a M0

T3 N1a M0

Medullary thyroid cancer bullStage I

bull T1 N0 M0 bullStage II

bull T2 N0 M0bullStage III

bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0

Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T2 N1b M0 T3 N1b M0 T4a N1b M0

Stage IVB T4b any N M0

Stage IVC Any T any N M1

bull Anaplastic thyroid cancer

bull All anaplastic carcinomas are considered stage IV

bull Stage IVA bull T4a any N M0

bull Stage IVB bull T4b any N M0

bull Stage IVC bull Any T any N M1

bull University of Chicago systembull Class Imdashdisease limited to the thyroid glandbull Class IImdashlymph node involvementbull Class IIImdashextrathyroidal invasionbull Class IVmdashdistant metastases

PROGNOSIS

PROGNOSIS

Prognostic schemes GAMES scoring (PAPILLARY amp

FOLLICULAR CANCER)bullG GradebullA Age of patient when tumor discoveredbullM Metastases of the tumor (other than Neck LN)bullE Extent of primary tumorbullS Size of tumor (gt5 cm)bullThe patient is then placed into a high or low risk category

Prognostic Risk Classification for Patients with Well-Differentiated Thyroid Cancer (GAMES )

Low Risk High Riskbull Grade Well Differentiated Poorly Differentiated

bull Age lt40 gt40

bull Mets None Regional or Distant

bull Extent No local extension Capsular invasion intrathyroidal extrathyroidal

bull Sex Female Male

MACIS ScoringbullDeveloped by the Mayo Clinic for stagingbullIt is known to be the most accurate predictor of a patients outcome with papillary thyroid cancer (M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)bullMAICS Score 20 year Survival

lt 6 = 99 6-7 = 89 7-8 = 56 gt 8 = 24

Treatment

Stage I and II Papillary and FollicularI-Total thyroidectomy bull Rationale1048708 Bilateral cancers are common (30-85)1048708 improved effectiveness for I131 ablation1048708 lowers dose needed for I131 ablation1048708 allows fu with thyroglobulin levels1048708 decreased recurrence in all groups1048708 improved survival in high risk pts1048708 Decreased risk of pulmonary metsbull Disadvantage higher incidence of hypoparathyroidism but this

complication may be reduced when a small amount of tissue remains on the contralateral side

II-Lobectomy

bull Rationale

1048708 Most patients are low risk and excellent prognosis

1048708 Role of adjuvant treatment not defined

1048708 Complications of Total

1048708 Occult multicentric tumor not clinically significant

1048708 Most local recurrences treated with surgery

1048708 Excellent outcome with lobectomy in low risk patients

bull Disadvantage

bull approximately 5 to 10 of patients will have a recurrence

Indications for total Thyroidectomy OR lobectomy (all present)

bull Age 15 y - 45 ybull No prior radiationbull No distant metastasesbull No cervical lymph node metastasesbull No extrathyroidal extensionbull Tumor lt 4 cm in diameterbull No aggressive variant

When complete total thyroidectomy after lobectomybull Aggressive variantbull Macroscopic multifocal diseasebull Positive isthmus marginsbull Cervical lymph node metastasesbull Extrathyroidal extension

Aggressive=Tall cell columnar cell insular oxyphilic or poorly differentiated features

bull Node removal

bull Selective node removal can be performed and radical

neck dissection is usually not required

bull This results in a decreased recurrence rate but has not

been shown to improve survival

Thyroid carcinoma after lobectomy for benign lesions

I-Completion of thyroidectomy

bull gt 4 cm

bull Positive margins

bull Extra-thyroidal invasion (T3 or T4(

II- Completion of Thyroidectomy or follow

up

bull Clinically suspicious lymph node

contralateral lesion or perithyroidal node

bull Aggressive variant

bull Macroscopic multifocal disease

bull ge1 cm in diameter

III- follow up

bull Negative margins

bull No contralateral lesion

bull lt 1 cm in diameter

bull No suspicious lymph

node

POSTSURGICAL EVALUATION AFTER THYROIDECTOMY

I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +

antithyroglobulin antibodies)

II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan

Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT

bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)

Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas

Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant

Pretherapy whole body iodine scan

bullIf performed a pretherapy scan should use a low dose of 131I

(1 to 5 mCi) or 123I

bull To detect residual thyroid tissue thyroid cancer and metastatic foci

bull To reduce the potential for sublethal radiation stunning of thyroid tissue that

prevents optimal uptake of future 131I therapy

bullStunning is defined as a reduction in uptake of the 131I

therapy dose induced by a pretreatment diagnostic dose

Dose of RAI

bullThe dosing of 131I for ablation is somewhat controversial

bullLow-dose ablation with less than 30 mCi administered on

an outpatient basis

bull For low-risk young patients

bullHigh-dose ablation with100 to 200 mCi

bull For high-risk patients

bull300 mCi

bull For all patients with metastatic disease that treated with repeated

therapeutic doses of 131I

Replacement therapy

bullPostoperative treatment with exogenous thyroid hormone

in doses sufficient to suppress thyroid-stimulating hormone

(TSH) with development of thyrotoxic manifestations

decreases incidence of recurrence

bullAdministration of Thyroid Hormone

To suppress TSH and growth of any residual thyroid

To maintain patient euthyroid

o Maintain TSH level 01uUml in low risk pts

o Maintain TSH Level lt 01uUml in high risk pts

Stage III Papillary and Follicular

A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease

B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients

Stage IV Papillary and Follicular 1) Adequate uptake of I131

bull I131

1) Inadequate uptake or not sensitive to I131

i Localized lesions

1) Radiation therapy

2) Resection of limited metastases dont uptake of I131

iiDisseminated disease

1) TSH suppression with thyroxine is effective

2) Chemotherapy has been reported to produce occasional complete

responses of long duration

3) Clinical trials testing new approaches to this disease

Medullary Thyroid Cancer treatment

bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck

dissections Why

bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival

advantage

bull Radioactive iodine has no place in the treatment of patients with MTC

bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in

patients with metastatic disease

bull No single drug regimen can be considered standard

bull Some patients with distant metastases will experience prolonged survival and can

be observed until they become symptomatic

Anaplastic Thyroid Cancer bull Surgery

bull Tracheostomy is frequently necessary

bull If the disease is confined to the local area which is rare total

thyroidectomy is warranted to reduce symptoms caused by the

tumor mass

bull Radiation therapy

bull Used in patients who are not surgical candidates or whose tumor

cannot be surgically excised

Anaplastic Thyroid Cancer bull Chemotherapy

bull Produce partial remissions in some patients

bull Approximately 30 of patients achieve a partial remission with

doxorubicin

bull The combination of doxorubicin plus cisplatin appears to be more

active than doxorubicin alone and has been reported to produce

more complete responses

Treatment options under clinical evaluation

bull The combination of chemotherapy plus radiation therapy in patients following

complete resection may provide prolonged survival but has not been compared to

any one modality alone

Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30

bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common

site of distant metastasis is the lung

bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type

Treatment of recurrent thyroid cancer

The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations

bull Adequate I131 uptake

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull I131 ablation

bull RT

bull Disseminated

bull I131 ablation

bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has

been reported to produce occasional objective responses usually of short

duration

Treatment of recurrent thyroid cancer

bull Inadequate I131 uptake or insensitive to I131

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull RT

bull Disseminated

bull Systemic chemotherapy

Treatment of recurrent thyroid cancer

Systemic chemotherapy

bull Doxorubicin alone

bull Cisplatin and doxorubicin (better)

bull BAP Cisplatin doxorubicin and bleomycin

bull CVD cyclophosphamide vincristine and dacarbazine

bull Dacarbazine and 5-fluorouracil

bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy

bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT

bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)

bull Improve OS and decrease RR

BAP regimenbull Schedule

bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5

bull Cell typebull Several histologic types of thyroid carcinoma responded but the

best responses were observed in medullary and anaplastic giant-cell carcinomas

bull Effectivenessbull BAP regime can achieve reasonable palliation and probably

increases survival in poor-prognosis thyroid cancers

CVD regimenbull Schedule

bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks

bull Cell typebull Medullary thyroid carcinoma

bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in

patients with advanced MTC

Dacarbazine and 5-fluorouracil

bull Schedule

bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and

12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks

Six cycles

bull Cell type

bull MTC

bull Effectiveness

bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to

have significant activity and was well tolerated

Target therapy

Take home messagesbull FNAC is not adequate for definite diagnosis of follicular

carcinomabull Because the mixed papillary-follicular variant tends to

behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis

bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer

bull Once medullary carcinoma is diagnosed familial predisposition should be checked up

bull If I131 is indicated stunning effect should be avoided

Take home messages

All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary

Epidemiology

bull Thyroid Cancer accounts for 15 of all cancers

bull The most common endocrine malignancy (95 of all

endocrine cancers)

bull Sex Female to Male Ratio 251 except anaplastic

carcinoma

bull Age most common after age 30

Risk Factors for Thyroid Cancer1 Neck irradiation

The only well-established risk factor for differentiated thyroid cancer

2 Genetic factors1 Papillary thyroid carcinoma may occur in several rare inherited

syndromes including iFamilial adenomatous polyposis

iiGardners syndrome

iiiCowdens disease

2 Medullary carcinoma in MEN syndrome

3 Other risk factors i History of goiter

ii family history of thyroid disease

iii Female gender

iv Asian race

Clinical Manifestation

bull Thyroid enlargement bull Most patients are euthyroid and present with a thyroid nodule

bull Symptoms such as dysphagia dyspnea and hoarseness usually indicate advanced disease

bull Cervical lymph node enlargement

Investigations

bull Serum TSHbull Fine Needle Aspiration Cytology (FNA)bull High Resolution Thyroid US- helpful in

detecting non palpable nodule and solid versus

cystic lesionbull Thyroid Isotope Scanning- to assess functional activity of

a nodule

bull FNAC indicationsISonar-based criteria

Solid nodule

1 More than 1 cm if associated with sonographic suspious features

2 More than 15 cm in absence of sonographic suspicion

Mixed solid and cystic 1 More than 15 cm if associated with sonographic suspicious features

2 More than 2 cm in absence of sonographic suspicion

Spongiform nodule (microcystic component gt 50 of nodules

IHigh risk Clinical feature

RT exposure

Genetic predisposition

Sonographic suspicious features (hypoechoic microcalcification increased central vascularity infiltrative margin or taller than wide in transverse plan)

Fine Needle AspirationbullProcedure of Choice ndash Fast minimally invasive and few riskbullIncidence of False positive 1bullIncidence of False negative 5bullFNA is not a tissue diagnosisbullLimitation of FNA

bull Cannot distinguish a benign follicular from a malignant lesion (cancer invade capsule)

FNA Results of Thyroid Nodulebull Benign(70) --gt FU 6-12 monthsbull Indeterminate(10) --gt repeat FNA I123 scan bull Follicular neoplasm(5) --gt I123 scan or surgerybull Suspicious (10) --gt surgerybull Carcinoma (5) --gt surgery

Classification and Incidence ofThyroid Cancer

Tumors of Follicular Cell Origin1048708 Differentiated Papillary 75 Follicular 10 Hurthle Cell 51048708 Undifferentiated Anaplastic 5 1-Small cell carcinoma 2-Giant cell carcinoma

Tumors of Parafollicular cells Medullary 5

Other 1 1-sarcomas 2-lymphomas 3-epidermoid carcinomas 4-Teratomas 5-metastasis from other cancers

Papillary Cancer The most common malignant thyroid tumor (70-80 of all cancers) Women predominance Age 38-45 Accounts for 90 of radiation induced thyroid cancer Prognosis directly related to tumor size

bull Papillary Cancer

1Histologic1 Psammoma bodies

2 Orphan Ann nucleus

2Multicentric 30-50

3Spread via Lymphatics- propensity for cervical node involvement

4Invasion of adjacent structures and distant mets uncommon

FOLLICULAR THYROID CANCER1Usually Encapsulated2More Common Among Older Patients3Woman gt Man4More Aggressive amp Less Curable Than Papillary5Vascular Invasion (veins and arteries) within the thyroid gland is common6Blood Spread (lung and bone)7Types

1 Follicular carcinoma 2 Follicular carcinoma variant Minimally Invasive Hurthle Cell

8Rarely associated with radiation exposure

Huumlrthle Cell Neoplasms

1More aggressive than other differentiated thyroid carcinomas (higher metslower survival rates)

2Less affinity for I131

3Need to differentiate from benignmalignant

4Metastasis may be more sensitive to I131 than primary

Medullary Thyroid Cancer 1 Usually present as a mass plusmn lymphadenopathy

2 It can also be diagnosed by fine-needle aspiration biopsy

microscopically typically

3 Family members should be screened for calcitonin

elevation andor for the RET proto-oncogene mutation

4 Not associated with radiation exposure

5 Residual disease (following surgery) or recurrence can be

detected by measuring calcitonin

Medullary Thyroid Cancer Occurs in Four Clinical Settings

I- Sporadic

180 of all cases of medullary thyroid cancer

2Typically unilateral

3No associated endocrinopathies

4Peak onset 40 - 60

5Females predominance 32 ratio

6One third will present with intractable diarrhea

Diarrhea is caused by increased gastrointestinal secretion and hypermotility due to

the hormones secreted by the tumor (calcitonin prostaglandins serotonin or VIP)

II-MEN II-A (Sipple Syndrome)

(Multiple Endocrine Neoplasia II A)

1Sipple syndrome has

[1] bilateral medullary carcinoma

[2] pheochromocytoma

[3] hyperparathyroidism

2This syndrome is inherited in an autosomal dominant fashion

Because of this males and females are equally affected

3Peak incidence of medullary carcinoma in these patients is in the

30s

III-MEN II B

1This syndrome has

[1] medullary carcinoma

[2] Pheochromocytoma

[3] mucosal ganglioneuromas and Marfanoid habitus

2Inheritance is autosomal dominant as in MEN IIA (m=f)

3Pheochromocytomas must be detected prior to any operation

4The idea here is to remove the pheochromocytoma first to remove

the risk of severe hypertensive episodes while the thyroid or

parathyroid is being operated on

IV-Inherited medullary carcinoma without associated endocrinopathies

This form of medullary carcinoma is the least aggressive Like other types of thyroid cancers the peak incidence is

between the ages of 40 and 50

Anaplastic cancer

1)Peak onset age 65 and older

Very rare in young patients

2)Males more common than females by 2 to 1 ratio

3)Undifferentiated

4)May arise many years (gt20) following radiation

exposure

5)Neck mass usually large diffuse and very hard

6)Rapidly growing often inoperable highly recurrent

7) Invade locally metastasize both locally and distantly

(to lungs or bones)

8) Cervical metastasis are present in the vast majority

(over 90) of cases at the time of diagnosis

9) Mean survival 6 months

10) Often requires the patient to get a tracheostomy to

maintain their airway

STAGING OF THYROID CANCER

In differentiated thyroid carcinoma several classification and

staging systems have been introduced However no clear

consensus has emerged favoring any one method over another

bull AMES systemAGES SystemGAMES system

bull TNM system

bull MACIS system

bull University of Chicago system

bull Ohio State University system

bull National Thyroid Cancer Treatment Cooperative Study

(NTCTCS)

TNM Staging bull Primary tumor (T) (All categories may be subdivided into (a)

solitary tumor or (b) multifocal tumor)

TX Primary tumor cannot be assessed

T0 No evidence of primary tumor

T1 Tumor le 2 cm limited to the thyroid

T2 Tumor gt 2 cm but le4 cm limited to the thyroid

T3 Tumor gt 4 cm limited to the thyroid or any tumor with

minimal extrathyroid extension (eg extension to

sternothyroid muscle or perithyroid soft tissues)

bull T4a Tumor of any size extending beyond the thyroid capsule to invade subcutaneous soft tissues larynx trachea esophagus or recurrent laryngeal nerve

bull T4b Tumor invades prevertebral fascia or encases carotid artery or mediastinal vessels

All anaplastic carcinomas are considered T4 tumorsbull T4a Intrathyroidal anaplastic carcinomamdashsurgically resectable bull T4b Extrathyroidal anaplastic carcinomamdashsurgically

unresectable

bull Regional lymph nodes (N) (Regional lymph nodes are the central compartment lateral cervical and upper

mediastinal lNs)

bull NX Regional lymph nodes cannot be assessed bull N0 No regional lymph node metastasis bull N1 Regional lymph node metastasis

bull N1a Metastasis to level VI (pretracheal paratracheal and prelaryngealDelphian on the cricothyroid membrane (precricoid) lymph nodes)

bull N1b Metastasis to unilateral or bilateral cervical or superior mediastinal lymph nodes

bull Distant metastases (M) bull MX Distant metastasis cannot be assessed bull M0 No distant metastasis bull M1 Distant metastasis

AJCC Stage Groupings Papillary or follicular thyroid cancer

bull Younger than 45 yearsbull Stage I

bull Any T any N M0 bull Stage II

bull Any T any N M1

bull Age 45 years and olderbull Stage I

bull T1 N0 M0bull Stage II

bull T2 N0 M0 bull Stage III

bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0

Papillary or follicular thyroid cancer

Age 45 years and older

Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T3 N1b M0 T2 N1b M0 T4a N1b M0

Stage IVB T4b any N M0

Stage IVC Any T any N M1

Stage I

T1 N0 M0

Stage II

T2 N0 M0

Stage III

T3 N0 M0

T1 N1a M0

T2 N1a M0

T3 N1a M0

Medullary thyroid cancer bullStage I

bull T1 N0 M0 bullStage II

bull T2 N0 M0bullStage III

bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0

Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T2 N1b M0 T3 N1b M0 T4a N1b M0

Stage IVB T4b any N M0

Stage IVC Any T any N M1

bull Anaplastic thyroid cancer

bull All anaplastic carcinomas are considered stage IV

bull Stage IVA bull T4a any N M0

bull Stage IVB bull T4b any N M0

bull Stage IVC bull Any T any N M1

bull University of Chicago systembull Class Imdashdisease limited to the thyroid glandbull Class IImdashlymph node involvementbull Class IIImdashextrathyroidal invasionbull Class IVmdashdistant metastases

PROGNOSIS

PROGNOSIS

Prognostic schemes GAMES scoring (PAPILLARY amp

FOLLICULAR CANCER)bullG GradebullA Age of patient when tumor discoveredbullM Metastases of the tumor (other than Neck LN)bullE Extent of primary tumorbullS Size of tumor (gt5 cm)bullThe patient is then placed into a high or low risk category

Prognostic Risk Classification for Patients with Well-Differentiated Thyroid Cancer (GAMES )

Low Risk High Riskbull Grade Well Differentiated Poorly Differentiated

bull Age lt40 gt40

bull Mets None Regional or Distant

bull Extent No local extension Capsular invasion intrathyroidal extrathyroidal

bull Sex Female Male

MACIS ScoringbullDeveloped by the Mayo Clinic for stagingbullIt is known to be the most accurate predictor of a patients outcome with papillary thyroid cancer (M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)bullMAICS Score 20 year Survival

lt 6 = 99 6-7 = 89 7-8 = 56 gt 8 = 24

Treatment

Stage I and II Papillary and FollicularI-Total thyroidectomy bull Rationale1048708 Bilateral cancers are common (30-85)1048708 improved effectiveness for I131 ablation1048708 lowers dose needed for I131 ablation1048708 allows fu with thyroglobulin levels1048708 decreased recurrence in all groups1048708 improved survival in high risk pts1048708 Decreased risk of pulmonary metsbull Disadvantage higher incidence of hypoparathyroidism but this

complication may be reduced when a small amount of tissue remains on the contralateral side

II-Lobectomy

bull Rationale

1048708 Most patients are low risk and excellent prognosis

1048708 Role of adjuvant treatment not defined

1048708 Complications of Total

1048708 Occult multicentric tumor not clinically significant

1048708 Most local recurrences treated with surgery

1048708 Excellent outcome with lobectomy in low risk patients

bull Disadvantage

bull approximately 5 to 10 of patients will have a recurrence

Indications for total Thyroidectomy OR lobectomy (all present)

bull Age 15 y - 45 ybull No prior radiationbull No distant metastasesbull No cervical lymph node metastasesbull No extrathyroidal extensionbull Tumor lt 4 cm in diameterbull No aggressive variant

When complete total thyroidectomy after lobectomybull Aggressive variantbull Macroscopic multifocal diseasebull Positive isthmus marginsbull Cervical lymph node metastasesbull Extrathyroidal extension

Aggressive=Tall cell columnar cell insular oxyphilic or poorly differentiated features

bull Node removal

bull Selective node removal can be performed and radical

neck dissection is usually not required

bull This results in a decreased recurrence rate but has not

been shown to improve survival

Thyroid carcinoma after lobectomy for benign lesions

I-Completion of thyroidectomy

bull gt 4 cm

bull Positive margins

bull Extra-thyroidal invasion (T3 or T4(

II- Completion of Thyroidectomy or follow

up

bull Clinically suspicious lymph node

contralateral lesion or perithyroidal node

bull Aggressive variant

bull Macroscopic multifocal disease

bull ge1 cm in diameter

III- follow up

bull Negative margins

bull No contralateral lesion

bull lt 1 cm in diameter

bull No suspicious lymph

node

POSTSURGICAL EVALUATION AFTER THYROIDECTOMY

I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +

antithyroglobulin antibodies)

II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan

Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT

bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)

Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas

Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant

Pretherapy whole body iodine scan

bullIf performed a pretherapy scan should use a low dose of 131I

(1 to 5 mCi) or 123I

bull To detect residual thyroid tissue thyroid cancer and metastatic foci

bull To reduce the potential for sublethal radiation stunning of thyroid tissue that

prevents optimal uptake of future 131I therapy

bullStunning is defined as a reduction in uptake of the 131I

therapy dose induced by a pretreatment diagnostic dose

Dose of RAI

bullThe dosing of 131I for ablation is somewhat controversial

bullLow-dose ablation with less than 30 mCi administered on

an outpatient basis

bull For low-risk young patients

bullHigh-dose ablation with100 to 200 mCi

bull For high-risk patients

bull300 mCi

bull For all patients with metastatic disease that treated with repeated

therapeutic doses of 131I

Replacement therapy

bullPostoperative treatment with exogenous thyroid hormone

in doses sufficient to suppress thyroid-stimulating hormone

(TSH) with development of thyrotoxic manifestations

decreases incidence of recurrence

bullAdministration of Thyroid Hormone

To suppress TSH and growth of any residual thyroid

To maintain patient euthyroid

o Maintain TSH level 01uUml in low risk pts

o Maintain TSH Level lt 01uUml in high risk pts

Stage III Papillary and Follicular

A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease

B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients

Stage IV Papillary and Follicular 1) Adequate uptake of I131

bull I131

1) Inadequate uptake or not sensitive to I131

i Localized lesions

1) Radiation therapy

2) Resection of limited metastases dont uptake of I131

iiDisseminated disease

1) TSH suppression with thyroxine is effective

2) Chemotherapy has been reported to produce occasional complete

responses of long duration

3) Clinical trials testing new approaches to this disease

Medullary Thyroid Cancer treatment

bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck

dissections Why

bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival

advantage

bull Radioactive iodine has no place in the treatment of patients with MTC

bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in

patients with metastatic disease

bull No single drug regimen can be considered standard

bull Some patients with distant metastases will experience prolonged survival and can

be observed until they become symptomatic

Anaplastic Thyroid Cancer bull Surgery

bull Tracheostomy is frequently necessary

bull If the disease is confined to the local area which is rare total

thyroidectomy is warranted to reduce symptoms caused by the

tumor mass

bull Radiation therapy

bull Used in patients who are not surgical candidates or whose tumor

cannot be surgically excised

Anaplastic Thyroid Cancer bull Chemotherapy

bull Produce partial remissions in some patients

bull Approximately 30 of patients achieve a partial remission with

doxorubicin

bull The combination of doxorubicin plus cisplatin appears to be more

active than doxorubicin alone and has been reported to produce

more complete responses

Treatment options under clinical evaluation

bull The combination of chemotherapy plus radiation therapy in patients following

complete resection may provide prolonged survival but has not been compared to

any one modality alone

Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30

bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common

site of distant metastasis is the lung

bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type

Treatment of recurrent thyroid cancer

The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations

bull Adequate I131 uptake

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull I131 ablation

bull RT

bull Disseminated

bull I131 ablation

bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has

been reported to produce occasional objective responses usually of short

duration

Treatment of recurrent thyroid cancer

bull Inadequate I131 uptake or insensitive to I131

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull RT

bull Disseminated

bull Systemic chemotherapy

Treatment of recurrent thyroid cancer

Systemic chemotherapy

bull Doxorubicin alone

bull Cisplatin and doxorubicin (better)

bull BAP Cisplatin doxorubicin and bleomycin

bull CVD cyclophosphamide vincristine and dacarbazine

bull Dacarbazine and 5-fluorouracil

bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy

bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT

bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)

bull Improve OS and decrease RR

BAP regimenbull Schedule

bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5

bull Cell typebull Several histologic types of thyroid carcinoma responded but the

best responses were observed in medullary and anaplastic giant-cell carcinomas

bull Effectivenessbull BAP regime can achieve reasonable palliation and probably

increases survival in poor-prognosis thyroid cancers

CVD regimenbull Schedule

bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks

bull Cell typebull Medullary thyroid carcinoma

bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in

patients with advanced MTC

Dacarbazine and 5-fluorouracil

bull Schedule

bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and

12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks

Six cycles

bull Cell type

bull MTC

bull Effectiveness

bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to

have significant activity and was well tolerated

Target therapy

Take home messagesbull FNAC is not adequate for definite diagnosis of follicular

carcinomabull Because the mixed papillary-follicular variant tends to

behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis

bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer

bull Once medullary carcinoma is diagnosed familial predisposition should be checked up

bull If I131 is indicated stunning effect should be avoided

Take home messages

All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary

Risk Factors for Thyroid Cancer1 Neck irradiation

The only well-established risk factor for differentiated thyroid cancer

2 Genetic factors1 Papillary thyroid carcinoma may occur in several rare inherited

syndromes including iFamilial adenomatous polyposis

iiGardners syndrome

iiiCowdens disease

2 Medullary carcinoma in MEN syndrome

3 Other risk factors i History of goiter

ii family history of thyroid disease

iii Female gender

iv Asian race

Clinical Manifestation

bull Thyroid enlargement bull Most patients are euthyroid and present with a thyroid nodule

bull Symptoms such as dysphagia dyspnea and hoarseness usually indicate advanced disease

bull Cervical lymph node enlargement

Investigations

bull Serum TSHbull Fine Needle Aspiration Cytology (FNA)bull High Resolution Thyroid US- helpful in

detecting non palpable nodule and solid versus

cystic lesionbull Thyroid Isotope Scanning- to assess functional activity of

a nodule

bull FNAC indicationsISonar-based criteria

Solid nodule

1 More than 1 cm if associated with sonographic suspious features

2 More than 15 cm in absence of sonographic suspicion

Mixed solid and cystic 1 More than 15 cm if associated with sonographic suspicious features

2 More than 2 cm in absence of sonographic suspicion

Spongiform nodule (microcystic component gt 50 of nodules

IHigh risk Clinical feature

RT exposure

Genetic predisposition

Sonographic suspicious features (hypoechoic microcalcification increased central vascularity infiltrative margin or taller than wide in transverse plan)

Fine Needle AspirationbullProcedure of Choice ndash Fast minimally invasive and few riskbullIncidence of False positive 1bullIncidence of False negative 5bullFNA is not a tissue diagnosisbullLimitation of FNA

bull Cannot distinguish a benign follicular from a malignant lesion (cancer invade capsule)

FNA Results of Thyroid Nodulebull Benign(70) --gt FU 6-12 monthsbull Indeterminate(10) --gt repeat FNA I123 scan bull Follicular neoplasm(5) --gt I123 scan or surgerybull Suspicious (10) --gt surgerybull Carcinoma (5) --gt surgery

Classification and Incidence ofThyroid Cancer

Tumors of Follicular Cell Origin1048708 Differentiated Papillary 75 Follicular 10 Hurthle Cell 51048708 Undifferentiated Anaplastic 5 1-Small cell carcinoma 2-Giant cell carcinoma

Tumors of Parafollicular cells Medullary 5

Other 1 1-sarcomas 2-lymphomas 3-epidermoid carcinomas 4-Teratomas 5-metastasis from other cancers

Papillary Cancer The most common malignant thyroid tumor (70-80 of all cancers) Women predominance Age 38-45 Accounts for 90 of radiation induced thyroid cancer Prognosis directly related to tumor size

bull Papillary Cancer

1Histologic1 Psammoma bodies

2 Orphan Ann nucleus

2Multicentric 30-50

3Spread via Lymphatics- propensity for cervical node involvement

4Invasion of adjacent structures and distant mets uncommon

FOLLICULAR THYROID CANCER1Usually Encapsulated2More Common Among Older Patients3Woman gt Man4More Aggressive amp Less Curable Than Papillary5Vascular Invasion (veins and arteries) within the thyroid gland is common6Blood Spread (lung and bone)7Types

1 Follicular carcinoma 2 Follicular carcinoma variant Minimally Invasive Hurthle Cell

8Rarely associated with radiation exposure

Huumlrthle Cell Neoplasms

1More aggressive than other differentiated thyroid carcinomas (higher metslower survival rates)

2Less affinity for I131

3Need to differentiate from benignmalignant

4Metastasis may be more sensitive to I131 than primary

Medullary Thyroid Cancer 1 Usually present as a mass plusmn lymphadenopathy

2 It can also be diagnosed by fine-needle aspiration biopsy

microscopically typically

3 Family members should be screened for calcitonin

elevation andor for the RET proto-oncogene mutation

4 Not associated with radiation exposure

5 Residual disease (following surgery) or recurrence can be

detected by measuring calcitonin

Medullary Thyroid Cancer Occurs in Four Clinical Settings

I- Sporadic

180 of all cases of medullary thyroid cancer

2Typically unilateral

3No associated endocrinopathies

4Peak onset 40 - 60

5Females predominance 32 ratio

6One third will present with intractable diarrhea

Diarrhea is caused by increased gastrointestinal secretion and hypermotility due to

the hormones secreted by the tumor (calcitonin prostaglandins serotonin or VIP)

II-MEN II-A (Sipple Syndrome)

(Multiple Endocrine Neoplasia II A)

1Sipple syndrome has

[1] bilateral medullary carcinoma

[2] pheochromocytoma

[3] hyperparathyroidism

2This syndrome is inherited in an autosomal dominant fashion

Because of this males and females are equally affected

3Peak incidence of medullary carcinoma in these patients is in the

30s

III-MEN II B

1This syndrome has

[1] medullary carcinoma

[2] Pheochromocytoma

[3] mucosal ganglioneuromas and Marfanoid habitus

2Inheritance is autosomal dominant as in MEN IIA (m=f)

3Pheochromocytomas must be detected prior to any operation

4The idea here is to remove the pheochromocytoma first to remove

the risk of severe hypertensive episodes while the thyroid or

parathyroid is being operated on

IV-Inherited medullary carcinoma without associated endocrinopathies

This form of medullary carcinoma is the least aggressive Like other types of thyroid cancers the peak incidence is

between the ages of 40 and 50

Anaplastic cancer

1)Peak onset age 65 and older

Very rare in young patients

2)Males more common than females by 2 to 1 ratio

3)Undifferentiated

4)May arise many years (gt20) following radiation

exposure

5)Neck mass usually large diffuse and very hard

6)Rapidly growing often inoperable highly recurrent

7) Invade locally metastasize both locally and distantly

(to lungs or bones)

8) Cervical metastasis are present in the vast majority

(over 90) of cases at the time of diagnosis

9) Mean survival 6 months

10) Often requires the patient to get a tracheostomy to

maintain their airway

STAGING OF THYROID CANCER

In differentiated thyroid carcinoma several classification and

staging systems have been introduced However no clear

consensus has emerged favoring any one method over another

bull AMES systemAGES SystemGAMES system

bull TNM system

bull MACIS system

bull University of Chicago system

bull Ohio State University system

bull National Thyroid Cancer Treatment Cooperative Study

(NTCTCS)

TNM Staging bull Primary tumor (T) (All categories may be subdivided into (a)

solitary tumor or (b) multifocal tumor)

TX Primary tumor cannot be assessed

T0 No evidence of primary tumor

T1 Tumor le 2 cm limited to the thyroid

T2 Tumor gt 2 cm but le4 cm limited to the thyroid

T3 Tumor gt 4 cm limited to the thyroid or any tumor with

minimal extrathyroid extension (eg extension to

sternothyroid muscle or perithyroid soft tissues)

bull T4a Tumor of any size extending beyond the thyroid capsule to invade subcutaneous soft tissues larynx trachea esophagus or recurrent laryngeal nerve

bull T4b Tumor invades prevertebral fascia or encases carotid artery or mediastinal vessels

All anaplastic carcinomas are considered T4 tumorsbull T4a Intrathyroidal anaplastic carcinomamdashsurgically resectable bull T4b Extrathyroidal anaplastic carcinomamdashsurgically

unresectable

bull Regional lymph nodes (N) (Regional lymph nodes are the central compartment lateral cervical and upper

mediastinal lNs)

bull NX Regional lymph nodes cannot be assessed bull N0 No regional lymph node metastasis bull N1 Regional lymph node metastasis

bull N1a Metastasis to level VI (pretracheal paratracheal and prelaryngealDelphian on the cricothyroid membrane (precricoid) lymph nodes)

bull N1b Metastasis to unilateral or bilateral cervical or superior mediastinal lymph nodes

bull Distant metastases (M) bull MX Distant metastasis cannot be assessed bull M0 No distant metastasis bull M1 Distant metastasis

AJCC Stage Groupings Papillary or follicular thyroid cancer

bull Younger than 45 yearsbull Stage I

bull Any T any N M0 bull Stage II

bull Any T any N M1

bull Age 45 years and olderbull Stage I

bull T1 N0 M0bull Stage II

bull T2 N0 M0 bull Stage III

bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0

Papillary or follicular thyroid cancer

Age 45 years and older

Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T3 N1b M0 T2 N1b M0 T4a N1b M0

Stage IVB T4b any N M0

Stage IVC Any T any N M1

Stage I

T1 N0 M0

Stage II

T2 N0 M0

Stage III

T3 N0 M0

T1 N1a M0

T2 N1a M0

T3 N1a M0

Medullary thyroid cancer bullStage I

bull T1 N0 M0 bullStage II

bull T2 N0 M0bullStage III

bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0

Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T2 N1b M0 T3 N1b M0 T4a N1b M0

Stage IVB T4b any N M0

Stage IVC Any T any N M1

bull Anaplastic thyroid cancer

bull All anaplastic carcinomas are considered stage IV

bull Stage IVA bull T4a any N M0

bull Stage IVB bull T4b any N M0

bull Stage IVC bull Any T any N M1

bull University of Chicago systembull Class Imdashdisease limited to the thyroid glandbull Class IImdashlymph node involvementbull Class IIImdashextrathyroidal invasionbull Class IVmdashdistant metastases

PROGNOSIS

PROGNOSIS

Prognostic schemes GAMES scoring (PAPILLARY amp

FOLLICULAR CANCER)bullG GradebullA Age of patient when tumor discoveredbullM Metastases of the tumor (other than Neck LN)bullE Extent of primary tumorbullS Size of tumor (gt5 cm)bullThe patient is then placed into a high or low risk category

Prognostic Risk Classification for Patients with Well-Differentiated Thyroid Cancer (GAMES )

Low Risk High Riskbull Grade Well Differentiated Poorly Differentiated

bull Age lt40 gt40

bull Mets None Regional or Distant

bull Extent No local extension Capsular invasion intrathyroidal extrathyroidal

bull Sex Female Male

MACIS ScoringbullDeveloped by the Mayo Clinic for stagingbullIt is known to be the most accurate predictor of a patients outcome with papillary thyroid cancer (M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)bullMAICS Score 20 year Survival

lt 6 = 99 6-7 = 89 7-8 = 56 gt 8 = 24

Treatment

Stage I and II Papillary and FollicularI-Total thyroidectomy bull Rationale1048708 Bilateral cancers are common (30-85)1048708 improved effectiveness for I131 ablation1048708 lowers dose needed for I131 ablation1048708 allows fu with thyroglobulin levels1048708 decreased recurrence in all groups1048708 improved survival in high risk pts1048708 Decreased risk of pulmonary metsbull Disadvantage higher incidence of hypoparathyroidism but this

complication may be reduced when a small amount of tissue remains on the contralateral side

II-Lobectomy

bull Rationale

1048708 Most patients are low risk and excellent prognosis

1048708 Role of adjuvant treatment not defined

1048708 Complications of Total

1048708 Occult multicentric tumor not clinically significant

1048708 Most local recurrences treated with surgery

1048708 Excellent outcome with lobectomy in low risk patients

bull Disadvantage

bull approximately 5 to 10 of patients will have a recurrence

Indications for total Thyroidectomy OR lobectomy (all present)

bull Age 15 y - 45 ybull No prior radiationbull No distant metastasesbull No cervical lymph node metastasesbull No extrathyroidal extensionbull Tumor lt 4 cm in diameterbull No aggressive variant

When complete total thyroidectomy after lobectomybull Aggressive variantbull Macroscopic multifocal diseasebull Positive isthmus marginsbull Cervical lymph node metastasesbull Extrathyroidal extension

Aggressive=Tall cell columnar cell insular oxyphilic or poorly differentiated features

bull Node removal

bull Selective node removal can be performed and radical

neck dissection is usually not required

bull This results in a decreased recurrence rate but has not

been shown to improve survival

Thyroid carcinoma after lobectomy for benign lesions

I-Completion of thyroidectomy

bull gt 4 cm

bull Positive margins

bull Extra-thyroidal invasion (T3 or T4(

II- Completion of Thyroidectomy or follow

up

bull Clinically suspicious lymph node

contralateral lesion or perithyroidal node

bull Aggressive variant

bull Macroscopic multifocal disease

bull ge1 cm in diameter

III- follow up

bull Negative margins

bull No contralateral lesion

bull lt 1 cm in diameter

bull No suspicious lymph

node

POSTSURGICAL EVALUATION AFTER THYROIDECTOMY

I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +

antithyroglobulin antibodies)

II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan

Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT

bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)

Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas

Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant

Pretherapy whole body iodine scan

bullIf performed a pretherapy scan should use a low dose of 131I

(1 to 5 mCi) or 123I

bull To detect residual thyroid tissue thyroid cancer and metastatic foci

bull To reduce the potential for sublethal radiation stunning of thyroid tissue that

prevents optimal uptake of future 131I therapy

bullStunning is defined as a reduction in uptake of the 131I

therapy dose induced by a pretreatment diagnostic dose

Dose of RAI

bullThe dosing of 131I for ablation is somewhat controversial

bullLow-dose ablation with less than 30 mCi administered on

an outpatient basis

bull For low-risk young patients

bullHigh-dose ablation with100 to 200 mCi

bull For high-risk patients

bull300 mCi

bull For all patients with metastatic disease that treated with repeated

therapeutic doses of 131I

Replacement therapy

bullPostoperative treatment with exogenous thyroid hormone

in doses sufficient to suppress thyroid-stimulating hormone

(TSH) with development of thyrotoxic manifestations

decreases incidence of recurrence

bullAdministration of Thyroid Hormone

To suppress TSH and growth of any residual thyroid

To maintain patient euthyroid

o Maintain TSH level 01uUml in low risk pts

o Maintain TSH Level lt 01uUml in high risk pts

Stage III Papillary and Follicular

A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease

B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients

Stage IV Papillary and Follicular 1) Adequate uptake of I131

bull I131

1) Inadequate uptake or not sensitive to I131

i Localized lesions

1) Radiation therapy

2) Resection of limited metastases dont uptake of I131

iiDisseminated disease

1) TSH suppression with thyroxine is effective

2) Chemotherapy has been reported to produce occasional complete

responses of long duration

3) Clinical trials testing new approaches to this disease

Medullary Thyroid Cancer treatment

bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck

dissections Why

bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival

advantage

bull Radioactive iodine has no place in the treatment of patients with MTC

bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in

patients with metastatic disease

bull No single drug regimen can be considered standard

bull Some patients with distant metastases will experience prolonged survival and can

be observed until they become symptomatic

Anaplastic Thyroid Cancer bull Surgery

bull Tracheostomy is frequently necessary

bull If the disease is confined to the local area which is rare total

thyroidectomy is warranted to reduce symptoms caused by the

tumor mass

bull Radiation therapy

bull Used in patients who are not surgical candidates or whose tumor

cannot be surgically excised

Anaplastic Thyroid Cancer bull Chemotherapy

bull Produce partial remissions in some patients

bull Approximately 30 of patients achieve a partial remission with

doxorubicin

bull The combination of doxorubicin plus cisplatin appears to be more

active than doxorubicin alone and has been reported to produce

more complete responses

Treatment options under clinical evaluation

bull The combination of chemotherapy plus radiation therapy in patients following

complete resection may provide prolonged survival but has not been compared to

any one modality alone

Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30

bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common

site of distant metastasis is the lung

bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type

Treatment of recurrent thyroid cancer

The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations

bull Adequate I131 uptake

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull I131 ablation

bull RT

bull Disseminated

bull I131 ablation

bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has

been reported to produce occasional objective responses usually of short

duration

Treatment of recurrent thyroid cancer

bull Inadequate I131 uptake or insensitive to I131

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull RT

bull Disseminated

bull Systemic chemotherapy

Treatment of recurrent thyroid cancer

Systemic chemotherapy

bull Doxorubicin alone

bull Cisplatin and doxorubicin (better)

bull BAP Cisplatin doxorubicin and bleomycin

bull CVD cyclophosphamide vincristine and dacarbazine

bull Dacarbazine and 5-fluorouracil

bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy

bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT

bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)

bull Improve OS and decrease RR

BAP regimenbull Schedule

bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5

bull Cell typebull Several histologic types of thyroid carcinoma responded but the

best responses were observed in medullary and anaplastic giant-cell carcinomas

bull Effectivenessbull BAP regime can achieve reasonable palliation and probably

increases survival in poor-prognosis thyroid cancers

CVD regimenbull Schedule

bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks

bull Cell typebull Medullary thyroid carcinoma

bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in

patients with advanced MTC

Dacarbazine and 5-fluorouracil

bull Schedule

bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and

12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks

Six cycles

bull Cell type

bull MTC

bull Effectiveness

bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to

have significant activity and was well tolerated

Target therapy

Take home messagesbull FNAC is not adequate for definite diagnosis of follicular

carcinomabull Because the mixed papillary-follicular variant tends to

behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis

bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer

bull Once medullary carcinoma is diagnosed familial predisposition should be checked up

bull If I131 is indicated stunning effect should be avoided

Take home messages

All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary

Clinical Manifestation

bull Thyroid enlargement bull Most patients are euthyroid and present with a thyroid nodule

bull Symptoms such as dysphagia dyspnea and hoarseness usually indicate advanced disease

bull Cervical lymph node enlargement

Investigations

bull Serum TSHbull Fine Needle Aspiration Cytology (FNA)bull High Resolution Thyroid US- helpful in

detecting non palpable nodule and solid versus

cystic lesionbull Thyroid Isotope Scanning- to assess functional activity of

a nodule

bull FNAC indicationsISonar-based criteria

Solid nodule

1 More than 1 cm if associated with sonographic suspious features

2 More than 15 cm in absence of sonographic suspicion

Mixed solid and cystic 1 More than 15 cm if associated with sonographic suspicious features

2 More than 2 cm in absence of sonographic suspicion

Spongiform nodule (microcystic component gt 50 of nodules

IHigh risk Clinical feature

RT exposure

Genetic predisposition

Sonographic suspicious features (hypoechoic microcalcification increased central vascularity infiltrative margin or taller than wide in transverse plan)

Fine Needle AspirationbullProcedure of Choice ndash Fast minimally invasive and few riskbullIncidence of False positive 1bullIncidence of False negative 5bullFNA is not a tissue diagnosisbullLimitation of FNA

bull Cannot distinguish a benign follicular from a malignant lesion (cancer invade capsule)

FNA Results of Thyroid Nodulebull Benign(70) --gt FU 6-12 monthsbull Indeterminate(10) --gt repeat FNA I123 scan bull Follicular neoplasm(5) --gt I123 scan or surgerybull Suspicious (10) --gt surgerybull Carcinoma (5) --gt surgery

Classification and Incidence ofThyroid Cancer

Tumors of Follicular Cell Origin1048708 Differentiated Papillary 75 Follicular 10 Hurthle Cell 51048708 Undifferentiated Anaplastic 5 1-Small cell carcinoma 2-Giant cell carcinoma

Tumors of Parafollicular cells Medullary 5

Other 1 1-sarcomas 2-lymphomas 3-epidermoid carcinomas 4-Teratomas 5-metastasis from other cancers

Papillary Cancer The most common malignant thyroid tumor (70-80 of all cancers) Women predominance Age 38-45 Accounts for 90 of radiation induced thyroid cancer Prognosis directly related to tumor size

bull Papillary Cancer

1Histologic1 Psammoma bodies

2 Orphan Ann nucleus

2Multicentric 30-50

3Spread via Lymphatics- propensity for cervical node involvement

4Invasion of adjacent structures and distant mets uncommon

FOLLICULAR THYROID CANCER1Usually Encapsulated2More Common Among Older Patients3Woman gt Man4More Aggressive amp Less Curable Than Papillary5Vascular Invasion (veins and arteries) within the thyroid gland is common6Blood Spread (lung and bone)7Types

1 Follicular carcinoma 2 Follicular carcinoma variant Minimally Invasive Hurthle Cell

8Rarely associated with radiation exposure

Huumlrthle Cell Neoplasms

1More aggressive than other differentiated thyroid carcinomas (higher metslower survival rates)

2Less affinity for I131

3Need to differentiate from benignmalignant

4Metastasis may be more sensitive to I131 than primary

Medullary Thyroid Cancer 1 Usually present as a mass plusmn lymphadenopathy

2 It can also be diagnosed by fine-needle aspiration biopsy

microscopically typically

3 Family members should be screened for calcitonin

elevation andor for the RET proto-oncogene mutation

4 Not associated with radiation exposure

5 Residual disease (following surgery) or recurrence can be

detected by measuring calcitonin

Medullary Thyroid Cancer Occurs in Four Clinical Settings

I- Sporadic

180 of all cases of medullary thyroid cancer

2Typically unilateral

3No associated endocrinopathies

4Peak onset 40 - 60

5Females predominance 32 ratio

6One third will present with intractable diarrhea

Diarrhea is caused by increased gastrointestinal secretion and hypermotility due to

the hormones secreted by the tumor (calcitonin prostaglandins serotonin or VIP)

II-MEN II-A (Sipple Syndrome)

(Multiple Endocrine Neoplasia II A)

1Sipple syndrome has

[1] bilateral medullary carcinoma

[2] pheochromocytoma

[3] hyperparathyroidism

2This syndrome is inherited in an autosomal dominant fashion

Because of this males and females are equally affected

3Peak incidence of medullary carcinoma in these patients is in the

30s

III-MEN II B

1This syndrome has

[1] medullary carcinoma

[2] Pheochromocytoma

[3] mucosal ganglioneuromas and Marfanoid habitus

2Inheritance is autosomal dominant as in MEN IIA (m=f)

3Pheochromocytomas must be detected prior to any operation

4The idea here is to remove the pheochromocytoma first to remove

the risk of severe hypertensive episodes while the thyroid or

parathyroid is being operated on

IV-Inherited medullary carcinoma without associated endocrinopathies

This form of medullary carcinoma is the least aggressive Like other types of thyroid cancers the peak incidence is

between the ages of 40 and 50

Anaplastic cancer

1)Peak onset age 65 and older

Very rare in young patients

2)Males more common than females by 2 to 1 ratio

3)Undifferentiated

4)May arise many years (gt20) following radiation

exposure

5)Neck mass usually large diffuse and very hard

6)Rapidly growing often inoperable highly recurrent

7) Invade locally metastasize both locally and distantly

(to lungs or bones)

8) Cervical metastasis are present in the vast majority

(over 90) of cases at the time of diagnosis

9) Mean survival 6 months

10) Often requires the patient to get a tracheostomy to

maintain their airway

STAGING OF THYROID CANCER

In differentiated thyroid carcinoma several classification and

staging systems have been introduced However no clear

consensus has emerged favoring any one method over another

bull AMES systemAGES SystemGAMES system

bull TNM system

bull MACIS system

bull University of Chicago system

bull Ohio State University system

bull National Thyroid Cancer Treatment Cooperative Study

(NTCTCS)

TNM Staging bull Primary tumor (T) (All categories may be subdivided into (a)

solitary tumor or (b) multifocal tumor)

TX Primary tumor cannot be assessed

T0 No evidence of primary tumor

T1 Tumor le 2 cm limited to the thyroid

T2 Tumor gt 2 cm but le4 cm limited to the thyroid

T3 Tumor gt 4 cm limited to the thyroid or any tumor with

minimal extrathyroid extension (eg extension to

sternothyroid muscle or perithyroid soft tissues)

bull T4a Tumor of any size extending beyond the thyroid capsule to invade subcutaneous soft tissues larynx trachea esophagus or recurrent laryngeal nerve

bull T4b Tumor invades prevertebral fascia or encases carotid artery or mediastinal vessels

All anaplastic carcinomas are considered T4 tumorsbull T4a Intrathyroidal anaplastic carcinomamdashsurgically resectable bull T4b Extrathyroidal anaplastic carcinomamdashsurgically

unresectable

bull Regional lymph nodes (N) (Regional lymph nodes are the central compartment lateral cervical and upper

mediastinal lNs)

bull NX Regional lymph nodes cannot be assessed bull N0 No regional lymph node metastasis bull N1 Regional lymph node metastasis

bull N1a Metastasis to level VI (pretracheal paratracheal and prelaryngealDelphian on the cricothyroid membrane (precricoid) lymph nodes)

bull N1b Metastasis to unilateral or bilateral cervical or superior mediastinal lymph nodes

bull Distant metastases (M) bull MX Distant metastasis cannot be assessed bull M0 No distant metastasis bull M1 Distant metastasis

AJCC Stage Groupings Papillary or follicular thyroid cancer

bull Younger than 45 yearsbull Stage I

bull Any T any N M0 bull Stage II

bull Any T any N M1

bull Age 45 years and olderbull Stage I

bull T1 N0 M0bull Stage II

bull T2 N0 M0 bull Stage III

bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0

Papillary or follicular thyroid cancer

Age 45 years and older

Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T3 N1b M0 T2 N1b M0 T4a N1b M0

Stage IVB T4b any N M0

Stage IVC Any T any N M1

Stage I

T1 N0 M0

Stage II

T2 N0 M0

Stage III

T3 N0 M0

T1 N1a M0

T2 N1a M0

T3 N1a M0

Medullary thyroid cancer bullStage I

bull T1 N0 M0 bullStage II

bull T2 N0 M0bullStage III

bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0

Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T2 N1b M0 T3 N1b M0 T4a N1b M0

Stage IVB T4b any N M0

Stage IVC Any T any N M1

bull Anaplastic thyroid cancer

bull All anaplastic carcinomas are considered stage IV

bull Stage IVA bull T4a any N M0

bull Stage IVB bull T4b any N M0

bull Stage IVC bull Any T any N M1

bull University of Chicago systembull Class Imdashdisease limited to the thyroid glandbull Class IImdashlymph node involvementbull Class IIImdashextrathyroidal invasionbull Class IVmdashdistant metastases

PROGNOSIS

PROGNOSIS

Prognostic schemes GAMES scoring (PAPILLARY amp

FOLLICULAR CANCER)bullG GradebullA Age of patient when tumor discoveredbullM Metastases of the tumor (other than Neck LN)bullE Extent of primary tumorbullS Size of tumor (gt5 cm)bullThe patient is then placed into a high or low risk category

Prognostic Risk Classification for Patients with Well-Differentiated Thyroid Cancer (GAMES )

Low Risk High Riskbull Grade Well Differentiated Poorly Differentiated

bull Age lt40 gt40

bull Mets None Regional or Distant

bull Extent No local extension Capsular invasion intrathyroidal extrathyroidal

bull Sex Female Male

MACIS ScoringbullDeveloped by the Mayo Clinic for stagingbullIt is known to be the most accurate predictor of a patients outcome with papillary thyroid cancer (M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)bullMAICS Score 20 year Survival

lt 6 = 99 6-7 = 89 7-8 = 56 gt 8 = 24

Treatment

Stage I and II Papillary and FollicularI-Total thyroidectomy bull Rationale1048708 Bilateral cancers are common (30-85)1048708 improved effectiveness for I131 ablation1048708 lowers dose needed for I131 ablation1048708 allows fu with thyroglobulin levels1048708 decreased recurrence in all groups1048708 improved survival in high risk pts1048708 Decreased risk of pulmonary metsbull Disadvantage higher incidence of hypoparathyroidism but this

complication may be reduced when a small amount of tissue remains on the contralateral side

II-Lobectomy

bull Rationale

1048708 Most patients are low risk and excellent prognosis

1048708 Role of adjuvant treatment not defined

1048708 Complications of Total

1048708 Occult multicentric tumor not clinically significant

1048708 Most local recurrences treated with surgery

1048708 Excellent outcome with lobectomy in low risk patients

bull Disadvantage

bull approximately 5 to 10 of patients will have a recurrence

Indications for total Thyroidectomy OR lobectomy (all present)

bull Age 15 y - 45 ybull No prior radiationbull No distant metastasesbull No cervical lymph node metastasesbull No extrathyroidal extensionbull Tumor lt 4 cm in diameterbull No aggressive variant

When complete total thyroidectomy after lobectomybull Aggressive variantbull Macroscopic multifocal diseasebull Positive isthmus marginsbull Cervical lymph node metastasesbull Extrathyroidal extension

Aggressive=Tall cell columnar cell insular oxyphilic or poorly differentiated features

bull Node removal

bull Selective node removal can be performed and radical

neck dissection is usually not required

bull This results in a decreased recurrence rate but has not

been shown to improve survival

Thyroid carcinoma after lobectomy for benign lesions

I-Completion of thyroidectomy

bull gt 4 cm

bull Positive margins

bull Extra-thyroidal invasion (T3 or T4(

II- Completion of Thyroidectomy or follow

up

bull Clinically suspicious lymph node

contralateral lesion or perithyroidal node

bull Aggressive variant

bull Macroscopic multifocal disease

bull ge1 cm in diameter

III- follow up

bull Negative margins

bull No contralateral lesion

bull lt 1 cm in diameter

bull No suspicious lymph

node

POSTSURGICAL EVALUATION AFTER THYROIDECTOMY

I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +

antithyroglobulin antibodies)

II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan

Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT

bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)

Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas

Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant

Pretherapy whole body iodine scan

bullIf performed a pretherapy scan should use a low dose of 131I

(1 to 5 mCi) or 123I

bull To detect residual thyroid tissue thyroid cancer and metastatic foci

bull To reduce the potential for sublethal radiation stunning of thyroid tissue that

prevents optimal uptake of future 131I therapy

bullStunning is defined as a reduction in uptake of the 131I

therapy dose induced by a pretreatment diagnostic dose

Dose of RAI

bullThe dosing of 131I for ablation is somewhat controversial

bullLow-dose ablation with less than 30 mCi administered on

an outpatient basis

bull For low-risk young patients

bullHigh-dose ablation with100 to 200 mCi

bull For high-risk patients

bull300 mCi

bull For all patients with metastatic disease that treated with repeated

therapeutic doses of 131I

Replacement therapy

bullPostoperative treatment with exogenous thyroid hormone

in doses sufficient to suppress thyroid-stimulating hormone

(TSH) with development of thyrotoxic manifestations

decreases incidence of recurrence

bullAdministration of Thyroid Hormone

To suppress TSH and growth of any residual thyroid

To maintain patient euthyroid

o Maintain TSH level 01uUml in low risk pts

o Maintain TSH Level lt 01uUml in high risk pts

Stage III Papillary and Follicular

A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease

B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients

Stage IV Papillary and Follicular 1) Adequate uptake of I131

bull I131

1) Inadequate uptake or not sensitive to I131

i Localized lesions

1) Radiation therapy

2) Resection of limited metastases dont uptake of I131

iiDisseminated disease

1) TSH suppression with thyroxine is effective

2) Chemotherapy has been reported to produce occasional complete

responses of long duration

3) Clinical trials testing new approaches to this disease

Medullary Thyroid Cancer treatment

bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck

dissections Why

bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival

advantage

bull Radioactive iodine has no place in the treatment of patients with MTC

bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in

patients with metastatic disease

bull No single drug regimen can be considered standard

bull Some patients with distant metastases will experience prolonged survival and can

be observed until they become symptomatic

Anaplastic Thyroid Cancer bull Surgery

bull Tracheostomy is frequently necessary

bull If the disease is confined to the local area which is rare total

thyroidectomy is warranted to reduce symptoms caused by the

tumor mass

bull Radiation therapy

bull Used in patients who are not surgical candidates or whose tumor

cannot be surgically excised

Anaplastic Thyroid Cancer bull Chemotherapy

bull Produce partial remissions in some patients

bull Approximately 30 of patients achieve a partial remission with

doxorubicin

bull The combination of doxorubicin plus cisplatin appears to be more

active than doxorubicin alone and has been reported to produce

more complete responses

Treatment options under clinical evaluation

bull The combination of chemotherapy plus radiation therapy in patients following

complete resection may provide prolonged survival but has not been compared to

any one modality alone

Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30

bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common

site of distant metastasis is the lung

bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type

Treatment of recurrent thyroid cancer

The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations

bull Adequate I131 uptake

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull I131 ablation

bull RT

bull Disseminated

bull I131 ablation

bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has

been reported to produce occasional objective responses usually of short

duration

Treatment of recurrent thyroid cancer

bull Inadequate I131 uptake or insensitive to I131

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull RT

bull Disseminated

bull Systemic chemotherapy

Treatment of recurrent thyroid cancer

Systemic chemotherapy

bull Doxorubicin alone

bull Cisplatin and doxorubicin (better)

bull BAP Cisplatin doxorubicin and bleomycin

bull CVD cyclophosphamide vincristine and dacarbazine

bull Dacarbazine and 5-fluorouracil

bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy

bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT

bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)

bull Improve OS and decrease RR

BAP regimenbull Schedule

bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5

bull Cell typebull Several histologic types of thyroid carcinoma responded but the

best responses were observed in medullary and anaplastic giant-cell carcinomas

bull Effectivenessbull BAP regime can achieve reasonable palliation and probably

increases survival in poor-prognosis thyroid cancers

CVD regimenbull Schedule

bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks

bull Cell typebull Medullary thyroid carcinoma

bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in

patients with advanced MTC

Dacarbazine and 5-fluorouracil

bull Schedule

bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and

12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks

Six cycles

bull Cell type

bull MTC

bull Effectiveness

bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to

have significant activity and was well tolerated

Target therapy

Take home messagesbull FNAC is not adequate for definite diagnosis of follicular

carcinomabull Because the mixed papillary-follicular variant tends to

behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis

bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer

bull Once medullary carcinoma is diagnosed familial predisposition should be checked up

bull If I131 is indicated stunning effect should be avoided

Take home messages

All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary

Investigations

bull Serum TSHbull Fine Needle Aspiration Cytology (FNA)bull High Resolution Thyroid US- helpful in

detecting non palpable nodule and solid versus

cystic lesionbull Thyroid Isotope Scanning- to assess functional activity of

a nodule

bull FNAC indicationsISonar-based criteria

Solid nodule

1 More than 1 cm if associated with sonographic suspious features

2 More than 15 cm in absence of sonographic suspicion

Mixed solid and cystic 1 More than 15 cm if associated with sonographic suspicious features

2 More than 2 cm in absence of sonographic suspicion

Spongiform nodule (microcystic component gt 50 of nodules

IHigh risk Clinical feature

RT exposure

Genetic predisposition

Sonographic suspicious features (hypoechoic microcalcification increased central vascularity infiltrative margin or taller than wide in transverse plan)

Fine Needle AspirationbullProcedure of Choice ndash Fast minimally invasive and few riskbullIncidence of False positive 1bullIncidence of False negative 5bullFNA is not a tissue diagnosisbullLimitation of FNA

bull Cannot distinguish a benign follicular from a malignant lesion (cancer invade capsule)

FNA Results of Thyroid Nodulebull Benign(70) --gt FU 6-12 monthsbull Indeterminate(10) --gt repeat FNA I123 scan bull Follicular neoplasm(5) --gt I123 scan or surgerybull Suspicious (10) --gt surgerybull Carcinoma (5) --gt surgery

Classification and Incidence ofThyroid Cancer

Tumors of Follicular Cell Origin1048708 Differentiated Papillary 75 Follicular 10 Hurthle Cell 51048708 Undifferentiated Anaplastic 5 1-Small cell carcinoma 2-Giant cell carcinoma

Tumors of Parafollicular cells Medullary 5

Other 1 1-sarcomas 2-lymphomas 3-epidermoid carcinomas 4-Teratomas 5-metastasis from other cancers

Papillary Cancer The most common malignant thyroid tumor (70-80 of all cancers) Women predominance Age 38-45 Accounts for 90 of radiation induced thyroid cancer Prognosis directly related to tumor size

bull Papillary Cancer

1Histologic1 Psammoma bodies

2 Orphan Ann nucleus

2Multicentric 30-50

3Spread via Lymphatics- propensity for cervical node involvement

4Invasion of adjacent structures and distant mets uncommon

FOLLICULAR THYROID CANCER1Usually Encapsulated2More Common Among Older Patients3Woman gt Man4More Aggressive amp Less Curable Than Papillary5Vascular Invasion (veins and arteries) within the thyroid gland is common6Blood Spread (lung and bone)7Types

1 Follicular carcinoma 2 Follicular carcinoma variant Minimally Invasive Hurthle Cell

8Rarely associated with radiation exposure

Huumlrthle Cell Neoplasms

1More aggressive than other differentiated thyroid carcinomas (higher metslower survival rates)

2Less affinity for I131

3Need to differentiate from benignmalignant

4Metastasis may be more sensitive to I131 than primary

Medullary Thyroid Cancer 1 Usually present as a mass plusmn lymphadenopathy

2 It can also be diagnosed by fine-needle aspiration biopsy

microscopically typically

3 Family members should be screened for calcitonin

elevation andor for the RET proto-oncogene mutation

4 Not associated with radiation exposure

5 Residual disease (following surgery) or recurrence can be

detected by measuring calcitonin

Medullary Thyroid Cancer Occurs in Four Clinical Settings

I- Sporadic

180 of all cases of medullary thyroid cancer

2Typically unilateral

3No associated endocrinopathies

4Peak onset 40 - 60

5Females predominance 32 ratio

6One third will present with intractable diarrhea

Diarrhea is caused by increased gastrointestinal secretion and hypermotility due to

the hormones secreted by the tumor (calcitonin prostaglandins serotonin or VIP)

II-MEN II-A (Sipple Syndrome)

(Multiple Endocrine Neoplasia II A)

1Sipple syndrome has

[1] bilateral medullary carcinoma

[2] pheochromocytoma

[3] hyperparathyroidism

2This syndrome is inherited in an autosomal dominant fashion

Because of this males and females are equally affected

3Peak incidence of medullary carcinoma in these patients is in the

30s

III-MEN II B

1This syndrome has

[1] medullary carcinoma

[2] Pheochromocytoma

[3] mucosal ganglioneuromas and Marfanoid habitus

2Inheritance is autosomal dominant as in MEN IIA (m=f)

3Pheochromocytomas must be detected prior to any operation

4The idea here is to remove the pheochromocytoma first to remove

the risk of severe hypertensive episodes while the thyroid or

parathyroid is being operated on

IV-Inherited medullary carcinoma without associated endocrinopathies

This form of medullary carcinoma is the least aggressive Like other types of thyroid cancers the peak incidence is

between the ages of 40 and 50

Anaplastic cancer

1)Peak onset age 65 and older

Very rare in young patients

2)Males more common than females by 2 to 1 ratio

3)Undifferentiated

4)May arise many years (gt20) following radiation

exposure

5)Neck mass usually large diffuse and very hard

6)Rapidly growing often inoperable highly recurrent

7) Invade locally metastasize both locally and distantly

(to lungs or bones)

8) Cervical metastasis are present in the vast majority

(over 90) of cases at the time of diagnosis

9) Mean survival 6 months

10) Often requires the patient to get a tracheostomy to

maintain their airway

STAGING OF THYROID CANCER

In differentiated thyroid carcinoma several classification and

staging systems have been introduced However no clear

consensus has emerged favoring any one method over another

bull AMES systemAGES SystemGAMES system

bull TNM system

bull MACIS system

bull University of Chicago system

bull Ohio State University system

bull National Thyroid Cancer Treatment Cooperative Study

(NTCTCS)

TNM Staging bull Primary tumor (T) (All categories may be subdivided into (a)

solitary tumor or (b) multifocal tumor)

TX Primary tumor cannot be assessed

T0 No evidence of primary tumor

T1 Tumor le 2 cm limited to the thyroid

T2 Tumor gt 2 cm but le4 cm limited to the thyroid

T3 Tumor gt 4 cm limited to the thyroid or any tumor with

minimal extrathyroid extension (eg extension to

sternothyroid muscle or perithyroid soft tissues)

bull T4a Tumor of any size extending beyond the thyroid capsule to invade subcutaneous soft tissues larynx trachea esophagus or recurrent laryngeal nerve

bull T4b Tumor invades prevertebral fascia or encases carotid artery or mediastinal vessels

All anaplastic carcinomas are considered T4 tumorsbull T4a Intrathyroidal anaplastic carcinomamdashsurgically resectable bull T4b Extrathyroidal anaplastic carcinomamdashsurgically

unresectable

bull Regional lymph nodes (N) (Regional lymph nodes are the central compartment lateral cervical and upper

mediastinal lNs)

bull NX Regional lymph nodes cannot be assessed bull N0 No regional lymph node metastasis bull N1 Regional lymph node metastasis

bull N1a Metastasis to level VI (pretracheal paratracheal and prelaryngealDelphian on the cricothyroid membrane (precricoid) lymph nodes)

bull N1b Metastasis to unilateral or bilateral cervical or superior mediastinal lymph nodes

bull Distant metastases (M) bull MX Distant metastasis cannot be assessed bull M0 No distant metastasis bull M1 Distant metastasis

AJCC Stage Groupings Papillary or follicular thyroid cancer

bull Younger than 45 yearsbull Stage I

bull Any T any N M0 bull Stage II

bull Any T any N M1

bull Age 45 years and olderbull Stage I

bull T1 N0 M0bull Stage II

bull T2 N0 M0 bull Stage III

bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0

Papillary or follicular thyroid cancer

Age 45 years and older

Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T3 N1b M0 T2 N1b M0 T4a N1b M0

Stage IVB T4b any N M0

Stage IVC Any T any N M1

Stage I

T1 N0 M0

Stage II

T2 N0 M0

Stage III

T3 N0 M0

T1 N1a M0

T2 N1a M0

T3 N1a M0

Medullary thyroid cancer bullStage I

bull T1 N0 M0 bullStage II

bull T2 N0 M0bullStage III

bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0

Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T2 N1b M0 T3 N1b M0 T4a N1b M0

Stage IVB T4b any N M0

Stage IVC Any T any N M1

bull Anaplastic thyroid cancer

bull All anaplastic carcinomas are considered stage IV

bull Stage IVA bull T4a any N M0

bull Stage IVB bull T4b any N M0

bull Stage IVC bull Any T any N M1

bull University of Chicago systembull Class Imdashdisease limited to the thyroid glandbull Class IImdashlymph node involvementbull Class IIImdashextrathyroidal invasionbull Class IVmdashdistant metastases

PROGNOSIS

PROGNOSIS

Prognostic schemes GAMES scoring (PAPILLARY amp

FOLLICULAR CANCER)bullG GradebullA Age of patient when tumor discoveredbullM Metastases of the tumor (other than Neck LN)bullE Extent of primary tumorbullS Size of tumor (gt5 cm)bullThe patient is then placed into a high or low risk category

Prognostic Risk Classification for Patients with Well-Differentiated Thyroid Cancer (GAMES )

Low Risk High Riskbull Grade Well Differentiated Poorly Differentiated

bull Age lt40 gt40

bull Mets None Regional or Distant

bull Extent No local extension Capsular invasion intrathyroidal extrathyroidal

bull Sex Female Male

MACIS ScoringbullDeveloped by the Mayo Clinic for stagingbullIt is known to be the most accurate predictor of a patients outcome with papillary thyroid cancer (M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)bullMAICS Score 20 year Survival

lt 6 = 99 6-7 = 89 7-8 = 56 gt 8 = 24

Treatment

Stage I and II Papillary and FollicularI-Total thyroidectomy bull Rationale1048708 Bilateral cancers are common (30-85)1048708 improved effectiveness for I131 ablation1048708 lowers dose needed for I131 ablation1048708 allows fu with thyroglobulin levels1048708 decreased recurrence in all groups1048708 improved survival in high risk pts1048708 Decreased risk of pulmonary metsbull Disadvantage higher incidence of hypoparathyroidism but this

complication may be reduced when a small amount of tissue remains on the contralateral side

II-Lobectomy

bull Rationale

1048708 Most patients are low risk and excellent prognosis

1048708 Role of adjuvant treatment not defined

1048708 Complications of Total

1048708 Occult multicentric tumor not clinically significant

1048708 Most local recurrences treated with surgery

1048708 Excellent outcome with lobectomy in low risk patients

bull Disadvantage

bull approximately 5 to 10 of patients will have a recurrence

Indications for total Thyroidectomy OR lobectomy (all present)

bull Age 15 y - 45 ybull No prior radiationbull No distant metastasesbull No cervical lymph node metastasesbull No extrathyroidal extensionbull Tumor lt 4 cm in diameterbull No aggressive variant

When complete total thyroidectomy after lobectomybull Aggressive variantbull Macroscopic multifocal diseasebull Positive isthmus marginsbull Cervical lymph node metastasesbull Extrathyroidal extension

Aggressive=Tall cell columnar cell insular oxyphilic or poorly differentiated features

bull Node removal

bull Selective node removal can be performed and radical

neck dissection is usually not required

bull This results in a decreased recurrence rate but has not

been shown to improve survival

Thyroid carcinoma after lobectomy for benign lesions

I-Completion of thyroidectomy

bull gt 4 cm

bull Positive margins

bull Extra-thyroidal invasion (T3 or T4(

II- Completion of Thyroidectomy or follow

up

bull Clinically suspicious lymph node

contralateral lesion or perithyroidal node

bull Aggressive variant

bull Macroscopic multifocal disease

bull ge1 cm in diameter

III- follow up

bull Negative margins

bull No contralateral lesion

bull lt 1 cm in diameter

bull No suspicious lymph

node

POSTSURGICAL EVALUATION AFTER THYROIDECTOMY

I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +

antithyroglobulin antibodies)

II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan

Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT

bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)

Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas

Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant

Pretherapy whole body iodine scan

bullIf performed a pretherapy scan should use a low dose of 131I

(1 to 5 mCi) or 123I

bull To detect residual thyroid tissue thyroid cancer and metastatic foci

bull To reduce the potential for sublethal radiation stunning of thyroid tissue that

prevents optimal uptake of future 131I therapy

bullStunning is defined as a reduction in uptake of the 131I

therapy dose induced by a pretreatment diagnostic dose

Dose of RAI

bullThe dosing of 131I for ablation is somewhat controversial

bullLow-dose ablation with less than 30 mCi administered on

an outpatient basis

bull For low-risk young patients

bullHigh-dose ablation with100 to 200 mCi

bull For high-risk patients

bull300 mCi

bull For all patients with metastatic disease that treated with repeated

therapeutic doses of 131I

Replacement therapy

bullPostoperative treatment with exogenous thyroid hormone

in doses sufficient to suppress thyroid-stimulating hormone

(TSH) with development of thyrotoxic manifestations

decreases incidence of recurrence

bullAdministration of Thyroid Hormone

To suppress TSH and growth of any residual thyroid

To maintain patient euthyroid

o Maintain TSH level 01uUml in low risk pts

o Maintain TSH Level lt 01uUml in high risk pts

Stage III Papillary and Follicular

A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease

B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients

Stage IV Papillary and Follicular 1) Adequate uptake of I131

bull I131

1) Inadequate uptake or not sensitive to I131

i Localized lesions

1) Radiation therapy

2) Resection of limited metastases dont uptake of I131

iiDisseminated disease

1) TSH suppression with thyroxine is effective

2) Chemotherapy has been reported to produce occasional complete

responses of long duration

3) Clinical trials testing new approaches to this disease

Medullary Thyroid Cancer treatment

bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck

dissections Why

bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival

advantage

bull Radioactive iodine has no place in the treatment of patients with MTC

bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in

patients with metastatic disease

bull No single drug regimen can be considered standard

bull Some patients with distant metastases will experience prolonged survival and can

be observed until they become symptomatic

Anaplastic Thyroid Cancer bull Surgery

bull Tracheostomy is frequently necessary

bull If the disease is confined to the local area which is rare total

thyroidectomy is warranted to reduce symptoms caused by the

tumor mass

bull Radiation therapy

bull Used in patients who are not surgical candidates or whose tumor

cannot be surgically excised

Anaplastic Thyroid Cancer bull Chemotherapy

bull Produce partial remissions in some patients

bull Approximately 30 of patients achieve a partial remission with

doxorubicin

bull The combination of doxorubicin plus cisplatin appears to be more

active than doxorubicin alone and has been reported to produce

more complete responses

Treatment options under clinical evaluation

bull The combination of chemotherapy plus radiation therapy in patients following

complete resection may provide prolonged survival but has not been compared to

any one modality alone

Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30

bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common

site of distant metastasis is the lung

bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type

Treatment of recurrent thyroid cancer

The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations

bull Adequate I131 uptake

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull I131 ablation

bull RT

bull Disseminated

bull I131 ablation

bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has

been reported to produce occasional objective responses usually of short

duration

Treatment of recurrent thyroid cancer

bull Inadequate I131 uptake or insensitive to I131

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull RT

bull Disseminated

bull Systemic chemotherapy

Treatment of recurrent thyroid cancer

Systemic chemotherapy

bull Doxorubicin alone

bull Cisplatin and doxorubicin (better)

bull BAP Cisplatin doxorubicin and bleomycin

bull CVD cyclophosphamide vincristine and dacarbazine

bull Dacarbazine and 5-fluorouracil

bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy

bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT

bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)

bull Improve OS and decrease RR

BAP regimenbull Schedule

bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5

bull Cell typebull Several histologic types of thyroid carcinoma responded but the

best responses were observed in medullary and anaplastic giant-cell carcinomas

bull Effectivenessbull BAP regime can achieve reasonable palliation and probably

increases survival in poor-prognosis thyroid cancers

CVD regimenbull Schedule

bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks

bull Cell typebull Medullary thyroid carcinoma

bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in

patients with advanced MTC

Dacarbazine and 5-fluorouracil

bull Schedule

bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and

12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks

Six cycles

bull Cell type

bull MTC

bull Effectiveness

bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to

have significant activity and was well tolerated

Target therapy

Take home messagesbull FNAC is not adequate for definite diagnosis of follicular

carcinomabull Because the mixed papillary-follicular variant tends to

behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis

bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer

bull Once medullary carcinoma is diagnosed familial predisposition should be checked up

bull If I131 is indicated stunning effect should be avoided

Take home messages

All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary

bull FNAC indicationsISonar-based criteria

Solid nodule

1 More than 1 cm if associated with sonographic suspious features

2 More than 15 cm in absence of sonographic suspicion

Mixed solid and cystic 1 More than 15 cm if associated with sonographic suspicious features

2 More than 2 cm in absence of sonographic suspicion

Spongiform nodule (microcystic component gt 50 of nodules

IHigh risk Clinical feature

RT exposure

Genetic predisposition

Sonographic suspicious features (hypoechoic microcalcification increased central vascularity infiltrative margin or taller than wide in transverse plan)

Fine Needle AspirationbullProcedure of Choice ndash Fast minimally invasive and few riskbullIncidence of False positive 1bullIncidence of False negative 5bullFNA is not a tissue diagnosisbullLimitation of FNA

bull Cannot distinguish a benign follicular from a malignant lesion (cancer invade capsule)

FNA Results of Thyroid Nodulebull Benign(70) --gt FU 6-12 monthsbull Indeterminate(10) --gt repeat FNA I123 scan bull Follicular neoplasm(5) --gt I123 scan or surgerybull Suspicious (10) --gt surgerybull Carcinoma (5) --gt surgery

Classification and Incidence ofThyroid Cancer

Tumors of Follicular Cell Origin1048708 Differentiated Papillary 75 Follicular 10 Hurthle Cell 51048708 Undifferentiated Anaplastic 5 1-Small cell carcinoma 2-Giant cell carcinoma

Tumors of Parafollicular cells Medullary 5

Other 1 1-sarcomas 2-lymphomas 3-epidermoid carcinomas 4-Teratomas 5-metastasis from other cancers

Papillary Cancer The most common malignant thyroid tumor (70-80 of all cancers) Women predominance Age 38-45 Accounts for 90 of radiation induced thyroid cancer Prognosis directly related to tumor size

bull Papillary Cancer

1Histologic1 Psammoma bodies

2 Orphan Ann nucleus

2Multicentric 30-50

3Spread via Lymphatics- propensity for cervical node involvement

4Invasion of adjacent structures and distant mets uncommon

FOLLICULAR THYROID CANCER1Usually Encapsulated2More Common Among Older Patients3Woman gt Man4More Aggressive amp Less Curable Than Papillary5Vascular Invasion (veins and arteries) within the thyroid gland is common6Blood Spread (lung and bone)7Types

1 Follicular carcinoma 2 Follicular carcinoma variant Minimally Invasive Hurthle Cell

8Rarely associated with radiation exposure

Huumlrthle Cell Neoplasms

1More aggressive than other differentiated thyroid carcinomas (higher metslower survival rates)

2Less affinity for I131

3Need to differentiate from benignmalignant

4Metastasis may be more sensitive to I131 than primary

Medullary Thyroid Cancer 1 Usually present as a mass plusmn lymphadenopathy

2 It can also be diagnosed by fine-needle aspiration biopsy

microscopically typically

3 Family members should be screened for calcitonin

elevation andor for the RET proto-oncogene mutation

4 Not associated with radiation exposure

5 Residual disease (following surgery) or recurrence can be

detected by measuring calcitonin

Medullary Thyroid Cancer Occurs in Four Clinical Settings

I- Sporadic

180 of all cases of medullary thyroid cancer

2Typically unilateral

3No associated endocrinopathies

4Peak onset 40 - 60

5Females predominance 32 ratio

6One third will present with intractable diarrhea

Diarrhea is caused by increased gastrointestinal secretion and hypermotility due to

the hormones secreted by the tumor (calcitonin prostaglandins serotonin or VIP)

II-MEN II-A (Sipple Syndrome)

(Multiple Endocrine Neoplasia II A)

1Sipple syndrome has

[1] bilateral medullary carcinoma

[2] pheochromocytoma

[3] hyperparathyroidism

2This syndrome is inherited in an autosomal dominant fashion

Because of this males and females are equally affected

3Peak incidence of medullary carcinoma in these patients is in the

30s

III-MEN II B

1This syndrome has

[1] medullary carcinoma

[2] Pheochromocytoma

[3] mucosal ganglioneuromas and Marfanoid habitus

2Inheritance is autosomal dominant as in MEN IIA (m=f)

3Pheochromocytomas must be detected prior to any operation

4The idea here is to remove the pheochromocytoma first to remove

the risk of severe hypertensive episodes while the thyroid or

parathyroid is being operated on

IV-Inherited medullary carcinoma without associated endocrinopathies

This form of medullary carcinoma is the least aggressive Like other types of thyroid cancers the peak incidence is

between the ages of 40 and 50

Anaplastic cancer

1)Peak onset age 65 and older

Very rare in young patients

2)Males more common than females by 2 to 1 ratio

3)Undifferentiated

4)May arise many years (gt20) following radiation

exposure

5)Neck mass usually large diffuse and very hard

6)Rapidly growing often inoperable highly recurrent

7) Invade locally metastasize both locally and distantly

(to lungs or bones)

8) Cervical metastasis are present in the vast majority

(over 90) of cases at the time of diagnosis

9) Mean survival 6 months

10) Often requires the patient to get a tracheostomy to

maintain their airway

STAGING OF THYROID CANCER

In differentiated thyroid carcinoma several classification and

staging systems have been introduced However no clear

consensus has emerged favoring any one method over another

bull AMES systemAGES SystemGAMES system

bull TNM system

bull MACIS system

bull University of Chicago system

bull Ohio State University system

bull National Thyroid Cancer Treatment Cooperative Study

(NTCTCS)

TNM Staging bull Primary tumor (T) (All categories may be subdivided into (a)

solitary tumor or (b) multifocal tumor)

TX Primary tumor cannot be assessed

T0 No evidence of primary tumor

T1 Tumor le 2 cm limited to the thyroid

T2 Tumor gt 2 cm but le4 cm limited to the thyroid

T3 Tumor gt 4 cm limited to the thyroid or any tumor with

minimal extrathyroid extension (eg extension to

sternothyroid muscle or perithyroid soft tissues)

bull T4a Tumor of any size extending beyond the thyroid capsule to invade subcutaneous soft tissues larynx trachea esophagus or recurrent laryngeal nerve

bull T4b Tumor invades prevertebral fascia or encases carotid artery or mediastinal vessels

All anaplastic carcinomas are considered T4 tumorsbull T4a Intrathyroidal anaplastic carcinomamdashsurgically resectable bull T4b Extrathyroidal anaplastic carcinomamdashsurgically

unresectable

bull Regional lymph nodes (N) (Regional lymph nodes are the central compartment lateral cervical and upper

mediastinal lNs)

bull NX Regional lymph nodes cannot be assessed bull N0 No regional lymph node metastasis bull N1 Regional lymph node metastasis

bull N1a Metastasis to level VI (pretracheal paratracheal and prelaryngealDelphian on the cricothyroid membrane (precricoid) lymph nodes)

bull N1b Metastasis to unilateral or bilateral cervical or superior mediastinal lymph nodes

bull Distant metastases (M) bull MX Distant metastasis cannot be assessed bull M0 No distant metastasis bull M1 Distant metastasis

AJCC Stage Groupings Papillary or follicular thyroid cancer

bull Younger than 45 yearsbull Stage I

bull Any T any N M0 bull Stage II

bull Any T any N M1

bull Age 45 years and olderbull Stage I

bull T1 N0 M0bull Stage II

bull T2 N0 M0 bull Stage III

bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0

Papillary or follicular thyroid cancer

Age 45 years and older

Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T3 N1b M0 T2 N1b M0 T4a N1b M0

Stage IVB T4b any N M0

Stage IVC Any T any N M1

Stage I

T1 N0 M0

Stage II

T2 N0 M0

Stage III

T3 N0 M0

T1 N1a M0

T2 N1a M0

T3 N1a M0

Medullary thyroid cancer bullStage I

bull T1 N0 M0 bullStage II

bull T2 N0 M0bullStage III

bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0

Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T2 N1b M0 T3 N1b M0 T4a N1b M0

Stage IVB T4b any N M0

Stage IVC Any T any N M1

bull Anaplastic thyroid cancer

bull All anaplastic carcinomas are considered stage IV

bull Stage IVA bull T4a any N M0

bull Stage IVB bull T4b any N M0

bull Stage IVC bull Any T any N M1

bull University of Chicago systembull Class Imdashdisease limited to the thyroid glandbull Class IImdashlymph node involvementbull Class IIImdashextrathyroidal invasionbull Class IVmdashdistant metastases

PROGNOSIS

PROGNOSIS

Prognostic schemes GAMES scoring (PAPILLARY amp

FOLLICULAR CANCER)bullG GradebullA Age of patient when tumor discoveredbullM Metastases of the tumor (other than Neck LN)bullE Extent of primary tumorbullS Size of tumor (gt5 cm)bullThe patient is then placed into a high or low risk category

Prognostic Risk Classification for Patients with Well-Differentiated Thyroid Cancer (GAMES )

Low Risk High Riskbull Grade Well Differentiated Poorly Differentiated

bull Age lt40 gt40

bull Mets None Regional or Distant

bull Extent No local extension Capsular invasion intrathyroidal extrathyroidal

bull Sex Female Male

MACIS ScoringbullDeveloped by the Mayo Clinic for stagingbullIt is known to be the most accurate predictor of a patients outcome with papillary thyroid cancer (M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)bullMAICS Score 20 year Survival

lt 6 = 99 6-7 = 89 7-8 = 56 gt 8 = 24

Treatment

Stage I and II Papillary and FollicularI-Total thyroidectomy bull Rationale1048708 Bilateral cancers are common (30-85)1048708 improved effectiveness for I131 ablation1048708 lowers dose needed for I131 ablation1048708 allows fu with thyroglobulin levels1048708 decreased recurrence in all groups1048708 improved survival in high risk pts1048708 Decreased risk of pulmonary metsbull Disadvantage higher incidence of hypoparathyroidism but this

complication may be reduced when a small amount of tissue remains on the contralateral side

II-Lobectomy

bull Rationale

1048708 Most patients are low risk and excellent prognosis

1048708 Role of adjuvant treatment not defined

1048708 Complications of Total

1048708 Occult multicentric tumor not clinically significant

1048708 Most local recurrences treated with surgery

1048708 Excellent outcome with lobectomy in low risk patients

bull Disadvantage

bull approximately 5 to 10 of patients will have a recurrence

Indications for total Thyroidectomy OR lobectomy (all present)

bull Age 15 y - 45 ybull No prior radiationbull No distant metastasesbull No cervical lymph node metastasesbull No extrathyroidal extensionbull Tumor lt 4 cm in diameterbull No aggressive variant

When complete total thyroidectomy after lobectomybull Aggressive variantbull Macroscopic multifocal diseasebull Positive isthmus marginsbull Cervical lymph node metastasesbull Extrathyroidal extension

Aggressive=Tall cell columnar cell insular oxyphilic or poorly differentiated features

bull Node removal

bull Selective node removal can be performed and radical

neck dissection is usually not required

bull This results in a decreased recurrence rate but has not

been shown to improve survival

Thyroid carcinoma after lobectomy for benign lesions

I-Completion of thyroidectomy

bull gt 4 cm

bull Positive margins

bull Extra-thyroidal invasion (T3 or T4(

II- Completion of Thyroidectomy or follow

up

bull Clinically suspicious lymph node

contralateral lesion or perithyroidal node

bull Aggressive variant

bull Macroscopic multifocal disease

bull ge1 cm in diameter

III- follow up

bull Negative margins

bull No contralateral lesion

bull lt 1 cm in diameter

bull No suspicious lymph

node

POSTSURGICAL EVALUATION AFTER THYROIDECTOMY

I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +

antithyroglobulin antibodies)

II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan

Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT

bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)

Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas

Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant

Pretherapy whole body iodine scan

bullIf performed a pretherapy scan should use a low dose of 131I

(1 to 5 mCi) or 123I

bull To detect residual thyroid tissue thyroid cancer and metastatic foci

bull To reduce the potential for sublethal radiation stunning of thyroid tissue that

prevents optimal uptake of future 131I therapy

bullStunning is defined as a reduction in uptake of the 131I

therapy dose induced by a pretreatment diagnostic dose

Dose of RAI

bullThe dosing of 131I for ablation is somewhat controversial

bullLow-dose ablation with less than 30 mCi administered on

an outpatient basis

bull For low-risk young patients

bullHigh-dose ablation with100 to 200 mCi

bull For high-risk patients

bull300 mCi

bull For all patients with metastatic disease that treated with repeated

therapeutic doses of 131I

Replacement therapy

bullPostoperative treatment with exogenous thyroid hormone

in doses sufficient to suppress thyroid-stimulating hormone

(TSH) with development of thyrotoxic manifestations

decreases incidence of recurrence

bullAdministration of Thyroid Hormone

To suppress TSH and growth of any residual thyroid

To maintain patient euthyroid

o Maintain TSH level 01uUml in low risk pts

o Maintain TSH Level lt 01uUml in high risk pts

Stage III Papillary and Follicular

A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease

B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients

Stage IV Papillary and Follicular 1) Adequate uptake of I131

bull I131

1) Inadequate uptake or not sensitive to I131

i Localized lesions

1) Radiation therapy

2) Resection of limited metastases dont uptake of I131

iiDisseminated disease

1) TSH suppression with thyroxine is effective

2) Chemotherapy has been reported to produce occasional complete

responses of long duration

3) Clinical trials testing new approaches to this disease

Medullary Thyroid Cancer treatment

bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck

dissections Why

bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival

advantage

bull Radioactive iodine has no place in the treatment of patients with MTC

bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in

patients with metastatic disease

bull No single drug regimen can be considered standard

bull Some patients with distant metastases will experience prolonged survival and can

be observed until they become symptomatic

Anaplastic Thyroid Cancer bull Surgery

bull Tracheostomy is frequently necessary

bull If the disease is confined to the local area which is rare total

thyroidectomy is warranted to reduce symptoms caused by the

tumor mass

bull Radiation therapy

bull Used in patients who are not surgical candidates or whose tumor

cannot be surgically excised

Anaplastic Thyroid Cancer bull Chemotherapy

bull Produce partial remissions in some patients

bull Approximately 30 of patients achieve a partial remission with

doxorubicin

bull The combination of doxorubicin plus cisplatin appears to be more

active than doxorubicin alone and has been reported to produce

more complete responses

Treatment options under clinical evaluation

bull The combination of chemotherapy plus radiation therapy in patients following

complete resection may provide prolonged survival but has not been compared to

any one modality alone

Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30

bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common

site of distant metastasis is the lung

bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type

Treatment of recurrent thyroid cancer

The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations

bull Adequate I131 uptake

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull I131 ablation

bull RT

bull Disseminated

bull I131 ablation

bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has

been reported to produce occasional objective responses usually of short

duration

Treatment of recurrent thyroid cancer

bull Inadequate I131 uptake or insensitive to I131

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull RT

bull Disseminated

bull Systemic chemotherapy

Treatment of recurrent thyroid cancer

Systemic chemotherapy

bull Doxorubicin alone

bull Cisplatin and doxorubicin (better)

bull BAP Cisplatin doxorubicin and bleomycin

bull CVD cyclophosphamide vincristine and dacarbazine

bull Dacarbazine and 5-fluorouracil

bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy

bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT

bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)

bull Improve OS and decrease RR

BAP regimenbull Schedule

bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5

bull Cell typebull Several histologic types of thyroid carcinoma responded but the

best responses were observed in medullary and anaplastic giant-cell carcinomas

bull Effectivenessbull BAP regime can achieve reasonable palliation and probably

increases survival in poor-prognosis thyroid cancers

CVD regimenbull Schedule

bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks

bull Cell typebull Medullary thyroid carcinoma

bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in

patients with advanced MTC

Dacarbazine and 5-fluorouracil

bull Schedule

bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and

12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks

Six cycles

bull Cell type

bull MTC

bull Effectiveness

bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to

have significant activity and was well tolerated

Target therapy

Take home messagesbull FNAC is not adequate for definite diagnosis of follicular

carcinomabull Because the mixed papillary-follicular variant tends to

behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis

bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer

bull Once medullary carcinoma is diagnosed familial predisposition should be checked up

bull If I131 is indicated stunning effect should be avoided

Take home messages

All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary

Fine Needle AspirationbullProcedure of Choice ndash Fast minimally invasive and few riskbullIncidence of False positive 1bullIncidence of False negative 5bullFNA is not a tissue diagnosisbullLimitation of FNA

bull Cannot distinguish a benign follicular from a malignant lesion (cancer invade capsule)

FNA Results of Thyroid Nodulebull Benign(70) --gt FU 6-12 monthsbull Indeterminate(10) --gt repeat FNA I123 scan bull Follicular neoplasm(5) --gt I123 scan or surgerybull Suspicious (10) --gt surgerybull Carcinoma (5) --gt surgery

Classification and Incidence ofThyroid Cancer

Tumors of Follicular Cell Origin1048708 Differentiated Papillary 75 Follicular 10 Hurthle Cell 51048708 Undifferentiated Anaplastic 5 1-Small cell carcinoma 2-Giant cell carcinoma

Tumors of Parafollicular cells Medullary 5

Other 1 1-sarcomas 2-lymphomas 3-epidermoid carcinomas 4-Teratomas 5-metastasis from other cancers

Papillary Cancer The most common malignant thyroid tumor (70-80 of all cancers) Women predominance Age 38-45 Accounts for 90 of radiation induced thyroid cancer Prognosis directly related to tumor size

bull Papillary Cancer

1Histologic1 Psammoma bodies

2 Orphan Ann nucleus

2Multicentric 30-50

3Spread via Lymphatics- propensity for cervical node involvement

4Invasion of adjacent structures and distant mets uncommon

FOLLICULAR THYROID CANCER1Usually Encapsulated2More Common Among Older Patients3Woman gt Man4More Aggressive amp Less Curable Than Papillary5Vascular Invasion (veins and arteries) within the thyroid gland is common6Blood Spread (lung and bone)7Types

1 Follicular carcinoma 2 Follicular carcinoma variant Minimally Invasive Hurthle Cell

8Rarely associated with radiation exposure

Huumlrthle Cell Neoplasms

1More aggressive than other differentiated thyroid carcinomas (higher metslower survival rates)

2Less affinity for I131

3Need to differentiate from benignmalignant

4Metastasis may be more sensitive to I131 than primary

Medullary Thyroid Cancer 1 Usually present as a mass plusmn lymphadenopathy

2 It can also be diagnosed by fine-needle aspiration biopsy

microscopically typically

3 Family members should be screened for calcitonin

elevation andor for the RET proto-oncogene mutation

4 Not associated with radiation exposure

5 Residual disease (following surgery) or recurrence can be

detected by measuring calcitonin

Medullary Thyroid Cancer Occurs in Four Clinical Settings

I- Sporadic

180 of all cases of medullary thyroid cancer

2Typically unilateral

3No associated endocrinopathies

4Peak onset 40 - 60

5Females predominance 32 ratio

6One third will present with intractable diarrhea

Diarrhea is caused by increased gastrointestinal secretion and hypermotility due to

the hormones secreted by the tumor (calcitonin prostaglandins serotonin or VIP)

II-MEN II-A (Sipple Syndrome)

(Multiple Endocrine Neoplasia II A)

1Sipple syndrome has

[1] bilateral medullary carcinoma

[2] pheochromocytoma

[3] hyperparathyroidism

2This syndrome is inherited in an autosomal dominant fashion

Because of this males and females are equally affected

3Peak incidence of medullary carcinoma in these patients is in the

30s

III-MEN II B

1This syndrome has

[1] medullary carcinoma

[2] Pheochromocytoma

[3] mucosal ganglioneuromas and Marfanoid habitus

2Inheritance is autosomal dominant as in MEN IIA (m=f)

3Pheochromocytomas must be detected prior to any operation

4The idea here is to remove the pheochromocytoma first to remove

the risk of severe hypertensive episodes while the thyroid or

parathyroid is being operated on

IV-Inherited medullary carcinoma without associated endocrinopathies

This form of medullary carcinoma is the least aggressive Like other types of thyroid cancers the peak incidence is

between the ages of 40 and 50

Anaplastic cancer

1)Peak onset age 65 and older

Very rare in young patients

2)Males more common than females by 2 to 1 ratio

3)Undifferentiated

4)May arise many years (gt20) following radiation

exposure

5)Neck mass usually large diffuse and very hard

6)Rapidly growing often inoperable highly recurrent

7) Invade locally metastasize both locally and distantly

(to lungs or bones)

8) Cervical metastasis are present in the vast majority

(over 90) of cases at the time of diagnosis

9) Mean survival 6 months

10) Often requires the patient to get a tracheostomy to

maintain their airway

STAGING OF THYROID CANCER

In differentiated thyroid carcinoma several classification and

staging systems have been introduced However no clear

consensus has emerged favoring any one method over another

bull AMES systemAGES SystemGAMES system

bull TNM system

bull MACIS system

bull University of Chicago system

bull Ohio State University system

bull National Thyroid Cancer Treatment Cooperative Study

(NTCTCS)

TNM Staging bull Primary tumor (T) (All categories may be subdivided into (a)

solitary tumor or (b) multifocal tumor)

TX Primary tumor cannot be assessed

T0 No evidence of primary tumor

T1 Tumor le 2 cm limited to the thyroid

T2 Tumor gt 2 cm but le4 cm limited to the thyroid

T3 Tumor gt 4 cm limited to the thyroid or any tumor with

minimal extrathyroid extension (eg extension to

sternothyroid muscle or perithyroid soft tissues)

bull T4a Tumor of any size extending beyond the thyroid capsule to invade subcutaneous soft tissues larynx trachea esophagus or recurrent laryngeal nerve

bull T4b Tumor invades prevertebral fascia or encases carotid artery or mediastinal vessels

All anaplastic carcinomas are considered T4 tumorsbull T4a Intrathyroidal anaplastic carcinomamdashsurgically resectable bull T4b Extrathyroidal anaplastic carcinomamdashsurgically

unresectable

bull Regional lymph nodes (N) (Regional lymph nodes are the central compartment lateral cervical and upper

mediastinal lNs)

bull NX Regional lymph nodes cannot be assessed bull N0 No regional lymph node metastasis bull N1 Regional lymph node metastasis

bull N1a Metastasis to level VI (pretracheal paratracheal and prelaryngealDelphian on the cricothyroid membrane (precricoid) lymph nodes)

bull N1b Metastasis to unilateral or bilateral cervical or superior mediastinal lymph nodes

bull Distant metastases (M) bull MX Distant metastasis cannot be assessed bull M0 No distant metastasis bull M1 Distant metastasis

AJCC Stage Groupings Papillary or follicular thyroid cancer

bull Younger than 45 yearsbull Stage I

bull Any T any N M0 bull Stage II

bull Any T any N M1

bull Age 45 years and olderbull Stage I

bull T1 N0 M0bull Stage II

bull T2 N0 M0 bull Stage III

bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0

Papillary or follicular thyroid cancer

Age 45 years and older

Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T3 N1b M0 T2 N1b M0 T4a N1b M0

Stage IVB T4b any N M0

Stage IVC Any T any N M1

Stage I

T1 N0 M0

Stage II

T2 N0 M0

Stage III

T3 N0 M0

T1 N1a M0

T2 N1a M0

T3 N1a M0

Medullary thyroid cancer bullStage I

bull T1 N0 M0 bullStage II

bull T2 N0 M0bullStage III

bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0

Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T2 N1b M0 T3 N1b M0 T4a N1b M0

Stage IVB T4b any N M0

Stage IVC Any T any N M1

bull Anaplastic thyroid cancer

bull All anaplastic carcinomas are considered stage IV

bull Stage IVA bull T4a any N M0

bull Stage IVB bull T4b any N M0

bull Stage IVC bull Any T any N M1

bull University of Chicago systembull Class Imdashdisease limited to the thyroid glandbull Class IImdashlymph node involvementbull Class IIImdashextrathyroidal invasionbull Class IVmdashdistant metastases

PROGNOSIS

PROGNOSIS

Prognostic schemes GAMES scoring (PAPILLARY amp

FOLLICULAR CANCER)bullG GradebullA Age of patient when tumor discoveredbullM Metastases of the tumor (other than Neck LN)bullE Extent of primary tumorbullS Size of tumor (gt5 cm)bullThe patient is then placed into a high or low risk category

Prognostic Risk Classification for Patients with Well-Differentiated Thyroid Cancer (GAMES )

Low Risk High Riskbull Grade Well Differentiated Poorly Differentiated

bull Age lt40 gt40

bull Mets None Regional or Distant

bull Extent No local extension Capsular invasion intrathyroidal extrathyroidal

bull Sex Female Male

MACIS ScoringbullDeveloped by the Mayo Clinic for stagingbullIt is known to be the most accurate predictor of a patients outcome with papillary thyroid cancer (M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)bullMAICS Score 20 year Survival

lt 6 = 99 6-7 = 89 7-8 = 56 gt 8 = 24

Treatment

Stage I and II Papillary and FollicularI-Total thyroidectomy bull Rationale1048708 Bilateral cancers are common (30-85)1048708 improved effectiveness for I131 ablation1048708 lowers dose needed for I131 ablation1048708 allows fu with thyroglobulin levels1048708 decreased recurrence in all groups1048708 improved survival in high risk pts1048708 Decreased risk of pulmonary metsbull Disadvantage higher incidence of hypoparathyroidism but this

complication may be reduced when a small amount of tissue remains on the contralateral side

II-Lobectomy

bull Rationale

1048708 Most patients are low risk and excellent prognosis

1048708 Role of adjuvant treatment not defined

1048708 Complications of Total

1048708 Occult multicentric tumor not clinically significant

1048708 Most local recurrences treated with surgery

1048708 Excellent outcome with lobectomy in low risk patients

bull Disadvantage

bull approximately 5 to 10 of patients will have a recurrence

Indications for total Thyroidectomy OR lobectomy (all present)

bull Age 15 y - 45 ybull No prior radiationbull No distant metastasesbull No cervical lymph node metastasesbull No extrathyroidal extensionbull Tumor lt 4 cm in diameterbull No aggressive variant

When complete total thyroidectomy after lobectomybull Aggressive variantbull Macroscopic multifocal diseasebull Positive isthmus marginsbull Cervical lymph node metastasesbull Extrathyroidal extension

Aggressive=Tall cell columnar cell insular oxyphilic or poorly differentiated features

bull Node removal

bull Selective node removal can be performed and radical

neck dissection is usually not required

bull This results in a decreased recurrence rate but has not

been shown to improve survival

Thyroid carcinoma after lobectomy for benign lesions

I-Completion of thyroidectomy

bull gt 4 cm

bull Positive margins

bull Extra-thyroidal invasion (T3 or T4(

II- Completion of Thyroidectomy or follow

up

bull Clinically suspicious lymph node

contralateral lesion or perithyroidal node

bull Aggressive variant

bull Macroscopic multifocal disease

bull ge1 cm in diameter

III- follow up

bull Negative margins

bull No contralateral lesion

bull lt 1 cm in diameter

bull No suspicious lymph

node

POSTSURGICAL EVALUATION AFTER THYROIDECTOMY

I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +

antithyroglobulin antibodies)

II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan

Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT

bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)

Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas

Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant

Pretherapy whole body iodine scan

bullIf performed a pretherapy scan should use a low dose of 131I

(1 to 5 mCi) or 123I

bull To detect residual thyroid tissue thyroid cancer and metastatic foci

bull To reduce the potential for sublethal radiation stunning of thyroid tissue that

prevents optimal uptake of future 131I therapy

bullStunning is defined as a reduction in uptake of the 131I

therapy dose induced by a pretreatment diagnostic dose

Dose of RAI

bullThe dosing of 131I for ablation is somewhat controversial

bullLow-dose ablation with less than 30 mCi administered on

an outpatient basis

bull For low-risk young patients

bullHigh-dose ablation with100 to 200 mCi

bull For high-risk patients

bull300 mCi

bull For all patients with metastatic disease that treated with repeated

therapeutic doses of 131I

Replacement therapy

bullPostoperative treatment with exogenous thyroid hormone

in doses sufficient to suppress thyroid-stimulating hormone

(TSH) with development of thyrotoxic manifestations

decreases incidence of recurrence

bullAdministration of Thyroid Hormone

To suppress TSH and growth of any residual thyroid

To maintain patient euthyroid

o Maintain TSH level 01uUml in low risk pts

o Maintain TSH Level lt 01uUml in high risk pts

Stage III Papillary and Follicular

A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease

B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients

Stage IV Papillary and Follicular 1) Adequate uptake of I131

bull I131

1) Inadequate uptake or not sensitive to I131

i Localized lesions

1) Radiation therapy

2) Resection of limited metastases dont uptake of I131

iiDisseminated disease

1) TSH suppression with thyroxine is effective

2) Chemotherapy has been reported to produce occasional complete

responses of long duration

3) Clinical trials testing new approaches to this disease

Medullary Thyroid Cancer treatment

bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck

dissections Why

bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival

advantage

bull Radioactive iodine has no place in the treatment of patients with MTC

bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in

patients with metastatic disease

bull No single drug regimen can be considered standard

bull Some patients with distant metastases will experience prolonged survival and can

be observed until they become symptomatic

Anaplastic Thyroid Cancer bull Surgery

bull Tracheostomy is frequently necessary

bull If the disease is confined to the local area which is rare total

thyroidectomy is warranted to reduce symptoms caused by the

tumor mass

bull Radiation therapy

bull Used in patients who are not surgical candidates or whose tumor

cannot be surgically excised

Anaplastic Thyroid Cancer bull Chemotherapy

bull Produce partial remissions in some patients

bull Approximately 30 of patients achieve a partial remission with

doxorubicin

bull The combination of doxorubicin plus cisplatin appears to be more

active than doxorubicin alone and has been reported to produce

more complete responses

Treatment options under clinical evaluation

bull The combination of chemotherapy plus radiation therapy in patients following

complete resection may provide prolonged survival but has not been compared to

any one modality alone

Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30

bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common

site of distant metastasis is the lung

bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type

Treatment of recurrent thyroid cancer

The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations

bull Adequate I131 uptake

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull I131 ablation

bull RT

bull Disseminated

bull I131 ablation

bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has

been reported to produce occasional objective responses usually of short

duration

Treatment of recurrent thyroid cancer

bull Inadequate I131 uptake or insensitive to I131

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull RT

bull Disseminated

bull Systemic chemotherapy

Treatment of recurrent thyroid cancer

Systemic chemotherapy

bull Doxorubicin alone

bull Cisplatin and doxorubicin (better)

bull BAP Cisplatin doxorubicin and bleomycin

bull CVD cyclophosphamide vincristine and dacarbazine

bull Dacarbazine and 5-fluorouracil

bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy

bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT

bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)

bull Improve OS and decrease RR

BAP regimenbull Schedule

bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5

bull Cell typebull Several histologic types of thyroid carcinoma responded but the

best responses were observed in medullary and anaplastic giant-cell carcinomas

bull Effectivenessbull BAP regime can achieve reasonable palliation and probably

increases survival in poor-prognosis thyroid cancers

CVD regimenbull Schedule

bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks

bull Cell typebull Medullary thyroid carcinoma

bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in

patients with advanced MTC

Dacarbazine and 5-fluorouracil

bull Schedule

bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and

12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks

Six cycles

bull Cell type

bull MTC

bull Effectiveness

bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to

have significant activity and was well tolerated

Target therapy

Take home messagesbull FNAC is not adequate for definite diagnosis of follicular

carcinomabull Because the mixed papillary-follicular variant tends to

behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis

bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer

bull Once medullary carcinoma is diagnosed familial predisposition should be checked up

bull If I131 is indicated stunning effect should be avoided

Take home messages

All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary

FNA Results of Thyroid Nodulebull Benign(70) --gt FU 6-12 monthsbull Indeterminate(10) --gt repeat FNA I123 scan bull Follicular neoplasm(5) --gt I123 scan or surgerybull Suspicious (10) --gt surgerybull Carcinoma (5) --gt surgery

Classification and Incidence ofThyroid Cancer

Tumors of Follicular Cell Origin1048708 Differentiated Papillary 75 Follicular 10 Hurthle Cell 51048708 Undifferentiated Anaplastic 5 1-Small cell carcinoma 2-Giant cell carcinoma

Tumors of Parafollicular cells Medullary 5

Other 1 1-sarcomas 2-lymphomas 3-epidermoid carcinomas 4-Teratomas 5-metastasis from other cancers

Papillary Cancer The most common malignant thyroid tumor (70-80 of all cancers) Women predominance Age 38-45 Accounts for 90 of radiation induced thyroid cancer Prognosis directly related to tumor size

bull Papillary Cancer

1Histologic1 Psammoma bodies

2 Orphan Ann nucleus

2Multicentric 30-50

3Spread via Lymphatics- propensity for cervical node involvement

4Invasion of adjacent structures and distant mets uncommon

FOLLICULAR THYROID CANCER1Usually Encapsulated2More Common Among Older Patients3Woman gt Man4More Aggressive amp Less Curable Than Papillary5Vascular Invasion (veins and arteries) within the thyroid gland is common6Blood Spread (lung and bone)7Types

1 Follicular carcinoma 2 Follicular carcinoma variant Minimally Invasive Hurthle Cell

8Rarely associated with radiation exposure

Huumlrthle Cell Neoplasms

1More aggressive than other differentiated thyroid carcinomas (higher metslower survival rates)

2Less affinity for I131

3Need to differentiate from benignmalignant

4Metastasis may be more sensitive to I131 than primary

Medullary Thyroid Cancer 1 Usually present as a mass plusmn lymphadenopathy

2 It can also be diagnosed by fine-needle aspiration biopsy

microscopically typically

3 Family members should be screened for calcitonin

elevation andor for the RET proto-oncogene mutation

4 Not associated with radiation exposure

5 Residual disease (following surgery) or recurrence can be

detected by measuring calcitonin

Medullary Thyroid Cancer Occurs in Four Clinical Settings

I- Sporadic

180 of all cases of medullary thyroid cancer

2Typically unilateral

3No associated endocrinopathies

4Peak onset 40 - 60

5Females predominance 32 ratio

6One third will present with intractable diarrhea

Diarrhea is caused by increased gastrointestinal secretion and hypermotility due to

the hormones secreted by the tumor (calcitonin prostaglandins serotonin or VIP)

II-MEN II-A (Sipple Syndrome)

(Multiple Endocrine Neoplasia II A)

1Sipple syndrome has

[1] bilateral medullary carcinoma

[2] pheochromocytoma

[3] hyperparathyroidism

2This syndrome is inherited in an autosomal dominant fashion

Because of this males and females are equally affected

3Peak incidence of medullary carcinoma in these patients is in the

30s

III-MEN II B

1This syndrome has

[1] medullary carcinoma

[2] Pheochromocytoma

[3] mucosal ganglioneuromas and Marfanoid habitus

2Inheritance is autosomal dominant as in MEN IIA (m=f)

3Pheochromocytomas must be detected prior to any operation

4The idea here is to remove the pheochromocytoma first to remove

the risk of severe hypertensive episodes while the thyroid or

parathyroid is being operated on

IV-Inherited medullary carcinoma without associated endocrinopathies

This form of medullary carcinoma is the least aggressive Like other types of thyroid cancers the peak incidence is

between the ages of 40 and 50

Anaplastic cancer

1)Peak onset age 65 and older

Very rare in young patients

2)Males more common than females by 2 to 1 ratio

3)Undifferentiated

4)May arise many years (gt20) following radiation

exposure

5)Neck mass usually large diffuse and very hard

6)Rapidly growing often inoperable highly recurrent

7) Invade locally metastasize both locally and distantly

(to lungs or bones)

8) Cervical metastasis are present in the vast majority

(over 90) of cases at the time of diagnosis

9) Mean survival 6 months

10) Often requires the patient to get a tracheostomy to

maintain their airway

STAGING OF THYROID CANCER

In differentiated thyroid carcinoma several classification and

staging systems have been introduced However no clear

consensus has emerged favoring any one method over another

bull AMES systemAGES SystemGAMES system

bull TNM system

bull MACIS system

bull University of Chicago system

bull Ohio State University system

bull National Thyroid Cancer Treatment Cooperative Study

(NTCTCS)

TNM Staging bull Primary tumor (T) (All categories may be subdivided into (a)

solitary tumor or (b) multifocal tumor)

TX Primary tumor cannot be assessed

T0 No evidence of primary tumor

T1 Tumor le 2 cm limited to the thyroid

T2 Tumor gt 2 cm but le4 cm limited to the thyroid

T3 Tumor gt 4 cm limited to the thyroid or any tumor with

minimal extrathyroid extension (eg extension to

sternothyroid muscle or perithyroid soft tissues)

bull T4a Tumor of any size extending beyond the thyroid capsule to invade subcutaneous soft tissues larynx trachea esophagus or recurrent laryngeal nerve

bull T4b Tumor invades prevertebral fascia or encases carotid artery or mediastinal vessels

All anaplastic carcinomas are considered T4 tumorsbull T4a Intrathyroidal anaplastic carcinomamdashsurgically resectable bull T4b Extrathyroidal anaplastic carcinomamdashsurgically

unresectable

bull Regional lymph nodes (N) (Regional lymph nodes are the central compartment lateral cervical and upper

mediastinal lNs)

bull NX Regional lymph nodes cannot be assessed bull N0 No regional lymph node metastasis bull N1 Regional lymph node metastasis

bull N1a Metastasis to level VI (pretracheal paratracheal and prelaryngealDelphian on the cricothyroid membrane (precricoid) lymph nodes)

bull N1b Metastasis to unilateral or bilateral cervical or superior mediastinal lymph nodes

bull Distant metastases (M) bull MX Distant metastasis cannot be assessed bull M0 No distant metastasis bull M1 Distant metastasis

AJCC Stage Groupings Papillary or follicular thyroid cancer

bull Younger than 45 yearsbull Stage I

bull Any T any N M0 bull Stage II

bull Any T any N M1

bull Age 45 years and olderbull Stage I

bull T1 N0 M0bull Stage II

bull T2 N0 M0 bull Stage III

bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0

Papillary or follicular thyroid cancer

Age 45 years and older

Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T3 N1b M0 T2 N1b M0 T4a N1b M0

Stage IVB T4b any N M0

Stage IVC Any T any N M1

Stage I

T1 N0 M0

Stage II

T2 N0 M0

Stage III

T3 N0 M0

T1 N1a M0

T2 N1a M0

T3 N1a M0

Medullary thyroid cancer bullStage I

bull T1 N0 M0 bullStage II

bull T2 N0 M0bullStage III

bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0

Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T2 N1b M0 T3 N1b M0 T4a N1b M0

Stage IVB T4b any N M0

Stage IVC Any T any N M1

bull Anaplastic thyroid cancer

bull All anaplastic carcinomas are considered stage IV

bull Stage IVA bull T4a any N M0

bull Stage IVB bull T4b any N M0

bull Stage IVC bull Any T any N M1

bull University of Chicago systembull Class Imdashdisease limited to the thyroid glandbull Class IImdashlymph node involvementbull Class IIImdashextrathyroidal invasionbull Class IVmdashdistant metastases

PROGNOSIS

PROGNOSIS

Prognostic schemes GAMES scoring (PAPILLARY amp

FOLLICULAR CANCER)bullG GradebullA Age of patient when tumor discoveredbullM Metastases of the tumor (other than Neck LN)bullE Extent of primary tumorbullS Size of tumor (gt5 cm)bullThe patient is then placed into a high or low risk category

Prognostic Risk Classification for Patients with Well-Differentiated Thyroid Cancer (GAMES )

Low Risk High Riskbull Grade Well Differentiated Poorly Differentiated

bull Age lt40 gt40

bull Mets None Regional or Distant

bull Extent No local extension Capsular invasion intrathyroidal extrathyroidal

bull Sex Female Male

MACIS ScoringbullDeveloped by the Mayo Clinic for stagingbullIt is known to be the most accurate predictor of a patients outcome with papillary thyroid cancer (M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)bullMAICS Score 20 year Survival

lt 6 = 99 6-7 = 89 7-8 = 56 gt 8 = 24

Treatment

Stage I and II Papillary and FollicularI-Total thyroidectomy bull Rationale1048708 Bilateral cancers are common (30-85)1048708 improved effectiveness for I131 ablation1048708 lowers dose needed for I131 ablation1048708 allows fu with thyroglobulin levels1048708 decreased recurrence in all groups1048708 improved survival in high risk pts1048708 Decreased risk of pulmonary metsbull Disadvantage higher incidence of hypoparathyroidism but this

complication may be reduced when a small amount of tissue remains on the contralateral side

II-Lobectomy

bull Rationale

1048708 Most patients are low risk and excellent prognosis

1048708 Role of adjuvant treatment not defined

1048708 Complications of Total

1048708 Occult multicentric tumor not clinically significant

1048708 Most local recurrences treated with surgery

1048708 Excellent outcome with lobectomy in low risk patients

bull Disadvantage

bull approximately 5 to 10 of patients will have a recurrence

Indications for total Thyroidectomy OR lobectomy (all present)

bull Age 15 y - 45 ybull No prior radiationbull No distant metastasesbull No cervical lymph node metastasesbull No extrathyroidal extensionbull Tumor lt 4 cm in diameterbull No aggressive variant

When complete total thyroidectomy after lobectomybull Aggressive variantbull Macroscopic multifocal diseasebull Positive isthmus marginsbull Cervical lymph node metastasesbull Extrathyroidal extension

Aggressive=Tall cell columnar cell insular oxyphilic or poorly differentiated features

bull Node removal

bull Selective node removal can be performed and radical

neck dissection is usually not required

bull This results in a decreased recurrence rate but has not

been shown to improve survival

Thyroid carcinoma after lobectomy for benign lesions

I-Completion of thyroidectomy

bull gt 4 cm

bull Positive margins

bull Extra-thyroidal invasion (T3 or T4(

II- Completion of Thyroidectomy or follow

up

bull Clinically suspicious lymph node

contralateral lesion or perithyroidal node

bull Aggressive variant

bull Macroscopic multifocal disease

bull ge1 cm in diameter

III- follow up

bull Negative margins

bull No contralateral lesion

bull lt 1 cm in diameter

bull No suspicious lymph

node

POSTSURGICAL EVALUATION AFTER THYROIDECTOMY

I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +

antithyroglobulin antibodies)

II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan

Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT

bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)

Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas

Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant

Pretherapy whole body iodine scan

bullIf performed a pretherapy scan should use a low dose of 131I

(1 to 5 mCi) or 123I

bull To detect residual thyroid tissue thyroid cancer and metastatic foci

bull To reduce the potential for sublethal radiation stunning of thyroid tissue that

prevents optimal uptake of future 131I therapy

bullStunning is defined as a reduction in uptake of the 131I

therapy dose induced by a pretreatment diagnostic dose

Dose of RAI

bullThe dosing of 131I for ablation is somewhat controversial

bullLow-dose ablation with less than 30 mCi administered on

an outpatient basis

bull For low-risk young patients

bullHigh-dose ablation with100 to 200 mCi

bull For high-risk patients

bull300 mCi

bull For all patients with metastatic disease that treated with repeated

therapeutic doses of 131I

Replacement therapy

bullPostoperative treatment with exogenous thyroid hormone

in doses sufficient to suppress thyroid-stimulating hormone

(TSH) with development of thyrotoxic manifestations

decreases incidence of recurrence

bullAdministration of Thyroid Hormone

To suppress TSH and growth of any residual thyroid

To maintain patient euthyroid

o Maintain TSH level 01uUml in low risk pts

o Maintain TSH Level lt 01uUml in high risk pts

Stage III Papillary and Follicular

A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease

B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients

Stage IV Papillary and Follicular 1) Adequate uptake of I131

bull I131

1) Inadequate uptake or not sensitive to I131

i Localized lesions

1) Radiation therapy

2) Resection of limited metastases dont uptake of I131

iiDisseminated disease

1) TSH suppression with thyroxine is effective

2) Chemotherapy has been reported to produce occasional complete

responses of long duration

3) Clinical trials testing new approaches to this disease

Medullary Thyroid Cancer treatment

bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck

dissections Why

bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival

advantage

bull Radioactive iodine has no place in the treatment of patients with MTC

bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in

patients with metastatic disease

bull No single drug regimen can be considered standard

bull Some patients with distant metastases will experience prolonged survival and can

be observed until they become symptomatic

Anaplastic Thyroid Cancer bull Surgery

bull Tracheostomy is frequently necessary

bull If the disease is confined to the local area which is rare total

thyroidectomy is warranted to reduce symptoms caused by the

tumor mass

bull Radiation therapy

bull Used in patients who are not surgical candidates or whose tumor

cannot be surgically excised

Anaplastic Thyroid Cancer bull Chemotherapy

bull Produce partial remissions in some patients

bull Approximately 30 of patients achieve a partial remission with

doxorubicin

bull The combination of doxorubicin plus cisplatin appears to be more

active than doxorubicin alone and has been reported to produce

more complete responses

Treatment options under clinical evaluation

bull The combination of chemotherapy plus radiation therapy in patients following

complete resection may provide prolonged survival but has not been compared to

any one modality alone

Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30

bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common

site of distant metastasis is the lung

bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type

Treatment of recurrent thyroid cancer

The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations

bull Adequate I131 uptake

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull I131 ablation

bull RT

bull Disseminated

bull I131 ablation

bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has

been reported to produce occasional objective responses usually of short

duration

Treatment of recurrent thyroid cancer

bull Inadequate I131 uptake or insensitive to I131

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull RT

bull Disseminated

bull Systemic chemotherapy

Treatment of recurrent thyroid cancer

Systemic chemotherapy

bull Doxorubicin alone

bull Cisplatin and doxorubicin (better)

bull BAP Cisplatin doxorubicin and bleomycin

bull CVD cyclophosphamide vincristine and dacarbazine

bull Dacarbazine and 5-fluorouracil

bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy

bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT

bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)

bull Improve OS and decrease RR

BAP regimenbull Schedule

bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5

bull Cell typebull Several histologic types of thyroid carcinoma responded but the

best responses were observed in medullary and anaplastic giant-cell carcinomas

bull Effectivenessbull BAP regime can achieve reasonable palliation and probably

increases survival in poor-prognosis thyroid cancers

CVD regimenbull Schedule

bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks

bull Cell typebull Medullary thyroid carcinoma

bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in

patients with advanced MTC

Dacarbazine and 5-fluorouracil

bull Schedule

bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and

12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks

Six cycles

bull Cell type

bull MTC

bull Effectiveness

bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to

have significant activity and was well tolerated

Target therapy

Take home messagesbull FNAC is not adequate for definite diagnosis of follicular

carcinomabull Because the mixed papillary-follicular variant tends to

behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis

bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer

bull Once medullary carcinoma is diagnosed familial predisposition should be checked up

bull If I131 is indicated stunning effect should be avoided

Take home messages

All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary

Classification and Incidence ofThyroid Cancer

Tumors of Follicular Cell Origin1048708 Differentiated Papillary 75 Follicular 10 Hurthle Cell 51048708 Undifferentiated Anaplastic 5 1-Small cell carcinoma 2-Giant cell carcinoma

Tumors of Parafollicular cells Medullary 5

Other 1 1-sarcomas 2-lymphomas 3-epidermoid carcinomas 4-Teratomas 5-metastasis from other cancers

Papillary Cancer The most common malignant thyroid tumor (70-80 of all cancers) Women predominance Age 38-45 Accounts for 90 of radiation induced thyroid cancer Prognosis directly related to tumor size

bull Papillary Cancer

1Histologic1 Psammoma bodies

2 Orphan Ann nucleus

2Multicentric 30-50

3Spread via Lymphatics- propensity for cervical node involvement

4Invasion of adjacent structures and distant mets uncommon

FOLLICULAR THYROID CANCER1Usually Encapsulated2More Common Among Older Patients3Woman gt Man4More Aggressive amp Less Curable Than Papillary5Vascular Invasion (veins and arteries) within the thyroid gland is common6Blood Spread (lung and bone)7Types

1 Follicular carcinoma 2 Follicular carcinoma variant Minimally Invasive Hurthle Cell

8Rarely associated with radiation exposure

Huumlrthle Cell Neoplasms

1More aggressive than other differentiated thyroid carcinomas (higher metslower survival rates)

2Less affinity for I131

3Need to differentiate from benignmalignant

4Metastasis may be more sensitive to I131 than primary

Medullary Thyroid Cancer 1 Usually present as a mass plusmn lymphadenopathy

2 It can also be diagnosed by fine-needle aspiration biopsy

microscopically typically

3 Family members should be screened for calcitonin

elevation andor for the RET proto-oncogene mutation

4 Not associated with radiation exposure

5 Residual disease (following surgery) or recurrence can be

detected by measuring calcitonin

Medullary Thyroid Cancer Occurs in Four Clinical Settings

I- Sporadic

180 of all cases of medullary thyroid cancer

2Typically unilateral

3No associated endocrinopathies

4Peak onset 40 - 60

5Females predominance 32 ratio

6One third will present with intractable diarrhea

Diarrhea is caused by increased gastrointestinal secretion and hypermotility due to

the hormones secreted by the tumor (calcitonin prostaglandins serotonin or VIP)

II-MEN II-A (Sipple Syndrome)

(Multiple Endocrine Neoplasia II A)

1Sipple syndrome has

[1] bilateral medullary carcinoma

[2] pheochromocytoma

[3] hyperparathyroidism

2This syndrome is inherited in an autosomal dominant fashion

Because of this males and females are equally affected

3Peak incidence of medullary carcinoma in these patients is in the

30s

III-MEN II B

1This syndrome has

[1] medullary carcinoma

[2] Pheochromocytoma

[3] mucosal ganglioneuromas and Marfanoid habitus

2Inheritance is autosomal dominant as in MEN IIA (m=f)

3Pheochromocytomas must be detected prior to any operation

4The idea here is to remove the pheochromocytoma first to remove

the risk of severe hypertensive episodes while the thyroid or

parathyroid is being operated on

IV-Inherited medullary carcinoma without associated endocrinopathies

This form of medullary carcinoma is the least aggressive Like other types of thyroid cancers the peak incidence is

between the ages of 40 and 50

Anaplastic cancer

1)Peak onset age 65 and older

Very rare in young patients

2)Males more common than females by 2 to 1 ratio

3)Undifferentiated

4)May arise many years (gt20) following radiation

exposure

5)Neck mass usually large diffuse and very hard

6)Rapidly growing often inoperable highly recurrent

7) Invade locally metastasize both locally and distantly

(to lungs or bones)

8) Cervical metastasis are present in the vast majority

(over 90) of cases at the time of diagnosis

9) Mean survival 6 months

10) Often requires the patient to get a tracheostomy to

maintain their airway

STAGING OF THYROID CANCER

In differentiated thyroid carcinoma several classification and

staging systems have been introduced However no clear

consensus has emerged favoring any one method over another

bull AMES systemAGES SystemGAMES system

bull TNM system

bull MACIS system

bull University of Chicago system

bull Ohio State University system

bull National Thyroid Cancer Treatment Cooperative Study

(NTCTCS)

TNM Staging bull Primary tumor (T) (All categories may be subdivided into (a)

solitary tumor or (b) multifocal tumor)

TX Primary tumor cannot be assessed

T0 No evidence of primary tumor

T1 Tumor le 2 cm limited to the thyroid

T2 Tumor gt 2 cm but le4 cm limited to the thyroid

T3 Tumor gt 4 cm limited to the thyroid or any tumor with

minimal extrathyroid extension (eg extension to

sternothyroid muscle or perithyroid soft tissues)

bull T4a Tumor of any size extending beyond the thyroid capsule to invade subcutaneous soft tissues larynx trachea esophagus or recurrent laryngeal nerve

bull T4b Tumor invades prevertebral fascia or encases carotid artery or mediastinal vessels

All anaplastic carcinomas are considered T4 tumorsbull T4a Intrathyroidal anaplastic carcinomamdashsurgically resectable bull T4b Extrathyroidal anaplastic carcinomamdashsurgically

unresectable

bull Regional lymph nodes (N) (Regional lymph nodes are the central compartment lateral cervical and upper

mediastinal lNs)

bull NX Regional lymph nodes cannot be assessed bull N0 No regional lymph node metastasis bull N1 Regional lymph node metastasis

bull N1a Metastasis to level VI (pretracheal paratracheal and prelaryngealDelphian on the cricothyroid membrane (precricoid) lymph nodes)

bull N1b Metastasis to unilateral or bilateral cervical or superior mediastinal lymph nodes

bull Distant metastases (M) bull MX Distant metastasis cannot be assessed bull M0 No distant metastasis bull M1 Distant metastasis

AJCC Stage Groupings Papillary or follicular thyroid cancer

bull Younger than 45 yearsbull Stage I

bull Any T any N M0 bull Stage II

bull Any T any N M1

bull Age 45 years and olderbull Stage I

bull T1 N0 M0bull Stage II

bull T2 N0 M0 bull Stage III

bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0

Papillary or follicular thyroid cancer

Age 45 years and older

Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T3 N1b M0 T2 N1b M0 T4a N1b M0

Stage IVB T4b any N M0

Stage IVC Any T any N M1

Stage I

T1 N0 M0

Stage II

T2 N0 M0

Stage III

T3 N0 M0

T1 N1a M0

T2 N1a M0

T3 N1a M0

Medullary thyroid cancer bullStage I

bull T1 N0 M0 bullStage II

bull T2 N0 M0bullStage III

bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0

Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T2 N1b M0 T3 N1b M0 T4a N1b M0

Stage IVB T4b any N M0

Stage IVC Any T any N M1

bull Anaplastic thyroid cancer

bull All anaplastic carcinomas are considered stage IV

bull Stage IVA bull T4a any N M0

bull Stage IVB bull T4b any N M0

bull Stage IVC bull Any T any N M1

bull University of Chicago systembull Class Imdashdisease limited to the thyroid glandbull Class IImdashlymph node involvementbull Class IIImdashextrathyroidal invasionbull Class IVmdashdistant metastases

PROGNOSIS

PROGNOSIS

Prognostic schemes GAMES scoring (PAPILLARY amp

FOLLICULAR CANCER)bullG GradebullA Age of patient when tumor discoveredbullM Metastases of the tumor (other than Neck LN)bullE Extent of primary tumorbullS Size of tumor (gt5 cm)bullThe patient is then placed into a high or low risk category

Prognostic Risk Classification for Patients with Well-Differentiated Thyroid Cancer (GAMES )

Low Risk High Riskbull Grade Well Differentiated Poorly Differentiated

bull Age lt40 gt40

bull Mets None Regional or Distant

bull Extent No local extension Capsular invasion intrathyroidal extrathyroidal

bull Sex Female Male

MACIS ScoringbullDeveloped by the Mayo Clinic for stagingbullIt is known to be the most accurate predictor of a patients outcome with papillary thyroid cancer (M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)bullMAICS Score 20 year Survival

lt 6 = 99 6-7 = 89 7-8 = 56 gt 8 = 24

Treatment

Stage I and II Papillary and FollicularI-Total thyroidectomy bull Rationale1048708 Bilateral cancers are common (30-85)1048708 improved effectiveness for I131 ablation1048708 lowers dose needed for I131 ablation1048708 allows fu with thyroglobulin levels1048708 decreased recurrence in all groups1048708 improved survival in high risk pts1048708 Decreased risk of pulmonary metsbull Disadvantage higher incidence of hypoparathyroidism but this

complication may be reduced when a small amount of tissue remains on the contralateral side

II-Lobectomy

bull Rationale

1048708 Most patients are low risk and excellent prognosis

1048708 Role of adjuvant treatment not defined

1048708 Complications of Total

1048708 Occult multicentric tumor not clinically significant

1048708 Most local recurrences treated with surgery

1048708 Excellent outcome with lobectomy in low risk patients

bull Disadvantage

bull approximately 5 to 10 of patients will have a recurrence

Indications for total Thyroidectomy OR lobectomy (all present)

bull Age 15 y - 45 ybull No prior radiationbull No distant metastasesbull No cervical lymph node metastasesbull No extrathyroidal extensionbull Tumor lt 4 cm in diameterbull No aggressive variant

When complete total thyroidectomy after lobectomybull Aggressive variantbull Macroscopic multifocal diseasebull Positive isthmus marginsbull Cervical lymph node metastasesbull Extrathyroidal extension

Aggressive=Tall cell columnar cell insular oxyphilic or poorly differentiated features

bull Node removal

bull Selective node removal can be performed and radical

neck dissection is usually not required

bull This results in a decreased recurrence rate but has not

been shown to improve survival

Thyroid carcinoma after lobectomy for benign lesions

I-Completion of thyroidectomy

bull gt 4 cm

bull Positive margins

bull Extra-thyroidal invasion (T3 or T4(

II- Completion of Thyroidectomy or follow

up

bull Clinically suspicious lymph node

contralateral lesion or perithyroidal node

bull Aggressive variant

bull Macroscopic multifocal disease

bull ge1 cm in diameter

III- follow up

bull Negative margins

bull No contralateral lesion

bull lt 1 cm in diameter

bull No suspicious lymph

node

POSTSURGICAL EVALUATION AFTER THYROIDECTOMY

I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +

antithyroglobulin antibodies)

II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan

Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT

bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)

Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas

Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant

Pretherapy whole body iodine scan

bullIf performed a pretherapy scan should use a low dose of 131I

(1 to 5 mCi) or 123I

bull To detect residual thyroid tissue thyroid cancer and metastatic foci

bull To reduce the potential for sublethal radiation stunning of thyroid tissue that

prevents optimal uptake of future 131I therapy

bullStunning is defined as a reduction in uptake of the 131I

therapy dose induced by a pretreatment diagnostic dose

Dose of RAI

bullThe dosing of 131I for ablation is somewhat controversial

bullLow-dose ablation with less than 30 mCi administered on

an outpatient basis

bull For low-risk young patients

bullHigh-dose ablation with100 to 200 mCi

bull For high-risk patients

bull300 mCi

bull For all patients with metastatic disease that treated with repeated

therapeutic doses of 131I

Replacement therapy

bullPostoperative treatment with exogenous thyroid hormone

in doses sufficient to suppress thyroid-stimulating hormone

(TSH) with development of thyrotoxic manifestations

decreases incidence of recurrence

bullAdministration of Thyroid Hormone

To suppress TSH and growth of any residual thyroid

To maintain patient euthyroid

o Maintain TSH level 01uUml in low risk pts

o Maintain TSH Level lt 01uUml in high risk pts

Stage III Papillary and Follicular

A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease

B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients

Stage IV Papillary and Follicular 1) Adequate uptake of I131

bull I131

1) Inadequate uptake or not sensitive to I131

i Localized lesions

1) Radiation therapy

2) Resection of limited metastases dont uptake of I131

iiDisseminated disease

1) TSH suppression with thyroxine is effective

2) Chemotherapy has been reported to produce occasional complete

responses of long duration

3) Clinical trials testing new approaches to this disease

Medullary Thyroid Cancer treatment

bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck

dissections Why

bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival

advantage

bull Radioactive iodine has no place in the treatment of patients with MTC

bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in

patients with metastatic disease

bull No single drug regimen can be considered standard

bull Some patients with distant metastases will experience prolonged survival and can

be observed until they become symptomatic

Anaplastic Thyroid Cancer bull Surgery

bull Tracheostomy is frequently necessary

bull If the disease is confined to the local area which is rare total

thyroidectomy is warranted to reduce symptoms caused by the

tumor mass

bull Radiation therapy

bull Used in patients who are not surgical candidates or whose tumor

cannot be surgically excised

Anaplastic Thyroid Cancer bull Chemotherapy

bull Produce partial remissions in some patients

bull Approximately 30 of patients achieve a partial remission with

doxorubicin

bull The combination of doxorubicin plus cisplatin appears to be more

active than doxorubicin alone and has been reported to produce

more complete responses

Treatment options under clinical evaluation

bull The combination of chemotherapy plus radiation therapy in patients following

complete resection may provide prolonged survival but has not been compared to

any one modality alone

Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30

bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common

site of distant metastasis is the lung

bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type

Treatment of recurrent thyroid cancer

The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations

bull Adequate I131 uptake

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull I131 ablation

bull RT

bull Disseminated

bull I131 ablation

bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has

been reported to produce occasional objective responses usually of short

duration

Treatment of recurrent thyroid cancer

bull Inadequate I131 uptake or insensitive to I131

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull RT

bull Disseminated

bull Systemic chemotherapy

Treatment of recurrent thyroid cancer

Systemic chemotherapy

bull Doxorubicin alone

bull Cisplatin and doxorubicin (better)

bull BAP Cisplatin doxorubicin and bleomycin

bull CVD cyclophosphamide vincristine and dacarbazine

bull Dacarbazine and 5-fluorouracil

bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy

bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT

bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)

bull Improve OS and decrease RR

BAP regimenbull Schedule

bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5

bull Cell typebull Several histologic types of thyroid carcinoma responded but the

best responses were observed in medullary and anaplastic giant-cell carcinomas

bull Effectivenessbull BAP regime can achieve reasonable palliation and probably

increases survival in poor-prognosis thyroid cancers

CVD regimenbull Schedule

bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks

bull Cell typebull Medullary thyroid carcinoma

bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in

patients with advanced MTC

Dacarbazine and 5-fluorouracil

bull Schedule

bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and

12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks

Six cycles

bull Cell type

bull MTC

bull Effectiveness

bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to

have significant activity and was well tolerated

Target therapy

Take home messagesbull FNAC is not adequate for definite diagnosis of follicular

carcinomabull Because the mixed papillary-follicular variant tends to

behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis

bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer

bull Once medullary carcinoma is diagnosed familial predisposition should be checked up

bull If I131 is indicated stunning effect should be avoided

Take home messages

All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary

Papillary Cancer The most common malignant thyroid tumor (70-80 of all cancers) Women predominance Age 38-45 Accounts for 90 of radiation induced thyroid cancer Prognosis directly related to tumor size

bull Papillary Cancer

1Histologic1 Psammoma bodies

2 Orphan Ann nucleus

2Multicentric 30-50

3Spread via Lymphatics- propensity for cervical node involvement

4Invasion of adjacent structures and distant mets uncommon

FOLLICULAR THYROID CANCER1Usually Encapsulated2More Common Among Older Patients3Woman gt Man4More Aggressive amp Less Curable Than Papillary5Vascular Invasion (veins and arteries) within the thyroid gland is common6Blood Spread (lung and bone)7Types

1 Follicular carcinoma 2 Follicular carcinoma variant Minimally Invasive Hurthle Cell

8Rarely associated with radiation exposure

Huumlrthle Cell Neoplasms

1More aggressive than other differentiated thyroid carcinomas (higher metslower survival rates)

2Less affinity for I131

3Need to differentiate from benignmalignant

4Metastasis may be more sensitive to I131 than primary

Medullary Thyroid Cancer 1 Usually present as a mass plusmn lymphadenopathy

2 It can also be diagnosed by fine-needle aspiration biopsy

microscopically typically

3 Family members should be screened for calcitonin

elevation andor for the RET proto-oncogene mutation

4 Not associated with radiation exposure

5 Residual disease (following surgery) or recurrence can be

detected by measuring calcitonin

Medullary Thyroid Cancer Occurs in Four Clinical Settings

I- Sporadic

180 of all cases of medullary thyroid cancer

2Typically unilateral

3No associated endocrinopathies

4Peak onset 40 - 60

5Females predominance 32 ratio

6One third will present with intractable diarrhea

Diarrhea is caused by increased gastrointestinal secretion and hypermotility due to

the hormones secreted by the tumor (calcitonin prostaglandins serotonin or VIP)

II-MEN II-A (Sipple Syndrome)

(Multiple Endocrine Neoplasia II A)

1Sipple syndrome has

[1] bilateral medullary carcinoma

[2] pheochromocytoma

[3] hyperparathyroidism

2This syndrome is inherited in an autosomal dominant fashion

Because of this males and females are equally affected

3Peak incidence of medullary carcinoma in these patients is in the

30s

III-MEN II B

1This syndrome has

[1] medullary carcinoma

[2] Pheochromocytoma

[3] mucosal ganglioneuromas and Marfanoid habitus

2Inheritance is autosomal dominant as in MEN IIA (m=f)

3Pheochromocytomas must be detected prior to any operation

4The idea here is to remove the pheochromocytoma first to remove

the risk of severe hypertensive episodes while the thyroid or

parathyroid is being operated on

IV-Inherited medullary carcinoma without associated endocrinopathies

This form of medullary carcinoma is the least aggressive Like other types of thyroid cancers the peak incidence is

between the ages of 40 and 50

Anaplastic cancer

1)Peak onset age 65 and older

Very rare in young patients

2)Males more common than females by 2 to 1 ratio

3)Undifferentiated

4)May arise many years (gt20) following radiation

exposure

5)Neck mass usually large diffuse and very hard

6)Rapidly growing often inoperable highly recurrent

7) Invade locally metastasize both locally and distantly

(to lungs or bones)

8) Cervical metastasis are present in the vast majority

(over 90) of cases at the time of diagnosis

9) Mean survival 6 months

10) Often requires the patient to get a tracheostomy to

maintain their airway

STAGING OF THYROID CANCER

In differentiated thyroid carcinoma several classification and

staging systems have been introduced However no clear

consensus has emerged favoring any one method over another

bull AMES systemAGES SystemGAMES system

bull TNM system

bull MACIS system

bull University of Chicago system

bull Ohio State University system

bull National Thyroid Cancer Treatment Cooperative Study

(NTCTCS)

TNM Staging bull Primary tumor (T) (All categories may be subdivided into (a)

solitary tumor or (b) multifocal tumor)

TX Primary tumor cannot be assessed

T0 No evidence of primary tumor

T1 Tumor le 2 cm limited to the thyroid

T2 Tumor gt 2 cm but le4 cm limited to the thyroid

T3 Tumor gt 4 cm limited to the thyroid or any tumor with

minimal extrathyroid extension (eg extension to

sternothyroid muscle or perithyroid soft tissues)

bull T4a Tumor of any size extending beyond the thyroid capsule to invade subcutaneous soft tissues larynx trachea esophagus or recurrent laryngeal nerve

bull T4b Tumor invades prevertebral fascia or encases carotid artery or mediastinal vessels

All anaplastic carcinomas are considered T4 tumorsbull T4a Intrathyroidal anaplastic carcinomamdashsurgically resectable bull T4b Extrathyroidal anaplastic carcinomamdashsurgically

unresectable

bull Regional lymph nodes (N) (Regional lymph nodes are the central compartment lateral cervical and upper

mediastinal lNs)

bull NX Regional lymph nodes cannot be assessed bull N0 No regional lymph node metastasis bull N1 Regional lymph node metastasis

bull N1a Metastasis to level VI (pretracheal paratracheal and prelaryngealDelphian on the cricothyroid membrane (precricoid) lymph nodes)

bull N1b Metastasis to unilateral or bilateral cervical or superior mediastinal lymph nodes

bull Distant metastases (M) bull MX Distant metastasis cannot be assessed bull M0 No distant metastasis bull M1 Distant metastasis

AJCC Stage Groupings Papillary or follicular thyroid cancer

bull Younger than 45 yearsbull Stage I

bull Any T any N M0 bull Stage II

bull Any T any N M1

bull Age 45 years and olderbull Stage I

bull T1 N0 M0bull Stage II

bull T2 N0 M0 bull Stage III

bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0

Papillary or follicular thyroid cancer

Age 45 years and older

Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T3 N1b M0 T2 N1b M0 T4a N1b M0

Stage IVB T4b any N M0

Stage IVC Any T any N M1

Stage I

T1 N0 M0

Stage II

T2 N0 M0

Stage III

T3 N0 M0

T1 N1a M0

T2 N1a M0

T3 N1a M0

Medullary thyroid cancer bullStage I

bull T1 N0 M0 bullStage II

bull T2 N0 M0bullStage III

bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0

Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T2 N1b M0 T3 N1b M0 T4a N1b M0

Stage IVB T4b any N M0

Stage IVC Any T any N M1

bull Anaplastic thyroid cancer

bull All anaplastic carcinomas are considered stage IV

bull Stage IVA bull T4a any N M0

bull Stage IVB bull T4b any N M0

bull Stage IVC bull Any T any N M1

bull University of Chicago systembull Class Imdashdisease limited to the thyroid glandbull Class IImdashlymph node involvementbull Class IIImdashextrathyroidal invasionbull Class IVmdashdistant metastases

PROGNOSIS

PROGNOSIS

Prognostic schemes GAMES scoring (PAPILLARY amp

FOLLICULAR CANCER)bullG GradebullA Age of patient when tumor discoveredbullM Metastases of the tumor (other than Neck LN)bullE Extent of primary tumorbullS Size of tumor (gt5 cm)bullThe patient is then placed into a high or low risk category

Prognostic Risk Classification for Patients with Well-Differentiated Thyroid Cancer (GAMES )

Low Risk High Riskbull Grade Well Differentiated Poorly Differentiated

bull Age lt40 gt40

bull Mets None Regional or Distant

bull Extent No local extension Capsular invasion intrathyroidal extrathyroidal

bull Sex Female Male

MACIS ScoringbullDeveloped by the Mayo Clinic for stagingbullIt is known to be the most accurate predictor of a patients outcome with papillary thyroid cancer (M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)bullMAICS Score 20 year Survival

lt 6 = 99 6-7 = 89 7-8 = 56 gt 8 = 24

Treatment

Stage I and II Papillary and FollicularI-Total thyroidectomy bull Rationale1048708 Bilateral cancers are common (30-85)1048708 improved effectiveness for I131 ablation1048708 lowers dose needed for I131 ablation1048708 allows fu with thyroglobulin levels1048708 decreased recurrence in all groups1048708 improved survival in high risk pts1048708 Decreased risk of pulmonary metsbull Disadvantage higher incidence of hypoparathyroidism but this

complication may be reduced when a small amount of tissue remains on the contralateral side

II-Lobectomy

bull Rationale

1048708 Most patients are low risk and excellent prognosis

1048708 Role of adjuvant treatment not defined

1048708 Complications of Total

1048708 Occult multicentric tumor not clinically significant

1048708 Most local recurrences treated with surgery

1048708 Excellent outcome with lobectomy in low risk patients

bull Disadvantage

bull approximately 5 to 10 of patients will have a recurrence

Indications for total Thyroidectomy OR lobectomy (all present)

bull Age 15 y - 45 ybull No prior radiationbull No distant metastasesbull No cervical lymph node metastasesbull No extrathyroidal extensionbull Tumor lt 4 cm in diameterbull No aggressive variant

When complete total thyroidectomy after lobectomybull Aggressive variantbull Macroscopic multifocal diseasebull Positive isthmus marginsbull Cervical lymph node metastasesbull Extrathyroidal extension

Aggressive=Tall cell columnar cell insular oxyphilic or poorly differentiated features

bull Node removal

bull Selective node removal can be performed and radical

neck dissection is usually not required

bull This results in a decreased recurrence rate but has not

been shown to improve survival

Thyroid carcinoma after lobectomy for benign lesions

I-Completion of thyroidectomy

bull gt 4 cm

bull Positive margins

bull Extra-thyroidal invasion (T3 or T4(

II- Completion of Thyroidectomy or follow

up

bull Clinically suspicious lymph node

contralateral lesion or perithyroidal node

bull Aggressive variant

bull Macroscopic multifocal disease

bull ge1 cm in diameter

III- follow up

bull Negative margins

bull No contralateral lesion

bull lt 1 cm in diameter

bull No suspicious lymph

node

POSTSURGICAL EVALUATION AFTER THYROIDECTOMY

I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +

antithyroglobulin antibodies)

II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan

Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT

bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)

Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas

Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant

Pretherapy whole body iodine scan

bullIf performed a pretherapy scan should use a low dose of 131I

(1 to 5 mCi) or 123I

bull To detect residual thyroid tissue thyroid cancer and metastatic foci

bull To reduce the potential for sublethal radiation stunning of thyroid tissue that

prevents optimal uptake of future 131I therapy

bullStunning is defined as a reduction in uptake of the 131I

therapy dose induced by a pretreatment diagnostic dose

Dose of RAI

bullThe dosing of 131I for ablation is somewhat controversial

bullLow-dose ablation with less than 30 mCi administered on

an outpatient basis

bull For low-risk young patients

bullHigh-dose ablation with100 to 200 mCi

bull For high-risk patients

bull300 mCi

bull For all patients with metastatic disease that treated with repeated

therapeutic doses of 131I

Replacement therapy

bullPostoperative treatment with exogenous thyroid hormone

in doses sufficient to suppress thyroid-stimulating hormone

(TSH) with development of thyrotoxic manifestations

decreases incidence of recurrence

bullAdministration of Thyroid Hormone

To suppress TSH and growth of any residual thyroid

To maintain patient euthyroid

o Maintain TSH level 01uUml in low risk pts

o Maintain TSH Level lt 01uUml in high risk pts

Stage III Papillary and Follicular

A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease

B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients

Stage IV Papillary and Follicular 1) Adequate uptake of I131

bull I131

1) Inadequate uptake or not sensitive to I131

i Localized lesions

1) Radiation therapy

2) Resection of limited metastases dont uptake of I131

iiDisseminated disease

1) TSH suppression with thyroxine is effective

2) Chemotherapy has been reported to produce occasional complete

responses of long duration

3) Clinical trials testing new approaches to this disease

Medullary Thyroid Cancer treatment

bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck

dissections Why

bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival

advantage

bull Radioactive iodine has no place in the treatment of patients with MTC

bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in

patients with metastatic disease

bull No single drug regimen can be considered standard

bull Some patients with distant metastases will experience prolonged survival and can

be observed until they become symptomatic

Anaplastic Thyroid Cancer bull Surgery

bull Tracheostomy is frequently necessary

bull If the disease is confined to the local area which is rare total

thyroidectomy is warranted to reduce symptoms caused by the

tumor mass

bull Radiation therapy

bull Used in patients who are not surgical candidates or whose tumor

cannot be surgically excised

Anaplastic Thyroid Cancer bull Chemotherapy

bull Produce partial remissions in some patients

bull Approximately 30 of patients achieve a partial remission with

doxorubicin

bull The combination of doxorubicin plus cisplatin appears to be more

active than doxorubicin alone and has been reported to produce

more complete responses

Treatment options under clinical evaluation

bull The combination of chemotherapy plus radiation therapy in patients following

complete resection may provide prolonged survival but has not been compared to

any one modality alone

Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30

bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common

site of distant metastasis is the lung

bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type

Treatment of recurrent thyroid cancer

The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations

bull Adequate I131 uptake

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull I131 ablation

bull RT

bull Disseminated

bull I131 ablation

bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has

been reported to produce occasional objective responses usually of short

duration

Treatment of recurrent thyroid cancer

bull Inadequate I131 uptake or insensitive to I131

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull RT

bull Disseminated

bull Systemic chemotherapy

Treatment of recurrent thyroid cancer

Systemic chemotherapy

bull Doxorubicin alone

bull Cisplatin and doxorubicin (better)

bull BAP Cisplatin doxorubicin and bleomycin

bull CVD cyclophosphamide vincristine and dacarbazine

bull Dacarbazine and 5-fluorouracil

bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy

bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT

bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)

bull Improve OS and decrease RR

BAP regimenbull Schedule

bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5

bull Cell typebull Several histologic types of thyroid carcinoma responded but the

best responses were observed in medullary and anaplastic giant-cell carcinomas

bull Effectivenessbull BAP regime can achieve reasonable palliation and probably

increases survival in poor-prognosis thyroid cancers

CVD regimenbull Schedule

bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks

bull Cell typebull Medullary thyroid carcinoma

bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in

patients with advanced MTC

Dacarbazine and 5-fluorouracil

bull Schedule

bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and

12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks

Six cycles

bull Cell type

bull MTC

bull Effectiveness

bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to

have significant activity and was well tolerated

Target therapy

Take home messagesbull FNAC is not adequate for definite diagnosis of follicular

carcinomabull Because the mixed papillary-follicular variant tends to

behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis

bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer

bull Once medullary carcinoma is diagnosed familial predisposition should be checked up

bull If I131 is indicated stunning effect should be avoided

Take home messages

All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary

bull Papillary Cancer

1Histologic1 Psammoma bodies

2 Orphan Ann nucleus

2Multicentric 30-50

3Spread via Lymphatics- propensity for cervical node involvement

4Invasion of adjacent structures and distant mets uncommon

FOLLICULAR THYROID CANCER1Usually Encapsulated2More Common Among Older Patients3Woman gt Man4More Aggressive amp Less Curable Than Papillary5Vascular Invasion (veins and arteries) within the thyroid gland is common6Blood Spread (lung and bone)7Types

1 Follicular carcinoma 2 Follicular carcinoma variant Minimally Invasive Hurthle Cell

8Rarely associated with radiation exposure

Huumlrthle Cell Neoplasms

1More aggressive than other differentiated thyroid carcinomas (higher metslower survival rates)

2Less affinity for I131

3Need to differentiate from benignmalignant

4Metastasis may be more sensitive to I131 than primary

Medullary Thyroid Cancer 1 Usually present as a mass plusmn lymphadenopathy

2 It can also be diagnosed by fine-needle aspiration biopsy

microscopically typically

3 Family members should be screened for calcitonin

elevation andor for the RET proto-oncogene mutation

4 Not associated with radiation exposure

5 Residual disease (following surgery) or recurrence can be

detected by measuring calcitonin

Medullary Thyroid Cancer Occurs in Four Clinical Settings

I- Sporadic

180 of all cases of medullary thyroid cancer

2Typically unilateral

3No associated endocrinopathies

4Peak onset 40 - 60

5Females predominance 32 ratio

6One third will present with intractable diarrhea

Diarrhea is caused by increased gastrointestinal secretion and hypermotility due to

the hormones secreted by the tumor (calcitonin prostaglandins serotonin or VIP)

II-MEN II-A (Sipple Syndrome)

(Multiple Endocrine Neoplasia II A)

1Sipple syndrome has

[1] bilateral medullary carcinoma

[2] pheochromocytoma

[3] hyperparathyroidism

2This syndrome is inherited in an autosomal dominant fashion

Because of this males and females are equally affected

3Peak incidence of medullary carcinoma in these patients is in the

30s

III-MEN II B

1This syndrome has

[1] medullary carcinoma

[2] Pheochromocytoma

[3] mucosal ganglioneuromas and Marfanoid habitus

2Inheritance is autosomal dominant as in MEN IIA (m=f)

3Pheochromocytomas must be detected prior to any operation

4The idea here is to remove the pheochromocytoma first to remove

the risk of severe hypertensive episodes while the thyroid or

parathyroid is being operated on

IV-Inherited medullary carcinoma without associated endocrinopathies

This form of medullary carcinoma is the least aggressive Like other types of thyroid cancers the peak incidence is

between the ages of 40 and 50

Anaplastic cancer

1)Peak onset age 65 and older

Very rare in young patients

2)Males more common than females by 2 to 1 ratio

3)Undifferentiated

4)May arise many years (gt20) following radiation

exposure

5)Neck mass usually large diffuse and very hard

6)Rapidly growing often inoperable highly recurrent

7) Invade locally metastasize both locally and distantly

(to lungs or bones)

8) Cervical metastasis are present in the vast majority

(over 90) of cases at the time of diagnosis

9) Mean survival 6 months

10) Often requires the patient to get a tracheostomy to

maintain their airway

STAGING OF THYROID CANCER

In differentiated thyroid carcinoma several classification and

staging systems have been introduced However no clear

consensus has emerged favoring any one method over another

bull AMES systemAGES SystemGAMES system

bull TNM system

bull MACIS system

bull University of Chicago system

bull Ohio State University system

bull National Thyroid Cancer Treatment Cooperative Study

(NTCTCS)

TNM Staging bull Primary tumor (T) (All categories may be subdivided into (a)

solitary tumor or (b) multifocal tumor)

TX Primary tumor cannot be assessed

T0 No evidence of primary tumor

T1 Tumor le 2 cm limited to the thyroid

T2 Tumor gt 2 cm but le4 cm limited to the thyroid

T3 Tumor gt 4 cm limited to the thyroid or any tumor with

minimal extrathyroid extension (eg extension to

sternothyroid muscle or perithyroid soft tissues)

bull T4a Tumor of any size extending beyond the thyroid capsule to invade subcutaneous soft tissues larynx trachea esophagus or recurrent laryngeal nerve

bull T4b Tumor invades prevertebral fascia or encases carotid artery or mediastinal vessels

All anaplastic carcinomas are considered T4 tumorsbull T4a Intrathyroidal anaplastic carcinomamdashsurgically resectable bull T4b Extrathyroidal anaplastic carcinomamdashsurgically

unresectable

bull Regional lymph nodes (N) (Regional lymph nodes are the central compartment lateral cervical and upper

mediastinal lNs)

bull NX Regional lymph nodes cannot be assessed bull N0 No regional lymph node metastasis bull N1 Regional lymph node metastasis

bull N1a Metastasis to level VI (pretracheal paratracheal and prelaryngealDelphian on the cricothyroid membrane (precricoid) lymph nodes)

bull N1b Metastasis to unilateral or bilateral cervical or superior mediastinal lymph nodes

bull Distant metastases (M) bull MX Distant metastasis cannot be assessed bull M0 No distant metastasis bull M1 Distant metastasis

AJCC Stage Groupings Papillary or follicular thyroid cancer

bull Younger than 45 yearsbull Stage I

bull Any T any N M0 bull Stage II

bull Any T any N M1

bull Age 45 years and olderbull Stage I

bull T1 N0 M0bull Stage II

bull T2 N0 M0 bull Stage III

bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0

Papillary or follicular thyroid cancer

Age 45 years and older

Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T3 N1b M0 T2 N1b M0 T4a N1b M0

Stage IVB T4b any N M0

Stage IVC Any T any N M1

Stage I

T1 N0 M0

Stage II

T2 N0 M0

Stage III

T3 N0 M0

T1 N1a M0

T2 N1a M0

T3 N1a M0

Medullary thyroid cancer bullStage I

bull T1 N0 M0 bullStage II

bull T2 N0 M0bullStage III

bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0

Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T2 N1b M0 T3 N1b M0 T4a N1b M0

Stage IVB T4b any N M0

Stage IVC Any T any N M1

bull Anaplastic thyroid cancer

bull All anaplastic carcinomas are considered stage IV

bull Stage IVA bull T4a any N M0

bull Stage IVB bull T4b any N M0

bull Stage IVC bull Any T any N M1

bull University of Chicago systembull Class Imdashdisease limited to the thyroid glandbull Class IImdashlymph node involvementbull Class IIImdashextrathyroidal invasionbull Class IVmdashdistant metastases

PROGNOSIS

PROGNOSIS

Prognostic schemes GAMES scoring (PAPILLARY amp

FOLLICULAR CANCER)bullG GradebullA Age of patient when tumor discoveredbullM Metastases of the tumor (other than Neck LN)bullE Extent of primary tumorbullS Size of tumor (gt5 cm)bullThe patient is then placed into a high or low risk category

Prognostic Risk Classification for Patients with Well-Differentiated Thyroid Cancer (GAMES )

Low Risk High Riskbull Grade Well Differentiated Poorly Differentiated

bull Age lt40 gt40

bull Mets None Regional or Distant

bull Extent No local extension Capsular invasion intrathyroidal extrathyroidal

bull Sex Female Male

MACIS ScoringbullDeveloped by the Mayo Clinic for stagingbullIt is known to be the most accurate predictor of a patients outcome with papillary thyroid cancer (M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)bullMAICS Score 20 year Survival

lt 6 = 99 6-7 = 89 7-8 = 56 gt 8 = 24

Treatment

Stage I and II Papillary and FollicularI-Total thyroidectomy bull Rationale1048708 Bilateral cancers are common (30-85)1048708 improved effectiveness for I131 ablation1048708 lowers dose needed for I131 ablation1048708 allows fu with thyroglobulin levels1048708 decreased recurrence in all groups1048708 improved survival in high risk pts1048708 Decreased risk of pulmonary metsbull Disadvantage higher incidence of hypoparathyroidism but this

complication may be reduced when a small amount of tissue remains on the contralateral side

II-Lobectomy

bull Rationale

1048708 Most patients are low risk and excellent prognosis

1048708 Role of adjuvant treatment not defined

1048708 Complications of Total

1048708 Occult multicentric tumor not clinically significant

1048708 Most local recurrences treated with surgery

1048708 Excellent outcome with lobectomy in low risk patients

bull Disadvantage

bull approximately 5 to 10 of patients will have a recurrence

Indications for total Thyroidectomy OR lobectomy (all present)

bull Age 15 y - 45 ybull No prior radiationbull No distant metastasesbull No cervical lymph node metastasesbull No extrathyroidal extensionbull Tumor lt 4 cm in diameterbull No aggressive variant

When complete total thyroidectomy after lobectomybull Aggressive variantbull Macroscopic multifocal diseasebull Positive isthmus marginsbull Cervical lymph node metastasesbull Extrathyroidal extension

Aggressive=Tall cell columnar cell insular oxyphilic or poorly differentiated features

bull Node removal

bull Selective node removal can be performed and radical

neck dissection is usually not required

bull This results in a decreased recurrence rate but has not

been shown to improve survival

Thyroid carcinoma after lobectomy for benign lesions

I-Completion of thyroidectomy

bull gt 4 cm

bull Positive margins

bull Extra-thyroidal invasion (T3 or T4(

II- Completion of Thyroidectomy or follow

up

bull Clinically suspicious lymph node

contralateral lesion or perithyroidal node

bull Aggressive variant

bull Macroscopic multifocal disease

bull ge1 cm in diameter

III- follow up

bull Negative margins

bull No contralateral lesion

bull lt 1 cm in diameter

bull No suspicious lymph

node

POSTSURGICAL EVALUATION AFTER THYROIDECTOMY

I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +

antithyroglobulin antibodies)

II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan

Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT

bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)

Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas

Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant

Pretherapy whole body iodine scan

bullIf performed a pretherapy scan should use a low dose of 131I

(1 to 5 mCi) or 123I

bull To detect residual thyroid tissue thyroid cancer and metastatic foci

bull To reduce the potential for sublethal radiation stunning of thyroid tissue that

prevents optimal uptake of future 131I therapy

bullStunning is defined as a reduction in uptake of the 131I

therapy dose induced by a pretreatment diagnostic dose

Dose of RAI

bullThe dosing of 131I for ablation is somewhat controversial

bullLow-dose ablation with less than 30 mCi administered on

an outpatient basis

bull For low-risk young patients

bullHigh-dose ablation with100 to 200 mCi

bull For high-risk patients

bull300 mCi

bull For all patients with metastatic disease that treated with repeated

therapeutic doses of 131I

Replacement therapy

bullPostoperative treatment with exogenous thyroid hormone

in doses sufficient to suppress thyroid-stimulating hormone

(TSH) with development of thyrotoxic manifestations

decreases incidence of recurrence

bullAdministration of Thyroid Hormone

To suppress TSH and growth of any residual thyroid

To maintain patient euthyroid

o Maintain TSH level 01uUml in low risk pts

o Maintain TSH Level lt 01uUml in high risk pts

Stage III Papillary and Follicular

A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease

B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients

Stage IV Papillary and Follicular 1) Adequate uptake of I131

bull I131

1) Inadequate uptake or not sensitive to I131

i Localized lesions

1) Radiation therapy

2) Resection of limited metastases dont uptake of I131

iiDisseminated disease

1) TSH suppression with thyroxine is effective

2) Chemotherapy has been reported to produce occasional complete

responses of long duration

3) Clinical trials testing new approaches to this disease

Medullary Thyroid Cancer treatment

bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck

dissections Why

bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival

advantage

bull Radioactive iodine has no place in the treatment of patients with MTC

bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in

patients with metastatic disease

bull No single drug regimen can be considered standard

bull Some patients with distant metastases will experience prolonged survival and can

be observed until they become symptomatic

Anaplastic Thyroid Cancer bull Surgery

bull Tracheostomy is frequently necessary

bull If the disease is confined to the local area which is rare total

thyroidectomy is warranted to reduce symptoms caused by the

tumor mass

bull Radiation therapy

bull Used in patients who are not surgical candidates or whose tumor

cannot be surgically excised

Anaplastic Thyroid Cancer bull Chemotherapy

bull Produce partial remissions in some patients

bull Approximately 30 of patients achieve a partial remission with

doxorubicin

bull The combination of doxorubicin plus cisplatin appears to be more

active than doxorubicin alone and has been reported to produce

more complete responses

Treatment options under clinical evaluation

bull The combination of chemotherapy plus radiation therapy in patients following

complete resection may provide prolonged survival but has not been compared to

any one modality alone

Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30

bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common

site of distant metastasis is the lung

bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type

Treatment of recurrent thyroid cancer

The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations

bull Adequate I131 uptake

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull I131 ablation

bull RT

bull Disseminated

bull I131 ablation

bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has

been reported to produce occasional objective responses usually of short

duration

Treatment of recurrent thyroid cancer

bull Inadequate I131 uptake or insensitive to I131

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull RT

bull Disseminated

bull Systemic chemotherapy

Treatment of recurrent thyroid cancer

Systemic chemotherapy

bull Doxorubicin alone

bull Cisplatin and doxorubicin (better)

bull BAP Cisplatin doxorubicin and bleomycin

bull CVD cyclophosphamide vincristine and dacarbazine

bull Dacarbazine and 5-fluorouracil

bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy

bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT

bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)

bull Improve OS and decrease RR

BAP regimenbull Schedule

bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5

bull Cell typebull Several histologic types of thyroid carcinoma responded but the

best responses were observed in medullary and anaplastic giant-cell carcinomas

bull Effectivenessbull BAP regime can achieve reasonable palliation and probably

increases survival in poor-prognosis thyroid cancers

CVD regimenbull Schedule

bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks

bull Cell typebull Medullary thyroid carcinoma

bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in

patients with advanced MTC

Dacarbazine and 5-fluorouracil

bull Schedule

bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and

12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks

Six cycles

bull Cell type

bull MTC

bull Effectiveness

bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to

have significant activity and was well tolerated

Target therapy

Take home messagesbull FNAC is not adequate for definite diagnosis of follicular

carcinomabull Because the mixed papillary-follicular variant tends to

behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis

bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer

bull Once medullary carcinoma is diagnosed familial predisposition should be checked up

bull If I131 is indicated stunning effect should be avoided

Take home messages

All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary

FOLLICULAR THYROID CANCER1Usually Encapsulated2More Common Among Older Patients3Woman gt Man4More Aggressive amp Less Curable Than Papillary5Vascular Invasion (veins and arteries) within the thyroid gland is common6Blood Spread (lung and bone)7Types

1 Follicular carcinoma 2 Follicular carcinoma variant Minimally Invasive Hurthle Cell

8Rarely associated with radiation exposure

Huumlrthle Cell Neoplasms

1More aggressive than other differentiated thyroid carcinomas (higher metslower survival rates)

2Less affinity for I131

3Need to differentiate from benignmalignant

4Metastasis may be more sensitive to I131 than primary

Medullary Thyroid Cancer 1 Usually present as a mass plusmn lymphadenopathy

2 It can also be diagnosed by fine-needle aspiration biopsy

microscopically typically

3 Family members should be screened for calcitonin

elevation andor for the RET proto-oncogene mutation

4 Not associated with radiation exposure

5 Residual disease (following surgery) or recurrence can be

detected by measuring calcitonin

Medullary Thyroid Cancer Occurs in Four Clinical Settings

I- Sporadic

180 of all cases of medullary thyroid cancer

2Typically unilateral

3No associated endocrinopathies

4Peak onset 40 - 60

5Females predominance 32 ratio

6One third will present with intractable diarrhea

Diarrhea is caused by increased gastrointestinal secretion and hypermotility due to

the hormones secreted by the tumor (calcitonin prostaglandins serotonin or VIP)

II-MEN II-A (Sipple Syndrome)

(Multiple Endocrine Neoplasia II A)

1Sipple syndrome has

[1] bilateral medullary carcinoma

[2] pheochromocytoma

[3] hyperparathyroidism

2This syndrome is inherited in an autosomal dominant fashion

Because of this males and females are equally affected

3Peak incidence of medullary carcinoma in these patients is in the

30s

III-MEN II B

1This syndrome has

[1] medullary carcinoma

[2] Pheochromocytoma

[3] mucosal ganglioneuromas and Marfanoid habitus

2Inheritance is autosomal dominant as in MEN IIA (m=f)

3Pheochromocytomas must be detected prior to any operation

4The idea here is to remove the pheochromocytoma first to remove

the risk of severe hypertensive episodes while the thyroid or

parathyroid is being operated on

IV-Inherited medullary carcinoma without associated endocrinopathies

This form of medullary carcinoma is the least aggressive Like other types of thyroid cancers the peak incidence is

between the ages of 40 and 50

Anaplastic cancer

1)Peak onset age 65 and older

Very rare in young patients

2)Males more common than females by 2 to 1 ratio

3)Undifferentiated

4)May arise many years (gt20) following radiation

exposure

5)Neck mass usually large diffuse and very hard

6)Rapidly growing often inoperable highly recurrent

7) Invade locally metastasize both locally and distantly

(to lungs or bones)

8) Cervical metastasis are present in the vast majority

(over 90) of cases at the time of diagnosis

9) Mean survival 6 months

10) Often requires the patient to get a tracheostomy to

maintain their airway

STAGING OF THYROID CANCER

In differentiated thyroid carcinoma several classification and

staging systems have been introduced However no clear

consensus has emerged favoring any one method over another

bull AMES systemAGES SystemGAMES system

bull TNM system

bull MACIS system

bull University of Chicago system

bull Ohio State University system

bull National Thyroid Cancer Treatment Cooperative Study

(NTCTCS)

TNM Staging bull Primary tumor (T) (All categories may be subdivided into (a)

solitary tumor or (b) multifocal tumor)

TX Primary tumor cannot be assessed

T0 No evidence of primary tumor

T1 Tumor le 2 cm limited to the thyroid

T2 Tumor gt 2 cm but le4 cm limited to the thyroid

T3 Tumor gt 4 cm limited to the thyroid or any tumor with

minimal extrathyroid extension (eg extension to

sternothyroid muscle or perithyroid soft tissues)

bull T4a Tumor of any size extending beyond the thyroid capsule to invade subcutaneous soft tissues larynx trachea esophagus or recurrent laryngeal nerve

bull T4b Tumor invades prevertebral fascia or encases carotid artery or mediastinal vessels

All anaplastic carcinomas are considered T4 tumorsbull T4a Intrathyroidal anaplastic carcinomamdashsurgically resectable bull T4b Extrathyroidal anaplastic carcinomamdashsurgically

unresectable

bull Regional lymph nodes (N) (Regional lymph nodes are the central compartment lateral cervical and upper

mediastinal lNs)

bull NX Regional lymph nodes cannot be assessed bull N0 No regional lymph node metastasis bull N1 Regional lymph node metastasis

bull N1a Metastasis to level VI (pretracheal paratracheal and prelaryngealDelphian on the cricothyroid membrane (precricoid) lymph nodes)

bull N1b Metastasis to unilateral or bilateral cervical or superior mediastinal lymph nodes

bull Distant metastases (M) bull MX Distant metastasis cannot be assessed bull M0 No distant metastasis bull M1 Distant metastasis

AJCC Stage Groupings Papillary or follicular thyroid cancer

bull Younger than 45 yearsbull Stage I

bull Any T any N M0 bull Stage II

bull Any T any N M1

bull Age 45 years and olderbull Stage I

bull T1 N0 M0bull Stage II

bull T2 N0 M0 bull Stage III

bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0

Papillary or follicular thyroid cancer

Age 45 years and older

Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T3 N1b M0 T2 N1b M0 T4a N1b M0

Stage IVB T4b any N M0

Stage IVC Any T any N M1

Stage I

T1 N0 M0

Stage II

T2 N0 M0

Stage III

T3 N0 M0

T1 N1a M0

T2 N1a M0

T3 N1a M0

Medullary thyroid cancer bullStage I

bull T1 N0 M0 bullStage II

bull T2 N0 M0bullStage III

bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0

Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T2 N1b M0 T3 N1b M0 T4a N1b M0

Stage IVB T4b any N M0

Stage IVC Any T any N M1

bull Anaplastic thyroid cancer

bull All anaplastic carcinomas are considered stage IV

bull Stage IVA bull T4a any N M0

bull Stage IVB bull T4b any N M0

bull Stage IVC bull Any T any N M1

bull University of Chicago systembull Class Imdashdisease limited to the thyroid glandbull Class IImdashlymph node involvementbull Class IIImdashextrathyroidal invasionbull Class IVmdashdistant metastases

PROGNOSIS

PROGNOSIS

Prognostic schemes GAMES scoring (PAPILLARY amp

FOLLICULAR CANCER)bullG GradebullA Age of patient when tumor discoveredbullM Metastases of the tumor (other than Neck LN)bullE Extent of primary tumorbullS Size of tumor (gt5 cm)bullThe patient is then placed into a high or low risk category

Prognostic Risk Classification for Patients with Well-Differentiated Thyroid Cancer (GAMES )

Low Risk High Riskbull Grade Well Differentiated Poorly Differentiated

bull Age lt40 gt40

bull Mets None Regional or Distant

bull Extent No local extension Capsular invasion intrathyroidal extrathyroidal

bull Sex Female Male

MACIS ScoringbullDeveloped by the Mayo Clinic for stagingbullIt is known to be the most accurate predictor of a patients outcome with papillary thyroid cancer (M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)bullMAICS Score 20 year Survival

lt 6 = 99 6-7 = 89 7-8 = 56 gt 8 = 24

Treatment

Stage I and II Papillary and FollicularI-Total thyroidectomy bull Rationale1048708 Bilateral cancers are common (30-85)1048708 improved effectiveness for I131 ablation1048708 lowers dose needed for I131 ablation1048708 allows fu with thyroglobulin levels1048708 decreased recurrence in all groups1048708 improved survival in high risk pts1048708 Decreased risk of pulmonary metsbull Disadvantage higher incidence of hypoparathyroidism but this

complication may be reduced when a small amount of tissue remains on the contralateral side

II-Lobectomy

bull Rationale

1048708 Most patients are low risk and excellent prognosis

1048708 Role of adjuvant treatment not defined

1048708 Complications of Total

1048708 Occult multicentric tumor not clinically significant

1048708 Most local recurrences treated with surgery

1048708 Excellent outcome with lobectomy in low risk patients

bull Disadvantage

bull approximately 5 to 10 of patients will have a recurrence

Indications for total Thyroidectomy OR lobectomy (all present)

bull Age 15 y - 45 ybull No prior radiationbull No distant metastasesbull No cervical lymph node metastasesbull No extrathyroidal extensionbull Tumor lt 4 cm in diameterbull No aggressive variant

When complete total thyroidectomy after lobectomybull Aggressive variantbull Macroscopic multifocal diseasebull Positive isthmus marginsbull Cervical lymph node metastasesbull Extrathyroidal extension

Aggressive=Tall cell columnar cell insular oxyphilic or poorly differentiated features

bull Node removal

bull Selective node removal can be performed and radical

neck dissection is usually not required

bull This results in a decreased recurrence rate but has not

been shown to improve survival

Thyroid carcinoma after lobectomy for benign lesions

I-Completion of thyroidectomy

bull gt 4 cm

bull Positive margins

bull Extra-thyroidal invasion (T3 or T4(

II- Completion of Thyroidectomy or follow

up

bull Clinically suspicious lymph node

contralateral lesion or perithyroidal node

bull Aggressive variant

bull Macroscopic multifocal disease

bull ge1 cm in diameter

III- follow up

bull Negative margins

bull No contralateral lesion

bull lt 1 cm in diameter

bull No suspicious lymph

node

POSTSURGICAL EVALUATION AFTER THYROIDECTOMY

I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +

antithyroglobulin antibodies)

II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan

Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT

bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)

Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas

Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant

Pretherapy whole body iodine scan

bullIf performed a pretherapy scan should use a low dose of 131I

(1 to 5 mCi) or 123I

bull To detect residual thyroid tissue thyroid cancer and metastatic foci

bull To reduce the potential for sublethal radiation stunning of thyroid tissue that

prevents optimal uptake of future 131I therapy

bullStunning is defined as a reduction in uptake of the 131I

therapy dose induced by a pretreatment diagnostic dose

Dose of RAI

bullThe dosing of 131I for ablation is somewhat controversial

bullLow-dose ablation with less than 30 mCi administered on

an outpatient basis

bull For low-risk young patients

bullHigh-dose ablation with100 to 200 mCi

bull For high-risk patients

bull300 mCi

bull For all patients with metastatic disease that treated with repeated

therapeutic doses of 131I

Replacement therapy

bullPostoperative treatment with exogenous thyroid hormone

in doses sufficient to suppress thyroid-stimulating hormone

(TSH) with development of thyrotoxic manifestations

decreases incidence of recurrence

bullAdministration of Thyroid Hormone

To suppress TSH and growth of any residual thyroid

To maintain patient euthyroid

o Maintain TSH level 01uUml in low risk pts

o Maintain TSH Level lt 01uUml in high risk pts

Stage III Papillary and Follicular

A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease

B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients

Stage IV Papillary and Follicular 1) Adequate uptake of I131

bull I131

1) Inadequate uptake or not sensitive to I131

i Localized lesions

1) Radiation therapy

2) Resection of limited metastases dont uptake of I131

iiDisseminated disease

1) TSH suppression with thyroxine is effective

2) Chemotherapy has been reported to produce occasional complete

responses of long duration

3) Clinical trials testing new approaches to this disease

Medullary Thyroid Cancer treatment

bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck

dissections Why

bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival

advantage

bull Radioactive iodine has no place in the treatment of patients with MTC

bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in

patients with metastatic disease

bull No single drug regimen can be considered standard

bull Some patients with distant metastases will experience prolonged survival and can

be observed until they become symptomatic

Anaplastic Thyroid Cancer bull Surgery

bull Tracheostomy is frequently necessary

bull If the disease is confined to the local area which is rare total

thyroidectomy is warranted to reduce symptoms caused by the

tumor mass

bull Radiation therapy

bull Used in patients who are not surgical candidates or whose tumor

cannot be surgically excised

Anaplastic Thyroid Cancer bull Chemotherapy

bull Produce partial remissions in some patients

bull Approximately 30 of patients achieve a partial remission with

doxorubicin

bull The combination of doxorubicin plus cisplatin appears to be more

active than doxorubicin alone and has been reported to produce

more complete responses

Treatment options under clinical evaluation

bull The combination of chemotherapy plus radiation therapy in patients following

complete resection may provide prolonged survival but has not been compared to

any one modality alone

Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30

bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common

site of distant metastasis is the lung

bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type

Treatment of recurrent thyroid cancer

The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations

bull Adequate I131 uptake

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull I131 ablation

bull RT

bull Disseminated

bull I131 ablation

bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has

been reported to produce occasional objective responses usually of short

duration

Treatment of recurrent thyroid cancer

bull Inadequate I131 uptake or insensitive to I131

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull RT

bull Disseminated

bull Systemic chemotherapy

Treatment of recurrent thyroid cancer

Systemic chemotherapy

bull Doxorubicin alone

bull Cisplatin and doxorubicin (better)

bull BAP Cisplatin doxorubicin and bleomycin

bull CVD cyclophosphamide vincristine and dacarbazine

bull Dacarbazine and 5-fluorouracil

bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy

bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT

bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)

bull Improve OS and decrease RR

BAP regimenbull Schedule

bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5

bull Cell typebull Several histologic types of thyroid carcinoma responded but the

best responses were observed in medullary and anaplastic giant-cell carcinomas

bull Effectivenessbull BAP regime can achieve reasonable palliation and probably

increases survival in poor-prognosis thyroid cancers

CVD regimenbull Schedule

bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks

bull Cell typebull Medullary thyroid carcinoma

bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in

patients with advanced MTC

Dacarbazine and 5-fluorouracil

bull Schedule

bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and

12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks

Six cycles

bull Cell type

bull MTC

bull Effectiveness

bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to

have significant activity and was well tolerated

Target therapy

Take home messagesbull FNAC is not adequate for definite diagnosis of follicular

carcinomabull Because the mixed papillary-follicular variant tends to

behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis

bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer

bull Once medullary carcinoma is diagnosed familial predisposition should be checked up

bull If I131 is indicated stunning effect should be avoided

Take home messages

All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary

Huumlrthle Cell Neoplasms

1More aggressive than other differentiated thyroid carcinomas (higher metslower survival rates)

2Less affinity for I131

3Need to differentiate from benignmalignant

4Metastasis may be more sensitive to I131 than primary

Medullary Thyroid Cancer 1 Usually present as a mass plusmn lymphadenopathy

2 It can also be diagnosed by fine-needle aspiration biopsy

microscopically typically

3 Family members should be screened for calcitonin

elevation andor for the RET proto-oncogene mutation

4 Not associated with radiation exposure

5 Residual disease (following surgery) or recurrence can be

detected by measuring calcitonin

Medullary Thyroid Cancer Occurs in Four Clinical Settings

I- Sporadic

180 of all cases of medullary thyroid cancer

2Typically unilateral

3No associated endocrinopathies

4Peak onset 40 - 60

5Females predominance 32 ratio

6One third will present with intractable diarrhea

Diarrhea is caused by increased gastrointestinal secretion and hypermotility due to

the hormones secreted by the tumor (calcitonin prostaglandins serotonin or VIP)

II-MEN II-A (Sipple Syndrome)

(Multiple Endocrine Neoplasia II A)

1Sipple syndrome has

[1] bilateral medullary carcinoma

[2] pheochromocytoma

[3] hyperparathyroidism

2This syndrome is inherited in an autosomal dominant fashion

Because of this males and females are equally affected

3Peak incidence of medullary carcinoma in these patients is in the

30s

III-MEN II B

1This syndrome has

[1] medullary carcinoma

[2] Pheochromocytoma

[3] mucosal ganglioneuromas and Marfanoid habitus

2Inheritance is autosomal dominant as in MEN IIA (m=f)

3Pheochromocytomas must be detected prior to any operation

4The idea here is to remove the pheochromocytoma first to remove

the risk of severe hypertensive episodes while the thyroid or

parathyroid is being operated on

IV-Inherited medullary carcinoma without associated endocrinopathies

This form of medullary carcinoma is the least aggressive Like other types of thyroid cancers the peak incidence is

between the ages of 40 and 50

Anaplastic cancer

1)Peak onset age 65 and older

Very rare in young patients

2)Males more common than females by 2 to 1 ratio

3)Undifferentiated

4)May arise many years (gt20) following radiation

exposure

5)Neck mass usually large diffuse and very hard

6)Rapidly growing often inoperable highly recurrent

7) Invade locally metastasize both locally and distantly

(to lungs or bones)

8) Cervical metastasis are present in the vast majority

(over 90) of cases at the time of diagnosis

9) Mean survival 6 months

10) Often requires the patient to get a tracheostomy to

maintain their airway

STAGING OF THYROID CANCER

In differentiated thyroid carcinoma several classification and

staging systems have been introduced However no clear

consensus has emerged favoring any one method over another

bull AMES systemAGES SystemGAMES system

bull TNM system

bull MACIS system

bull University of Chicago system

bull Ohio State University system

bull National Thyroid Cancer Treatment Cooperative Study

(NTCTCS)

TNM Staging bull Primary tumor (T) (All categories may be subdivided into (a)

solitary tumor or (b) multifocal tumor)

TX Primary tumor cannot be assessed

T0 No evidence of primary tumor

T1 Tumor le 2 cm limited to the thyroid

T2 Tumor gt 2 cm but le4 cm limited to the thyroid

T3 Tumor gt 4 cm limited to the thyroid or any tumor with

minimal extrathyroid extension (eg extension to

sternothyroid muscle or perithyroid soft tissues)

bull T4a Tumor of any size extending beyond the thyroid capsule to invade subcutaneous soft tissues larynx trachea esophagus or recurrent laryngeal nerve

bull T4b Tumor invades prevertebral fascia or encases carotid artery or mediastinal vessels

All anaplastic carcinomas are considered T4 tumorsbull T4a Intrathyroidal anaplastic carcinomamdashsurgically resectable bull T4b Extrathyroidal anaplastic carcinomamdashsurgically

unresectable

bull Regional lymph nodes (N) (Regional lymph nodes are the central compartment lateral cervical and upper

mediastinal lNs)

bull NX Regional lymph nodes cannot be assessed bull N0 No regional lymph node metastasis bull N1 Regional lymph node metastasis

bull N1a Metastasis to level VI (pretracheal paratracheal and prelaryngealDelphian on the cricothyroid membrane (precricoid) lymph nodes)

bull N1b Metastasis to unilateral or bilateral cervical or superior mediastinal lymph nodes

bull Distant metastases (M) bull MX Distant metastasis cannot be assessed bull M0 No distant metastasis bull M1 Distant metastasis

AJCC Stage Groupings Papillary or follicular thyroid cancer

bull Younger than 45 yearsbull Stage I

bull Any T any N M0 bull Stage II

bull Any T any N M1

bull Age 45 years and olderbull Stage I

bull T1 N0 M0bull Stage II

bull T2 N0 M0 bull Stage III

bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0

Papillary or follicular thyroid cancer

Age 45 years and older

Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T3 N1b M0 T2 N1b M0 T4a N1b M0

Stage IVB T4b any N M0

Stage IVC Any T any N M1

Stage I

T1 N0 M0

Stage II

T2 N0 M0

Stage III

T3 N0 M0

T1 N1a M0

T2 N1a M0

T3 N1a M0

Medullary thyroid cancer bullStage I

bull T1 N0 M0 bullStage II

bull T2 N0 M0bullStage III

bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0

Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T2 N1b M0 T3 N1b M0 T4a N1b M0

Stage IVB T4b any N M0

Stage IVC Any T any N M1

bull Anaplastic thyroid cancer

bull All anaplastic carcinomas are considered stage IV

bull Stage IVA bull T4a any N M0

bull Stage IVB bull T4b any N M0

bull Stage IVC bull Any T any N M1

bull University of Chicago systembull Class Imdashdisease limited to the thyroid glandbull Class IImdashlymph node involvementbull Class IIImdashextrathyroidal invasionbull Class IVmdashdistant metastases

PROGNOSIS

PROGNOSIS

Prognostic schemes GAMES scoring (PAPILLARY amp

FOLLICULAR CANCER)bullG GradebullA Age of patient when tumor discoveredbullM Metastases of the tumor (other than Neck LN)bullE Extent of primary tumorbullS Size of tumor (gt5 cm)bullThe patient is then placed into a high or low risk category

Prognostic Risk Classification for Patients with Well-Differentiated Thyroid Cancer (GAMES )

Low Risk High Riskbull Grade Well Differentiated Poorly Differentiated

bull Age lt40 gt40

bull Mets None Regional or Distant

bull Extent No local extension Capsular invasion intrathyroidal extrathyroidal

bull Sex Female Male

MACIS ScoringbullDeveloped by the Mayo Clinic for stagingbullIt is known to be the most accurate predictor of a patients outcome with papillary thyroid cancer (M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)bullMAICS Score 20 year Survival

lt 6 = 99 6-7 = 89 7-8 = 56 gt 8 = 24

Treatment

Stage I and II Papillary and FollicularI-Total thyroidectomy bull Rationale1048708 Bilateral cancers are common (30-85)1048708 improved effectiveness for I131 ablation1048708 lowers dose needed for I131 ablation1048708 allows fu with thyroglobulin levels1048708 decreased recurrence in all groups1048708 improved survival in high risk pts1048708 Decreased risk of pulmonary metsbull Disadvantage higher incidence of hypoparathyroidism but this

complication may be reduced when a small amount of tissue remains on the contralateral side

II-Lobectomy

bull Rationale

1048708 Most patients are low risk and excellent prognosis

1048708 Role of adjuvant treatment not defined

1048708 Complications of Total

1048708 Occult multicentric tumor not clinically significant

1048708 Most local recurrences treated with surgery

1048708 Excellent outcome with lobectomy in low risk patients

bull Disadvantage

bull approximately 5 to 10 of patients will have a recurrence

Indications for total Thyroidectomy OR lobectomy (all present)

bull Age 15 y - 45 ybull No prior radiationbull No distant metastasesbull No cervical lymph node metastasesbull No extrathyroidal extensionbull Tumor lt 4 cm in diameterbull No aggressive variant

When complete total thyroidectomy after lobectomybull Aggressive variantbull Macroscopic multifocal diseasebull Positive isthmus marginsbull Cervical lymph node metastasesbull Extrathyroidal extension

Aggressive=Tall cell columnar cell insular oxyphilic or poorly differentiated features

bull Node removal

bull Selective node removal can be performed and radical

neck dissection is usually not required

bull This results in a decreased recurrence rate but has not

been shown to improve survival

Thyroid carcinoma after lobectomy for benign lesions

I-Completion of thyroidectomy

bull gt 4 cm

bull Positive margins

bull Extra-thyroidal invasion (T3 or T4(

II- Completion of Thyroidectomy or follow

up

bull Clinically suspicious lymph node

contralateral lesion or perithyroidal node

bull Aggressive variant

bull Macroscopic multifocal disease

bull ge1 cm in diameter

III- follow up

bull Negative margins

bull No contralateral lesion

bull lt 1 cm in diameter

bull No suspicious lymph

node

POSTSURGICAL EVALUATION AFTER THYROIDECTOMY

I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +

antithyroglobulin antibodies)

II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan

Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT

bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)

Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas

Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant

Pretherapy whole body iodine scan

bullIf performed a pretherapy scan should use a low dose of 131I

(1 to 5 mCi) or 123I

bull To detect residual thyroid tissue thyroid cancer and metastatic foci

bull To reduce the potential for sublethal radiation stunning of thyroid tissue that

prevents optimal uptake of future 131I therapy

bullStunning is defined as a reduction in uptake of the 131I

therapy dose induced by a pretreatment diagnostic dose

Dose of RAI

bullThe dosing of 131I for ablation is somewhat controversial

bullLow-dose ablation with less than 30 mCi administered on

an outpatient basis

bull For low-risk young patients

bullHigh-dose ablation with100 to 200 mCi

bull For high-risk patients

bull300 mCi

bull For all patients with metastatic disease that treated with repeated

therapeutic doses of 131I

Replacement therapy

bullPostoperative treatment with exogenous thyroid hormone

in doses sufficient to suppress thyroid-stimulating hormone

(TSH) with development of thyrotoxic manifestations

decreases incidence of recurrence

bullAdministration of Thyroid Hormone

To suppress TSH and growth of any residual thyroid

To maintain patient euthyroid

o Maintain TSH level 01uUml in low risk pts

o Maintain TSH Level lt 01uUml in high risk pts

Stage III Papillary and Follicular

A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease

B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients

Stage IV Papillary and Follicular 1) Adequate uptake of I131

bull I131

1) Inadequate uptake or not sensitive to I131

i Localized lesions

1) Radiation therapy

2) Resection of limited metastases dont uptake of I131

iiDisseminated disease

1) TSH suppression with thyroxine is effective

2) Chemotherapy has been reported to produce occasional complete

responses of long duration

3) Clinical trials testing new approaches to this disease

Medullary Thyroid Cancer treatment

bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck

dissections Why

bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival

advantage

bull Radioactive iodine has no place in the treatment of patients with MTC

bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in

patients with metastatic disease

bull No single drug regimen can be considered standard

bull Some patients with distant metastases will experience prolonged survival and can

be observed until they become symptomatic

Anaplastic Thyroid Cancer bull Surgery

bull Tracheostomy is frequently necessary

bull If the disease is confined to the local area which is rare total

thyroidectomy is warranted to reduce symptoms caused by the

tumor mass

bull Radiation therapy

bull Used in patients who are not surgical candidates or whose tumor

cannot be surgically excised

Anaplastic Thyroid Cancer bull Chemotherapy

bull Produce partial remissions in some patients

bull Approximately 30 of patients achieve a partial remission with

doxorubicin

bull The combination of doxorubicin plus cisplatin appears to be more

active than doxorubicin alone and has been reported to produce

more complete responses

Treatment options under clinical evaluation

bull The combination of chemotherapy plus radiation therapy in patients following

complete resection may provide prolonged survival but has not been compared to

any one modality alone

Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30

bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common

site of distant metastasis is the lung

bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type

Treatment of recurrent thyroid cancer

The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations

bull Adequate I131 uptake

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull I131 ablation

bull RT

bull Disseminated

bull I131 ablation

bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has

been reported to produce occasional objective responses usually of short

duration

Treatment of recurrent thyroid cancer

bull Inadequate I131 uptake or insensitive to I131

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull RT

bull Disseminated

bull Systemic chemotherapy

Treatment of recurrent thyroid cancer

Systemic chemotherapy

bull Doxorubicin alone

bull Cisplatin and doxorubicin (better)

bull BAP Cisplatin doxorubicin and bleomycin

bull CVD cyclophosphamide vincristine and dacarbazine

bull Dacarbazine and 5-fluorouracil

bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy

bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT

bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)

bull Improve OS and decrease RR

BAP regimenbull Schedule

bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5

bull Cell typebull Several histologic types of thyroid carcinoma responded but the

best responses were observed in medullary and anaplastic giant-cell carcinomas

bull Effectivenessbull BAP regime can achieve reasonable palliation and probably

increases survival in poor-prognosis thyroid cancers

CVD regimenbull Schedule

bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks

bull Cell typebull Medullary thyroid carcinoma

bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in

patients with advanced MTC

Dacarbazine and 5-fluorouracil

bull Schedule

bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and

12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks

Six cycles

bull Cell type

bull MTC

bull Effectiveness

bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to

have significant activity and was well tolerated

Target therapy

Take home messagesbull FNAC is not adequate for definite diagnosis of follicular

carcinomabull Because the mixed papillary-follicular variant tends to

behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis

bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer

bull Once medullary carcinoma is diagnosed familial predisposition should be checked up

bull If I131 is indicated stunning effect should be avoided

Take home messages

All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary

Medullary Thyroid Cancer 1 Usually present as a mass plusmn lymphadenopathy

2 It can also be diagnosed by fine-needle aspiration biopsy

microscopically typically

3 Family members should be screened for calcitonin

elevation andor for the RET proto-oncogene mutation

4 Not associated with radiation exposure

5 Residual disease (following surgery) or recurrence can be

detected by measuring calcitonin

Medullary Thyroid Cancer Occurs in Four Clinical Settings

I- Sporadic

180 of all cases of medullary thyroid cancer

2Typically unilateral

3No associated endocrinopathies

4Peak onset 40 - 60

5Females predominance 32 ratio

6One third will present with intractable diarrhea

Diarrhea is caused by increased gastrointestinal secretion and hypermotility due to

the hormones secreted by the tumor (calcitonin prostaglandins serotonin or VIP)

II-MEN II-A (Sipple Syndrome)

(Multiple Endocrine Neoplasia II A)

1Sipple syndrome has

[1] bilateral medullary carcinoma

[2] pheochromocytoma

[3] hyperparathyroidism

2This syndrome is inherited in an autosomal dominant fashion

Because of this males and females are equally affected

3Peak incidence of medullary carcinoma in these patients is in the

30s

III-MEN II B

1This syndrome has

[1] medullary carcinoma

[2] Pheochromocytoma

[3] mucosal ganglioneuromas and Marfanoid habitus

2Inheritance is autosomal dominant as in MEN IIA (m=f)

3Pheochromocytomas must be detected prior to any operation

4The idea here is to remove the pheochromocytoma first to remove

the risk of severe hypertensive episodes while the thyroid or

parathyroid is being operated on

IV-Inherited medullary carcinoma without associated endocrinopathies

This form of medullary carcinoma is the least aggressive Like other types of thyroid cancers the peak incidence is

between the ages of 40 and 50

Anaplastic cancer

1)Peak onset age 65 and older

Very rare in young patients

2)Males more common than females by 2 to 1 ratio

3)Undifferentiated

4)May arise many years (gt20) following radiation

exposure

5)Neck mass usually large diffuse and very hard

6)Rapidly growing often inoperable highly recurrent

7) Invade locally metastasize both locally and distantly

(to lungs or bones)

8) Cervical metastasis are present in the vast majority

(over 90) of cases at the time of diagnosis

9) Mean survival 6 months

10) Often requires the patient to get a tracheostomy to

maintain their airway

STAGING OF THYROID CANCER

In differentiated thyroid carcinoma several classification and

staging systems have been introduced However no clear

consensus has emerged favoring any one method over another

bull AMES systemAGES SystemGAMES system

bull TNM system

bull MACIS system

bull University of Chicago system

bull Ohio State University system

bull National Thyroid Cancer Treatment Cooperative Study

(NTCTCS)

TNM Staging bull Primary tumor (T) (All categories may be subdivided into (a)

solitary tumor or (b) multifocal tumor)

TX Primary tumor cannot be assessed

T0 No evidence of primary tumor

T1 Tumor le 2 cm limited to the thyroid

T2 Tumor gt 2 cm but le4 cm limited to the thyroid

T3 Tumor gt 4 cm limited to the thyroid or any tumor with

minimal extrathyroid extension (eg extension to

sternothyroid muscle or perithyroid soft tissues)

bull T4a Tumor of any size extending beyond the thyroid capsule to invade subcutaneous soft tissues larynx trachea esophagus or recurrent laryngeal nerve

bull T4b Tumor invades prevertebral fascia or encases carotid artery or mediastinal vessels

All anaplastic carcinomas are considered T4 tumorsbull T4a Intrathyroidal anaplastic carcinomamdashsurgically resectable bull T4b Extrathyroidal anaplastic carcinomamdashsurgically

unresectable

bull Regional lymph nodes (N) (Regional lymph nodes are the central compartment lateral cervical and upper

mediastinal lNs)

bull NX Regional lymph nodes cannot be assessed bull N0 No regional lymph node metastasis bull N1 Regional lymph node metastasis

bull N1a Metastasis to level VI (pretracheal paratracheal and prelaryngealDelphian on the cricothyroid membrane (precricoid) lymph nodes)

bull N1b Metastasis to unilateral or bilateral cervical or superior mediastinal lymph nodes

bull Distant metastases (M) bull MX Distant metastasis cannot be assessed bull M0 No distant metastasis bull M1 Distant metastasis

AJCC Stage Groupings Papillary or follicular thyroid cancer

bull Younger than 45 yearsbull Stage I

bull Any T any N M0 bull Stage II

bull Any T any N M1

bull Age 45 years and olderbull Stage I

bull T1 N0 M0bull Stage II

bull T2 N0 M0 bull Stage III

bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0

Papillary or follicular thyroid cancer

Age 45 years and older

Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T3 N1b M0 T2 N1b M0 T4a N1b M0

Stage IVB T4b any N M0

Stage IVC Any T any N M1

Stage I

T1 N0 M0

Stage II

T2 N0 M0

Stage III

T3 N0 M0

T1 N1a M0

T2 N1a M0

T3 N1a M0

Medullary thyroid cancer bullStage I

bull T1 N0 M0 bullStage II

bull T2 N0 M0bullStage III

bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0

Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T2 N1b M0 T3 N1b M0 T4a N1b M0

Stage IVB T4b any N M0

Stage IVC Any T any N M1

bull Anaplastic thyroid cancer

bull All anaplastic carcinomas are considered stage IV

bull Stage IVA bull T4a any N M0

bull Stage IVB bull T4b any N M0

bull Stage IVC bull Any T any N M1

bull University of Chicago systembull Class Imdashdisease limited to the thyroid glandbull Class IImdashlymph node involvementbull Class IIImdashextrathyroidal invasionbull Class IVmdashdistant metastases

PROGNOSIS

PROGNOSIS

Prognostic schemes GAMES scoring (PAPILLARY amp

FOLLICULAR CANCER)bullG GradebullA Age of patient when tumor discoveredbullM Metastases of the tumor (other than Neck LN)bullE Extent of primary tumorbullS Size of tumor (gt5 cm)bullThe patient is then placed into a high or low risk category

Prognostic Risk Classification for Patients with Well-Differentiated Thyroid Cancer (GAMES )

Low Risk High Riskbull Grade Well Differentiated Poorly Differentiated

bull Age lt40 gt40

bull Mets None Regional or Distant

bull Extent No local extension Capsular invasion intrathyroidal extrathyroidal

bull Sex Female Male

MACIS ScoringbullDeveloped by the Mayo Clinic for stagingbullIt is known to be the most accurate predictor of a patients outcome with papillary thyroid cancer (M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)bullMAICS Score 20 year Survival

lt 6 = 99 6-7 = 89 7-8 = 56 gt 8 = 24

Treatment

Stage I and II Papillary and FollicularI-Total thyroidectomy bull Rationale1048708 Bilateral cancers are common (30-85)1048708 improved effectiveness for I131 ablation1048708 lowers dose needed for I131 ablation1048708 allows fu with thyroglobulin levels1048708 decreased recurrence in all groups1048708 improved survival in high risk pts1048708 Decreased risk of pulmonary metsbull Disadvantage higher incidence of hypoparathyroidism but this

complication may be reduced when a small amount of tissue remains on the contralateral side

II-Lobectomy

bull Rationale

1048708 Most patients are low risk and excellent prognosis

1048708 Role of adjuvant treatment not defined

1048708 Complications of Total

1048708 Occult multicentric tumor not clinically significant

1048708 Most local recurrences treated with surgery

1048708 Excellent outcome with lobectomy in low risk patients

bull Disadvantage

bull approximately 5 to 10 of patients will have a recurrence

Indications for total Thyroidectomy OR lobectomy (all present)

bull Age 15 y - 45 ybull No prior radiationbull No distant metastasesbull No cervical lymph node metastasesbull No extrathyroidal extensionbull Tumor lt 4 cm in diameterbull No aggressive variant

When complete total thyroidectomy after lobectomybull Aggressive variantbull Macroscopic multifocal diseasebull Positive isthmus marginsbull Cervical lymph node metastasesbull Extrathyroidal extension

Aggressive=Tall cell columnar cell insular oxyphilic or poorly differentiated features

bull Node removal

bull Selective node removal can be performed and radical

neck dissection is usually not required

bull This results in a decreased recurrence rate but has not

been shown to improve survival

Thyroid carcinoma after lobectomy for benign lesions

I-Completion of thyroidectomy

bull gt 4 cm

bull Positive margins

bull Extra-thyroidal invasion (T3 or T4(

II- Completion of Thyroidectomy or follow

up

bull Clinically suspicious lymph node

contralateral lesion or perithyroidal node

bull Aggressive variant

bull Macroscopic multifocal disease

bull ge1 cm in diameter

III- follow up

bull Negative margins

bull No contralateral lesion

bull lt 1 cm in diameter

bull No suspicious lymph

node

POSTSURGICAL EVALUATION AFTER THYROIDECTOMY

I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +

antithyroglobulin antibodies)

II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan

Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT

bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)

Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas

Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant

Pretherapy whole body iodine scan

bullIf performed a pretherapy scan should use a low dose of 131I

(1 to 5 mCi) or 123I

bull To detect residual thyroid tissue thyroid cancer and metastatic foci

bull To reduce the potential for sublethal radiation stunning of thyroid tissue that

prevents optimal uptake of future 131I therapy

bullStunning is defined as a reduction in uptake of the 131I

therapy dose induced by a pretreatment diagnostic dose

Dose of RAI

bullThe dosing of 131I for ablation is somewhat controversial

bullLow-dose ablation with less than 30 mCi administered on

an outpatient basis

bull For low-risk young patients

bullHigh-dose ablation with100 to 200 mCi

bull For high-risk patients

bull300 mCi

bull For all patients with metastatic disease that treated with repeated

therapeutic doses of 131I

Replacement therapy

bullPostoperative treatment with exogenous thyroid hormone

in doses sufficient to suppress thyroid-stimulating hormone

(TSH) with development of thyrotoxic manifestations

decreases incidence of recurrence

bullAdministration of Thyroid Hormone

To suppress TSH and growth of any residual thyroid

To maintain patient euthyroid

o Maintain TSH level 01uUml in low risk pts

o Maintain TSH Level lt 01uUml in high risk pts

Stage III Papillary and Follicular

A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease

B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients

Stage IV Papillary and Follicular 1) Adequate uptake of I131

bull I131

1) Inadequate uptake or not sensitive to I131

i Localized lesions

1) Radiation therapy

2) Resection of limited metastases dont uptake of I131

iiDisseminated disease

1) TSH suppression with thyroxine is effective

2) Chemotherapy has been reported to produce occasional complete

responses of long duration

3) Clinical trials testing new approaches to this disease

Medullary Thyroid Cancer treatment

bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck

dissections Why

bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival

advantage

bull Radioactive iodine has no place in the treatment of patients with MTC

bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in

patients with metastatic disease

bull No single drug regimen can be considered standard

bull Some patients with distant metastases will experience prolonged survival and can

be observed until they become symptomatic

Anaplastic Thyroid Cancer bull Surgery

bull Tracheostomy is frequently necessary

bull If the disease is confined to the local area which is rare total

thyroidectomy is warranted to reduce symptoms caused by the

tumor mass

bull Radiation therapy

bull Used in patients who are not surgical candidates or whose tumor

cannot be surgically excised

Anaplastic Thyroid Cancer bull Chemotherapy

bull Produce partial remissions in some patients

bull Approximately 30 of patients achieve a partial remission with

doxorubicin

bull The combination of doxorubicin plus cisplatin appears to be more

active than doxorubicin alone and has been reported to produce

more complete responses

Treatment options under clinical evaluation

bull The combination of chemotherapy plus radiation therapy in patients following

complete resection may provide prolonged survival but has not been compared to

any one modality alone

Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30

bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common

site of distant metastasis is the lung

bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type

Treatment of recurrent thyroid cancer

The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations

bull Adequate I131 uptake

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull I131 ablation

bull RT

bull Disseminated

bull I131 ablation

bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has

been reported to produce occasional objective responses usually of short

duration

Treatment of recurrent thyroid cancer

bull Inadequate I131 uptake or insensitive to I131

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull RT

bull Disseminated

bull Systemic chemotherapy

Treatment of recurrent thyroid cancer

Systemic chemotherapy

bull Doxorubicin alone

bull Cisplatin and doxorubicin (better)

bull BAP Cisplatin doxorubicin and bleomycin

bull CVD cyclophosphamide vincristine and dacarbazine

bull Dacarbazine and 5-fluorouracil

bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy

bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT

bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)

bull Improve OS and decrease RR

BAP regimenbull Schedule

bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5

bull Cell typebull Several histologic types of thyroid carcinoma responded but the

best responses were observed in medullary and anaplastic giant-cell carcinomas

bull Effectivenessbull BAP regime can achieve reasonable palliation and probably

increases survival in poor-prognosis thyroid cancers

CVD regimenbull Schedule

bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks

bull Cell typebull Medullary thyroid carcinoma

bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in

patients with advanced MTC

Dacarbazine and 5-fluorouracil

bull Schedule

bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and

12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks

Six cycles

bull Cell type

bull MTC

bull Effectiveness

bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to

have significant activity and was well tolerated

Target therapy

Take home messagesbull FNAC is not adequate for definite diagnosis of follicular

carcinomabull Because the mixed papillary-follicular variant tends to

behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis

bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer

bull Once medullary carcinoma is diagnosed familial predisposition should be checked up

bull If I131 is indicated stunning effect should be avoided

Take home messages

All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary

Medullary Thyroid Cancer Occurs in Four Clinical Settings

I- Sporadic

180 of all cases of medullary thyroid cancer

2Typically unilateral

3No associated endocrinopathies

4Peak onset 40 - 60

5Females predominance 32 ratio

6One third will present with intractable diarrhea

Diarrhea is caused by increased gastrointestinal secretion and hypermotility due to

the hormones secreted by the tumor (calcitonin prostaglandins serotonin or VIP)

II-MEN II-A (Sipple Syndrome)

(Multiple Endocrine Neoplasia II A)

1Sipple syndrome has

[1] bilateral medullary carcinoma

[2] pheochromocytoma

[3] hyperparathyroidism

2This syndrome is inherited in an autosomal dominant fashion

Because of this males and females are equally affected

3Peak incidence of medullary carcinoma in these patients is in the

30s

III-MEN II B

1This syndrome has

[1] medullary carcinoma

[2] Pheochromocytoma

[3] mucosal ganglioneuromas and Marfanoid habitus

2Inheritance is autosomal dominant as in MEN IIA (m=f)

3Pheochromocytomas must be detected prior to any operation

4The idea here is to remove the pheochromocytoma first to remove

the risk of severe hypertensive episodes while the thyroid or

parathyroid is being operated on

IV-Inherited medullary carcinoma without associated endocrinopathies

This form of medullary carcinoma is the least aggressive Like other types of thyroid cancers the peak incidence is

between the ages of 40 and 50

Anaplastic cancer

1)Peak onset age 65 and older

Very rare in young patients

2)Males more common than females by 2 to 1 ratio

3)Undifferentiated

4)May arise many years (gt20) following radiation

exposure

5)Neck mass usually large diffuse and very hard

6)Rapidly growing often inoperable highly recurrent

7) Invade locally metastasize both locally and distantly

(to lungs or bones)

8) Cervical metastasis are present in the vast majority

(over 90) of cases at the time of diagnosis

9) Mean survival 6 months

10) Often requires the patient to get a tracheostomy to

maintain their airway

STAGING OF THYROID CANCER

In differentiated thyroid carcinoma several classification and

staging systems have been introduced However no clear

consensus has emerged favoring any one method over another

bull AMES systemAGES SystemGAMES system

bull TNM system

bull MACIS system

bull University of Chicago system

bull Ohio State University system

bull National Thyroid Cancer Treatment Cooperative Study

(NTCTCS)

TNM Staging bull Primary tumor (T) (All categories may be subdivided into (a)

solitary tumor or (b) multifocal tumor)

TX Primary tumor cannot be assessed

T0 No evidence of primary tumor

T1 Tumor le 2 cm limited to the thyroid

T2 Tumor gt 2 cm but le4 cm limited to the thyroid

T3 Tumor gt 4 cm limited to the thyroid or any tumor with

minimal extrathyroid extension (eg extension to

sternothyroid muscle or perithyroid soft tissues)

bull T4a Tumor of any size extending beyond the thyroid capsule to invade subcutaneous soft tissues larynx trachea esophagus or recurrent laryngeal nerve

bull T4b Tumor invades prevertebral fascia or encases carotid artery or mediastinal vessels

All anaplastic carcinomas are considered T4 tumorsbull T4a Intrathyroidal anaplastic carcinomamdashsurgically resectable bull T4b Extrathyroidal anaplastic carcinomamdashsurgically

unresectable

bull Regional lymph nodes (N) (Regional lymph nodes are the central compartment lateral cervical and upper

mediastinal lNs)

bull NX Regional lymph nodes cannot be assessed bull N0 No regional lymph node metastasis bull N1 Regional lymph node metastasis

bull N1a Metastasis to level VI (pretracheal paratracheal and prelaryngealDelphian on the cricothyroid membrane (precricoid) lymph nodes)

bull N1b Metastasis to unilateral or bilateral cervical or superior mediastinal lymph nodes

bull Distant metastases (M) bull MX Distant metastasis cannot be assessed bull M0 No distant metastasis bull M1 Distant metastasis

AJCC Stage Groupings Papillary or follicular thyroid cancer

bull Younger than 45 yearsbull Stage I

bull Any T any N M0 bull Stage II

bull Any T any N M1

bull Age 45 years and olderbull Stage I

bull T1 N0 M0bull Stage II

bull T2 N0 M0 bull Stage III

bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0

Papillary or follicular thyroid cancer

Age 45 years and older

Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T3 N1b M0 T2 N1b M0 T4a N1b M0

Stage IVB T4b any N M0

Stage IVC Any T any N M1

Stage I

T1 N0 M0

Stage II

T2 N0 M0

Stage III

T3 N0 M0

T1 N1a M0

T2 N1a M0

T3 N1a M0

Medullary thyroid cancer bullStage I

bull T1 N0 M0 bullStage II

bull T2 N0 M0bullStage III

bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0

Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T2 N1b M0 T3 N1b M0 T4a N1b M0

Stage IVB T4b any N M0

Stage IVC Any T any N M1

bull Anaplastic thyroid cancer

bull All anaplastic carcinomas are considered stage IV

bull Stage IVA bull T4a any N M0

bull Stage IVB bull T4b any N M0

bull Stage IVC bull Any T any N M1

bull University of Chicago systembull Class Imdashdisease limited to the thyroid glandbull Class IImdashlymph node involvementbull Class IIImdashextrathyroidal invasionbull Class IVmdashdistant metastases

PROGNOSIS

PROGNOSIS

Prognostic schemes GAMES scoring (PAPILLARY amp

FOLLICULAR CANCER)bullG GradebullA Age of patient when tumor discoveredbullM Metastases of the tumor (other than Neck LN)bullE Extent of primary tumorbullS Size of tumor (gt5 cm)bullThe patient is then placed into a high or low risk category

Prognostic Risk Classification for Patients with Well-Differentiated Thyroid Cancer (GAMES )

Low Risk High Riskbull Grade Well Differentiated Poorly Differentiated

bull Age lt40 gt40

bull Mets None Regional or Distant

bull Extent No local extension Capsular invasion intrathyroidal extrathyroidal

bull Sex Female Male

MACIS ScoringbullDeveloped by the Mayo Clinic for stagingbullIt is known to be the most accurate predictor of a patients outcome with papillary thyroid cancer (M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)bullMAICS Score 20 year Survival

lt 6 = 99 6-7 = 89 7-8 = 56 gt 8 = 24

Treatment

Stage I and II Papillary and FollicularI-Total thyroidectomy bull Rationale1048708 Bilateral cancers are common (30-85)1048708 improved effectiveness for I131 ablation1048708 lowers dose needed for I131 ablation1048708 allows fu with thyroglobulin levels1048708 decreased recurrence in all groups1048708 improved survival in high risk pts1048708 Decreased risk of pulmonary metsbull Disadvantage higher incidence of hypoparathyroidism but this

complication may be reduced when a small amount of tissue remains on the contralateral side

II-Lobectomy

bull Rationale

1048708 Most patients are low risk and excellent prognosis

1048708 Role of adjuvant treatment not defined

1048708 Complications of Total

1048708 Occult multicentric tumor not clinically significant

1048708 Most local recurrences treated with surgery

1048708 Excellent outcome with lobectomy in low risk patients

bull Disadvantage

bull approximately 5 to 10 of patients will have a recurrence

Indications for total Thyroidectomy OR lobectomy (all present)

bull Age 15 y - 45 ybull No prior radiationbull No distant metastasesbull No cervical lymph node metastasesbull No extrathyroidal extensionbull Tumor lt 4 cm in diameterbull No aggressive variant

When complete total thyroidectomy after lobectomybull Aggressive variantbull Macroscopic multifocal diseasebull Positive isthmus marginsbull Cervical lymph node metastasesbull Extrathyroidal extension

Aggressive=Tall cell columnar cell insular oxyphilic or poorly differentiated features

bull Node removal

bull Selective node removal can be performed and radical

neck dissection is usually not required

bull This results in a decreased recurrence rate but has not

been shown to improve survival

Thyroid carcinoma after lobectomy for benign lesions

I-Completion of thyroidectomy

bull gt 4 cm

bull Positive margins

bull Extra-thyroidal invasion (T3 or T4(

II- Completion of Thyroidectomy or follow

up

bull Clinically suspicious lymph node

contralateral lesion or perithyroidal node

bull Aggressive variant

bull Macroscopic multifocal disease

bull ge1 cm in diameter

III- follow up

bull Negative margins

bull No contralateral lesion

bull lt 1 cm in diameter

bull No suspicious lymph

node

POSTSURGICAL EVALUATION AFTER THYROIDECTOMY

I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +

antithyroglobulin antibodies)

II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan

Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT

bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)

Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas

Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant

Pretherapy whole body iodine scan

bullIf performed a pretherapy scan should use a low dose of 131I

(1 to 5 mCi) or 123I

bull To detect residual thyroid tissue thyroid cancer and metastatic foci

bull To reduce the potential for sublethal radiation stunning of thyroid tissue that

prevents optimal uptake of future 131I therapy

bullStunning is defined as a reduction in uptake of the 131I

therapy dose induced by a pretreatment diagnostic dose

Dose of RAI

bullThe dosing of 131I for ablation is somewhat controversial

bullLow-dose ablation with less than 30 mCi administered on

an outpatient basis

bull For low-risk young patients

bullHigh-dose ablation with100 to 200 mCi

bull For high-risk patients

bull300 mCi

bull For all patients with metastatic disease that treated with repeated

therapeutic doses of 131I

Replacement therapy

bullPostoperative treatment with exogenous thyroid hormone

in doses sufficient to suppress thyroid-stimulating hormone

(TSH) with development of thyrotoxic manifestations

decreases incidence of recurrence

bullAdministration of Thyroid Hormone

To suppress TSH and growth of any residual thyroid

To maintain patient euthyroid

o Maintain TSH level 01uUml in low risk pts

o Maintain TSH Level lt 01uUml in high risk pts

Stage III Papillary and Follicular

A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease

B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients

Stage IV Papillary and Follicular 1) Adequate uptake of I131

bull I131

1) Inadequate uptake or not sensitive to I131

i Localized lesions

1) Radiation therapy

2) Resection of limited metastases dont uptake of I131

iiDisseminated disease

1) TSH suppression with thyroxine is effective

2) Chemotherapy has been reported to produce occasional complete

responses of long duration

3) Clinical trials testing new approaches to this disease

Medullary Thyroid Cancer treatment

bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck

dissections Why

bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival

advantage

bull Radioactive iodine has no place in the treatment of patients with MTC

bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in

patients with metastatic disease

bull No single drug regimen can be considered standard

bull Some patients with distant metastases will experience prolonged survival and can

be observed until they become symptomatic

Anaplastic Thyroid Cancer bull Surgery

bull Tracheostomy is frequently necessary

bull If the disease is confined to the local area which is rare total

thyroidectomy is warranted to reduce symptoms caused by the

tumor mass

bull Radiation therapy

bull Used in patients who are not surgical candidates or whose tumor

cannot be surgically excised

Anaplastic Thyroid Cancer bull Chemotherapy

bull Produce partial remissions in some patients

bull Approximately 30 of patients achieve a partial remission with

doxorubicin

bull The combination of doxorubicin plus cisplatin appears to be more

active than doxorubicin alone and has been reported to produce

more complete responses

Treatment options under clinical evaluation

bull The combination of chemotherapy plus radiation therapy in patients following

complete resection may provide prolonged survival but has not been compared to

any one modality alone

Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30

bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common

site of distant metastasis is the lung

bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type

Treatment of recurrent thyroid cancer

The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations

bull Adequate I131 uptake

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull I131 ablation

bull RT

bull Disseminated

bull I131 ablation

bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has

been reported to produce occasional objective responses usually of short

duration

Treatment of recurrent thyroid cancer

bull Inadequate I131 uptake or insensitive to I131

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull RT

bull Disseminated

bull Systemic chemotherapy

Treatment of recurrent thyroid cancer

Systemic chemotherapy

bull Doxorubicin alone

bull Cisplatin and doxorubicin (better)

bull BAP Cisplatin doxorubicin and bleomycin

bull CVD cyclophosphamide vincristine and dacarbazine

bull Dacarbazine and 5-fluorouracil

bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy

bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT

bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)

bull Improve OS and decrease RR

BAP regimenbull Schedule

bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5

bull Cell typebull Several histologic types of thyroid carcinoma responded but the

best responses were observed in medullary and anaplastic giant-cell carcinomas

bull Effectivenessbull BAP regime can achieve reasonable palliation and probably

increases survival in poor-prognosis thyroid cancers

CVD regimenbull Schedule

bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks

bull Cell typebull Medullary thyroid carcinoma

bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in

patients with advanced MTC

Dacarbazine and 5-fluorouracil

bull Schedule

bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and

12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks

Six cycles

bull Cell type

bull MTC

bull Effectiveness

bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to

have significant activity and was well tolerated

Target therapy

Take home messagesbull FNAC is not adequate for definite diagnosis of follicular

carcinomabull Because the mixed papillary-follicular variant tends to

behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis

bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer

bull Once medullary carcinoma is diagnosed familial predisposition should be checked up

bull If I131 is indicated stunning effect should be avoided

Take home messages

All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary

II-MEN II-A (Sipple Syndrome)

(Multiple Endocrine Neoplasia II A)

1Sipple syndrome has

[1] bilateral medullary carcinoma

[2] pheochromocytoma

[3] hyperparathyroidism

2This syndrome is inherited in an autosomal dominant fashion

Because of this males and females are equally affected

3Peak incidence of medullary carcinoma in these patients is in the

30s

III-MEN II B

1This syndrome has

[1] medullary carcinoma

[2] Pheochromocytoma

[3] mucosal ganglioneuromas and Marfanoid habitus

2Inheritance is autosomal dominant as in MEN IIA (m=f)

3Pheochromocytomas must be detected prior to any operation

4The idea here is to remove the pheochromocytoma first to remove

the risk of severe hypertensive episodes while the thyroid or

parathyroid is being operated on

IV-Inherited medullary carcinoma without associated endocrinopathies

This form of medullary carcinoma is the least aggressive Like other types of thyroid cancers the peak incidence is

between the ages of 40 and 50

Anaplastic cancer

1)Peak onset age 65 and older

Very rare in young patients

2)Males more common than females by 2 to 1 ratio

3)Undifferentiated

4)May arise many years (gt20) following radiation

exposure

5)Neck mass usually large diffuse and very hard

6)Rapidly growing often inoperable highly recurrent

7) Invade locally metastasize both locally and distantly

(to lungs or bones)

8) Cervical metastasis are present in the vast majority

(over 90) of cases at the time of diagnosis

9) Mean survival 6 months

10) Often requires the patient to get a tracheostomy to

maintain their airway

STAGING OF THYROID CANCER

In differentiated thyroid carcinoma several classification and

staging systems have been introduced However no clear

consensus has emerged favoring any one method over another

bull AMES systemAGES SystemGAMES system

bull TNM system

bull MACIS system

bull University of Chicago system

bull Ohio State University system

bull National Thyroid Cancer Treatment Cooperative Study

(NTCTCS)

TNM Staging bull Primary tumor (T) (All categories may be subdivided into (a)

solitary tumor or (b) multifocal tumor)

TX Primary tumor cannot be assessed

T0 No evidence of primary tumor

T1 Tumor le 2 cm limited to the thyroid

T2 Tumor gt 2 cm but le4 cm limited to the thyroid

T3 Tumor gt 4 cm limited to the thyroid or any tumor with

minimal extrathyroid extension (eg extension to

sternothyroid muscle or perithyroid soft tissues)

bull T4a Tumor of any size extending beyond the thyroid capsule to invade subcutaneous soft tissues larynx trachea esophagus or recurrent laryngeal nerve

bull T4b Tumor invades prevertebral fascia or encases carotid artery or mediastinal vessels

All anaplastic carcinomas are considered T4 tumorsbull T4a Intrathyroidal anaplastic carcinomamdashsurgically resectable bull T4b Extrathyroidal anaplastic carcinomamdashsurgically

unresectable

bull Regional lymph nodes (N) (Regional lymph nodes are the central compartment lateral cervical and upper

mediastinal lNs)

bull NX Regional lymph nodes cannot be assessed bull N0 No regional lymph node metastasis bull N1 Regional lymph node metastasis

bull N1a Metastasis to level VI (pretracheal paratracheal and prelaryngealDelphian on the cricothyroid membrane (precricoid) lymph nodes)

bull N1b Metastasis to unilateral or bilateral cervical or superior mediastinal lymph nodes

bull Distant metastases (M) bull MX Distant metastasis cannot be assessed bull M0 No distant metastasis bull M1 Distant metastasis

AJCC Stage Groupings Papillary or follicular thyroid cancer

bull Younger than 45 yearsbull Stage I

bull Any T any N M0 bull Stage II

bull Any T any N M1

bull Age 45 years and olderbull Stage I

bull T1 N0 M0bull Stage II

bull T2 N0 M0 bull Stage III

bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0

Papillary or follicular thyroid cancer

Age 45 years and older

Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T3 N1b M0 T2 N1b M0 T4a N1b M0

Stage IVB T4b any N M0

Stage IVC Any T any N M1

Stage I

T1 N0 M0

Stage II

T2 N0 M0

Stage III

T3 N0 M0

T1 N1a M0

T2 N1a M0

T3 N1a M0

Medullary thyroid cancer bullStage I

bull T1 N0 M0 bullStage II

bull T2 N0 M0bullStage III

bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0

Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T2 N1b M0 T3 N1b M0 T4a N1b M0

Stage IVB T4b any N M0

Stage IVC Any T any N M1

bull Anaplastic thyroid cancer

bull All anaplastic carcinomas are considered stage IV

bull Stage IVA bull T4a any N M0

bull Stage IVB bull T4b any N M0

bull Stage IVC bull Any T any N M1

bull University of Chicago systembull Class Imdashdisease limited to the thyroid glandbull Class IImdashlymph node involvementbull Class IIImdashextrathyroidal invasionbull Class IVmdashdistant metastases

PROGNOSIS

PROGNOSIS

Prognostic schemes GAMES scoring (PAPILLARY amp

FOLLICULAR CANCER)bullG GradebullA Age of patient when tumor discoveredbullM Metastases of the tumor (other than Neck LN)bullE Extent of primary tumorbullS Size of tumor (gt5 cm)bullThe patient is then placed into a high or low risk category

Prognostic Risk Classification for Patients with Well-Differentiated Thyroid Cancer (GAMES )

Low Risk High Riskbull Grade Well Differentiated Poorly Differentiated

bull Age lt40 gt40

bull Mets None Regional or Distant

bull Extent No local extension Capsular invasion intrathyroidal extrathyroidal

bull Sex Female Male

MACIS ScoringbullDeveloped by the Mayo Clinic for stagingbullIt is known to be the most accurate predictor of a patients outcome with papillary thyroid cancer (M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)bullMAICS Score 20 year Survival

lt 6 = 99 6-7 = 89 7-8 = 56 gt 8 = 24

Treatment

Stage I and II Papillary and FollicularI-Total thyroidectomy bull Rationale1048708 Bilateral cancers are common (30-85)1048708 improved effectiveness for I131 ablation1048708 lowers dose needed for I131 ablation1048708 allows fu with thyroglobulin levels1048708 decreased recurrence in all groups1048708 improved survival in high risk pts1048708 Decreased risk of pulmonary metsbull Disadvantage higher incidence of hypoparathyroidism but this

complication may be reduced when a small amount of tissue remains on the contralateral side

II-Lobectomy

bull Rationale

1048708 Most patients are low risk and excellent prognosis

1048708 Role of adjuvant treatment not defined

1048708 Complications of Total

1048708 Occult multicentric tumor not clinically significant

1048708 Most local recurrences treated with surgery

1048708 Excellent outcome with lobectomy in low risk patients

bull Disadvantage

bull approximately 5 to 10 of patients will have a recurrence

Indications for total Thyroidectomy OR lobectomy (all present)

bull Age 15 y - 45 ybull No prior radiationbull No distant metastasesbull No cervical lymph node metastasesbull No extrathyroidal extensionbull Tumor lt 4 cm in diameterbull No aggressive variant

When complete total thyroidectomy after lobectomybull Aggressive variantbull Macroscopic multifocal diseasebull Positive isthmus marginsbull Cervical lymph node metastasesbull Extrathyroidal extension

Aggressive=Tall cell columnar cell insular oxyphilic or poorly differentiated features

bull Node removal

bull Selective node removal can be performed and radical

neck dissection is usually not required

bull This results in a decreased recurrence rate but has not

been shown to improve survival

Thyroid carcinoma after lobectomy for benign lesions

I-Completion of thyroidectomy

bull gt 4 cm

bull Positive margins

bull Extra-thyroidal invasion (T3 or T4(

II- Completion of Thyroidectomy or follow

up

bull Clinically suspicious lymph node

contralateral lesion or perithyroidal node

bull Aggressive variant

bull Macroscopic multifocal disease

bull ge1 cm in diameter

III- follow up

bull Negative margins

bull No contralateral lesion

bull lt 1 cm in diameter

bull No suspicious lymph

node

POSTSURGICAL EVALUATION AFTER THYROIDECTOMY

I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +

antithyroglobulin antibodies)

II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan

Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT

bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)

Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas

Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant

Pretherapy whole body iodine scan

bullIf performed a pretherapy scan should use a low dose of 131I

(1 to 5 mCi) or 123I

bull To detect residual thyroid tissue thyroid cancer and metastatic foci

bull To reduce the potential for sublethal radiation stunning of thyroid tissue that

prevents optimal uptake of future 131I therapy

bullStunning is defined as a reduction in uptake of the 131I

therapy dose induced by a pretreatment diagnostic dose

Dose of RAI

bullThe dosing of 131I for ablation is somewhat controversial

bullLow-dose ablation with less than 30 mCi administered on

an outpatient basis

bull For low-risk young patients

bullHigh-dose ablation with100 to 200 mCi

bull For high-risk patients

bull300 mCi

bull For all patients with metastatic disease that treated with repeated

therapeutic doses of 131I

Replacement therapy

bullPostoperative treatment with exogenous thyroid hormone

in doses sufficient to suppress thyroid-stimulating hormone

(TSH) with development of thyrotoxic manifestations

decreases incidence of recurrence

bullAdministration of Thyroid Hormone

To suppress TSH and growth of any residual thyroid

To maintain patient euthyroid

o Maintain TSH level 01uUml in low risk pts

o Maintain TSH Level lt 01uUml in high risk pts

Stage III Papillary and Follicular

A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease

B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients

Stage IV Papillary and Follicular 1) Adequate uptake of I131

bull I131

1) Inadequate uptake or not sensitive to I131

i Localized lesions

1) Radiation therapy

2) Resection of limited metastases dont uptake of I131

iiDisseminated disease

1) TSH suppression with thyroxine is effective

2) Chemotherapy has been reported to produce occasional complete

responses of long duration

3) Clinical trials testing new approaches to this disease

Medullary Thyroid Cancer treatment

bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck

dissections Why

bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival

advantage

bull Radioactive iodine has no place in the treatment of patients with MTC

bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in

patients with metastatic disease

bull No single drug regimen can be considered standard

bull Some patients with distant metastases will experience prolonged survival and can

be observed until they become symptomatic

Anaplastic Thyroid Cancer bull Surgery

bull Tracheostomy is frequently necessary

bull If the disease is confined to the local area which is rare total

thyroidectomy is warranted to reduce symptoms caused by the

tumor mass

bull Radiation therapy

bull Used in patients who are not surgical candidates or whose tumor

cannot be surgically excised

Anaplastic Thyroid Cancer bull Chemotherapy

bull Produce partial remissions in some patients

bull Approximately 30 of patients achieve a partial remission with

doxorubicin

bull The combination of doxorubicin plus cisplatin appears to be more

active than doxorubicin alone and has been reported to produce

more complete responses

Treatment options under clinical evaluation

bull The combination of chemotherapy plus radiation therapy in patients following

complete resection may provide prolonged survival but has not been compared to

any one modality alone

Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30

bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common

site of distant metastasis is the lung

bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type

Treatment of recurrent thyroid cancer

The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations

bull Adequate I131 uptake

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull I131 ablation

bull RT

bull Disseminated

bull I131 ablation

bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has

been reported to produce occasional objective responses usually of short

duration

Treatment of recurrent thyroid cancer

bull Inadequate I131 uptake or insensitive to I131

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull RT

bull Disseminated

bull Systemic chemotherapy

Treatment of recurrent thyroid cancer

Systemic chemotherapy

bull Doxorubicin alone

bull Cisplatin and doxorubicin (better)

bull BAP Cisplatin doxorubicin and bleomycin

bull CVD cyclophosphamide vincristine and dacarbazine

bull Dacarbazine and 5-fluorouracil

bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy

bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT

bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)

bull Improve OS and decrease RR

BAP regimenbull Schedule

bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5

bull Cell typebull Several histologic types of thyroid carcinoma responded but the

best responses were observed in medullary and anaplastic giant-cell carcinomas

bull Effectivenessbull BAP regime can achieve reasonable palliation and probably

increases survival in poor-prognosis thyroid cancers

CVD regimenbull Schedule

bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks

bull Cell typebull Medullary thyroid carcinoma

bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in

patients with advanced MTC

Dacarbazine and 5-fluorouracil

bull Schedule

bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and

12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks

Six cycles

bull Cell type

bull MTC

bull Effectiveness

bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to

have significant activity and was well tolerated

Target therapy

Take home messagesbull FNAC is not adequate for definite diagnosis of follicular

carcinomabull Because the mixed papillary-follicular variant tends to

behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis

bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer

bull Once medullary carcinoma is diagnosed familial predisposition should be checked up

bull If I131 is indicated stunning effect should be avoided

Take home messages

All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary

III-MEN II B

1This syndrome has

[1] medullary carcinoma

[2] Pheochromocytoma

[3] mucosal ganglioneuromas and Marfanoid habitus

2Inheritance is autosomal dominant as in MEN IIA (m=f)

3Pheochromocytomas must be detected prior to any operation

4The idea here is to remove the pheochromocytoma first to remove

the risk of severe hypertensive episodes while the thyroid or

parathyroid is being operated on

IV-Inherited medullary carcinoma without associated endocrinopathies

This form of medullary carcinoma is the least aggressive Like other types of thyroid cancers the peak incidence is

between the ages of 40 and 50

Anaplastic cancer

1)Peak onset age 65 and older

Very rare in young patients

2)Males more common than females by 2 to 1 ratio

3)Undifferentiated

4)May arise many years (gt20) following radiation

exposure

5)Neck mass usually large diffuse and very hard

6)Rapidly growing often inoperable highly recurrent

7) Invade locally metastasize both locally and distantly

(to lungs or bones)

8) Cervical metastasis are present in the vast majority

(over 90) of cases at the time of diagnosis

9) Mean survival 6 months

10) Often requires the patient to get a tracheostomy to

maintain their airway

STAGING OF THYROID CANCER

In differentiated thyroid carcinoma several classification and

staging systems have been introduced However no clear

consensus has emerged favoring any one method over another

bull AMES systemAGES SystemGAMES system

bull TNM system

bull MACIS system

bull University of Chicago system

bull Ohio State University system

bull National Thyroid Cancer Treatment Cooperative Study

(NTCTCS)

TNM Staging bull Primary tumor (T) (All categories may be subdivided into (a)

solitary tumor or (b) multifocal tumor)

TX Primary tumor cannot be assessed

T0 No evidence of primary tumor

T1 Tumor le 2 cm limited to the thyroid

T2 Tumor gt 2 cm but le4 cm limited to the thyroid

T3 Tumor gt 4 cm limited to the thyroid or any tumor with

minimal extrathyroid extension (eg extension to

sternothyroid muscle or perithyroid soft tissues)

bull T4a Tumor of any size extending beyond the thyroid capsule to invade subcutaneous soft tissues larynx trachea esophagus or recurrent laryngeal nerve

bull T4b Tumor invades prevertebral fascia or encases carotid artery or mediastinal vessels

All anaplastic carcinomas are considered T4 tumorsbull T4a Intrathyroidal anaplastic carcinomamdashsurgically resectable bull T4b Extrathyroidal anaplastic carcinomamdashsurgically

unresectable

bull Regional lymph nodes (N) (Regional lymph nodes are the central compartment lateral cervical and upper

mediastinal lNs)

bull NX Regional lymph nodes cannot be assessed bull N0 No regional lymph node metastasis bull N1 Regional lymph node metastasis

bull N1a Metastasis to level VI (pretracheal paratracheal and prelaryngealDelphian on the cricothyroid membrane (precricoid) lymph nodes)

bull N1b Metastasis to unilateral or bilateral cervical or superior mediastinal lymph nodes

bull Distant metastases (M) bull MX Distant metastasis cannot be assessed bull M0 No distant metastasis bull M1 Distant metastasis

AJCC Stage Groupings Papillary or follicular thyroid cancer

bull Younger than 45 yearsbull Stage I

bull Any T any N M0 bull Stage II

bull Any T any N M1

bull Age 45 years and olderbull Stage I

bull T1 N0 M0bull Stage II

bull T2 N0 M0 bull Stage III

bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0

Papillary or follicular thyroid cancer

Age 45 years and older

Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T3 N1b M0 T2 N1b M0 T4a N1b M0

Stage IVB T4b any N M0

Stage IVC Any T any N M1

Stage I

T1 N0 M0

Stage II

T2 N0 M0

Stage III

T3 N0 M0

T1 N1a M0

T2 N1a M0

T3 N1a M0

Medullary thyroid cancer bullStage I

bull T1 N0 M0 bullStage II

bull T2 N0 M0bullStage III

bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0

Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T2 N1b M0 T3 N1b M0 T4a N1b M0

Stage IVB T4b any N M0

Stage IVC Any T any N M1

bull Anaplastic thyroid cancer

bull All anaplastic carcinomas are considered stage IV

bull Stage IVA bull T4a any N M0

bull Stage IVB bull T4b any N M0

bull Stage IVC bull Any T any N M1

bull University of Chicago systembull Class Imdashdisease limited to the thyroid glandbull Class IImdashlymph node involvementbull Class IIImdashextrathyroidal invasionbull Class IVmdashdistant metastases

PROGNOSIS

PROGNOSIS

Prognostic schemes GAMES scoring (PAPILLARY amp

FOLLICULAR CANCER)bullG GradebullA Age of patient when tumor discoveredbullM Metastases of the tumor (other than Neck LN)bullE Extent of primary tumorbullS Size of tumor (gt5 cm)bullThe patient is then placed into a high or low risk category

Prognostic Risk Classification for Patients with Well-Differentiated Thyroid Cancer (GAMES )

Low Risk High Riskbull Grade Well Differentiated Poorly Differentiated

bull Age lt40 gt40

bull Mets None Regional or Distant

bull Extent No local extension Capsular invasion intrathyroidal extrathyroidal

bull Sex Female Male

MACIS ScoringbullDeveloped by the Mayo Clinic for stagingbullIt is known to be the most accurate predictor of a patients outcome with papillary thyroid cancer (M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)bullMAICS Score 20 year Survival

lt 6 = 99 6-7 = 89 7-8 = 56 gt 8 = 24

Treatment

Stage I and II Papillary and FollicularI-Total thyroidectomy bull Rationale1048708 Bilateral cancers are common (30-85)1048708 improved effectiveness for I131 ablation1048708 lowers dose needed for I131 ablation1048708 allows fu with thyroglobulin levels1048708 decreased recurrence in all groups1048708 improved survival in high risk pts1048708 Decreased risk of pulmonary metsbull Disadvantage higher incidence of hypoparathyroidism but this

complication may be reduced when a small amount of tissue remains on the contralateral side

II-Lobectomy

bull Rationale

1048708 Most patients are low risk and excellent prognosis

1048708 Role of adjuvant treatment not defined

1048708 Complications of Total

1048708 Occult multicentric tumor not clinically significant

1048708 Most local recurrences treated with surgery

1048708 Excellent outcome with lobectomy in low risk patients

bull Disadvantage

bull approximately 5 to 10 of patients will have a recurrence

Indications for total Thyroidectomy OR lobectomy (all present)

bull Age 15 y - 45 ybull No prior radiationbull No distant metastasesbull No cervical lymph node metastasesbull No extrathyroidal extensionbull Tumor lt 4 cm in diameterbull No aggressive variant

When complete total thyroidectomy after lobectomybull Aggressive variantbull Macroscopic multifocal diseasebull Positive isthmus marginsbull Cervical lymph node metastasesbull Extrathyroidal extension

Aggressive=Tall cell columnar cell insular oxyphilic or poorly differentiated features

bull Node removal

bull Selective node removal can be performed and radical

neck dissection is usually not required

bull This results in a decreased recurrence rate but has not

been shown to improve survival

Thyroid carcinoma after lobectomy for benign lesions

I-Completion of thyroidectomy

bull gt 4 cm

bull Positive margins

bull Extra-thyroidal invasion (T3 or T4(

II- Completion of Thyroidectomy or follow

up

bull Clinically suspicious lymph node

contralateral lesion or perithyroidal node

bull Aggressive variant

bull Macroscopic multifocal disease

bull ge1 cm in diameter

III- follow up

bull Negative margins

bull No contralateral lesion

bull lt 1 cm in diameter

bull No suspicious lymph

node

POSTSURGICAL EVALUATION AFTER THYROIDECTOMY

I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +

antithyroglobulin antibodies)

II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan

Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT

bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)

Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas

Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant

Pretherapy whole body iodine scan

bullIf performed a pretherapy scan should use a low dose of 131I

(1 to 5 mCi) or 123I

bull To detect residual thyroid tissue thyroid cancer and metastatic foci

bull To reduce the potential for sublethal radiation stunning of thyroid tissue that

prevents optimal uptake of future 131I therapy

bullStunning is defined as a reduction in uptake of the 131I

therapy dose induced by a pretreatment diagnostic dose

Dose of RAI

bullThe dosing of 131I for ablation is somewhat controversial

bullLow-dose ablation with less than 30 mCi administered on

an outpatient basis

bull For low-risk young patients

bullHigh-dose ablation with100 to 200 mCi

bull For high-risk patients

bull300 mCi

bull For all patients with metastatic disease that treated with repeated

therapeutic doses of 131I

Replacement therapy

bullPostoperative treatment with exogenous thyroid hormone

in doses sufficient to suppress thyroid-stimulating hormone

(TSH) with development of thyrotoxic manifestations

decreases incidence of recurrence

bullAdministration of Thyroid Hormone

To suppress TSH and growth of any residual thyroid

To maintain patient euthyroid

o Maintain TSH level 01uUml in low risk pts

o Maintain TSH Level lt 01uUml in high risk pts

Stage III Papillary and Follicular

A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease

B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients

Stage IV Papillary and Follicular 1) Adequate uptake of I131

bull I131

1) Inadequate uptake or not sensitive to I131

i Localized lesions

1) Radiation therapy

2) Resection of limited metastases dont uptake of I131

iiDisseminated disease

1) TSH suppression with thyroxine is effective

2) Chemotherapy has been reported to produce occasional complete

responses of long duration

3) Clinical trials testing new approaches to this disease

Medullary Thyroid Cancer treatment

bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck

dissections Why

bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival

advantage

bull Radioactive iodine has no place in the treatment of patients with MTC

bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in

patients with metastatic disease

bull No single drug regimen can be considered standard

bull Some patients with distant metastases will experience prolonged survival and can

be observed until they become symptomatic

Anaplastic Thyroid Cancer bull Surgery

bull Tracheostomy is frequently necessary

bull If the disease is confined to the local area which is rare total

thyroidectomy is warranted to reduce symptoms caused by the

tumor mass

bull Radiation therapy

bull Used in patients who are not surgical candidates or whose tumor

cannot be surgically excised

Anaplastic Thyroid Cancer bull Chemotherapy

bull Produce partial remissions in some patients

bull Approximately 30 of patients achieve a partial remission with

doxorubicin

bull The combination of doxorubicin plus cisplatin appears to be more

active than doxorubicin alone and has been reported to produce

more complete responses

Treatment options under clinical evaluation

bull The combination of chemotherapy plus radiation therapy in patients following

complete resection may provide prolonged survival but has not been compared to

any one modality alone

Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30

bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common

site of distant metastasis is the lung

bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type

Treatment of recurrent thyroid cancer

The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations

bull Adequate I131 uptake

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull I131 ablation

bull RT

bull Disseminated

bull I131 ablation

bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has

been reported to produce occasional objective responses usually of short

duration

Treatment of recurrent thyroid cancer

bull Inadequate I131 uptake or insensitive to I131

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull RT

bull Disseminated

bull Systemic chemotherapy

Treatment of recurrent thyroid cancer

Systemic chemotherapy

bull Doxorubicin alone

bull Cisplatin and doxorubicin (better)

bull BAP Cisplatin doxorubicin and bleomycin

bull CVD cyclophosphamide vincristine and dacarbazine

bull Dacarbazine and 5-fluorouracil

bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy

bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT

bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)

bull Improve OS and decrease RR

BAP regimenbull Schedule

bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5

bull Cell typebull Several histologic types of thyroid carcinoma responded but the

best responses were observed in medullary and anaplastic giant-cell carcinomas

bull Effectivenessbull BAP regime can achieve reasonable palliation and probably

increases survival in poor-prognosis thyroid cancers

CVD regimenbull Schedule

bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks

bull Cell typebull Medullary thyroid carcinoma

bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in

patients with advanced MTC

Dacarbazine and 5-fluorouracil

bull Schedule

bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and

12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks

Six cycles

bull Cell type

bull MTC

bull Effectiveness

bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to

have significant activity and was well tolerated

Target therapy

Take home messagesbull FNAC is not adequate for definite diagnosis of follicular

carcinomabull Because the mixed papillary-follicular variant tends to

behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis

bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer

bull Once medullary carcinoma is diagnosed familial predisposition should be checked up

bull If I131 is indicated stunning effect should be avoided

Take home messages

All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary

IV-Inherited medullary carcinoma without associated endocrinopathies

This form of medullary carcinoma is the least aggressive Like other types of thyroid cancers the peak incidence is

between the ages of 40 and 50

Anaplastic cancer

1)Peak onset age 65 and older

Very rare in young patients

2)Males more common than females by 2 to 1 ratio

3)Undifferentiated

4)May arise many years (gt20) following radiation

exposure

5)Neck mass usually large diffuse and very hard

6)Rapidly growing often inoperable highly recurrent

7) Invade locally metastasize both locally and distantly

(to lungs or bones)

8) Cervical metastasis are present in the vast majority

(over 90) of cases at the time of diagnosis

9) Mean survival 6 months

10) Often requires the patient to get a tracheostomy to

maintain their airway

STAGING OF THYROID CANCER

In differentiated thyroid carcinoma several classification and

staging systems have been introduced However no clear

consensus has emerged favoring any one method over another

bull AMES systemAGES SystemGAMES system

bull TNM system

bull MACIS system

bull University of Chicago system

bull Ohio State University system

bull National Thyroid Cancer Treatment Cooperative Study

(NTCTCS)

TNM Staging bull Primary tumor (T) (All categories may be subdivided into (a)

solitary tumor or (b) multifocal tumor)

TX Primary tumor cannot be assessed

T0 No evidence of primary tumor

T1 Tumor le 2 cm limited to the thyroid

T2 Tumor gt 2 cm but le4 cm limited to the thyroid

T3 Tumor gt 4 cm limited to the thyroid or any tumor with

minimal extrathyroid extension (eg extension to

sternothyroid muscle or perithyroid soft tissues)

bull T4a Tumor of any size extending beyond the thyroid capsule to invade subcutaneous soft tissues larynx trachea esophagus or recurrent laryngeal nerve

bull T4b Tumor invades prevertebral fascia or encases carotid artery or mediastinal vessels

All anaplastic carcinomas are considered T4 tumorsbull T4a Intrathyroidal anaplastic carcinomamdashsurgically resectable bull T4b Extrathyroidal anaplastic carcinomamdashsurgically

unresectable

bull Regional lymph nodes (N) (Regional lymph nodes are the central compartment lateral cervical and upper

mediastinal lNs)

bull NX Regional lymph nodes cannot be assessed bull N0 No regional lymph node metastasis bull N1 Regional lymph node metastasis

bull N1a Metastasis to level VI (pretracheal paratracheal and prelaryngealDelphian on the cricothyroid membrane (precricoid) lymph nodes)

bull N1b Metastasis to unilateral or bilateral cervical or superior mediastinal lymph nodes

bull Distant metastases (M) bull MX Distant metastasis cannot be assessed bull M0 No distant metastasis bull M1 Distant metastasis

AJCC Stage Groupings Papillary or follicular thyroid cancer

bull Younger than 45 yearsbull Stage I

bull Any T any N M0 bull Stage II

bull Any T any N M1

bull Age 45 years and olderbull Stage I

bull T1 N0 M0bull Stage II

bull T2 N0 M0 bull Stage III

bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0

Papillary or follicular thyroid cancer

Age 45 years and older

Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T3 N1b M0 T2 N1b M0 T4a N1b M0

Stage IVB T4b any N M0

Stage IVC Any T any N M1

Stage I

T1 N0 M0

Stage II

T2 N0 M0

Stage III

T3 N0 M0

T1 N1a M0

T2 N1a M0

T3 N1a M0

Medullary thyroid cancer bullStage I

bull T1 N0 M0 bullStage II

bull T2 N0 M0bullStage III

bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0

Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T2 N1b M0 T3 N1b M0 T4a N1b M0

Stage IVB T4b any N M0

Stage IVC Any T any N M1

bull Anaplastic thyroid cancer

bull All anaplastic carcinomas are considered stage IV

bull Stage IVA bull T4a any N M0

bull Stage IVB bull T4b any N M0

bull Stage IVC bull Any T any N M1

bull University of Chicago systembull Class Imdashdisease limited to the thyroid glandbull Class IImdashlymph node involvementbull Class IIImdashextrathyroidal invasionbull Class IVmdashdistant metastases

PROGNOSIS

PROGNOSIS

Prognostic schemes GAMES scoring (PAPILLARY amp

FOLLICULAR CANCER)bullG GradebullA Age of patient when tumor discoveredbullM Metastases of the tumor (other than Neck LN)bullE Extent of primary tumorbullS Size of tumor (gt5 cm)bullThe patient is then placed into a high or low risk category

Prognostic Risk Classification for Patients with Well-Differentiated Thyroid Cancer (GAMES )

Low Risk High Riskbull Grade Well Differentiated Poorly Differentiated

bull Age lt40 gt40

bull Mets None Regional or Distant

bull Extent No local extension Capsular invasion intrathyroidal extrathyroidal

bull Sex Female Male

MACIS ScoringbullDeveloped by the Mayo Clinic for stagingbullIt is known to be the most accurate predictor of a patients outcome with papillary thyroid cancer (M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)bullMAICS Score 20 year Survival

lt 6 = 99 6-7 = 89 7-8 = 56 gt 8 = 24

Treatment

Stage I and II Papillary and FollicularI-Total thyroidectomy bull Rationale1048708 Bilateral cancers are common (30-85)1048708 improved effectiveness for I131 ablation1048708 lowers dose needed for I131 ablation1048708 allows fu with thyroglobulin levels1048708 decreased recurrence in all groups1048708 improved survival in high risk pts1048708 Decreased risk of pulmonary metsbull Disadvantage higher incidence of hypoparathyroidism but this

complication may be reduced when a small amount of tissue remains on the contralateral side

II-Lobectomy

bull Rationale

1048708 Most patients are low risk and excellent prognosis

1048708 Role of adjuvant treatment not defined

1048708 Complications of Total

1048708 Occult multicentric tumor not clinically significant

1048708 Most local recurrences treated with surgery

1048708 Excellent outcome with lobectomy in low risk patients

bull Disadvantage

bull approximately 5 to 10 of patients will have a recurrence

Indications for total Thyroidectomy OR lobectomy (all present)

bull Age 15 y - 45 ybull No prior radiationbull No distant metastasesbull No cervical lymph node metastasesbull No extrathyroidal extensionbull Tumor lt 4 cm in diameterbull No aggressive variant

When complete total thyroidectomy after lobectomybull Aggressive variantbull Macroscopic multifocal diseasebull Positive isthmus marginsbull Cervical lymph node metastasesbull Extrathyroidal extension

Aggressive=Tall cell columnar cell insular oxyphilic or poorly differentiated features

bull Node removal

bull Selective node removal can be performed and radical

neck dissection is usually not required

bull This results in a decreased recurrence rate but has not

been shown to improve survival

Thyroid carcinoma after lobectomy for benign lesions

I-Completion of thyroidectomy

bull gt 4 cm

bull Positive margins

bull Extra-thyroidal invasion (T3 or T4(

II- Completion of Thyroidectomy or follow

up

bull Clinically suspicious lymph node

contralateral lesion or perithyroidal node

bull Aggressive variant

bull Macroscopic multifocal disease

bull ge1 cm in diameter

III- follow up

bull Negative margins

bull No contralateral lesion

bull lt 1 cm in diameter

bull No suspicious lymph

node

POSTSURGICAL EVALUATION AFTER THYROIDECTOMY

I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +

antithyroglobulin antibodies)

II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan

Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT

bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)

Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas

Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant

Pretherapy whole body iodine scan

bullIf performed a pretherapy scan should use a low dose of 131I

(1 to 5 mCi) or 123I

bull To detect residual thyroid tissue thyroid cancer and metastatic foci

bull To reduce the potential for sublethal radiation stunning of thyroid tissue that

prevents optimal uptake of future 131I therapy

bullStunning is defined as a reduction in uptake of the 131I

therapy dose induced by a pretreatment diagnostic dose

Dose of RAI

bullThe dosing of 131I for ablation is somewhat controversial

bullLow-dose ablation with less than 30 mCi administered on

an outpatient basis

bull For low-risk young patients

bullHigh-dose ablation with100 to 200 mCi

bull For high-risk patients

bull300 mCi

bull For all patients with metastatic disease that treated with repeated

therapeutic doses of 131I

Replacement therapy

bullPostoperative treatment with exogenous thyroid hormone

in doses sufficient to suppress thyroid-stimulating hormone

(TSH) with development of thyrotoxic manifestations

decreases incidence of recurrence

bullAdministration of Thyroid Hormone

To suppress TSH and growth of any residual thyroid

To maintain patient euthyroid

o Maintain TSH level 01uUml in low risk pts

o Maintain TSH Level lt 01uUml in high risk pts

Stage III Papillary and Follicular

A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease

B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients

Stage IV Papillary and Follicular 1) Adequate uptake of I131

bull I131

1) Inadequate uptake or not sensitive to I131

i Localized lesions

1) Radiation therapy

2) Resection of limited metastases dont uptake of I131

iiDisseminated disease

1) TSH suppression with thyroxine is effective

2) Chemotherapy has been reported to produce occasional complete

responses of long duration

3) Clinical trials testing new approaches to this disease

Medullary Thyroid Cancer treatment

bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck

dissections Why

bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival

advantage

bull Radioactive iodine has no place in the treatment of patients with MTC

bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in

patients with metastatic disease

bull No single drug regimen can be considered standard

bull Some patients with distant metastases will experience prolonged survival and can

be observed until they become symptomatic

Anaplastic Thyroid Cancer bull Surgery

bull Tracheostomy is frequently necessary

bull If the disease is confined to the local area which is rare total

thyroidectomy is warranted to reduce symptoms caused by the

tumor mass

bull Radiation therapy

bull Used in patients who are not surgical candidates or whose tumor

cannot be surgically excised

Anaplastic Thyroid Cancer bull Chemotherapy

bull Produce partial remissions in some patients

bull Approximately 30 of patients achieve a partial remission with

doxorubicin

bull The combination of doxorubicin plus cisplatin appears to be more

active than doxorubicin alone and has been reported to produce

more complete responses

Treatment options under clinical evaluation

bull The combination of chemotherapy plus radiation therapy in patients following

complete resection may provide prolonged survival but has not been compared to

any one modality alone

Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30

bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common

site of distant metastasis is the lung

bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type

Treatment of recurrent thyroid cancer

The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations

bull Adequate I131 uptake

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull I131 ablation

bull RT

bull Disseminated

bull I131 ablation

bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has

been reported to produce occasional objective responses usually of short

duration

Treatment of recurrent thyroid cancer

bull Inadequate I131 uptake or insensitive to I131

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull RT

bull Disseminated

bull Systemic chemotherapy

Treatment of recurrent thyroid cancer

Systemic chemotherapy

bull Doxorubicin alone

bull Cisplatin and doxorubicin (better)

bull BAP Cisplatin doxorubicin and bleomycin

bull CVD cyclophosphamide vincristine and dacarbazine

bull Dacarbazine and 5-fluorouracil

bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy

bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT

bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)

bull Improve OS and decrease RR

BAP regimenbull Schedule

bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5

bull Cell typebull Several histologic types of thyroid carcinoma responded but the

best responses were observed in medullary and anaplastic giant-cell carcinomas

bull Effectivenessbull BAP regime can achieve reasonable palliation and probably

increases survival in poor-prognosis thyroid cancers

CVD regimenbull Schedule

bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks

bull Cell typebull Medullary thyroid carcinoma

bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in

patients with advanced MTC

Dacarbazine and 5-fluorouracil

bull Schedule

bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and

12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks

Six cycles

bull Cell type

bull MTC

bull Effectiveness

bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to

have significant activity and was well tolerated

Target therapy

Take home messagesbull FNAC is not adequate for definite diagnosis of follicular

carcinomabull Because the mixed papillary-follicular variant tends to

behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis

bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer

bull Once medullary carcinoma is diagnosed familial predisposition should be checked up

bull If I131 is indicated stunning effect should be avoided

Take home messages

All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary

Anaplastic cancer

1)Peak onset age 65 and older

Very rare in young patients

2)Males more common than females by 2 to 1 ratio

3)Undifferentiated

4)May arise many years (gt20) following radiation

exposure

5)Neck mass usually large diffuse and very hard

6)Rapidly growing often inoperable highly recurrent

7) Invade locally metastasize both locally and distantly

(to lungs or bones)

8) Cervical metastasis are present in the vast majority

(over 90) of cases at the time of diagnosis

9) Mean survival 6 months

10) Often requires the patient to get a tracheostomy to

maintain their airway

STAGING OF THYROID CANCER

In differentiated thyroid carcinoma several classification and

staging systems have been introduced However no clear

consensus has emerged favoring any one method over another

bull AMES systemAGES SystemGAMES system

bull TNM system

bull MACIS system

bull University of Chicago system

bull Ohio State University system

bull National Thyroid Cancer Treatment Cooperative Study

(NTCTCS)

TNM Staging bull Primary tumor (T) (All categories may be subdivided into (a)

solitary tumor or (b) multifocal tumor)

TX Primary tumor cannot be assessed

T0 No evidence of primary tumor

T1 Tumor le 2 cm limited to the thyroid

T2 Tumor gt 2 cm but le4 cm limited to the thyroid

T3 Tumor gt 4 cm limited to the thyroid or any tumor with

minimal extrathyroid extension (eg extension to

sternothyroid muscle or perithyroid soft tissues)

bull T4a Tumor of any size extending beyond the thyroid capsule to invade subcutaneous soft tissues larynx trachea esophagus or recurrent laryngeal nerve

bull T4b Tumor invades prevertebral fascia or encases carotid artery or mediastinal vessels

All anaplastic carcinomas are considered T4 tumorsbull T4a Intrathyroidal anaplastic carcinomamdashsurgically resectable bull T4b Extrathyroidal anaplastic carcinomamdashsurgically

unresectable

bull Regional lymph nodes (N) (Regional lymph nodes are the central compartment lateral cervical and upper

mediastinal lNs)

bull NX Regional lymph nodes cannot be assessed bull N0 No regional lymph node metastasis bull N1 Regional lymph node metastasis

bull N1a Metastasis to level VI (pretracheal paratracheal and prelaryngealDelphian on the cricothyroid membrane (precricoid) lymph nodes)

bull N1b Metastasis to unilateral or bilateral cervical or superior mediastinal lymph nodes

bull Distant metastases (M) bull MX Distant metastasis cannot be assessed bull M0 No distant metastasis bull M1 Distant metastasis

AJCC Stage Groupings Papillary or follicular thyroid cancer

bull Younger than 45 yearsbull Stage I

bull Any T any N M0 bull Stage II

bull Any T any N M1

bull Age 45 years and olderbull Stage I

bull T1 N0 M0bull Stage II

bull T2 N0 M0 bull Stage III

bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0

Papillary or follicular thyroid cancer

Age 45 years and older

Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T3 N1b M0 T2 N1b M0 T4a N1b M0

Stage IVB T4b any N M0

Stage IVC Any T any N M1

Stage I

T1 N0 M0

Stage II

T2 N0 M0

Stage III

T3 N0 M0

T1 N1a M0

T2 N1a M0

T3 N1a M0

Medullary thyroid cancer bullStage I

bull T1 N0 M0 bullStage II

bull T2 N0 M0bullStage III

bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0

Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T2 N1b M0 T3 N1b M0 T4a N1b M0

Stage IVB T4b any N M0

Stage IVC Any T any N M1

bull Anaplastic thyroid cancer

bull All anaplastic carcinomas are considered stage IV

bull Stage IVA bull T4a any N M0

bull Stage IVB bull T4b any N M0

bull Stage IVC bull Any T any N M1

bull University of Chicago systembull Class Imdashdisease limited to the thyroid glandbull Class IImdashlymph node involvementbull Class IIImdashextrathyroidal invasionbull Class IVmdashdistant metastases

PROGNOSIS

PROGNOSIS

Prognostic schemes GAMES scoring (PAPILLARY amp

FOLLICULAR CANCER)bullG GradebullA Age of patient when tumor discoveredbullM Metastases of the tumor (other than Neck LN)bullE Extent of primary tumorbullS Size of tumor (gt5 cm)bullThe patient is then placed into a high or low risk category

Prognostic Risk Classification for Patients with Well-Differentiated Thyroid Cancer (GAMES )

Low Risk High Riskbull Grade Well Differentiated Poorly Differentiated

bull Age lt40 gt40

bull Mets None Regional or Distant

bull Extent No local extension Capsular invasion intrathyroidal extrathyroidal

bull Sex Female Male

MACIS ScoringbullDeveloped by the Mayo Clinic for stagingbullIt is known to be the most accurate predictor of a patients outcome with papillary thyroid cancer (M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)bullMAICS Score 20 year Survival

lt 6 = 99 6-7 = 89 7-8 = 56 gt 8 = 24

Treatment

Stage I and II Papillary and FollicularI-Total thyroidectomy bull Rationale1048708 Bilateral cancers are common (30-85)1048708 improved effectiveness for I131 ablation1048708 lowers dose needed for I131 ablation1048708 allows fu with thyroglobulin levels1048708 decreased recurrence in all groups1048708 improved survival in high risk pts1048708 Decreased risk of pulmonary metsbull Disadvantage higher incidence of hypoparathyroidism but this

complication may be reduced when a small amount of tissue remains on the contralateral side

II-Lobectomy

bull Rationale

1048708 Most patients are low risk and excellent prognosis

1048708 Role of adjuvant treatment not defined

1048708 Complications of Total

1048708 Occult multicentric tumor not clinically significant

1048708 Most local recurrences treated with surgery

1048708 Excellent outcome with lobectomy in low risk patients

bull Disadvantage

bull approximately 5 to 10 of patients will have a recurrence

Indications for total Thyroidectomy OR lobectomy (all present)

bull Age 15 y - 45 ybull No prior radiationbull No distant metastasesbull No cervical lymph node metastasesbull No extrathyroidal extensionbull Tumor lt 4 cm in diameterbull No aggressive variant

When complete total thyroidectomy after lobectomybull Aggressive variantbull Macroscopic multifocal diseasebull Positive isthmus marginsbull Cervical lymph node metastasesbull Extrathyroidal extension

Aggressive=Tall cell columnar cell insular oxyphilic or poorly differentiated features

bull Node removal

bull Selective node removal can be performed and radical

neck dissection is usually not required

bull This results in a decreased recurrence rate but has not

been shown to improve survival

Thyroid carcinoma after lobectomy for benign lesions

I-Completion of thyroidectomy

bull gt 4 cm

bull Positive margins

bull Extra-thyroidal invasion (T3 or T4(

II- Completion of Thyroidectomy or follow

up

bull Clinically suspicious lymph node

contralateral lesion or perithyroidal node

bull Aggressive variant

bull Macroscopic multifocal disease

bull ge1 cm in diameter

III- follow up

bull Negative margins

bull No contralateral lesion

bull lt 1 cm in diameter

bull No suspicious lymph

node

POSTSURGICAL EVALUATION AFTER THYROIDECTOMY

I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +

antithyroglobulin antibodies)

II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan

Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT

bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)

Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas

Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant

Pretherapy whole body iodine scan

bullIf performed a pretherapy scan should use a low dose of 131I

(1 to 5 mCi) or 123I

bull To detect residual thyroid tissue thyroid cancer and metastatic foci

bull To reduce the potential for sublethal radiation stunning of thyroid tissue that

prevents optimal uptake of future 131I therapy

bullStunning is defined as a reduction in uptake of the 131I

therapy dose induced by a pretreatment diagnostic dose

Dose of RAI

bullThe dosing of 131I for ablation is somewhat controversial

bullLow-dose ablation with less than 30 mCi administered on

an outpatient basis

bull For low-risk young patients

bullHigh-dose ablation with100 to 200 mCi

bull For high-risk patients

bull300 mCi

bull For all patients with metastatic disease that treated with repeated

therapeutic doses of 131I

Replacement therapy

bullPostoperative treatment with exogenous thyroid hormone

in doses sufficient to suppress thyroid-stimulating hormone

(TSH) with development of thyrotoxic manifestations

decreases incidence of recurrence

bullAdministration of Thyroid Hormone

To suppress TSH and growth of any residual thyroid

To maintain patient euthyroid

o Maintain TSH level 01uUml in low risk pts

o Maintain TSH Level lt 01uUml in high risk pts

Stage III Papillary and Follicular

A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease

B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients

Stage IV Papillary and Follicular 1) Adequate uptake of I131

bull I131

1) Inadequate uptake or not sensitive to I131

i Localized lesions

1) Radiation therapy

2) Resection of limited metastases dont uptake of I131

iiDisseminated disease

1) TSH suppression with thyroxine is effective

2) Chemotherapy has been reported to produce occasional complete

responses of long duration

3) Clinical trials testing new approaches to this disease

Medullary Thyroid Cancer treatment

bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck

dissections Why

bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival

advantage

bull Radioactive iodine has no place in the treatment of patients with MTC

bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in

patients with metastatic disease

bull No single drug regimen can be considered standard

bull Some patients with distant metastases will experience prolonged survival and can

be observed until they become symptomatic

Anaplastic Thyroid Cancer bull Surgery

bull Tracheostomy is frequently necessary

bull If the disease is confined to the local area which is rare total

thyroidectomy is warranted to reduce symptoms caused by the

tumor mass

bull Radiation therapy

bull Used in patients who are not surgical candidates or whose tumor

cannot be surgically excised

Anaplastic Thyroid Cancer bull Chemotherapy

bull Produce partial remissions in some patients

bull Approximately 30 of patients achieve a partial remission with

doxorubicin

bull The combination of doxorubicin plus cisplatin appears to be more

active than doxorubicin alone and has been reported to produce

more complete responses

Treatment options under clinical evaluation

bull The combination of chemotherapy plus radiation therapy in patients following

complete resection may provide prolonged survival but has not been compared to

any one modality alone

Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30

bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common

site of distant metastasis is the lung

bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type

Treatment of recurrent thyroid cancer

The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations

bull Adequate I131 uptake

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull I131 ablation

bull RT

bull Disseminated

bull I131 ablation

bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has

been reported to produce occasional objective responses usually of short

duration

Treatment of recurrent thyroid cancer

bull Inadequate I131 uptake or insensitive to I131

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull RT

bull Disseminated

bull Systemic chemotherapy

Treatment of recurrent thyroid cancer

Systemic chemotherapy

bull Doxorubicin alone

bull Cisplatin and doxorubicin (better)

bull BAP Cisplatin doxorubicin and bleomycin

bull CVD cyclophosphamide vincristine and dacarbazine

bull Dacarbazine and 5-fluorouracil

bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy

bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT

bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)

bull Improve OS and decrease RR

BAP regimenbull Schedule

bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5

bull Cell typebull Several histologic types of thyroid carcinoma responded but the

best responses were observed in medullary and anaplastic giant-cell carcinomas

bull Effectivenessbull BAP regime can achieve reasonable palliation and probably

increases survival in poor-prognosis thyroid cancers

CVD regimenbull Schedule

bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks

bull Cell typebull Medullary thyroid carcinoma

bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in

patients with advanced MTC

Dacarbazine and 5-fluorouracil

bull Schedule

bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and

12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks

Six cycles

bull Cell type

bull MTC

bull Effectiveness

bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to

have significant activity and was well tolerated

Target therapy

Take home messagesbull FNAC is not adequate for definite diagnosis of follicular

carcinomabull Because the mixed papillary-follicular variant tends to

behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis

bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer

bull Once medullary carcinoma is diagnosed familial predisposition should be checked up

bull If I131 is indicated stunning effect should be avoided

Take home messages

All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary

7) Invade locally metastasize both locally and distantly

(to lungs or bones)

8) Cervical metastasis are present in the vast majority

(over 90) of cases at the time of diagnosis

9) Mean survival 6 months

10) Often requires the patient to get a tracheostomy to

maintain their airway

STAGING OF THYROID CANCER

In differentiated thyroid carcinoma several classification and

staging systems have been introduced However no clear

consensus has emerged favoring any one method over another

bull AMES systemAGES SystemGAMES system

bull TNM system

bull MACIS system

bull University of Chicago system

bull Ohio State University system

bull National Thyroid Cancer Treatment Cooperative Study

(NTCTCS)

TNM Staging bull Primary tumor (T) (All categories may be subdivided into (a)

solitary tumor or (b) multifocal tumor)

TX Primary tumor cannot be assessed

T0 No evidence of primary tumor

T1 Tumor le 2 cm limited to the thyroid

T2 Tumor gt 2 cm but le4 cm limited to the thyroid

T3 Tumor gt 4 cm limited to the thyroid or any tumor with

minimal extrathyroid extension (eg extension to

sternothyroid muscle or perithyroid soft tissues)

bull T4a Tumor of any size extending beyond the thyroid capsule to invade subcutaneous soft tissues larynx trachea esophagus or recurrent laryngeal nerve

bull T4b Tumor invades prevertebral fascia or encases carotid artery or mediastinal vessels

All anaplastic carcinomas are considered T4 tumorsbull T4a Intrathyroidal anaplastic carcinomamdashsurgically resectable bull T4b Extrathyroidal anaplastic carcinomamdashsurgically

unresectable

bull Regional lymph nodes (N) (Regional lymph nodes are the central compartment lateral cervical and upper

mediastinal lNs)

bull NX Regional lymph nodes cannot be assessed bull N0 No regional lymph node metastasis bull N1 Regional lymph node metastasis

bull N1a Metastasis to level VI (pretracheal paratracheal and prelaryngealDelphian on the cricothyroid membrane (precricoid) lymph nodes)

bull N1b Metastasis to unilateral or bilateral cervical or superior mediastinal lymph nodes

bull Distant metastases (M) bull MX Distant metastasis cannot be assessed bull M0 No distant metastasis bull M1 Distant metastasis

AJCC Stage Groupings Papillary or follicular thyroid cancer

bull Younger than 45 yearsbull Stage I

bull Any T any N M0 bull Stage II

bull Any T any N M1

bull Age 45 years and olderbull Stage I

bull T1 N0 M0bull Stage II

bull T2 N0 M0 bull Stage III

bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0

Papillary or follicular thyroid cancer

Age 45 years and older

Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T3 N1b M0 T2 N1b M0 T4a N1b M0

Stage IVB T4b any N M0

Stage IVC Any T any N M1

Stage I

T1 N0 M0

Stage II

T2 N0 M0

Stage III

T3 N0 M0

T1 N1a M0

T2 N1a M0

T3 N1a M0

Medullary thyroid cancer bullStage I

bull T1 N0 M0 bullStage II

bull T2 N0 M0bullStage III

bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0

Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T2 N1b M0 T3 N1b M0 T4a N1b M0

Stage IVB T4b any N M0

Stage IVC Any T any N M1

bull Anaplastic thyroid cancer

bull All anaplastic carcinomas are considered stage IV

bull Stage IVA bull T4a any N M0

bull Stage IVB bull T4b any N M0

bull Stage IVC bull Any T any N M1

bull University of Chicago systembull Class Imdashdisease limited to the thyroid glandbull Class IImdashlymph node involvementbull Class IIImdashextrathyroidal invasionbull Class IVmdashdistant metastases

PROGNOSIS

PROGNOSIS

Prognostic schemes GAMES scoring (PAPILLARY amp

FOLLICULAR CANCER)bullG GradebullA Age of patient when tumor discoveredbullM Metastases of the tumor (other than Neck LN)bullE Extent of primary tumorbullS Size of tumor (gt5 cm)bullThe patient is then placed into a high or low risk category

Prognostic Risk Classification for Patients with Well-Differentiated Thyroid Cancer (GAMES )

Low Risk High Riskbull Grade Well Differentiated Poorly Differentiated

bull Age lt40 gt40

bull Mets None Regional or Distant

bull Extent No local extension Capsular invasion intrathyroidal extrathyroidal

bull Sex Female Male

MACIS ScoringbullDeveloped by the Mayo Clinic for stagingbullIt is known to be the most accurate predictor of a patients outcome with papillary thyroid cancer (M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)bullMAICS Score 20 year Survival

lt 6 = 99 6-7 = 89 7-8 = 56 gt 8 = 24

Treatment

Stage I and II Papillary and FollicularI-Total thyroidectomy bull Rationale1048708 Bilateral cancers are common (30-85)1048708 improved effectiveness for I131 ablation1048708 lowers dose needed for I131 ablation1048708 allows fu with thyroglobulin levels1048708 decreased recurrence in all groups1048708 improved survival in high risk pts1048708 Decreased risk of pulmonary metsbull Disadvantage higher incidence of hypoparathyroidism but this

complication may be reduced when a small amount of tissue remains on the contralateral side

II-Lobectomy

bull Rationale

1048708 Most patients are low risk and excellent prognosis

1048708 Role of adjuvant treatment not defined

1048708 Complications of Total

1048708 Occult multicentric tumor not clinically significant

1048708 Most local recurrences treated with surgery

1048708 Excellent outcome with lobectomy in low risk patients

bull Disadvantage

bull approximately 5 to 10 of patients will have a recurrence

Indications for total Thyroidectomy OR lobectomy (all present)

bull Age 15 y - 45 ybull No prior radiationbull No distant metastasesbull No cervical lymph node metastasesbull No extrathyroidal extensionbull Tumor lt 4 cm in diameterbull No aggressive variant

When complete total thyroidectomy after lobectomybull Aggressive variantbull Macroscopic multifocal diseasebull Positive isthmus marginsbull Cervical lymph node metastasesbull Extrathyroidal extension

Aggressive=Tall cell columnar cell insular oxyphilic or poorly differentiated features

bull Node removal

bull Selective node removal can be performed and radical

neck dissection is usually not required

bull This results in a decreased recurrence rate but has not

been shown to improve survival

Thyroid carcinoma after lobectomy for benign lesions

I-Completion of thyroidectomy

bull gt 4 cm

bull Positive margins

bull Extra-thyroidal invasion (T3 or T4(

II- Completion of Thyroidectomy or follow

up

bull Clinically suspicious lymph node

contralateral lesion or perithyroidal node

bull Aggressive variant

bull Macroscopic multifocal disease

bull ge1 cm in diameter

III- follow up

bull Negative margins

bull No contralateral lesion

bull lt 1 cm in diameter

bull No suspicious lymph

node

POSTSURGICAL EVALUATION AFTER THYROIDECTOMY

I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +

antithyroglobulin antibodies)

II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan

Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT

bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)

Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas

Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant

Pretherapy whole body iodine scan

bullIf performed a pretherapy scan should use a low dose of 131I

(1 to 5 mCi) or 123I

bull To detect residual thyroid tissue thyroid cancer and metastatic foci

bull To reduce the potential for sublethal radiation stunning of thyroid tissue that

prevents optimal uptake of future 131I therapy

bullStunning is defined as a reduction in uptake of the 131I

therapy dose induced by a pretreatment diagnostic dose

Dose of RAI

bullThe dosing of 131I for ablation is somewhat controversial

bullLow-dose ablation with less than 30 mCi administered on

an outpatient basis

bull For low-risk young patients

bullHigh-dose ablation with100 to 200 mCi

bull For high-risk patients

bull300 mCi

bull For all patients with metastatic disease that treated with repeated

therapeutic doses of 131I

Replacement therapy

bullPostoperative treatment with exogenous thyroid hormone

in doses sufficient to suppress thyroid-stimulating hormone

(TSH) with development of thyrotoxic manifestations

decreases incidence of recurrence

bullAdministration of Thyroid Hormone

To suppress TSH and growth of any residual thyroid

To maintain patient euthyroid

o Maintain TSH level 01uUml in low risk pts

o Maintain TSH Level lt 01uUml in high risk pts

Stage III Papillary and Follicular

A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease

B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients

Stage IV Papillary and Follicular 1) Adequate uptake of I131

bull I131

1) Inadequate uptake or not sensitive to I131

i Localized lesions

1) Radiation therapy

2) Resection of limited metastases dont uptake of I131

iiDisseminated disease

1) TSH suppression with thyroxine is effective

2) Chemotherapy has been reported to produce occasional complete

responses of long duration

3) Clinical trials testing new approaches to this disease

Medullary Thyroid Cancer treatment

bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck

dissections Why

bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival

advantage

bull Radioactive iodine has no place in the treatment of patients with MTC

bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in

patients with metastatic disease

bull No single drug regimen can be considered standard

bull Some patients with distant metastases will experience prolonged survival and can

be observed until they become symptomatic

Anaplastic Thyroid Cancer bull Surgery

bull Tracheostomy is frequently necessary

bull If the disease is confined to the local area which is rare total

thyroidectomy is warranted to reduce symptoms caused by the

tumor mass

bull Radiation therapy

bull Used in patients who are not surgical candidates or whose tumor

cannot be surgically excised

Anaplastic Thyroid Cancer bull Chemotherapy

bull Produce partial remissions in some patients

bull Approximately 30 of patients achieve a partial remission with

doxorubicin

bull The combination of doxorubicin plus cisplatin appears to be more

active than doxorubicin alone and has been reported to produce

more complete responses

Treatment options under clinical evaluation

bull The combination of chemotherapy plus radiation therapy in patients following

complete resection may provide prolonged survival but has not been compared to

any one modality alone

Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30

bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common

site of distant metastasis is the lung

bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type

Treatment of recurrent thyroid cancer

The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations

bull Adequate I131 uptake

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull I131 ablation

bull RT

bull Disseminated

bull I131 ablation

bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has

been reported to produce occasional objective responses usually of short

duration

Treatment of recurrent thyroid cancer

bull Inadequate I131 uptake or insensitive to I131

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull RT

bull Disseminated

bull Systemic chemotherapy

Treatment of recurrent thyroid cancer

Systemic chemotherapy

bull Doxorubicin alone

bull Cisplatin and doxorubicin (better)

bull BAP Cisplatin doxorubicin and bleomycin

bull CVD cyclophosphamide vincristine and dacarbazine

bull Dacarbazine and 5-fluorouracil

bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy

bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT

bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)

bull Improve OS and decrease RR

BAP regimenbull Schedule

bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5

bull Cell typebull Several histologic types of thyroid carcinoma responded but the

best responses were observed in medullary and anaplastic giant-cell carcinomas

bull Effectivenessbull BAP regime can achieve reasonable palliation and probably

increases survival in poor-prognosis thyroid cancers

CVD regimenbull Schedule

bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks

bull Cell typebull Medullary thyroid carcinoma

bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in

patients with advanced MTC

Dacarbazine and 5-fluorouracil

bull Schedule

bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and

12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks

Six cycles

bull Cell type

bull MTC

bull Effectiveness

bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to

have significant activity and was well tolerated

Target therapy

Take home messagesbull FNAC is not adequate for definite diagnosis of follicular

carcinomabull Because the mixed papillary-follicular variant tends to

behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis

bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer

bull Once medullary carcinoma is diagnosed familial predisposition should be checked up

bull If I131 is indicated stunning effect should be avoided

Take home messages

All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary

STAGING OF THYROID CANCER

In differentiated thyroid carcinoma several classification and

staging systems have been introduced However no clear

consensus has emerged favoring any one method over another

bull AMES systemAGES SystemGAMES system

bull TNM system

bull MACIS system

bull University of Chicago system

bull Ohio State University system

bull National Thyroid Cancer Treatment Cooperative Study

(NTCTCS)

TNM Staging bull Primary tumor (T) (All categories may be subdivided into (a)

solitary tumor or (b) multifocal tumor)

TX Primary tumor cannot be assessed

T0 No evidence of primary tumor

T1 Tumor le 2 cm limited to the thyroid

T2 Tumor gt 2 cm but le4 cm limited to the thyroid

T3 Tumor gt 4 cm limited to the thyroid or any tumor with

minimal extrathyroid extension (eg extension to

sternothyroid muscle or perithyroid soft tissues)

bull T4a Tumor of any size extending beyond the thyroid capsule to invade subcutaneous soft tissues larynx trachea esophagus or recurrent laryngeal nerve

bull T4b Tumor invades prevertebral fascia or encases carotid artery or mediastinal vessels

All anaplastic carcinomas are considered T4 tumorsbull T4a Intrathyroidal anaplastic carcinomamdashsurgically resectable bull T4b Extrathyroidal anaplastic carcinomamdashsurgically

unresectable

bull Regional lymph nodes (N) (Regional lymph nodes are the central compartment lateral cervical and upper

mediastinal lNs)

bull NX Regional lymph nodes cannot be assessed bull N0 No regional lymph node metastasis bull N1 Regional lymph node metastasis

bull N1a Metastasis to level VI (pretracheal paratracheal and prelaryngealDelphian on the cricothyroid membrane (precricoid) lymph nodes)

bull N1b Metastasis to unilateral or bilateral cervical or superior mediastinal lymph nodes

bull Distant metastases (M) bull MX Distant metastasis cannot be assessed bull M0 No distant metastasis bull M1 Distant metastasis

AJCC Stage Groupings Papillary or follicular thyroid cancer

bull Younger than 45 yearsbull Stage I

bull Any T any N M0 bull Stage II

bull Any T any N M1

bull Age 45 years and olderbull Stage I

bull T1 N0 M0bull Stage II

bull T2 N0 M0 bull Stage III

bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0

Papillary or follicular thyroid cancer

Age 45 years and older

Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T3 N1b M0 T2 N1b M0 T4a N1b M0

Stage IVB T4b any N M0

Stage IVC Any T any N M1

Stage I

T1 N0 M0

Stage II

T2 N0 M0

Stage III

T3 N0 M0

T1 N1a M0

T2 N1a M0

T3 N1a M0

Medullary thyroid cancer bullStage I

bull T1 N0 M0 bullStage II

bull T2 N0 M0bullStage III

bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0

Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T2 N1b M0 T3 N1b M0 T4a N1b M0

Stage IVB T4b any N M0

Stage IVC Any T any N M1

bull Anaplastic thyroid cancer

bull All anaplastic carcinomas are considered stage IV

bull Stage IVA bull T4a any N M0

bull Stage IVB bull T4b any N M0

bull Stage IVC bull Any T any N M1

bull University of Chicago systembull Class Imdashdisease limited to the thyroid glandbull Class IImdashlymph node involvementbull Class IIImdashextrathyroidal invasionbull Class IVmdashdistant metastases

PROGNOSIS

PROGNOSIS

Prognostic schemes GAMES scoring (PAPILLARY amp

FOLLICULAR CANCER)bullG GradebullA Age of patient when tumor discoveredbullM Metastases of the tumor (other than Neck LN)bullE Extent of primary tumorbullS Size of tumor (gt5 cm)bullThe patient is then placed into a high or low risk category

Prognostic Risk Classification for Patients with Well-Differentiated Thyroid Cancer (GAMES )

Low Risk High Riskbull Grade Well Differentiated Poorly Differentiated

bull Age lt40 gt40

bull Mets None Regional or Distant

bull Extent No local extension Capsular invasion intrathyroidal extrathyroidal

bull Sex Female Male

MACIS ScoringbullDeveloped by the Mayo Clinic for stagingbullIt is known to be the most accurate predictor of a patients outcome with papillary thyroid cancer (M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)bullMAICS Score 20 year Survival

lt 6 = 99 6-7 = 89 7-8 = 56 gt 8 = 24

Treatment

Stage I and II Papillary and FollicularI-Total thyroidectomy bull Rationale1048708 Bilateral cancers are common (30-85)1048708 improved effectiveness for I131 ablation1048708 lowers dose needed for I131 ablation1048708 allows fu with thyroglobulin levels1048708 decreased recurrence in all groups1048708 improved survival in high risk pts1048708 Decreased risk of pulmonary metsbull Disadvantage higher incidence of hypoparathyroidism but this

complication may be reduced when a small amount of tissue remains on the contralateral side

II-Lobectomy

bull Rationale

1048708 Most patients are low risk and excellent prognosis

1048708 Role of adjuvant treatment not defined

1048708 Complications of Total

1048708 Occult multicentric tumor not clinically significant

1048708 Most local recurrences treated with surgery

1048708 Excellent outcome with lobectomy in low risk patients

bull Disadvantage

bull approximately 5 to 10 of patients will have a recurrence

Indications for total Thyroidectomy OR lobectomy (all present)

bull Age 15 y - 45 ybull No prior radiationbull No distant metastasesbull No cervical lymph node metastasesbull No extrathyroidal extensionbull Tumor lt 4 cm in diameterbull No aggressive variant

When complete total thyroidectomy after lobectomybull Aggressive variantbull Macroscopic multifocal diseasebull Positive isthmus marginsbull Cervical lymph node metastasesbull Extrathyroidal extension

Aggressive=Tall cell columnar cell insular oxyphilic or poorly differentiated features

bull Node removal

bull Selective node removal can be performed and radical

neck dissection is usually not required

bull This results in a decreased recurrence rate but has not

been shown to improve survival

Thyroid carcinoma after lobectomy for benign lesions

I-Completion of thyroidectomy

bull gt 4 cm

bull Positive margins

bull Extra-thyroidal invasion (T3 or T4(

II- Completion of Thyroidectomy or follow

up

bull Clinically suspicious lymph node

contralateral lesion or perithyroidal node

bull Aggressive variant

bull Macroscopic multifocal disease

bull ge1 cm in diameter

III- follow up

bull Negative margins

bull No contralateral lesion

bull lt 1 cm in diameter

bull No suspicious lymph

node

POSTSURGICAL EVALUATION AFTER THYROIDECTOMY

I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +

antithyroglobulin antibodies)

II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan

Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT

bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)

Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas

Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant

Pretherapy whole body iodine scan

bullIf performed a pretherapy scan should use a low dose of 131I

(1 to 5 mCi) or 123I

bull To detect residual thyroid tissue thyroid cancer and metastatic foci

bull To reduce the potential for sublethal radiation stunning of thyroid tissue that

prevents optimal uptake of future 131I therapy

bullStunning is defined as a reduction in uptake of the 131I

therapy dose induced by a pretreatment diagnostic dose

Dose of RAI

bullThe dosing of 131I for ablation is somewhat controversial

bullLow-dose ablation with less than 30 mCi administered on

an outpatient basis

bull For low-risk young patients

bullHigh-dose ablation with100 to 200 mCi

bull For high-risk patients

bull300 mCi

bull For all patients with metastatic disease that treated with repeated

therapeutic doses of 131I

Replacement therapy

bullPostoperative treatment with exogenous thyroid hormone

in doses sufficient to suppress thyroid-stimulating hormone

(TSH) with development of thyrotoxic manifestations

decreases incidence of recurrence

bullAdministration of Thyroid Hormone

To suppress TSH and growth of any residual thyroid

To maintain patient euthyroid

o Maintain TSH level 01uUml in low risk pts

o Maintain TSH Level lt 01uUml in high risk pts

Stage III Papillary and Follicular

A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease

B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients

Stage IV Papillary and Follicular 1) Adequate uptake of I131

bull I131

1) Inadequate uptake or not sensitive to I131

i Localized lesions

1) Radiation therapy

2) Resection of limited metastases dont uptake of I131

iiDisseminated disease

1) TSH suppression with thyroxine is effective

2) Chemotherapy has been reported to produce occasional complete

responses of long duration

3) Clinical trials testing new approaches to this disease

Medullary Thyroid Cancer treatment

bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck

dissections Why

bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival

advantage

bull Radioactive iodine has no place in the treatment of patients with MTC

bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in

patients with metastatic disease

bull No single drug regimen can be considered standard

bull Some patients with distant metastases will experience prolonged survival and can

be observed until they become symptomatic

Anaplastic Thyroid Cancer bull Surgery

bull Tracheostomy is frequently necessary

bull If the disease is confined to the local area which is rare total

thyroidectomy is warranted to reduce symptoms caused by the

tumor mass

bull Radiation therapy

bull Used in patients who are not surgical candidates or whose tumor

cannot be surgically excised

Anaplastic Thyroid Cancer bull Chemotherapy

bull Produce partial remissions in some patients

bull Approximately 30 of patients achieve a partial remission with

doxorubicin

bull The combination of doxorubicin plus cisplatin appears to be more

active than doxorubicin alone and has been reported to produce

more complete responses

Treatment options under clinical evaluation

bull The combination of chemotherapy plus radiation therapy in patients following

complete resection may provide prolonged survival but has not been compared to

any one modality alone

Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30

bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common

site of distant metastasis is the lung

bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type

Treatment of recurrent thyroid cancer

The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations

bull Adequate I131 uptake

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull I131 ablation

bull RT

bull Disseminated

bull I131 ablation

bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has

been reported to produce occasional objective responses usually of short

duration

Treatment of recurrent thyroid cancer

bull Inadequate I131 uptake or insensitive to I131

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull RT

bull Disseminated

bull Systemic chemotherapy

Treatment of recurrent thyroid cancer

Systemic chemotherapy

bull Doxorubicin alone

bull Cisplatin and doxorubicin (better)

bull BAP Cisplatin doxorubicin and bleomycin

bull CVD cyclophosphamide vincristine and dacarbazine

bull Dacarbazine and 5-fluorouracil

bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy

bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT

bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)

bull Improve OS and decrease RR

BAP regimenbull Schedule

bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5

bull Cell typebull Several histologic types of thyroid carcinoma responded but the

best responses were observed in medullary and anaplastic giant-cell carcinomas

bull Effectivenessbull BAP regime can achieve reasonable palliation and probably

increases survival in poor-prognosis thyroid cancers

CVD regimenbull Schedule

bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks

bull Cell typebull Medullary thyroid carcinoma

bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in

patients with advanced MTC

Dacarbazine and 5-fluorouracil

bull Schedule

bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and

12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks

Six cycles

bull Cell type

bull MTC

bull Effectiveness

bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to

have significant activity and was well tolerated

Target therapy

Take home messagesbull FNAC is not adequate for definite diagnosis of follicular

carcinomabull Because the mixed papillary-follicular variant tends to

behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis

bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer

bull Once medullary carcinoma is diagnosed familial predisposition should be checked up

bull If I131 is indicated stunning effect should be avoided

Take home messages

All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary

TNM Staging bull Primary tumor (T) (All categories may be subdivided into (a)

solitary tumor or (b) multifocal tumor)

TX Primary tumor cannot be assessed

T0 No evidence of primary tumor

T1 Tumor le 2 cm limited to the thyroid

T2 Tumor gt 2 cm but le4 cm limited to the thyroid

T3 Tumor gt 4 cm limited to the thyroid or any tumor with

minimal extrathyroid extension (eg extension to

sternothyroid muscle or perithyroid soft tissues)

bull T4a Tumor of any size extending beyond the thyroid capsule to invade subcutaneous soft tissues larynx trachea esophagus or recurrent laryngeal nerve

bull T4b Tumor invades prevertebral fascia or encases carotid artery or mediastinal vessels

All anaplastic carcinomas are considered T4 tumorsbull T4a Intrathyroidal anaplastic carcinomamdashsurgically resectable bull T4b Extrathyroidal anaplastic carcinomamdashsurgically

unresectable

bull Regional lymph nodes (N) (Regional lymph nodes are the central compartment lateral cervical and upper

mediastinal lNs)

bull NX Regional lymph nodes cannot be assessed bull N0 No regional lymph node metastasis bull N1 Regional lymph node metastasis

bull N1a Metastasis to level VI (pretracheal paratracheal and prelaryngealDelphian on the cricothyroid membrane (precricoid) lymph nodes)

bull N1b Metastasis to unilateral or bilateral cervical or superior mediastinal lymph nodes

bull Distant metastases (M) bull MX Distant metastasis cannot be assessed bull M0 No distant metastasis bull M1 Distant metastasis

AJCC Stage Groupings Papillary or follicular thyroid cancer

bull Younger than 45 yearsbull Stage I

bull Any T any N M0 bull Stage II

bull Any T any N M1

bull Age 45 years and olderbull Stage I

bull T1 N0 M0bull Stage II

bull T2 N0 M0 bull Stage III

bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0

Papillary or follicular thyroid cancer

Age 45 years and older

Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T3 N1b M0 T2 N1b M0 T4a N1b M0

Stage IVB T4b any N M0

Stage IVC Any T any N M1

Stage I

T1 N0 M0

Stage II

T2 N0 M0

Stage III

T3 N0 M0

T1 N1a M0

T2 N1a M0

T3 N1a M0

Medullary thyroid cancer bullStage I

bull T1 N0 M0 bullStage II

bull T2 N0 M0bullStage III

bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0

Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T2 N1b M0 T3 N1b M0 T4a N1b M0

Stage IVB T4b any N M0

Stage IVC Any T any N M1

bull Anaplastic thyroid cancer

bull All anaplastic carcinomas are considered stage IV

bull Stage IVA bull T4a any N M0

bull Stage IVB bull T4b any N M0

bull Stage IVC bull Any T any N M1

bull University of Chicago systembull Class Imdashdisease limited to the thyroid glandbull Class IImdashlymph node involvementbull Class IIImdashextrathyroidal invasionbull Class IVmdashdistant metastases

PROGNOSIS

PROGNOSIS

Prognostic schemes GAMES scoring (PAPILLARY amp

FOLLICULAR CANCER)bullG GradebullA Age of patient when tumor discoveredbullM Metastases of the tumor (other than Neck LN)bullE Extent of primary tumorbullS Size of tumor (gt5 cm)bullThe patient is then placed into a high or low risk category

Prognostic Risk Classification for Patients with Well-Differentiated Thyroid Cancer (GAMES )

Low Risk High Riskbull Grade Well Differentiated Poorly Differentiated

bull Age lt40 gt40

bull Mets None Regional or Distant

bull Extent No local extension Capsular invasion intrathyroidal extrathyroidal

bull Sex Female Male

MACIS ScoringbullDeveloped by the Mayo Clinic for stagingbullIt is known to be the most accurate predictor of a patients outcome with papillary thyroid cancer (M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)bullMAICS Score 20 year Survival

lt 6 = 99 6-7 = 89 7-8 = 56 gt 8 = 24

Treatment

Stage I and II Papillary and FollicularI-Total thyroidectomy bull Rationale1048708 Bilateral cancers are common (30-85)1048708 improved effectiveness for I131 ablation1048708 lowers dose needed for I131 ablation1048708 allows fu with thyroglobulin levels1048708 decreased recurrence in all groups1048708 improved survival in high risk pts1048708 Decreased risk of pulmonary metsbull Disadvantage higher incidence of hypoparathyroidism but this

complication may be reduced when a small amount of tissue remains on the contralateral side

II-Lobectomy

bull Rationale

1048708 Most patients are low risk and excellent prognosis

1048708 Role of adjuvant treatment not defined

1048708 Complications of Total

1048708 Occult multicentric tumor not clinically significant

1048708 Most local recurrences treated with surgery

1048708 Excellent outcome with lobectomy in low risk patients

bull Disadvantage

bull approximately 5 to 10 of patients will have a recurrence

Indications for total Thyroidectomy OR lobectomy (all present)

bull Age 15 y - 45 ybull No prior radiationbull No distant metastasesbull No cervical lymph node metastasesbull No extrathyroidal extensionbull Tumor lt 4 cm in diameterbull No aggressive variant

When complete total thyroidectomy after lobectomybull Aggressive variantbull Macroscopic multifocal diseasebull Positive isthmus marginsbull Cervical lymph node metastasesbull Extrathyroidal extension

Aggressive=Tall cell columnar cell insular oxyphilic or poorly differentiated features

bull Node removal

bull Selective node removal can be performed and radical

neck dissection is usually not required

bull This results in a decreased recurrence rate but has not

been shown to improve survival

Thyroid carcinoma after lobectomy for benign lesions

I-Completion of thyroidectomy

bull gt 4 cm

bull Positive margins

bull Extra-thyroidal invasion (T3 or T4(

II- Completion of Thyroidectomy or follow

up

bull Clinically suspicious lymph node

contralateral lesion or perithyroidal node

bull Aggressive variant

bull Macroscopic multifocal disease

bull ge1 cm in diameter

III- follow up

bull Negative margins

bull No contralateral lesion

bull lt 1 cm in diameter

bull No suspicious lymph

node

POSTSURGICAL EVALUATION AFTER THYROIDECTOMY

I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +

antithyroglobulin antibodies)

II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan

Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT

bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)

Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas

Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant

Pretherapy whole body iodine scan

bullIf performed a pretherapy scan should use a low dose of 131I

(1 to 5 mCi) or 123I

bull To detect residual thyroid tissue thyroid cancer and metastatic foci

bull To reduce the potential for sublethal radiation stunning of thyroid tissue that

prevents optimal uptake of future 131I therapy

bullStunning is defined as a reduction in uptake of the 131I

therapy dose induced by a pretreatment diagnostic dose

Dose of RAI

bullThe dosing of 131I for ablation is somewhat controversial

bullLow-dose ablation with less than 30 mCi administered on

an outpatient basis

bull For low-risk young patients

bullHigh-dose ablation with100 to 200 mCi

bull For high-risk patients

bull300 mCi

bull For all patients with metastatic disease that treated with repeated

therapeutic doses of 131I

Replacement therapy

bullPostoperative treatment with exogenous thyroid hormone

in doses sufficient to suppress thyroid-stimulating hormone

(TSH) with development of thyrotoxic manifestations

decreases incidence of recurrence

bullAdministration of Thyroid Hormone

To suppress TSH and growth of any residual thyroid

To maintain patient euthyroid

o Maintain TSH level 01uUml in low risk pts

o Maintain TSH Level lt 01uUml in high risk pts

Stage III Papillary and Follicular

A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease

B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients

Stage IV Papillary and Follicular 1) Adequate uptake of I131

bull I131

1) Inadequate uptake or not sensitive to I131

i Localized lesions

1) Radiation therapy

2) Resection of limited metastases dont uptake of I131

iiDisseminated disease

1) TSH suppression with thyroxine is effective

2) Chemotherapy has been reported to produce occasional complete

responses of long duration

3) Clinical trials testing new approaches to this disease

Medullary Thyroid Cancer treatment

bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck

dissections Why

bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival

advantage

bull Radioactive iodine has no place in the treatment of patients with MTC

bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in

patients with metastatic disease

bull No single drug regimen can be considered standard

bull Some patients with distant metastases will experience prolonged survival and can

be observed until they become symptomatic

Anaplastic Thyroid Cancer bull Surgery

bull Tracheostomy is frequently necessary

bull If the disease is confined to the local area which is rare total

thyroidectomy is warranted to reduce symptoms caused by the

tumor mass

bull Radiation therapy

bull Used in patients who are not surgical candidates or whose tumor

cannot be surgically excised

Anaplastic Thyroid Cancer bull Chemotherapy

bull Produce partial remissions in some patients

bull Approximately 30 of patients achieve a partial remission with

doxorubicin

bull The combination of doxorubicin plus cisplatin appears to be more

active than doxorubicin alone and has been reported to produce

more complete responses

Treatment options under clinical evaluation

bull The combination of chemotherapy plus radiation therapy in patients following

complete resection may provide prolonged survival but has not been compared to

any one modality alone

Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30

bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common

site of distant metastasis is the lung

bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type

Treatment of recurrent thyroid cancer

The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations

bull Adequate I131 uptake

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull I131 ablation

bull RT

bull Disseminated

bull I131 ablation

bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has

been reported to produce occasional objective responses usually of short

duration

Treatment of recurrent thyroid cancer

bull Inadequate I131 uptake or insensitive to I131

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull RT

bull Disseminated

bull Systemic chemotherapy

Treatment of recurrent thyroid cancer

Systemic chemotherapy

bull Doxorubicin alone

bull Cisplatin and doxorubicin (better)

bull BAP Cisplatin doxorubicin and bleomycin

bull CVD cyclophosphamide vincristine and dacarbazine

bull Dacarbazine and 5-fluorouracil

bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy

bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT

bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)

bull Improve OS and decrease RR

BAP regimenbull Schedule

bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5

bull Cell typebull Several histologic types of thyroid carcinoma responded but the

best responses were observed in medullary and anaplastic giant-cell carcinomas

bull Effectivenessbull BAP regime can achieve reasonable palliation and probably

increases survival in poor-prognosis thyroid cancers

CVD regimenbull Schedule

bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks

bull Cell typebull Medullary thyroid carcinoma

bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in

patients with advanced MTC

Dacarbazine and 5-fluorouracil

bull Schedule

bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and

12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks

Six cycles

bull Cell type

bull MTC

bull Effectiveness

bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to

have significant activity and was well tolerated

Target therapy

Take home messagesbull FNAC is not adequate for definite diagnosis of follicular

carcinomabull Because the mixed papillary-follicular variant tends to

behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis

bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer

bull Once medullary carcinoma is diagnosed familial predisposition should be checked up

bull If I131 is indicated stunning effect should be avoided

Take home messages

All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary

bull T4a Tumor of any size extending beyond the thyroid capsule to invade subcutaneous soft tissues larynx trachea esophagus or recurrent laryngeal nerve

bull T4b Tumor invades prevertebral fascia or encases carotid artery or mediastinal vessels

All anaplastic carcinomas are considered T4 tumorsbull T4a Intrathyroidal anaplastic carcinomamdashsurgically resectable bull T4b Extrathyroidal anaplastic carcinomamdashsurgically

unresectable

bull Regional lymph nodes (N) (Regional lymph nodes are the central compartment lateral cervical and upper

mediastinal lNs)

bull NX Regional lymph nodes cannot be assessed bull N0 No regional lymph node metastasis bull N1 Regional lymph node metastasis

bull N1a Metastasis to level VI (pretracheal paratracheal and prelaryngealDelphian on the cricothyroid membrane (precricoid) lymph nodes)

bull N1b Metastasis to unilateral or bilateral cervical or superior mediastinal lymph nodes

bull Distant metastases (M) bull MX Distant metastasis cannot be assessed bull M0 No distant metastasis bull M1 Distant metastasis

AJCC Stage Groupings Papillary or follicular thyroid cancer

bull Younger than 45 yearsbull Stage I

bull Any T any N M0 bull Stage II

bull Any T any N M1

bull Age 45 years and olderbull Stage I

bull T1 N0 M0bull Stage II

bull T2 N0 M0 bull Stage III

bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0

Papillary or follicular thyroid cancer

Age 45 years and older

Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T3 N1b M0 T2 N1b M0 T4a N1b M0

Stage IVB T4b any N M0

Stage IVC Any T any N M1

Stage I

T1 N0 M0

Stage II

T2 N0 M0

Stage III

T3 N0 M0

T1 N1a M0

T2 N1a M0

T3 N1a M0

Medullary thyroid cancer bullStage I

bull T1 N0 M0 bullStage II

bull T2 N0 M0bullStage III

bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0

Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T2 N1b M0 T3 N1b M0 T4a N1b M0

Stage IVB T4b any N M0

Stage IVC Any T any N M1

bull Anaplastic thyroid cancer

bull All anaplastic carcinomas are considered stage IV

bull Stage IVA bull T4a any N M0

bull Stage IVB bull T4b any N M0

bull Stage IVC bull Any T any N M1

bull University of Chicago systembull Class Imdashdisease limited to the thyroid glandbull Class IImdashlymph node involvementbull Class IIImdashextrathyroidal invasionbull Class IVmdashdistant metastases

PROGNOSIS

PROGNOSIS

Prognostic schemes GAMES scoring (PAPILLARY amp

FOLLICULAR CANCER)bullG GradebullA Age of patient when tumor discoveredbullM Metastases of the tumor (other than Neck LN)bullE Extent of primary tumorbullS Size of tumor (gt5 cm)bullThe patient is then placed into a high or low risk category

Prognostic Risk Classification for Patients with Well-Differentiated Thyroid Cancer (GAMES )

Low Risk High Riskbull Grade Well Differentiated Poorly Differentiated

bull Age lt40 gt40

bull Mets None Regional or Distant

bull Extent No local extension Capsular invasion intrathyroidal extrathyroidal

bull Sex Female Male

MACIS ScoringbullDeveloped by the Mayo Clinic for stagingbullIt is known to be the most accurate predictor of a patients outcome with papillary thyroid cancer (M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)bullMAICS Score 20 year Survival

lt 6 = 99 6-7 = 89 7-8 = 56 gt 8 = 24

Treatment

Stage I and II Papillary and FollicularI-Total thyroidectomy bull Rationale1048708 Bilateral cancers are common (30-85)1048708 improved effectiveness for I131 ablation1048708 lowers dose needed for I131 ablation1048708 allows fu with thyroglobulin levels1048708 decreased recurrence in all groups1048708 improved survival in high risk pts1048708 Decreased risk of pulmonary metsbull Disadvantage higher incidence of hypoparathyroidism but this

complication may be reduced when a small amount of tissue remains on the contralateral side

II-Lobectomy

bull Rationale

1048708 Most patients are low risk and excellent prognosis

1048708 Role of adjuvant treatment not defined

1048708 Complications of Total

1048708 Occult multicentric tumor not clinically significant

1048708 Most local recurrences treated with surgery

1048708 Excellent outcome with lobectomy in low risk patients

bull Disadvantage

bull approximately 5 to 10 of patients will have a recurrence

Indications for total Thyroidectomy OR lobectomy (all present)

bull Age 15 y - 45 ybull No prior radiationbull No distant metastasesbull No cervical lymph node metastasesbull No extrathyroidal extensionbull Tumor lt 4 cm in diameterbull No aggressive variant

When complete total thyroidectomy after lobectomybull Aggressive variantbull Macroscopic multifocal diseasebull Positive isthmus marginsbull Cervical lymph node metastasesbull Extrathyroidal extension

Aggressive=Tall cell columnar cell insular oxyphilic or poorly differentiated features

bull Node removal

bull Selective node removal can be performed and radical

neck dissection is usually not required

bull This results in a decreased recurrence rate but has not

been shown to improve survival

Thyroid carcinoma after lobectomy for benign lesions

I-Completion of thyroidectomy

bull gt 4 cm

bull Positive margins

bull Extra-thyroidal invasion (T3 or T4(

II- Completion of Thyroidectomy or follow

up

bull Clinically suspicious lymph node

contralateral lesion or perithyroidal node

bull Aggressive variant

bull Macroscopic multifocal disease

bull ge1 cm in diameter

III- follow up

bull Negative margins

bull No contralateral lesion

bull lt 1 cm in diameter

bull No suspicious lymph

node

POSTSURGICAL EVALUATION AFTER THYROIDECTOMY

I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +

antithyroglobulin antibodies)

II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan

Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT

bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)

Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas

Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant

Pretherapy whole body iodine scan

bullIf performed a pretherapy scan should use a low dose of 131I

(1 to 5 mCi) or 123I

bull To detect residual thyroid tissue thyroid cancer and metastatic foci

bull To reduce the potential for sublethal radiation stunning of thyroid tissue that

prevents optimal uptake of future 131I therapy

bullStunning is defined as a reduction in uptake of the 131I

therapy dose induced by a pretreatment diagnostic dose

Dose of RAI

bullThe dosing of 131I for ablation is somewhat controversial

bullLow-dose ablation with less than 30 mCi administered on

an outpatient basis

bull For low-risk young patients

bullHigh-dose ablation with100 to 200 mCi

bull For high-risk patients

bull300 mCi

bull For all patients with metastatic disease that treated with repeated

therapeutic doses of 131I

Replacement therapy

bullPostoperative treatment with exogenous thyroid hormone

in doses sufficient to suppress thyroid-stimulating hormone

(TSH) with development of thyrotoxic manifestations

decreases incidence of recurrence

bullAdministration of Thyroid Hormone

To suppress TSH and growth of any residual thyroid

To maintain patient euthyroid

o Maintain TSH level 01uUml in low risk pts

o Maintain TSH Level lt 01uUml in high risk pts

Stage III Papillary and Follicular

A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease

B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients

Stage IV Papillary and Follicular 1) Adequate uptake of I131

bull I131

1) Inadequate uptake or not sensitive to I131

i Localized lesions

1) Radiation therapy

2) Resection of limited metastases dont uptake of I131

iiDisseminated disease

1) TSH suppression with thyroxine is effective

2) Chemotherapy has been reported to produce occasional complete

responses of long duration

3) Clinical trials testing new approaches to this disease

Medullary Thyroid Cancer treatment

bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck

dissections Why

bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival

advantage

bull Radioactive iodine has no place in the treatment of patients with MTC

bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in

patients with metastatic disease

bull No single drug regimen can be considered standard

bull Some patients with distant metastases will experience prolonged survival and can

be observed until they become symptomatic

Anaplastic Thyroid Cancer bull Surgery

bull Tracheostomy is frequently necessary

bull If the disease is confined to the local area which is rare total

thyroidectomy is warranted to reduce symptoms caused by the

tumor mass

bull Radiation therapy

bull Used in patients who are not surgical candidates or whose tumor

cannot be surgically excised

Anaplastic Thyroid Cancer bull Chemotherapy

bull Produce partial remissions in some patients

bull Approximately 30 of patients achieve a partial remission with

doxorubicin

bull The combination of doxorubicin plus cisplatin appears to be more

active than doxorubicin alone and has been reported to produce

more complete responses

Treatment options under clinical evaluation

bull The combination of chemotherapy plus radiation therapy in patients following

complete resection may provide prolonged survival but has not been compared to

any one modality alone

Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30

bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common

site of distant metastasis is the lung

bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type

Treatment of recurrent thyroid cancer

The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations

bull Adequate I131 uptake

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull I131 ablation

bull RT

bull Disseminated

bull I131 ablation

bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has

been reported to produce occasional objective responses usually of short

duration

Treatment of recurrent thyroid cancer

bull Inadequate I131 uptake or insensitive to I131

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull RT

bull Disseminated

bull Systemic chemotherapy

Treatment of recurrent thyroid cancer

Systemic chemotherapy

bull Doxorubicin alone

bull Cisplatin and doxorubicin (better)

bull BAP Cisplatin doxorubicin and bleomycin

bull CVD cyclophosphamide vincristine and dacarbazine

bull Dacarbazine and 5-fluorouracil

bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy

bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT

bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)

bull Improve OS and decrease RR

BAP regimenbull Schedule

bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5

bull Cell typebull Several histologic types of thyroid carcinoma responded but the

best responses were observed in medullary and anaplastic giant-cell carcinomas

bull Effectivenessbull BAP regime can achieve reasonable palliation and probably

increases survival in poor-prognosis thyroid cancers

CVD regimenbull Schedule

bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks

bull Cell typebull Medullary thyroid carcinoma

bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in

patients with advanced MTC

Dacarbazine and 5-fluorouracil

bull Schedule

bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and

12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks

Six cycles

bull Cell type

bull MTC

bull Effectiveness

bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to

have significant activity and was well tolerated

Target therapy

Take home messagesbull FNAC is not adequate for definite diagnosis of follicular

carcinomabull Because the mixed papillary-follicular variant tends to

behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis

bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer

bull Once medullary carcinoma is diagnosed familial predisposition should be checked up

bull If I131 is indicated stunning effect should be avoided

Take home messages

All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary

bull Regional lymph nodes (N) (Regional lymph nodes are the central compartment lateral cervical and upper

mediastinal lNs)

bull NX Regional lymph nodes cannot be assessed bull N0 No regional lymph node metastasis bull N1 Regional lymph node metastasis

bull N1a Metastasis to level VI (pretracheal paratracheal and prelaryngealDelphian on the cricothyroid membrane (precricoid) lymph nodes)

bull N1b Metastasis to unilateral or bilateral cervical or superior mediastinal lymph nodes

bull Distant metastases (M) bull MX Distant metastasis cannot be assessed bull M0 No distant metastasis bull M1 Distant metastasis

AJCC Stage Groupings Papillary or follicular thyroid cancer

bull Younger than 45 yearsbull Stage I

bull Any T any N M0 bull Stage II

bull Any T any N M1

bull Age 45 years and olderbull Stage I

bull T1 N0 M0bull Stage II

bull T2 N0 M0 bull Stage III

bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0

Papillary or follicular thyroid cancer

Age 45 years and older

Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T3 N1b M0 T2 N1b M0 T4a N1b M0

Stage IVB T4b any N M0

Stage IVC Any T any N M1

Stage I

T1 N0 M0

Stage II

T2 N0 M0

Stage III

T3 N0 M0

T1 N1a M0

T2 N1a M0

T3 N1a M0

Medullary thyroid cancer bullStage I

bull T1 N0 M0 bullStage II

bull T2 N0 M0bullStage III

bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0

Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T2 N1b M0 T3 N1b M0 T4a N1b M0

Stage IVB T4b any N M0

Stage IVC Any T any N M1

bull Anaplastic thyroid cancer

bull All anaplastic carcinomas are considered stage IV

bull Stage IVA bull T4a any N M0

bull Stage IVB bull T4b any N M0

bull Stage IVC bull Any T any N M1

bull University of Chicago systembull Class Imdashdisease limited to the thyroid glandbull Class IImdashlymph node involvementbull Class IIImdashextrathyroidal invasionbull Class IVmdashdistant metastases

PROGNOSIS

PROGNOSIS

Prognostic schemes GAMES scoring (PAPILLARY amp

FOLLICULAR CANCER)bullG GradebullA Age of patient when tumor discoveredbullM Metastases of the tumor (other than Neck LN)bullE Extent of primary tumorbullS Size of tumor (gt5 cm)bullThe patient is then placed into a high or low risk category

Prognostic Risk Classification for Patients with Well-Differentiated Thyroid Cancer (GAMES )

Low Risk High Riskbull Grade Well Differentiated Poorly Differentiated

bull Age lt40 gt40

bull Mets None Regional or Distant

bull Extent No local extension Capsular invasion intrathyroidal extrathyroidal

bull Sex Female Male

MACIS ScoringbullDeveloped by the Mayo Clinic for stagingbullIt is known to be the most accurate predictor of a patients outcome with papillary thyroid cancer (M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)bullMAICS Score 20 year Survival

lt 6 = 99 6-7 = 89 7-8 = 56 gt 8 = 24

Treatment

Stage I and II Papillary and FollicularI-Total thyroidectomy bull Rationale1048708 Bilateral cancers are common (30-85)1048708 improved effectiveness for I131 ablation1048708 lowers dose needed for I131 ablation1048708 allows fu with thyroglobulin levels1048708 decreased recurrence in all groups1048708 improved survival in high risk pts1048708 Decreased risk of pulmonary metsbull Disadvantage higher incidence of hypoparathyroidism but this

complication may be reduced when a small amount of tissue remains on the contralateral side

II-Lobectomy

bull Rationale

1048708 Most patients are low risk and excellent prognosis

1048708 Role of adjuvant treatment not defined

1048708 Complications of Total

1048708 Occult multicentric tumor not clinically significant

1048708 Most local recurrences treated with surgery

1048708 Excellent outcome with lobectomy in low risk patients

bull Disadvantage

bull approximately 5 to 10 of patients will have a recurrence

Indications for total Thyroidectomy OR lobectomy (all present)

bull Age 15 y - 45 ybull No prior radiationbull No distant metastasesbull No cervical lymph node metastasesbull No extrathyroidal extensionbull Tumor lt 4 cm in diameterbull No aggressive variant

When complete total thyroidectomy after lobectomybull Aggressive variantbull Macroscopic multifocal diseasebull Positive isthmus marginsbull Cervical lymph node metastasesbull Extrathyroidal extension

Aggressive=Tall cell columnar cell insular oxyphilic or poorly differentiated features

bull Node removal

bull Selective node removal can be performed and radical

neck dissection is usually not required

bull This results in a decreased recurrence rate but has not

been shown to improve survival

Thyroid carcinoma after lobectomy for benign lesions

I-Completion of thyroidectomy

bull gt 4 cm

bull Positive margins

bull Extra-thyroidal invasion (T3 or T4(

II- Completion of Thyroidectomy or follow

up

bull Clinically suspicious lymph node

contralateral lesion or perithyroidal node

bull Aggressive variant

bull Macroscopic multifocal disease

bull ge1 cm in diameter

III- follow up

bull Negative margins

bull No contralateral lesion

bull lt 1 cm in diameter

bull No suspicious lymph

node

POSTSURGICAL EVALUATION AFTER THYROIDECTOMY

I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +

antithyroglobulin antibodies)

II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan

Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT

bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)

Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas

Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant

Pretherapy whole body iodine scan

bullIf performed a pretherapy scan should use a low dose of 131I

(1 to 5 mCi) or 123I

bull To detect residual thyroid tissue thyroid cancer and metastatic foci

bull To reduce the potential for sublethal radiation stunning of thyroid tissue that

prevents optimal uptake of future 131I therapy

bullStunning is defined as a reduction in uptake of the 131I

therapy dose induced by a pretreatment diagnostic dose

Dose of RAI

bullThe dosing of 131I for ablation is somewhat controversial

bullLow-dose ablation with less than 30 mCi administered on

an outpatient basis

bull For low-risk young patients

bullHigh-dose ablation with100 to 200 mCi

bull For high-risk patients

bull300 mCi

bull For all patients with metastatic disease that treated with repeated

therapeutic doses of 131I

Replacement therapy

bullPostoperative treatment with exogenous thyroid hormone

in doses sufficient to suppress thyroid-stimulating hormone

(TSH) with development of thyrotoxic manifestations

decreases incidence of recurrence

bullAdministration of Thyroid Hormone

To suppress TSH and growth of any residual thyroid

To maintain patient euthyroid

o Maintain TSH level 01uUml in low risk pts

o Maintain TSH Level lt 01uUml in high risk pts

Stage III Papillary and Follicular

A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease

B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients

Stage IV Papillary and Follicular 1) Adequate uptake of I131

bull I131

1) Inadequate uptake or not sensitive to I131

i Localized lesions

1) Radiation therapy

2) Resection of limited metastases dont uptake of I131

iiDisseminated disease

1) TSH suppression with thyroxine is effective

2) Chemotherapy has been reported to produce occasional complete

responses of long duration

3) Clinical trials testing new approaches to this disease

Medullary Thyroid Cancer treatment

bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck

dissections Why

bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival

advantage

bull Radioactive iodine has no place in the treatment of patients with MTC

bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in

patients with metastatic disease

bull No single drug regimen can be considered standard

bull Some patients with distant metastases will experience prolonged survival and can

be observed until they become symptomatic

Anaplastic Thyroid Cancer bull Surgery

bull Tracheostomy is frequently necessary

bull If the disease is confined to the local area which is rare total

thyroidectomy is warranted to reduce symptoms caused by the

tumor mass

bull Radiation therapy

bull Used in patients who are not surgical candidates or whose tumor

cannot be surgically excised

Anaplastic Thyroid Cancer bull Chemotherapy

bull Produce partial remissions in some patients

bull Approximately 30 of patients achieve a partial remission with

doxorubicin

bull The combination of doxorubicin plus cisplatin appears to be more

active than doxorubicin alone and has been reported to produce

more complete responses

Treatment options under clinical evaluation

bull The combination of chemotherapy plus radiation therapy in patients following

complete resection may provide prolonged survival but has not been compared to

any one modality alone

Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30

bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common

site of distant metastasis is the lung

bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type

Treatment of recurrent thyroid cancer

The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations

bull Adequate I131 uptake

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull I131 ablation

bull RT

bull Disseminated

bull I131 ablation

bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has

been reported to produce occasional objective responses usually of short

duration

Treatment of recurrent thyroid cancer

bull Inadequate I131 uptake or insensitive to I131

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull RT

bull Disseminated

bull Systemic chemotherapy

Treatment of recurrent thyroid cancer

Systemic chemotherapy

bull Doxorubicin alone

bull Cisplatin and doxorubicin (better)

bull BAP Cisplatin doxorubicin and bleomycin

bull CVD cyclophosphamide vincristine and dacarbazine

bull Dacarbazine and 5-fluorouracil

bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy

bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT

bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)

bull Improve OS and decrease RR

BAP regimenbull Schedule

bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5

bull Cell typebull Several histologic types of thyroid carcinoma responded but the

best responses were observed in medullary and anaplastic giant-cell carcinomas

bull Effectivenessbull BAP regime can achieve reasonable palliation and probably

increases survival in poor-prognosis thyroid cancers

CVD regimenbull Schedule

bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks

bull Cell typebull Medullary thyroid carcinoma

bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in

patients with advanced MTC

Dacarbazine and 5-fluorouracil

bull Schedule

bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and

12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks

Six cycles

bull Cell type

bull MTC

bull Effectiveness

bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to

have significant activity and was well tolerated

Target therapy

Take home messagesbull FNAC is not adequate for definite diagnosis of follicular

carcinomabull Because the mixed papillary-follicular variant tends to

behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis

bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer

bull Once medullary carcinoma is diagnosed familial predisposition should be checked up

bull If I131 is indicated stunning effect should be avoided

Take home messages

All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary

bull Distant metastases (M) bull MX Distant metastasis cannot be assessed bull M0 No distant metastasis bull M1 Distant metastasis

AJCC Stage Groupings Papillary or follicular thyroid cancer

bull Younger than 45 yearsbull Stage I

bull Any T any N M0 bull Stage II

bull Any T any N M1

bull Age 45 years and olderbull Stage I

bull T1 N0 M0bull Stage II

bull T2 N0 M0 bull Stage III

bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0

Papillary or follicular thyroid cancer

Age 45 years and older

Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T3 N1b M0 T2 N1b M0 T4a N1b M0

Stage IVB T4b any N M0

Stage IVC Any T any N M1

Stage I

T1 N0 M0

Stage II

T2 N0 M0

Stage III

T3 N0 M0

T1 N1a M0

T2 N1a M0

T3 N1a M0

Medullary thyroid cancer bullStage I

bull T1 N0 M0 bullStage II

bull T2 N0 M0bullStage III

bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0

Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T2 N1b M0 T3 N1b M0 T4a N1b M0

Stage IVB T4b any N M0

Stage IVC Any T any N M1

bull Anaplastic thyroid cancer

bull All anaplastic carcinomas are considered stage IV

bull Stage IVA bull T4a any N M0

bull Stage IVB bull T4b any N M0

bull Stage IVC bull Any T any N M1

bull University of Chicago systembull Class Imdashdisease limited to the thyroid glandbull Class IImdashlymph node involvementbull Class IIImdashextrathyroidal invasionbull Class IVmdashdistant metastases

PROGNOSIS

PROGNOSIS

Prognostic schemes GAMES scoring (PAPILLARY amp

FOLLICULAR CANCER)bullG GradebullA Age of patient when tumor discoveredbullM Metastases of the tumor (other than Neck LN)bullE Extent of primary tumorbullS Size of tumor (gt5 cm)bullThe patient is then placed into a high or low risk category

Prognostic Risk Classification for Patients with Well-Differentiated Thyroid Cancer (GAMES )

Low Risk High Riskbull Grade Well Differentiated Poorly Differentiated

bull Age lt40 gt40

bull Mets None Regional or Distant

bull Extent No local extension Capsular invasion intrathyroidal extrathyroidal

bull Sex Female Male

MACIS ScoringbullDeveloped by the Mayo Clinic for stagingbullIt is known to be the most accurate predictor of a patients outcome with papillary thyroid cancer (M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)bullMAICS Score 20 year Survival

lt 6 = 99 6-7 = 89 7-8 = 56 gt 8 = 24

Treatment

Stage I and II Papillary and FollicularI-Total thyroidectomy bull Rationale1048708 Bilateral cancers are common (30-85)1048708 improved effectiveness for I131 ablation1048708 lowers dose needed for I131 ablation1048708 allows fu with thyroglobulin levels1048708 decreased recurrence in all groups1048708 improved survival in high risk pts1048708 Decreased risk of pulmonary metsbull Disadvantage higher incidence of hypoparathyroidism but this

complication may be reduced when a small amount of tissue remains on the contralateral side

II-Lobectomy

bull Rationale

1048708 Most patients are low risk and excellent prognosis

1048708 Role of adjuvant treatment not defined

1048708 Complications of Total

1048708 Occult multicentric tumor not clinically significant

1048708 Most local recurrences treated with surgery

1048708 Excellent outcome with lobectomy in low risk patients

bull Disadvantage

bull approximately 5 to 10 of patients will have a recurrence

Indications for total Thyroidectomy OR lobectomy (all present)

bull Age 15 y - 45 ybull No prior radiationbull No distant metastasesbull No cervical lymph node metastasesbull No extrathyroidal extensionbull Tumor lt 4 cm in diameterbull No aggressive variant

When complete total thyroidectomy after lobectomybull Aggressive variantbull Macroscopic multifocal diseasebull Positive isthmus marginsbull Cervical lymph node metastasesbull Extrathyroidal extension

Aggressive=Tall cell columnar cell insular oxyphilic or poorly differentiated features

bull Node removal

bull Selective node removal can be performed and radical

neck dissection is usually not required

bull This results in a decreased recurrence rate but has not

been shown to improve survival

Thyroid carcinoma after lobectomy for benign lesions

I-Completion of thyroidectomy

bull gt 4 cm

bull Positive margins

bull Extra-thyroidal invasion (T3 or T4(

II- Completion of Thyroidectomy or follow

up

bull Clinically suspicious lymph node

contralateral lesion or perithyroidal node

bull Aggressive variant

bull Macroscopic multifocal disease

bull ge1 cm in diameter

III- follow up

bull Negative margins

bull No contralateral lesion

bull lt 1 cm in diameter

bull No suspicious lymph

node

POSTSURGICAL EVALUATION AFTER THYROIDECTOMY

I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +

antithyroglobulin antibodies)

II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan

Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT

bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)

Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas

Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant

Pretherapy whole body iodine scan

bullIf performed a pretherapy scan should use a low dose of 131I

(1 to 5 mCi) or 123I

bull To detect residual thyroid tissue thyroid cancer and metastatic foci

bull To reduce the potential for sublethal radiation stunning of thyroid tissue that

prevents optimal uptake of future 131I therapy

bullStunning is defined as a reduction in uptake of the 131I

therapy dose induced by a pretreatment diagnostic dose

Dose of RAI

bullThe dosing of 131I for ablation is somewhat controversial

bullLow-dose ablation with less than 30 mCi administered on

an outpatient basis

bull For low-risk young patients

bullHigh-dose ablation with100 to 200 mCi

bull For high-risk patients

bull300 mCi

bull For all patients with metastatic disease that treated with repeated

therapeutic doses of 131I

Replacement therapy

bullPostoperative treatment with exogenous thyroid hormone

in doses sufficient to suppress thyroid-stimulating hormone

(TSH) with development of thyrotoxic manifestations

decreases incidence of recurrence

bullAdministration of Thyroid Hormone

To suppress TSH and growth of any residual thyroid

To maintain patient euthyroid

o Maintain TSH level 01uUml in low risk pts

o Maintain TSH Level lt 01uUml in high risk pts

Stage III Papillary and Follicular

A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease

B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients

Stage IV Papillary and Follicular 1) Adequate uptake of I131

bull I131

1) Inadequate uptake or not sensitive to I131

i Localized lesions

1) Radiation therapy

2) Resection of limited metastases dont uptake of I131

iiDisseminated disease

1) TSH suppression with thyroxine is effective

2) Chemotherapy has been reported to produce occasional complete

responses of long duration

3) Clinical trials testing new approaches to this disease

Medullary Thyroid Cancer treatment

bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck

dissections Why

bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival

advantage

bull Radioactive iodine has no place in the treatment of patients with MTC

bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in

patients with metastatic disease

bull No single drug regimen can be considered standard

bull Some patients with distant metastases will experience prolonged survival and can

be observed until they become symptomatic

Anaplastic Thyroid Cancer bull Surgery

bull Tracheostomy is frequently necessary

bull If the disease is confined to the local area which is rare total

thyroidectomy is warranted to reduce symptoms caused by the

tumor mass

bull Radiation therapy

bull Used in patients who are not surgical candidates or whose tumor

cannot be surgically excised

Anaplastic Thyroid Cancer bull Chemotherapy

bull Produce partial remissions in some patients

bull Approximately 30 of patients achieve a partial remission with

doxorubicin

bull The combination of doxorubicin plus cisplatin appears to be more

active than doxorubicin alone and has been reported to produce

more complete responses

Treatment options under clinical evaluation

bull The combination of chemotherapy plus radiation therapy in patients following

complete resection may provide prolonged survival but has not been compared to

any one modality alone

Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30

bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common

site of distant metastasis is the lung

bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type

Treatment of recurrent thyroid cancer

The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations

bull Adequate I131 uptake

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull I131 ablation

bull RT

bull Disseminated

bull I131 ablation

bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has

been reported to produce occasional objective responses usually of short

duration

Treatment of recurrent thyroid cancer

bull Inadequate I131 uptake or insensitive to I131

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull RT

bull Disseminated

bull Systemic chemotherapy

Treatment of recurrent thyroid cancer

Systemic chemotherapy

bull Doxorubicin alone

bull Cisplatin and doxorubicin (better)

bull BAP Cisplatin doxorubicin and bleomycin

bull CVD cyclophosphamide vincristine and dacarbazine

bull Dacarbazine and 5-fluorouracil

bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy

bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT

bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)

bull Improve OS and decrease RR

BAP regimenbull Schedule

bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5

bull Cell typebull Several histologic types of thyroid carcinoma responded but the

best responses were observed in medullary and anaplastic giant-cell carcinomas

bull Effectivenessbull BAP regime can achieve reasonable palliation and probably

increases survival in poor-prognosis thyroid cancers

CVD regimenbull Schedule

bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks

bull Cell typebull Medullary thyroid carcinoma

bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in

patients with advanced MTC

Dacarbazine and 5-fluorouracil

bull Schedule

bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and

12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks

Six cycles

bull Cell type

bull MTC

bull Effectiveness

bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to

have significant activity and was well tolerated

Target therapy

Take home messagesbull FNAC is not adequate for definite diagnosis of follicular

carcinomabull Because the mixed papillary-follicular variant tends to

behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis

bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer

bull Once medullary carcinoma is diagnosed familial predisposition should be checked up

bull If I131 is indicated stunning effect should be avoided

Take home messages

All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary

AJCC Stage Groupings Papillary or follicular thyroid cancer

bull Younger than 45 yearsbull Stage I

bull Any T any N M0 bull Stage II

bull Any T any N M1

bull Age 45 years and olderbull Stage I

bull T1 N0 M0bull Stage II

bull T2 N0 M0 bull Stage III

bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0

Papillary or follicular thyroid cancer

Age 45 years and older

Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T3 N1b M0 T2 N1b M0 T4a N1b M0

Stage IVB T4b any N M0

Stage IVC Any T any N M1

Stage I

T1 N0 M0

Stage II

T2 N0 M0

Stage III

T3 N0 M0

T1 N1a M0

T2 N1a M0

T3 N1a M0

Medullary thyroid cancer bullStage I

bull T1 N0 M0 bullStage II

bull T2 N0 M0bullStage III

bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0

Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T2 N1b M0 T3 N1b M0 T4a N1b M0

Stage IVB T4b any N M0

Stage IVC Any T any N M1

bull Anaplastic thyroid cancer

bull All anaplastic carcinomas are considered stage IV

bull Stage IVA bull T4a any N M0

bull Stage IVB bull T4b any N M0

bull Stage IVC bull Any T any N M1

bull University of Chicago systembull Class Imdashdisease limited to the thyroid glandbull Class IImdashlymph node involvementbull Class IIImdashextrathyroidal invasionbull Class IVmdashdistant metastases

PROGNOSIS

PROGNOSIS

Prognostic schemes GAMES scoring (PAPILLARY amp

FOLLICULAR CANCER)bullG GradebullA Age of patient when tumor discoveredbullM Metastases of the tumor (other than Neck LN)bullE Extent of primary tumorbullS Size of tumor (gt5 cm)bullThe patient is then placed into a high or low risk category

Prognostic Risk Classification for Patients with Well-Differentiated Thyroid Cancer (GAMES )

Low Risk High Riskbull Grade Well Differentiated Poorly Differentiated

bull Age lt40 gt40

bull Mets None Regional or Distant

bull Extent No local extension Capsular invasion intrathyroidal extrathyroidal

bull Sex Female Male

MACIS ScoringbullDeveloped by the Mayo Clinic for stagingbullIt is known to be the most accurate predictor of a patients outcome with papillary thyroid cancer (M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)bullMAICS Score 20 year Survival

lt 6 = 99 6-7 = 89 7-8 = 56 gt 8 = 24

Treatment

Stage I and II Papillary and FollicularI-Total thyroidectomy bull Rationale1048708 Bilateral cancers are common (30-85)1048708 improved effectiveness for I131 ablation1048708 lowers dose needed for I131 ablation1048708 allows fu with thyroglobulin levels1048708 decreased recurrence in all groups1048708 improved survival in high risk pts1048708 Decreased risk of pulmonary metsbull Disadvantage higher incidence of hypoparathyroidism but this

complication may be reduced when a small amount of tissue remains on the contralateral side

II-Lobectomy

bull Rationale

1048708 Most patients are low risk and excellent prognosis

1048708 Role of adjuvant treatment not defined

1048708 Complications of Total

1048708 Occult multicentric tumor not clinically significant

1048708 Most local recurrences treated with surgery

1048708 Excellent outcome with lobectomy in low risk patients

bull Disadvantage

bull approximately 5 to 10 of patients will have a recurrence

Indications for total Thyroidectomy OR lobectomy (all present)

bull Age 15 y - 45 ybull No prior radiationbull No distant metastasesbull No cervical lymph node metastasesbull No extrathyroidal extensionbull Tumor lt 4 cm in diameterbull No aggressive variant

When complete total thyroidectomy after lobectomybull Aggressive variantbull Macroscopic multifocal diseasebull Positive isthmus marginsbull Cervical lymph node metastasesbull Extrathyroidal extension

Aggressive=Tall cell columnar cell insular oxyphilic or poorly differentiated features

bull Node removal

bull Selective node removal can be performed and radical

neck dissection is usually not required

bull This results in a decreased recurrence rate but has not

been shown to improve survival

Thyroid carcinoma after lobectomy for benign lesions

I-Completion of thyroidectomy

bull gt 4 cm

bull Positive margins

bull Extra-thyroidal invasion (T3 or T4(

II- Completion of Thyroidectomy or follow

up

bull Clinically suspicious lymph node

contralateral lesion or perithyroidal node

bull Aggressive variant

bull Macroscopic multifocal disease

bull ge1 cm in diameter

III- follow up

bull Negative margins

bull No contralateral lesion

bull lt 1 cm in diameter

bull No suspicious lymph

node

POSTSURGICAL EVALUATION AFTER THYROIDECTOMY

I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +

antithyroglobulin antibodies)

II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan

Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT

bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)

Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas

Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant

Pretherapy whole body iodine scan

bullIf performed a pretherapy scan should use a low dose of 131I

(1 to 5 mCi) or 123I

bull To detect residual thyroid tissue thyroid cancer and metastatic foci

bull To reduce the potential for sublethal radiation stunning of thyroid tissue that

prevents optimal uptake of future 131I therapy

bullStunning is defined as a reduction in uptake of the 131I

therapy dose induced by a pretreatment diagnostic dose

Dose of RAI

bullThe dosing of 131I for ablation is somewhat controversial

bullLow-dose ablation with less than 30 mCi administered on

an outpatient basis

bull For low-risk young patients

bullHigh-dose ablation with100 to 200 mCi

bull For high-risk patients

bull300 mCi

bull For all patients with metastatic disease that treated with repeated

therapeutic doses of 131I

Replacement therapy

bullPostoperative treatment with exogenous thyroid hormone

in doses sufficient to suppress thyroid-stimulating hormone

(TSH) with development of thyrotoxic manifestations

decreases incidence of recurrence

bullAdministration of Thyroid Hormone

To suppress TSH and growth of any residual thyroid

To maintain patient euthyroid

o Maintain TSH level 01uUml in low risk pts

o Maintain TSH Level lt 01uUml in high risk pts

Stage III Papillary and Follicular

A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease

B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients

Stage IV Papillary and Follicular 1) Adequate uptake of I131

bull I131

1) Inadequate uptake or not sensitive to I131

i Localized lesions

1) Radiation therapy

2) Resection of limited metastases dont uptake of I131

iiDisseminated disease

1) TSH suppression with thyroxine is effective

2) Chemotherapy has been reported to produce occasional complete

responses of long duration

3) Clinical trials testing new approaches to this disease

Medullary Thyroid Cancer treatment

bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck

dissections Why

bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival

advantage

bull Radioactive iodine has no place in the treatment of patients with MTC

bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in

patients with metastatic disease

bull No single drug regimen can be considered standard

bull Some patients with distant metastases will experience prolonged survival and can

be observed until they become symptomatic

Anaplastic Thyroid Cancer bull Surgery

bull Tracheostomy is frequently necessary

bull If the disease is confined to the local area which is rare total

thyroidectomy is warranted to reduce symptoms caused by the

tumor mass

bull Radiation therapy

bull Used in patients who are not surgical candidates or whose tumor

cannot be surgically excised

Anaplastic Thyroid Cancer bull Chemotherapy

bull Produce partial remissions in some patients

bull Approximately 30 of patients achieve a partial remission with

doxorubicin

bull The combination of doxorubicin plus cisplatin appears to be more

active than doxorubicin alone and has been reported to produce

more complete responses

Treatment options under clinical evaluation

bull The combination of chemotherapy plus radiation therapy in patients following

complete resection may provide prolonged survival but has not been compared to

any one modality alone

Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30

bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common

site of distant metastasis is the lung

bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type

Treatment of recurrent thyroid cancer

The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations

bull Adequate I131 uptake

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull I131 ablation

bull RT

bull Disseminated

bull I131 ablation

bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has

been reported to produce occasional objective responses usually of short

duration

Treatment of recurrent thyroid cancer

bull Inadequate I131 uptake or insensitive to I131

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull RT

bull Disseminated

bull Systemic chemotherapy

Treatment of recurrent thyroid cancer

Systemic chemotherapy

bull Doxorubicin alone

bull Cisplatin and doxorubicin (better)

bull BAP Cisplatin doxorubicin and bleomycin

bull CVD cyclophosphamide vincristine and dacarbazine

bull Dacarbazine and 5-fluorouracil

bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy

bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT

bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)

bull Improve OS and decrease RR

BAP regimenbull Schedule

bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5

bull Cell typebull Several histologic types of thyroid carcinoma responded but the

best responses were observed in medullary and anaplastic giant-cell carcinomas

bull Effectivenessbull BAP regime can achieve reasonable palliation and probably

increases survival in poor-prognosis thyroid cancers

CVD regimenbull Schedule

bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks

bull Cell typebull Medullary thyroid carcinoma

bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in

patients with advanced MTC

Dacarbazine and 5-fluorouracil

bull Schedule

bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and

12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks

Six cycles

bull Cell type

bull MTC

bull Effectiveness

bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to

have significant activity and was well tolerated

Target therapy

Take home messagesbull FNAC is not adequate for definite diagnosis of follicular

carcinomabull Because the mixed papillary-follicular variant tends to

behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis

bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer

bull Once medullary carcinoma is diagnosed familial predisposition should be checked up

bull If I131 is indicated stunning effect should be avoided

Take home messages

All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary

Papillary or follicular thyroid cancer

Age 45 years and older

Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T3 N1b M0 T2 N1b M0 T4a N1b M0

Stage IVB T4b any N M0

Stage IVC Any T any N M1

Stage I

T1 N0 M0

Stage II

T2 N0 M0

Stage III

T3 N0 M0

T1 N1a M0

T2 N1a M0

T3 N1a M0

Medullary thyroid cancer bullStage I

bull T1 N0 M0 bullStage II

bull T2 N0 M0bullStage III

bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0

Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T2 N1b M0 T3 N1b M0 T4a N1b M0

Stage IVB T4b any N M0

Stage IVC Any T any N M1

bull Anaplastic thyroid cancer

bull All anaplastic carcinomas are considered stage IV

bull Stage IVA bull T4a any N M0

bull Stage IVB bull T4b any N M0

bull Stage IVC bull Any T any N M1

bull University of Chicago systembull Class Imdashdisease limited to the thyroid glandbull Class IImdashlymph node involvementbull Class IIImdashextrathyroidal invasionbull Class IVmdashdistant metastases

PROGNOSIS

PROGNOSIS

Prognostic schemes GAMES scoring (PAPILLARY amp

FOLLICULAR CANCER)bullG GradebullA Age of patient when tumor discoveredbullM Metastases of the tumor (other than Neck LN)bullE Extent of primary tumorbullS Size of tumor (gt5 cm)bullThe patient is then placed into a high or low risk category

Prognostic Risk Classification for Patients with Well-Differentiated Thyroid Cancer (GAMES )

Low Risk High Riskbull Grade Well Differentiated Poorly Differentiated

bull Age lt40 gt40

bull Mets None Regional or Distant

bull Extent No local extension Capsular invasion intrathyroidal extrathyroidal

bull Sex Female Male

MACIS ScoringbullDeveloped by the Mayo Clinic for stagingbullIt is known to be the most accurate predictor of a patients outcome with papillary thyroid cancer (M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)bullMAICS Score 20 year Survival

lt 6 = 99 6-7 = 89 7-8 = 56 gt 8 = 24

Treatment

Stage I and II Papillary and FollicularI-Total thyroidectomy bull Rationale1048708 Bilateral cancers are common (30-85)1048708 improved effectiveness for I131 ablation1048708 lowers dose needed for I131 ablation1048708 allows fu with thyroglobulin levels1048708 decreased recurrence in all groups1048708 improved survival in high risk pts1048708 Decreased risk of pulmonary metsbull Disadvantage higher incidence of hypoparathyroidism but this

complication may be reduced when a small amount of tissue remains on the contralateral side

II-Lobectomy

bull Rationale

1048708 Most patients are low risk and excellent prognosis

1048708 Role of adjuvant treatment not defined

1048708 Complications of Total

1048708 Occult multicentric tumor not clinically significant

1048708 Most local recurrences treated with surgery

1048708 Excellent outcome with lobectomy in low risk patients

bull Disadvantage

bull approximately 5 to 10 of patients will have a recurrence

Indications for total Thyroidectomy OR lobectomy (all present)

bull Age 15 y - 45 ybull No prior radiationbull No distant metastasesbull No cervical lymph node metastasesbull No extrathyroidal extensionbull Tumor lt 4 cm in diameterbull No aggressive variant

When complete total thyroidectomy after lobectomybull Aggressive variantbull Macroscopic multifocal diseasebull Positive isthmus marginsbull Cervical lymph node metastasesbull Extrathyroidal extension

Aggressive=Tall cell columnar cell insular oxyphilic or poorly differentiated features

bull Node removal

bull Selective node removal can be performed and radical

neck dissection is usually not required

bull This results in a decreased recurrence rate but has not

been shown to improve survival

Thyroid carcinoma after lobectomy for benign lesions

I-Completion of thyroidectomy

bull gt 4 cm

bull Positive margins

bull Extra-thyroidal invasion (T3 or T4(

II- Completion of Thyroidectomy or follow

up

bull Clinically suspicious lymph node

contralateral lesion or perithyroidal node

bull Aggressive variant

bull Macroscopic multifocal disease

bull ge1 cm in diameter

III- follow up

bull Negative margins

bull No contralateral lesion

bull lt 1 cm in diameter

bull No suspicious lymph

node

POSTSURGICAL EVALUATION AFTER THYROIDECTOMY

I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +

antithyroglobulin antibodies)

II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan

Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT

bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)

Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas

Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant

Pretherapy whole body iodine scan

bullIf performed a pretherapy scan should use a low dose of 131I

(1 to 5 mCi) or 123I

bull To detect residual thyroid tissue thyroid cancer and metastatic foci

bull To reduce the potential for sublethal radiation stunning of thyroid tissue that

prevents optimal uptake of future 131I therapy

bullStunning is defined as a reduction in uptake of the 131I

therapy dose induced by a pretreatment diagnostic dose

Dose of RAI

bullThe dosing of 131I for ablation is somewhat controversial

bullLow-dose ablation with less than 30 mCi administered on

an outpatient basis

bull For low-risk young patients

bullHigh-dose ablation with100 to 200 mCi

bull For high-risk patients

bull300 mCi

bull For all patients with metastatic disease that treated with repeated

therapeutic doses of 131I

Replacement therapy

bullPostoperative treatment with exogenous thyroid hormone

in doses sufficient to suppress thyroid-stimulating hormone

(TSH) with development of thyrotoxic manifestations

decreases incidence of recurrence

bullAdministration of Thyroid Hormone

To suppress TSH and growth of any residual thyroid

To maintain patient euthyroid

o Maintain TSH level 01uUml in low risk pts

o Maintain TSH Level lt 01uUml in high risk pts

Stage III Papillary and Follicular

A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease

B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients

Stage IV Papillary and Follicular 1) Adequate uptake of I131

bull I131

1) Inadequate uptake or not sensitive to I131

i Localized lesions

1) Radiation therapy

2) Resection of limited metastases dont uptake of I131

iiDisseminated disease

1) TSH suppression with thyroxine is effective

2) Chemotherapy has been reported to produce occasional complete

responses of long duration

3) Clinical trials testing new approaches to this disease

Medullary Thyroid Cancer treatment

bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck

dissections Why

bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival

advantage

bull Radioactive iodine has no place in the treatment of patients with MTC

bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in

patients with metastatic disease

bull No single drug regimen can be considered standard

bull Some patients with distant metastases will experience prolonged survival and can

be observed until they become symptomatic

Anaplastic Thyroid Cancer bull Surgery

bull Tracheostomy is frequently necessary

bull If the disease is confined to the local area which is rare total

thyroidectomy is warranted to reduce symptoms caused by the

tumor mass

bull Radiation therapy

bull Used in patients who are not surgical candidates or whose tumor

cannot be surgically excised

Anaplastic Thyroid Cancer bull Chemotherapy

bull Produce partial remissions in some patients

bull Approximately 30 of patients achieve a partial remission with

doxorubicin

bull The combination of doxorubicin plus cisplatin appears to be more

active than doxorubicin alone and has been reported to produce

more complete responses

Treatment options under clinical evaluation

bull The combination of chemotherapy plus radiation therapy in patients following

complete resection may provide prolonged survival but has not been compared to

any one modality alone

Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30

bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common

site of distant metastasis is the lung

bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type

Treatment of recurrent thyroid cancer

The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations

bull Adequate I131 uptake

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull I131 ablation

bull RT

bull Disseminated

bull I131 ablation

bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has

been reported to produce occasional objective responses usually of short

duration

Treatment of recurrent thyroid cancer

bull Inadequate I131 uptake or insensitive to I131

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull RT

bull Disseminated

bull Systemic chemotherapy

Treatment of recurrent thyroid cancer

Systemic chemotherapy

bull Doxorubicin alone

bull Cisplatin and doxorubicin (better)

bull BAP Cisplatin doxorubicin and bleomycin

bull CVD cyclophosphamide vincristine and dacarbazine

bull Dacarbazine and 5-fluorouracil

bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy

bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT

bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)

bull Improve OS and decrease RR

BAP regimenbull Schedule

bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5

bull Cell typebull Several histologic types of thyroid carcinoma responded but the

best responses were observed in medullary and anaplastic giant-cell carcinomas

bull Effectivenessbull BAP regime can achieve reasonable palliation and probably

increases survival in poor-prognosis thyroid cancers

CVD regimenbull Schedule

bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks

bull Cell typebull Medullary thyroid carcinoma

bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in

patients with advanced MTC

Dacarbazine and 5-fluorouracil

bull Schedule

bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and

12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks

Six cycles

bull Cell type

bull MTC

bull Effectiveness

bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to

have significant activity and was well tolerated

Target therapy

Take home messagesbull FNAC is not adequate for definite diagnosis of follicular

carcinomabull Because the mixed papillary-follicular variant tends to

behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis

bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer

bull Once medullary carcinoma is diagnosed familial predisposition should be checked up

bull If I131 is indicated stunning effect should be avoided

Take home messages

All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary

Medullary thyroid cancer bullStage I

bull T1 N0 M0 bullStage II

bull T2 N0 M0bullStage III

bull T3 N0 M0 bull T1 N1a M0 bull T2 N1a M0 bull T3 N1a M0

Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T2 N1b M0 T3 N1b M0 T4a N1b M0

Stage IVB T4b any N M0

Stage IVC Any T any N M1

bull Anaplastic thyroid cancer

bull All anaplastic carcinomas are considered stage IV

bull Stage IVA bull T4a any N M0

bull Stage IVB bull T4b any N M0

bull Stage IVC bull Any T any N M1

bull University of Chicago systembull Class Imdashdisease limited to the thyroid glandbull Class IImdashlymph node involvementbull Class IIImdashextrathyroidal invasionbull Class IVmdashdistant metastases

PROGNOSIS

PROGNOSIS

Prognostic schemes GAMES scoring (PAPILLARY amp

FOLLICULAR CANCER)bullG GradebullA Age of patient when tumor discoveredbullM Metastases of the tumor (other than Neck LN)bullE Extent of primary tumorbullS Size of tumor (gt5 cm)bullThe patient is then placed into a high or low risk category

Prognostic Risk Classification for Patients with Well-Differentiated Thyroid Cancer (GAMES )

Low Risk High Riskbull Grade Well Differentiated Poorly Differentiated

bull Age lt40 gt40

bull Mets None Regional or Distant

bull Extent No local extension Capsular invasion intrathyroidal extrathyroidal

bull Sex Female Male

MACIS ScoringbullDeveloped by the Mayo Clinic for stagingbullIt is known to be the most accurate predictor of a patients outcome with papillary thyroid cancer (M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)bullMAICS Score 20 year Survival

lt 6 = 99 6-7 = 89 7-8 = 56 gt 8 = 24

Treatment

Stage I and II Papillary and FollicularI-Total thyroidectomy bull Rationale1048708 Bilateral cancers are common (30-85)1048708 improved effectiveness for I131 ablation1048708 lowers dose needed for I131 ablation1048708 allows fu with thyroglobulin levels1048708 decreased recurrence in all groups1048708 improved survival in high risk pts1048708 Decreased risk of pulmonary metsbull Disadvantage higher incidence of hypoparathyroidism but this

complication may be reduced when a small amount of tissue remains on the contralateral side

II-Lobectomy

bull Rationale

1048708 Most patients are low risk and excellent prognosis

1048708 Role of adjuvant treatment not defined

1048708 Complications of Total

1048708 Occult multicentric tumor not clinically significant

1048708 Most local recurrences treated with surgery

1048708 Excellent outcome with lobectomy in low risk patients

bull Disadvantage

bull approximately 5 to 10 of patients will have a recurrence

Indications for total Thyroidectomy OR lobectomy (all present)

bull Age 15 y - 45 ybull No prior radiationbull No distant metastasesbull No cervical lymph node metastasesbull No extrathyroidal extensionbull Tumor lt 4 cm in diameterbull No aggressive variant

When complete total thyroidectomy after lobectomybull Aggressive variantbull Macroscopic multifocal diseasebull Positive isthmus marginsbull Cervical lymph node metastasesbull Extrathyroidal extension

Aggressive=Tall cell columnar cell insular oxyphilic or poorly differentiated features

bull Node removal

bull Selective node removal can be performed and radical

neck dissection is usually not required

bull This results in a decreased recurrence rate but has not

been shown to improve survival

Thyroid carcinoma after lobectomy for benign lesions

I-Completion of thyroidectomy

bull gt 4 cm

bull Positive margins

bull Extra-thyroidal invasion (T3 or T4(

II- Completion of Thyroidectomy or follow

up

bull Clinically suspicious lymph node

contralateral lesion or perithyroidal node

bull Aggressive variant

bull Macroscopic multifocal disease

bull ge1 cm in diameter

III- follow up

bull Negative margins

bull No contralateral lesion

bull lt 1 cm in diameter

bull No suspicious lymph

node

POSTSURGICAL EVALUATION AFTER THYROIDECTOMY

I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +

antithyroglobulin antibodies)

II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan

Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT

bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)

Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas

Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant

Pretherapy whole body iodine scan

bullIf performed a pretherapy scan should use a low dose of 131I

(1 to 5 mCi) or 123I

bull To detect residual thyroid tissue thyroid cancer and metastatic foci

bull To reduce the potential for sublethal radiation stunning of thyroid tissue that

prevents optimal uptake of future 131I therapy

bullStunning is defined as a reduction in uptake of the 131I

therapy dose induced by a pretreatment diagnostic dose

Dose of RAI

bullThe dosing of 131I for ablation is somewhat controversial

bullLow-dose ablation with less than 30 mCi administered on

an outpatient basis

bull For low-risk young patients

bullHigh-dose ablation with100 to 200 mCi

bull For high-risk patients

bull300 mCi

bull For all patients with metastatic disease that treated with repeated

therapeutic doses of 131I

Replacement therapy

bullPostoperative treatment with exogenous thyroid hormone

in doses sufficient to suppress thyroid-stimulating hormone

(TSH) with development of thyrotoxic manifestations

decreases incidence of recurrence

bullAdministration of Thyroid Hormone

To suppress TSH and growth of any residual thyroid

To maintain patient euthyroid

o Maintain TSH level 01uUml in low risk pts

o Maintain TSH Level lt 01uUml in high risk pts

Stage III Papillary and Follicular

A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease

B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients

Stage IV Papillary and Follicular 1) Adequate uptake of I131

bull I131

1) Inadequate uptake or not sensitive to I131

i Localized lesions

1) Radiation therapy

2) Resection of limited metastases dont uptake of I131

iiDisseminated disease

1) TSH suppression with thyroxine is effective

2) Chemotherapy has been reported to produce occasional complete

responses of long duration

3) Clinical trials testing new approaches to this disease

Medullary Thyroid Cancer treatment

bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck

dissections Why

bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival

advantage

bull Radioactive iodine has no place in the treatment of patients with MTC

bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in

patients with metastatic disease

bull No single drug regimen can be considered standard

bull Some patients with distant metastases will experience prolonged survival and can

be observed until they become symptomatic

Anaplastic Thyroid Cancer bull Surgery

bull Tracheostomy is frequently necessary

bull If the disease is confined to the local area which is rare total

thyroidectomy is warranted to reduce symptoms caused by the

tumor mass

bull Radiation therapy

bull Used in patients who are not surgical candidates or whose tumor

cannot be surgically excised

Anaplastic Thyroid Cancer bull Chemotherapy

bull Produce partial remissions in some patients

bull Approximately 30 of patients achieve a partial remission with

doxorubicin

bull The combination of doxorubicin plus cisplatin appears to be more

active than doxorubicin alone and has been reported to produce

more complete responses

Treatment options under clinical evaluation

bull The combination of chemotherapy plus radiation therapy in patients following

complete resection may provide prolonged survival but has not been compared to

any one modality alone

Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30

bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common

site of distant metastasis is the lung

bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type

Treatment of recurrent thyroid cancer

The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations

bull Adequate I131 uptake

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull I131 ablation

bull RT

bull Disseminated

bull I131 ablation

bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has

been reported to produce occasional objective responses usually of short

duration

Treatment of recurrent thyroid cancer

bull Inadequate I131 uptake or insensitive to I131

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull RT

bull Disseminated

bull Systemic chemotherapy

Treatment of recurrent thyroid cancer

Systemic chemotherapy

bull Doxorubicin alone

bull Cisplatin and doxorubicin (better)

bull BAP Cisplatin doxorubicin and bleomycin

bull CVD cyclophosphamide vincristine and dacarbazine

bull Dacarbazine and 5-fluorouracil

bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy

bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT

bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)

bull Improve OS and decrease RR

BAP regimenbull Schedule

bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5

bull Cell typebull Several histologic types of thyroid carcinoma responded but the

best responses were observed in medullary and anaplastic giant-cell carcinomas

bull Effectivenessbull BAP regime can achieve reasonable palliation and probably

increases survival in poor-prognosis thyroid cancers

CVD regimenbull Schedule

bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks

bull Cell typebull Medullary thyroid carcinoma

bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in

patients with advanced MTC

Dacarbazine and 5-fluorouracil

bull Schedule

bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and

12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks

Six cycles

bull Cell type

bull MTC

bull Effectiveness

bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to

have significant activity and was well tolerated

Target therapy

Take home messagesbull FNAC is not adequate for definite diagnosis of follicular

carcinomabull Because the mixed papillary-follicular variant tends to

behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis

bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer

bull Once medullary carcinoma is diagnosed familial predisposition should be checked up

bull If I131 is indicated stunning effect should be avoided

Take home messages

All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary

bull Anaplastic thyroid cancer

bull All anaplastic carcinomas are considered stage IV

bull Stage IVA bull T4a any N M0

bull Stage IVB bull T4b any N M0

bull Stage IVC bull Any T any N M1

bull University of Chicago systembull Class Imdashdisease limited to the thyroid glandbull Class IImdashlymph node involvementbull Class IIImdashextrathyroidal invasionbull Class IVmdashdistant metastases

PROGNOSIS

PROGNOSIS

Prognostic schemes GAMES scoring (PAPILLARY amp

FOLLICULAR CANCER)bullG GradebullA Age of patient when tumor discoveredbullM Metastases of the tumor (other than Neck LN)bullE Extent of primary tumorbullS Size of tumor (gt5 cm)bullThe patient is then placed into a high or low risk category

Prognostic Risk Classification for Patients with Well-Differentiated Thyroid Cancer (GAMES )

Low Risk High Riskbull Grade Well Differentiated Poorly Differentiated

bull Age lt40 gt40

bull Mets None Regional or Distant

bull Extent No local extension Capsular invasion intrathyroidal extrathyroidal

bull Sex Female Male

MACIS ScoringbullDeveloped by the Mayo Clinic for stagingbullIt is known to be the most accurate predictor of a patients outcome with papillary thyroid cancer (M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)bullMAICS Score 20 year Survival

lt 6 = 99 6-7 = 89 7-8 = 56 gt 8 = 24

Treatment

Stage I and II Papillary and FollicularI-Total thyroidectomy bull Rationale1048708 Bilateral cancers are common (30-85)1048708 improved effectiveness for I131 ablation1048708 lowers dose needed for I131 ablation1048708 allows fu with thyroglobulin levels1048708 decreased recurrence in all groups1048708 improved survival in high risk pts1048708 Decreased risk of pulmonary metsbull Disadvantage higher incidence of hypoparathyroidism but this

complication may be reduced when a small amount of tissue remains on the contralateral side

II-Lobectomy

bull Rationale

1048708 Most patients are low risk and excellent prognosis

1048708 Role of adjuvant treatment not defined

1048708 Complications of Total

1048708 Occult multicentric tumor not clinically significant

1048708 Most local recurrences treated with surgery

1048708 Excellent outcome with lobectomy in low risk patients

bull Disadvantage

bull approximately 5 to 10 of patients will have a recurrence

Indications for total Thyroidectomy OR lobectomy (all present)

bull Age 15 y - 45 ybull No prior radiationbull No distant metastasesbull No cervical lymph node metastasesbull No extrathyroidal extensionbull Tumor lt 4 cm in diameterbull No aggressive variant

When complete total thyroidectomy after lobectomybull Aggressive variantbull Macroscopic multifocal diseasebull Positive isthmus marginsbull Cervical lymph node metastasesbull Extrathyroidal extension

Aggressive=Tall cell columnar cell insular oxyphilic or poorly differentiated features

bull Node removal

bull Selective node removal can be performed and radical

neck dissection is usually not required

bull This results in a decreased recurrence rate but has not

been shown to improve survival

Thyroid carcinoma after lobectomy for benign lesions

I-Completion of thyroidectomy

bull gt 4 cm

bull Positive margins

bull Extra-thyroidal invasion (T3 or T4(

II- Completion of Thyroidectomy or follow

up

bull Clinically suspicious lymph node

contralateral lesion or perithyroidal node

bull Aggressive variant

bull Macroscopic multifocal disease

bull ge1 cm in diameter

III- follow up

bull Negative margins

bull No contralateral lesion

bull lt 1 cm in diameter

bull No suspicious lymph

node

POSTSURGICAL EVALUATION AFTER THYROIDECTOMY

I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +

antithyroglobulin antibodies)

II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan

Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT

bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)

Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas

Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant

Pretherapy whole body iodine scan

bullIf performed a pretherapy scan should use a low dose of 131I

(1 to 5 mCi) or 123I

bull To detect residual thyroid tissue thyroid cancer and metastatic foci

bull To reduce the potential for sublethal radiation stunning of thyroid tissue that

prevents optimal uptake of future 131I therapy

bullStunning is defined as a reduction in uptake of the 131I

therapy dose induced by a pretreatment diagnostic dose

Dose of RAI

bullThe dosing of 131I for ablation is somewhat controversial

bullLow-dose ablation with less than 30 mCi administered on

an outpatient basis

bull For low-risk young patients

bullHigh-dose ablation with100 to 200 mCi

bull For high-risk patients

bull300 mCi

bull For all patients with metastatic disease that treated with repeated

therapeutic doses of 131I

Replacement therapy

bullPostoperative treatment with exogenous thyroid hormone

in doses sufficient to suppress thyroid-stimulating hormone

(TSH) with development of thyrotoxic manifestations

decreases incidence of recurrence

bullAdministration of Thyroid Hormone

To suppress TSH and growth of any residual thyroid

To maintain patient euthyroid

o Maintain TSH level 01uUml in low risk pts

o Maintain TSH Level lt 01uUml in high risk pts

Stage III Papillary and Follicular

A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease

B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients

Stage IV Papillary and Follicular 1) Adequate uptake of I131

bull I131

1) Inadequate uptake or not sensitive to I131

i Localized lesions

1) Radiation therapy

2) Resection of limited metastases dont uptake of I131

iiDisseminated disease

1) TSH suppression with thyroxine is effective

2) Chemotherapy has been reported to produce occasional complete

responses of long duration

3) Clinical trials testing new approaches to this disease

Medullary Thyroid Cancer treatment

bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck

dissections Why

bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival

advantage

bull Radioactive iodine has no place in the treatment of patients with MTC

bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in

patients with metastatic disease

bull No single drug regimen can be considered standard

bull Some patients with distant metastases will experience prolonged survival and can

be observed until they become symptomatic

Anaplastic Thyroid Cancer bull Surgery

bull Tracheostomy is frequently necessary

bull If the disease is confined to the local area which is rare total

thyroidectomy is warranted to reduce symptoms caused by the

tumor mass

bull Radiation therapy

bull Used in patients who are not surgical candidates or whose tumor

cannot be surgically excised

Anaplastic Thyroid Cancer bull Chemotherapy

bull Produce partial remissions in some patients

bull Approximately 30 of patients achieve a partial remission with

doxorubicin

bull The combination of doxorubicin plus cisplatin appears to be more

active than doxorubicin alone and has been reported to produce

more complete responses

Treatment options under clinical evaluation

bull The combination of chemotherapy plus radiation therapy in patients following

complete resection may provide prolonged survival but has not been compared to

any one modality alone

Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30

bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common

site of distant metastasis is the lung

bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type

Treatment of recurrent thyroid cancer

The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations

bull Adequate I131 uptake

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull I131 ablation

bull RT

bull Disseminated

bull I131 ablation

bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has

been reported to produce occasional objective responses usually of short

duration

Treatment of recurrent thyroid cancer

bull Inadequate I131 uptake or insensitive to I131

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull RT

bull Disseminated

bull Systemic chemotherapy

Treatment of recurrent thyroid cancer

Systemic chemotherapy

bull Doxorubicin alone

bull Cisplatin and doxorubicin (better)

bull BAP Cisplatin doxorubicin and bleomycin

bull CVD cyclophosphamide vincristine and dacarbazine

bull Dacarbazine and 5-fluorouracil

bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy

bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT

bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)

bull Improve OS and decrease RR

BAP regimenbull Schedule

bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5

bull Cell typebull Several histologic types of thyroid carcinoma responded but the

best responses were observed in medullary and anaplastic giant-cell carcinomas

bull Effectivenessbull BAP regime can achieve reasonable palliation and probably

increases survival in poor-prognosis thyroid cancers

CVD regimenbull Schedule

bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks

bull Cell typebull Medullary thyroid carcinoma

bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in

patients with advanced MTC

Dacarbazine and 5-fluorouracil

bull Schedule

bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and

12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks

Six cycles

bull Cell type

bull MTC

bull Effectiveness

bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to

have significant activity and was well tolerated

Target therapy

Take home messagesbull FNAC is not adequate for definite diagnosis of follicular

carcinomabull Because the mixed papillary-follicular variant tends to

behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis

bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer

bull Once medullary carcinoma is diagnosed familial predisposition should be checked up

bull If I131 is indicated stunning effect should be avoided

Take home messages

All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary

bull University of Chicago systembull Class Imdashdisease limited to the thyroid glandbull Class IImdashlymph node involvementbull Class IIImdashextrathyroidal invasionbull Class IVmdashdistant metastases

PROGNOSIS

PROGNOSIS

Prognostic schemes GAMES scoring (PAPILLARY amp

FOLLICULAR CANCER)bullG GradebullA Age of patient when tumor discoveredbullM Metastases of the tumor (other than Neck LN)bullE Extent of primary tumorbullS Size of tumor (gt5 cm)bullThe patient is then placed into a high or low risk category

Prognostic Risk Classification for Patients with Well-Differentiated Thyroid Cancer (GAMES )

Low Risk High Riskbull Grade Well Differentiated Poorly Differentiated

bull Age lt40 gt40

bull Mets None Regional or Distant

bull Extent No local extension Capsular invasion intrathyroidal extrathyroidal

bull Sex Female Male

MACIS ScoringbullDeveloped by the Mayo Clinic for stagingbullIt is known to be the most accurate predictor of a patients outcome with papillary thyroid cancer (M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)bullMAICS Score 20 year Survival

lt 6 = 99 6-7 = 89 7-8 = 56 gt 8 = 24

Treatment

Stage I and II Papillary and FollicularI-Total thyroidectomy bull Rationale1048708 Bilateral cancers are common (30-85)1048708 improved effectiveness for I131 ablation1048708 lowers dose needed for I131 ablation1048708 allows fu with thyroglobulin levels1048708 decreased recurrence in all groups1048708 improved survival in high risk pts1048708 Decreased risk of pulmonary metsbull Disadvantage higher incidence of hypoparathyroidism but this

complication may be reduced when a small amount of tissue remains on the contralateral side

II-Lobectomy

bull Rationale

1048708 Most patients are low risk and excellent prognosis

1048708 Role of adjuvant treatment not defined

1048708 Complications of Total

1048708 Occult multicentric tumor not clinically significant

1048708 Most local recurrences treated with surgery

1048708 Excellent outcome with lobectomy in low risk patients

bull Disadvantage

bull approximately 5 to 10 of patients will have a recurrence

Indications for total Thyroidectomy OR lobectomy (all present)

bull Age 15 y - 45 ybull No prior radiationbull No distant metastasesbull No cervical lymph node metastasesbull No extrathyroidal extensionbull Tumor lt 4 cm in diameterbull No aggressive variant

When complete total thyroidectomy after lobectomybull Aggressive variantbull Macroscopic multifocal diseasebull Positive isthmus marginsbull Cervical lymph node metastasesbull Extrathyroidal extension

Aggressive=Tall cell columnar cell insular oxyphilic or poorly differentiated features

bull Node removal

bull Selective node removal can be performed and radical

neck dissection is usually not required

bull This results in a decreased recurrence rate but has not

been shown to improve survival

Thyroid carcinoma after lobectomy for benign lesions

I-Completion of thyroidectomy

bull gt 4 cm

bull Positive margins

bull Extra-thyroidal invasion (T3 or T4(

II- Completion of Thyroidectomy or follow

up

bull Clinically suspicious lymph node

contralateral lesion or perithyroidal node

bull Aggressive variant

bull Macroscopic multifocal disease

bull ge1 cm in diameter

III- follow up

bull Negative margins

bull No contralateral lesion

bull lt 1 cm in diameter

bull No suspicious lymph

node

POSTSURGICAL EVALUATION AFTER THYROIDECTOMY

I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +

antithyroglobulin antibodies)

II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan

Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT

bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)

Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas

Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant

Pretherapy whole body iodine scan

bullIf performed a pretherapy scan should use a low dose of 131I

(1 to 5 mCi) or 123I

bull To detect residual thyroid tissue thyroid cancer and metastatic foci

bull To reduce the potential for sublethal radiation stunning of thyroid tissue that

prevents optimal uptake of future 131I therapy

bullStunning is defined as a reduction in uptake of the 131I

therapy dose induced by a pretreatment diagnostic dose

Dose of RAI

bullThe dosing of 131I for ablation is somewhat controversial

bullLow-dose ablation with less than 30 mCi administered on

an outpatient basis

bull For low-risk young patients

bullHigh-dose ablation with100 to 200 mCi

bull For high-risk patients

bull300 mCi

bull For all patients with metastatic disease that treated with repeated

therapeutic doses of 131I

Replacement therapy

bullPostoperative treatment with exogenous thyroid hormone

in doses sufficient to suppress thyroid-stimulating hormone

(TSH) with development of thyrotoxic manifestations

decreases incidence of recurrence

bullAdministration of Thyroid Hormone

To suppress TSH and growth of any residual thyroid

To maintain patient euthyroid

o Maintain TSH level 01uUml in low risk pts

o Maintain TSH Level lt 01uUml in high risk pts

Stage III Papillary and Follicular

A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease

B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients

Stage IV Papillary and Follicular 1) Adequate uptake of I131

bull I131

1) Inadequate uptake or not sensitive to I131

i Localized lesions

1) Radiation therapy

2) Resection of limited metastases dont uptake of I131

iiDisseminated disease

1) TSH suppression with thyroxine is effective

2) Chemotherapy has been reported to produce occasional complete

responses of long duration

3) Clinical trials testing new approaches to this disease

Medullary Thyroid Cancer treatment

bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck

dissections Why

bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival

advantage

bull Radioactive iodine has no place in the treatment of patients with MTC

bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in

patients with metastatic disease

bull No single drug regimen can be considered standard

bull Some patients with distant metastases will experience prolonged survival and can

be observed until they become symptomatic

Anaplastic Thyroid Cancer bull Surgery

bull Tracheostomy is frequently necessary

bull If the disease is confined to the local area which is rare total

thyroidectomy is warranted to reduce symptoms caused by the

tumor mass

bull Radiation therapy

bull Used in patients who are not surgical candidates or whose tumor

cannot be surgically excised

Anaplastic Thyroid Cancer bull Chemotherapy

bull Produce partial remissions in some patients

bull Approximately 30 of patients achieve a partial remission with

doxorubicin

bull The combination of doxorubicin plus cisplatin appears to be more

active than doxorubicin alone and has been reported to produce

more complete responses

Treatment options under clinical evaluation

bull The combination of chemotherapy plus radiation therapy in patients following

complete resection may provide prolonged survival but has not been compared to

any one modality alone

Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30

bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common

site of distant metastasis is the lung

bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type

Treatment of recurrent thyroid cancer

The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations

bull Adequate I131 uptake

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull I131 ablation

bull RT

bull Disseminated

bull I131 ablation

bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has

been reported to produce occasional objective responses usually of short

duration

Treatment of recurrent thyroid cancer

bull Inadequate I131 uptake or insensitive to I131

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull RT

bull Disseminated

bull Systemic chemotherapy

Treatment of recurrent thyroid cancer

Systemic chemotherapy

bull Doxorubicin alone

bull Cisplatin and doxorubicin (better)

bull BAP Cisplatin doxorubicin and bleomycin

bull CVD cyclophosphamide vincristine and dacarbazine

bull Dacarbazine and 5-fluorouracil

bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy

bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT

bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)

bull Improve OS and decrease RR

BAP regimenbull Schedule

bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5

bull Cell typebull Several histologic types of thyroid carcinoma responded but the

best responses were observed in medullary and anaplastic giant-cell carcinomas

bull Effectivenessbull BAP regime can achieve reasonable palliation and probably

increases survival in poor-prognosis thyroid cancers

CVD regimenbull Schedule

bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks

bull Cell typebull Medullary thyroid carcinoma

bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in

patients with advanced MTC

Dacarbazine and 5-fluorouracil

bull Schedule

bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and

12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks

Six cycles

bull Cell type

bull MTC

bull Effectiveness

bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to

have significant activity and was well tolerated

Target therapy

Take home messagesbull FNAC is not adequate for definite diagnosis of follicular

carcinomabull Because the mixed papillary-follicular variant tends to

behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis

bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer

bull Once medullary carcinoma is diagnosed familial predisposition should be checked up

bull If I131 is indicated stunning effect should be avoided

Take home messages

All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary

PROGNOSIS

PROGNOSIS

Prognostic schemes GAMES scoring (PAPILLARY amp

FOLLICULAR CANCER)bullG GradebullA Age of patient when tumor discoveredbullM Metastases of the tumor (other than Neck LN)bullE Extent of primary tumorbullS Size of tumor (gt5 cm)bullThe patient is then placed into a high or low risk category

Prognostic Risk Classification for Patients with Well-Differentiated Thyroid Cancer (GAMES )

Low Risk High Riskbull Grade Well Differentiated Poorly Differentiated

bull Age lt40 gt40

bull Mets None Regional or Distant

bull Extent No local extension Capsular invasion intrathyroidal extrathyroidal

bull Sex Female Male

MACIS ScoringbullDeveloped by the Mayo Clinic for stagingbullIt is known to be the most accurate predictor of a patients outcome with papillary thyroid cancer (M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)bullMAICS Score 20 year Survival

lt 6 = 99 6-7 = 89 7-8 = 56 gt 8 = 24

Treatment

Stage I and II Papillary and FollicularI-Total thyroidectomy bull Rationale1048708 Bilateral cancers are common (30-85)1048708 improved effectiveness for I131 ablation1048708 lowers dose needed for I131 ablation1048708 allows fu with thyroglobulin levels1048708 decreased recurrence in all groups1048708 improved survival in high risk pts1048708 Decreased risk of pulmonary metsbull Disadvantage higher incidence of hypoparathyroidism but this

complication may be reduced when a small amount of tissue remains on the contralateral side

II-Lobectomy

bull Rationale

1048708 Most patients are low risk and excellent prognosis

1048708 Role of adjuvant treatment not defined

1048708 Complications of Total

1048708 Occult multicentric tumor not clinically significant

1048708 Most local recurrences treated with surgery

1048708 Excellent outcome with lobectomy in low risk patients

bull Disadvantage

bull approximately 5 to 10 of patients will have a recurrence

Indications for total Thyroidectomy OR lobectomy (all present)

bull Age 15 y - 45 ybull No prior radiationbull No distant metastasesbull No cervical lymph node metastasesbull No extrathyroidal extensionbull Tumor lt 4 cm in diameterbull No aggressive variant

When complete total thyroidectomy after lobectomybull Aggressive variantbull Macroscopic multifocal diseasebull Positive isthmus marginsbull Cervical lymph node metastasesbull Extrathyroidal extension

Aggressive=Tall cell columnar cell insular oxyphilic or poorly differentiated features

bull Node removal

bull Selective node removal can be performed and radical

neck dissection is usually not required

bull This results in a decreased recurrence rate but has not

been shown to improve survival

Thyroid carcinoma after lobectomy for benign lesions

I-Completion of thyroidectomy

bull gt 4 cm

bull Positive margins

bull Extra-thyroidal invasion (T3 or T4(

II- Completion of Thyroidectomy or follow

up

bull Clinically suspicious lymph node

contralateral lesion or perithyroidal node

bull Aggressive variant

bull Macroscopic multifocal disease

bull ge1 cm in diameter

III- follow up

bull Negative margins

bull No contralateral lesion

bull lt 1 cm in diameter

bull No suspicious lymph

node

POSTSURGICAL EVALUATION AFTER THYROIDECTOMY

I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +

antithyroglobulin antibodies)

II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan

Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT

bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)

Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas

Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant

Pretherapy whole body iodine scan

bullIf performed a pretherapy scan should use a low dose of 131I

(1 to 5 mCi) or 123I

bull To detect residual thyroid tissue thyroid cancer and metastatic foci

bull To reduce the potential for sublethal radiation stunning of thyroid tissue that

prevents optimal uptake of future 131I therapy

bullStunning is defined as a reduction in uptake of the 131I

therapy dose induced by a pretreatment diagnostic dose

Dose of RAI

bullThe dosing of 131I for ablation is somewhat controversial

bullLow-dose ablation with less than 30 mCi administered on

an outpatient basis

bull For low-risk young patients

bullHigh-dose ablation with100 to 200 mCi

bull For high-risk patients

bull300 mCi

bull For all patients with metastatic disease that treated with repeated

therapeutic doses of 131I

Replacement therapy

bullPostoperative treatment with exogenous thyroid hormone

in doses sufficient to suppress thyroid-stimulating hormone

(TSH) with development of thyrotoxic manifestations

decreases incidence of recurrence

bullAdministration of Thyroid Hormone

To suppress TSH and growth of any residual thyroid

To maintain patient euthyroid

o Maintain TSH level 01uUml in low risk pts

o Maintain TSH Level lt 01uUml in high risk pts

Stage III Papillary and Follicular

A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease

B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients

Stage IV Papillary and Follicular 1) Adequate uptake of I131

bull I131

1) Inadequate uptake or not sensitive to I131

i Localized lesions

1) Radiation therapy

2) Resection of limited metastases dont uptake of I131

iiDisseminated disease

1) TSH suppression with thyroxine is effective

2) Chemotherapy has been reported to produce occasional complete

responses of long duration

3) Clinical trials testing new approaches to this disease

Medullary Thyroid Cancer treatment

bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck

dissections Why

bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival

advantage

bull Radioactive iodine has no place in the treatment of patients with MTC

bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in

patients with metastatic disease

bull No single drug regimen can be considered standard

bull Some patients with distant metastases will experience prolonged survival and can

be observed until they become symptomatic

Anaplastic Thyroid Cancer bull Surgery

bull Tracheostomy is frequently necessary

bull If the disease is confined to the local area which is rare total

thyroidectomy is warranted to reduce symptoms caused by the

tumor mass

bull Radiation therapy

bull Used in patients who are not surgical candidates or whose tumor

cannot be surgically excised

Anaplastic Thyroid Cancer bull Chemotherapy

bull Produce partial remissions in some patients

bull Approximately 30 of patients achieve a partial remission with

doxorubicin

bull The combination of doxorubicin plus cisplatin appears to be more

active than doxorubicin alone and has been reported to produce

more complete responses

Treatment options under clinical evaluation

bull The combination of chemotherapy plus radiation therapy in patients following

complete resection may provide prolonged survival but has not been compared to

any one modality alone

Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30

bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common

site of distant metastasis is the lung

bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type

Treatment of recurrent thyroid cancer

The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations

bull Adequate I131 uptake

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull I131 ablation

bull RT

bull Disseminated

bull I131 ablation

bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has

been reported to produce occasional objective responses usually of short

duration

Treatment of recurrent thyroid cancer

bull Inadequate I131 uptake or insensitive to I131

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull RT

bull Disseminated

bull Systemic chemotherapy

Treatment of recurrent thyroid cancer

Systemic chemotherapy

bull Doxorubicin alone

bull Cisplatin and doxorubicin (better)

bull BAP Cisplatin doxorubicin and bleomycin

bull CVD cyclophosphamide vincristine and dacarbazine

bull Dacarbazine and 5-fluorouracil

bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy

bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT

bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)

bull Improve OS and decrease RR

BAP regimenbull Schedule

bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5

bull Cell typebull Several histologic types of thyroid carcinoma responded but the

best responses were observed in medullary and anaplastic giant-cell carcinomas

bull Effectivenessbull BAP regime can achieve reasonable palliation and probably

increases survival in poor-prognosis thyroid cancers

CVD regimenbull Schedule

bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks

bull Cell typebull Medullary thyroid carcinoma

bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in

patients with advanced MTC

Dacarbazine and 5-fluorouracil

bull Schedule

bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and

12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks

Six cycles

bull Cell type

bull MTC

bull Effectiveness

bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to

have significant activity and was well tolerated

Target therapy

Take home messagesbull FNAC is not adequate for definite diagnosis of follicular

carcinomabull Because the mixed papillary-follicular variant tends to

behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis

bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer

bull Once medullary carcinoma is diagnosed familial predisposition should be checked up

bull If I131 is indicated stunning effect should be avoided

Take home messages

All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary

PROGNOSIS

Prognostic schemes GAMES scoring (PAPILLARY amp

FOLLICULAR CANCER)bullG GradebullA Age of patient when tumor discoveredbullM Metastases of the tumor (other than Neck LN)bullE Extent of primary tumorbullS Size of tumor (gt5 cm)bullThe patient is then placed into a high or low risk category

Prognostic Risk Classification for Patients with Well-Differentiated Thyroid Cancer (GAMES )

Low Risk High Riskbull Grade Well Differentiated Poorly Differentiated

bull Age lt40 gt40

bull Mets None Regional or Distant

bull Extent No local extension Capsular invasion intrathyroidal extrathyroidal

bull Sex Female Male

MACIS ScoringbullDeveloped by the Mayo Clinic for stagingbullIt is known to be the most accurate predictor of a patients outcome with papillary thyroid cancer (M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)bullMAICS Score 20 year Survival

lt 6 = 99 6-7 = 89 7-8 = 56 gt 8 = 24

Treatment

Stage I and II Papillary and FollicularI-Total thyroidectomy bull Rationale1048708 Bilateral cancers are common (30-85)1048708 improved effectiveness for I131 ablation1048708 lowers dose needed for I131 ablation1048708 allows fu with thyroglobulin levels1048708 decreased recurrence in all groups1048708 improved survival in high risk pts1048708 Decreased risk of pulmonary metsbull Disadvantage higher incidence of hypoparathyroidism but this

complication may be reduced when a small amount of tissue remains on the contralateral side

II-Lobectomy

bull Rationale

1048708 Most patients are low risk and excellent prognosis

1048708 Role of adjuvant treatment not defined

1048708 Complications of Total

1048708 Occult multicentric tumor not clinically significant

1048708 Most local recurrences treated with surgery

1048708 Excellent outcome with lobectomy in low risk patients

bull Disadvantage

bull approximately 5 to 10 of patients will have a recurrence

Indications for total Thyroidectomy OR lobectomy (all present)

bull Age 15 y - 45 ybull No prior radiationbull No distant metastasesbull No cervical lymph node metastasesbull No extrathyroidal extensionbull Tumor lt 4 cm in diameterbull No aggressive variant

When complete total thyroidectomy after lobectomybull Aggressive variantbull Macroscopic multifocal diseasebull Positive isthmus marginsbull Cervical lymph node metastasesbull Extrathyroidal extension

Aggressive=Tall cell columnar cell insular oxyphilic or poorly differentiated features

bull Node removal

bull Selective node removal can be performed and radical

neck dissection is usually not required

bull This results in a decreased recurrence rate but has not

been shown to improve survival

Thyroid carcinoma after lobectomy for benign lesions

I-Completion of thyroidectomy

bull gt 4 cm

bull Positive margins

bull Extra-thyroidal invasion (T3 or T4(

II- Completion of Thyroidectomy or follow

up

bull Clinically suspicious lymph node

contralateral lesion or perithyroidal node

bull Aggressive variant

bull Macroscopic multifocal disease

bull ge1 cm in diameter

III- follow up

bull Negative margins

bull No contralateral lesion

bull lt 1 cm in diameter

bull No suspicious lymph

node

POSTSURGICAL EVALUATION AFTER THYROIDECTOMY

I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +

antithyroglobulin antibodies)

II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan

Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT

bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)

Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas

Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant

Pretherapy whole body iodine scan

bullIf performed a pretherapy scan should use a low dose of 131I

(1 to 5 mCi) or 123I

bull To detect residual thyroid tissue thyroid cancer and metastatic foci

bull To reduce the potential for sublethal radiation stunning of thyroid tissue that

prevents optimal uptake of future 131I therapy

bullStunning is defined as a reduction in uptake of the 131I

therapy dose induced by a pretreatment diagnostic dose

Dose of RAI

bullThe dosing of 131I for ablation is somewhat controversial

bullLow-dose ablation with less than 30 mCi administered on

an outpatient basis

bull For low-risk young patients

bullHigh-dose ablation with100 to 200 mCi

bull For high-risk patients

bull300 mCi

bull For all patients with metastatic disease that treated with repeated

therapeutic doses of 131I

Replacement therapy

bullPostoperative treatment with exogenous thyroid hormone

in doses sufficient to suppress thyroid-stimulating hormone

(TSH) with development of thyrotoxic manifestations

decreases incidence of recurrence

bullAdministration of Thyroid Hormone

To suppress TSH and growth of any residual thyroid

To maintain patient euthyroid

o Maintain TSH level 01uUml in low risk pts

o Maintain TSH Level lt 01uUml in high risk pts

Stage III Papillary and Follicular

A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease

B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients

Stage IV Papillary and Follicular 1) Adequate uptake of I131

bull I131

1) Inadequate uptake or not sensitive to I131

i Localized lesions

1) Radiation therapy

2) Resection of limited metastases dont uptake of I131

iiDisseminated disease

1) TSH suppression with thyroxine is effective

2) Chemotherapy has been reported to produce occasional complete

responses of long duration

3) Clinical trials testing new approaches to this disease

Medullary Thyroid Cancer treatment

bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck

dissections Why

bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival

advantage

bull Radioactive iodine has no place in the treatment of patients with MTC

bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in

patients with metastatic disease

bull No single drug regimen can be considered standard

bull Some patients with distant metastases will experience prolonged survival and can

be observed until they become symptomatic

Anaplastic Thyroid Cancer bull Surgery

bull Tracheostomy is frequently necessary

bull If the disease is confined to the local area which is rare total

thyroidectomy is warranted to reduce symptoms caused by the

tumor mass

bull Radiation therapy

bull Used in patients who are not surgical candidates or whose tumor

cannot be surgically excised

Anaplastic Thyroid Cancer bull Chemotherapy

bull Produce partial remissions in some patients

bull Approximately 30 of patients achieve a partial remission with

doxorubicin

bull The combination of doxorubicin plus cisplatin appears to be more

active than doxorubicin alone and has been reported to produce

more complete responses

Treatment options under clinical evaluation

bull The combination of chemotherapy plus radiation therapy in patients following

complete resection may provide prolonged survival but has not been compared to

any one modality alone

Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30

bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common

site of distant metastasis is the lung

bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type

Treatment of recurrent thyroid cancer

The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations

bull Adequate I131 uptake

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull I131 ablation

bull RT

bull Disseminated

bull I131 ablation

bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has

been reported to produce occasional objective responses usually of short

duration

Treatment of recurrent thyroid cancer

bull Inadequate I131 uptake or insensitive to I131

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull RT

bull Disseminated

bull Systemic chemotherapy

Treatment of recurrent thyroid cancer

Systemic chemotherapy

bull Doxorubicin alone

bull Cisplatin and doxorubicin (better)

bull BAP Cisplatin doxorubicin and bleomycin

bull CVD cyclophosphamide vincristine and dacarbazine

bull Dacarbazine and 5-fluorouracil

bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy

bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT

bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)

bull Improve OS and decrease RR

BAP regimenbull Schedule

bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5

bull Cell typebull Several histologic types of thyroid carcinoma responded but the

best responses were observed in medullary and anaplastic giant-cell carcinomas

bull Effectivenessbull BAP regime can achieve reasonable palliation and probably

increases survival in poor-prognosis thyroid cancers

CVD regimenbull Schedule

bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks

bull Cell typebull Medullary thyroid carcinoma

bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in

patients with advanced MTC

Dacarbazine and 5-fluorouracil

bull Schedule

bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and

12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks

Six cycles

bull Cell type

bull MTC

bull Effectiveness

bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to

have significant activity and was well tolerated

Target therapy

Take home messagesbull FNAC is not adequate for definite diagnosis of follicular

carcinomabull Because the mixed papillary-follicular variant tends to

behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis

bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer

bull Once medullary carcinoma is diagnosed familial predisposition should be checked up

bull If I131 is indicated stunning effect should be avoided

Take home messages

All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary

Prognostic Risk Classification for Patients with Well-Differentiated Thyroid Cancer (GAMES )

Low Risk High Riskbull Grade Well Differentiated Poorly Differentiated

bull Age lt40 gt40

bull Mets None Regional or Distant

bull Extent No local extension Capsular invasion intrathyroidal extrathyroidal

bull Sex Female Male

MACIS ScoringbullDeveloped by the Mayo Clinic for stagingbullIt is known to be the most accurate predictor of a patients outcome with papillary thyroid cancer (M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)bullMAICS Score 20 year Survival

lt 6 = 99 6-7 = 89 7-8 = 56 gt 8 = 24

Treatment

Stage I and II Papillary and FollicularI-Total thyroidectomy bull Rationale1048708 Bilateral cancers are common (30-85)1048708 improved effectiveness for I131 ablation1048708 lowers dose needed for I131 ablation1048708 allows fu with thyroglobulin levels1048708 decreased recurrence in all groups1048708 improved survival in high risk pts1048708 Decreased risk of pulmonary metsbull Disadvantage higher incidence of hypoparathyroidism but this

complication may be reduced when a small amount of tissue remains on the contralateral side

II-Lobectomy

bull Rationale

1048708 Most patients are low risk and excellent prognosis

1048708 Role of adjuvant treatment not defined

1048708 Complications of Total

1048708 Occult multicentric tumor not clinically significant

1048708 Most local recurrences treated with surgery

1048708 Excellent outcome with lobectomy in low risk patients

bull Disadvantage

bull approximately 5 to 10 of patients will have a recurrence

Indications for total Thyroidectomy OR lobectomy (all present)

bull Age 15 y - 45 ybull No prior radiationbull No distant metastasesbull No cervical lymph node metastasesbull No extrathyroidal extensionbull Tumor lt 4 cm in diameterbull No aggressive variant

When complete total thyroidectomy after lobectomybull Aggressive variantbull Macroscopic multifocal diseasebull Positive isthmus marginsbull Cervical lymph node metastasesbull Extrathyroidal extension

Aggressive=Tall cell columnar cell insular oxyphilic or poorly differentiated features

bull Node removal

bull Selective node removal can be performed and radical

neck dissection is usually not required

bull This results in a decreased recurrence rate but has not

been shown to improve survival

Thyroid carcinoma after lobectomy for benign lesions

I-Completion of thyroidectomy

bull gt 4 cm

bull Positive margins

bull Extra-thyroidal invasion (T3 or T4(

II- Completion of Thyroidectomy or follow

up

bull Clinically suspicious lymph node

contralateral lesion or perithyroidal node

bull Aggressive variant

bull Macroscopic multifocal disease

bull ge1 cm in diameter

III- follow up

bull Negative margins

bull No contralateral lesion

bull lt 1 cm in diameter

bull No suspicious lymph

node

POSTSURGICAL EVALUATION AFTER THYROIDECTOMY

I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +

antithyroglobulin antibodies)

II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan

Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT

bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)

Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas

Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant

Pretherapy whole body iodine scan

bullIf performed a pretherapy scan should use a low dose of 131I

(1 to 5 mCi) or 123I

bull To detect residual thyroid tissue thyroid cancer and metastatic foci

bull To reduce the potential for sublethal radiation stunning of thyroid tissue that

prevents optimal uptake of future 131I therapy

bullStunning is defined as a reduction in uptake of the 131I

therapy dose induced by a pretreatment diagnostic dose

Dose of RAI

bullThe dosing of 131I for ablation is somewhat controversial

bullLow-dose ablation with less than 30 mCi administered on

an outpatient basis

bull For low-risk young patients

bullHigh-dose ablation with100 to 200 mCi

bull For high-risk patients

bull300 mCi

bull For all patients with metastatic disease that treated with repeated

therapeutic doses of 131I

Replacement therapy

bullPostoperative treatment with exogenous thyroid hormone

in doses sufficient to suppress thyroid-stimulating hormone

(TSH) with development of thyrotoxic manifestations

decreases incidence of recurrence

bullAdministration of Thyroid Hormone

To suppress TSH and growth of any residual thyroid

To maintain patient euthyroid

o Maintain TSH level 01uUml in low risk pts

o Maintain TSH Level lt 01uUml in high risk pts

Stage III Papillary and Follicular

A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease

B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients

Stage IV Papillary and Follicular 1) Adequate uptake of I131

bull I131

1) Inadequate uptake or not sensitive to I131

i Localized lesions

1) Radiation therapy

2) Resection of limited metastases dont uptake of I131

iiDisseminated disease

1) TSH suppression with thyroxine is effective

2) Chemotherapy has been reported to produce occasional complete

responses of long duration

3) Clinical trials testing new approaches to this disease

Medullary Thyroid Cancer treatment

bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck

dissections Why

bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival

advantage

bull Radioactive iodine has no place in the treatment of patients with MTC

bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in

patients with metastatic disease

bull No single drug regimen can be considered standard

bull Some patients with distant metastases will experience prolonged survival and can

be observed until they become symptomatic

Anaplastic Thyroid Cancer bull Surgery

bull Tracheostomy is frequently necessary

bull If the disease is confined to the local area which is rare total

thyroidectomy is warranted to reduce symptoms caused by the

tumor mass

bull Radiation therapy

bull Used in patients who are not surgical candidates or whose tumor

cannot be surgically excised

Anaplastic Thyroid Cancer bull Chemotherapy

bull Produce partial remissions in some patients

bull Approximately 30 of patients achieve a partial remission with

doxorubicin

bull The combination of doxorubicin plus cisplatin appears to be more

active than doxorubicin alone and has been reported to produce

more complete responses

Treatment options under clinical evaluation

bull The combination of chemotherapy plus radiation therapy in patients following

complete resection may provide prolonged survival but has not been compared to

any one modality alone

Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30

bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common

site of distant metastasis is the lung

bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type

Treatment of recurrent thyroid cancer

The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations

bull Adequate I131 uptake

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull I131 ablation

bull RT

bull Disseminated

bull I131 ablation

bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has

been reported to produce occasional objective responses usually of short

duration

Treatment of recurrent thyroid cancer

bull Inadequate I131 uptake or insensitive to I131

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull RT

bull Disseminated

bull Systemic chemotherapy

Treatment of recurrent thyroid cancer

Systemic chemotherapy

bull Doxorubicin alone

bull Cisplatin and doxorubicin (better)

bull BAP Cisplatin doxorubicin and bleomycin

bull CVD cyclophosphamide vincristine and dacarbazine

bull Dacarbazine and 5-fluorouracil

bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy

bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT

bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)

bull Improve OS and decrease RR

BAP regimenbull Schedule

bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5

bull Cell typebull Several histologic types of thyroid carcinoma responded but the

best responses were observed in medullary and anaplastic giant-cell carcinomas

bull Effectivenessbull BAP regime can achieve reasonable palliation and probably

increases survival in poor-prognosis thyroid cancers

CVD regimenbull Schedule

bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks

bull Cell typebull Medullary thyroid carcinoma

bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in

patients with advanced MTC

Dacarbazine and 5-fluorouracil

bull Schedule

bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and

12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks

Six cycles

bull Cell type

bull MTC

bull Effectiveness

bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to

have significant activity and was well tolerated

Target therapy

Take home messagesbull FNAC is not adequate for definite diagnosis of follicular

carcinomabull Because the mixed papillary-follicular variant tends to

behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis

bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer

bull Once medullary carcinoma is diagnosed familial predisposition should be checked up

bull If I131 is indicated stunning effect should be avoided

Take home messages

All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary

MACIS ScoringbullDeveloped by the Mayo Clinic for stagingbullIt is known to be the most accurate predictor of a patients outcome with papillary thyroid cancer (M = Metastasis A = Age I = Invasion C = Completeness of Resection S = Size)bullMAICS Score 20 year Survival

lt 6 = 99 6-7 = 89 7-8 = 56 gt 8 = 24

Treatment

Stage I and II Papillary and FollicularI-Total thyroidectomy bull Rationale1048708 Bilateral cancers are common (30-85)1048708 improved effectiveness for I131 ablation1048708 lowers dose needed for I131 ablation1048708 allows fu with thyroglobulin levels1048708 decreased recurrence in all groups1048708 improved survival in high risk pts1048708 Decreased risk of pulmonary metsbull Disadvantage higher incidence of hypoparathyroidism but this

complication may be reduced when a small amount of tissue remains on the contralateral side

II-Lobectomy

bull Rationale

1048708 Most patients are low risk and excellent prognosis

1048708 Role of adjuvant treatment not defined

1048708 Complications of Total

1048708 Occult multicentric tumor not clinically significant

1048708 Most local recurrences treated with surgery

1048708 Excellent outcome with lobectomy in low risk patients

bull Disadvantage

bull approximately 5 to 10 of patients will have a recurrence

Indications for total Thyroidectomy OR lobectomy (all present)

bull Age 15 y - 45 ybull No prior radiationbull No distant metastasesbull No cervical lymph node metastasesbull No extrathyroidal extensionbull Tumor lt 4 cm in diameterbull No aggressive variant

When complete total thyroidectomy after lobectomybull Aggressive variantbull Macroscopic multifocal diseasebull Positive isthmus marginsbull Cervical lymph node metastasesbull Extrathyroidal extension

Aggressive=Tall cell columnar cell insular oxyphilic or poorly differentiated features

bull Node removal

bull Selective node removal can be performed and radical

neck dissection is usually not required

bull This results in a decreased recurrence rate but has not

been shown to improve survival

Thyroid carcinoma after lobectomy for benign lesions

I-Completion of thyroidectomy

bull gt 4 cm

bull Positive margins

bull Extra-thyroidal invasion (T3 or T4(

II- Completion of Thyroidectomy or follow

up

bull Clinically suspicious lymph node

contralateral lesion or perithyroidal node

bull Aggressive variant

bull Macroscopic multifocal disease

bull ge1 cm in diameter

III- follow up

bull Negative margins

bull No contralateral lesion

bull lt 1 cm in diameter

bull No suspicious lymph

node

POSTSURGICAL EVALUATION AFTER THYROIDECTOMY

I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +

antithyroglobulin antibodies)

II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan

Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT

bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)

Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas

Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant

Pretherapy whole body iodine scan

bullIf performed a pretherapy scan should use a low dose of 131I

(1 to 5 mCi) or 123I

bull To detect residual thyroid tissue thyroid cancer and metastatic foci

bull To reduce the potential for sublethal radiation stunning of thyroid tissue that

prevents optimal uptake of future 131I therapy

bullStunning is defined as a reduction in uptake of the 131I

therapy dose induced by a pretreatment diagnostic dose

Dose of RAI

bullThe dosing of 131I for ablation is somewhat controversial

bullLow-dose ablation with less than 30 mCi administered on

an outpatient basis

bull For low-risk young patients

bullHigh-dose ablation with100 to 200 mCi

bull For high-risk patients

bull300 mCi

bull For all patients with metastatic disease that treated with repeated

therapeutic doses of 131I

Replacement therapy

bullPostoperative treatment with exogenous thyroid hormone

in doses sufficient to suppress thyroid-stimulating hormone

(TSH) with development of thyrotoxic manifestations

decreases incidence of recurrence

bullAdministration of Thyroid Hormone

To suppress TSH and growth of any residual thyroid

To maintain patient euthyroid

o Maintain TSH level 01uUml in low risk pts

o Maintain TSH Level lt 01uUml in high risk pts

Stage III Papillary and Follicular

A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease

B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients

Stage IV Papillary and Follicular 1) Adequate uptake of I131

bull I131

1) Inadequate uptake or not sensitive to I131

i Localized lesions

1) Radiation therapy

2) Resection of limited metastases dont uptake of I131

iiDisseminated disease

1) TSH suppression with thyroxine is effective

2) Chemotherapy has been reported to produce occasional complete

responses of long duration

3) Clinical trials testing new approaches to this disease

Medullary Thyroid Cancer treatment

bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck

dissections Why

bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival

advantage

bull Radioactive iodine has no place in the treatment of patients with MTC

bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in

patients with metastatic disease

bull No single drug regimen can be considered standard

bull Some patients with distant metastases will experience prolonged survival and can

be observed until they become symptomatic

Anaplastic Thyroid Cancer bull Surgery

bull Tracheostomy is frequently necessary

bull If the disease is confined to the local area which is rare total

thyroidectomy is warranted to reduce symptoms caused by the

tumor mass

bull Radiation therapy

bull Used in patients who are not surgical candidates or whose tumor

cannot be surgically excised

Anaplastic Thyroid Cancer bull Chemotherapy

bull Produce partial remissions in some patients

bull Approximately 30 of patients achieve a partial remission with

doxorubicin

bull The combination of doxorubicin plus cisplatin appears to be more

active than doxorubicin alone and has been reported to produce

more complete responses

Treatment options under clinical evaluation

bull The combination of chemotherapy plus radiation therapy in patients following

complete resection may provide prolonged survival but has not been compared to

any one modality alone

Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30

bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common

site of distant metastasis is the lung

bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type

Treatment of recurrent thyroid cancer

The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations

bull Adequate I131 uptake

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull I131 ablation

bull RT

bull Disseminated

bull I131 ablation

bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has

been reported to produce occasional objective responses usually of short

duration

Treatment of recurrent thyroid cancer

bull Inadequate I131 uptake or insensitive to I131

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull RT

bull Disseminated

bull Systemic chemotherapy

Treatment of recurrent thyroid cancer

Systemic chemotherapy

bull Doxorubicin alone

bull Cisplatin and doxorubicin (better)

bull BAP Cisplatin doxorubicin and bleomycin

bull CVD cyclophosphamide vincristine and dacarbazine

bull Dacarbazine and 5-fluorouracil

bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy

bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT

bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)

bull Improve OS and decrease RR

BAP regimenbull Schedule

bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5

bull Cell typebull Several histologic types of thyroid carcinoma responded but the

best responses were observed in medullary and anaplastic giant-cell carcinomas

bull Effectivenessbull BAP regime can achieve reasonable palliation and probably

increases survival in poor-prognosis thyroid cancers

CVD regimenbull Schedule

bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks

bull Cell typebull Medullary thyroid carcinoma

bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in

patients with advanced MTC

Dacarbazine and 5-fluorouracil

bull Schedule

bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and

12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks

Six cycles

bull Cell type

bull MTC

bull Effectiveness

bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to

have significant activity and was well tolerated

Target therapy

Take home messagesbull FNAC is not adequate for definite diagnosis of follicular

carcinomabull Because the mixed papillary-follicular variant tends to

behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis

bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer

bull Once medullary carcinoma is diagnosed familial predisposition should be checked up

bull If I131 is indicated stunning effect should be avoided

Take home messages

All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary

Treatment

Stage I and II Papillary and FollicularI-Total thyroidectomy bull Rationale1048708 Bilateral cancers are common (30-85)1048708 improved effectiveness for I131 ablation1048708 lowers dose needed for I131 ablation1048708 allows fu with thyroglobulin levels1048708 decreased recurrence in all groups1048708 improved survival in high risk pts1048708 Decreased risk of pulmonary metsbull Disadvantage higher incidence of hypoparathyroidism but this

complication may be reduced when a small amount of tissue remains on the contralateral side

II-Lobectomy

bull Rationale

1048708 Most patients are low risk and excellent prognosis

1048708 Role of adjuvant treatment not defined

1048708 Complications of Total

1048708 Occult multicentric tumor not clinically significant

1048708 Most local recurrences treated with surgery

1048708 Excellent outcome with lobectomy in low risk patients

bull Disadvantage

bull approximately 5 to 10 of patients will have a recurrence

Indications for total Thyroidectomy OR lobectomy (all present)

bull Age 15 y - 45 ybull No prior radiationbull No distant metastasesbull No cervical lymph node metastasesbull No extrathyroidal extensionbull Tumor lt 4 cm in diameterbull No aggressive variant

When complete total thyroidectomy after lobectomybull Aggressive variantbull Macroscopic multifocal diseasebull Positive isthmus marginsbull Cervical lymph node metastasesbull Extrathyroidal extension

Aggressive=Tall cell columnar cell insular oxyphilic or poorly differentiated features

bull Node removal

bull Selective node removal can be performed and radical

neck dissection is usually not required

bull This results in a decreased recurrence rate but has not

been shown to improve survival

Thyroid carcinoma after lobectomy for benign lesions

I-Completion of thyroidectomy

bull gt 4 cm

bull Positive margins

bull Extra-thyroidal invasion (T3 or T4(

II- Completion of Thyroidectomy or follow

up

bull Clinically suspicious lymph node

contralateral lesion or perithyroidal node

bull Aggressive variant

bull Macroscopic multifocal disease

bull ge1 cm in diameter

III- follow up

bull Negative margins

bull No contralateral lesion

bull lt 1 cm in diameter

bull No suspicious lymph

node

POSTSURGICAL EVALUATION AFTER THYROIDECTOMY

I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +

antithyroglobulin antibodies)

II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan

Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT

bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)

Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas

Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant

Pretherapy whole body iodine scan

bullIf performed a pretherapy scan should use a low dose of 131I

(1 to 5 mCi) or 123I

bull To detect residual thyroid tissue thyroid cancer and metastatic foci

bull To reduce the potential for sublethal radiation stunning of thyroid tissue that

prevents optimal uptake of future 131I therapy

bullStunning is defined as a reduction in uptake of the 131I

therapy dose induced by a pretreatment diagnostic dose

Dose of RAI

bullThe dosing of 131I for ablation is somewhat controversial

bullLow-dose ablation with less than 30 mCi administered on

an outpatient basis

bull For low-risk young patients

bullHigh-dose ablation with100 to 200 mCi

bull For high-risk patients

bull300 mCi

bull For all patients with metastatic disease that treated with repeated

therapeutic doses of 131I

Replacement therapy

bullPostoperative treatment with exogenous thyroid hormone

in doses sufficient to suppress thyroid-stimulating hormone

(TSH) with development of thyrotoxic manifestations

decreases incidence of recurrence

bullAdministration of Thyroid Hormone

To suppress TSH and growth of any residual thyroid

To maintain patient euthyroid

o Maintain TSH level 01uUml in low risk pts

o Maintain TSH Level lt 01uUml in high risk pts

Stage III Papillary and Follicular

A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease

B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients

Stage IV Papillary and Follicular 1) Adequate uptake of I131

bull I131

1) Inadequate uptake or not sensitive to I131

i Localized lesions

1) Radiation therapy

2) Resection of limited metastases dont uptake of I131

iiDisseminated disease

1) TSH suppression with thyroxine is effective

2) Chemotherapy has been reported to produce occasional complete

responses of long duration

3) Clinical trials testing new approaches to this disease

Medullary Thyroid Cancer treatment

bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck

dissections Why

bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival

advantage

bull Radioactive iodine has no place in the treatment of patients with MTC

bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in

patients with metastatic disease

bull No single drug regimen can be considered standard

bull Some patients with distant metastases will experience prolonged survival and can

be observed until they become symptomatic

Anaplastic Thyroid Cancer bull Surgery

bull Tracheostomy is frequently necessary

bull If the disease is confined to the local area which is rare total

thyroidectomy is warranted to reduce symptoms caused by the

tumor mass

bull Radiation therapy

bull Used in patients who are not surgical candidates or whose tumor

cannot be surgically excised

Anaplastic Thyroid Cancer bull Chemotherapy

bull Produce partial remissions in some patients

bull Approximately 30 of patients achieve a partial remission with

doxorubicin

bull The combination of doxorubicin plus cisplatin appears to be more

active than doxorubicin alone and has been reported to produce

more complete responses

Treatment options under clinical evaluation

bull The combination of chemotherapy plus radiation therapy in patients following

complete resection may provide prolonged survival but has not been compared to

any one modality alone

Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30

bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common

site of distant metastasis is the lung

bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type

Treatment of recurrent thyroid cancer

The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations

bull Adequate I131 uptake

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull I131 ablation

bull RT

bull Disseminated

bull I131 ablation

bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has

been reported to produce occasional objective responses usually of short

duration

Treatment of recurrent thyroid cancer

bull Inadequate I131 uptake or insensitive to I131

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull RT

bull Disseminated

bull Systemic chemotherapy

Treatment of recurrent thyroid cancer

Systemic chemotherapy

bull Doxorubicin alone

bull Cisplatin and doxorubicin (better)

bull BAP Cisplatin doxorubicin and bleomycin

bull CVD cyclophosphamide vincristine and dacarbazine

bull Dacarbazine and 5-fluorouracil

bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy

bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT

bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)

bull Improve OS and decrease RR

BAP regimenbull Schedule

bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5

bull Cell typebull Several histologic types of thyroid carcinoma responded but the

best responses were observed in medullary and anaplastic giant-cell carcinomas

bull Effectivenessbull BAP regime can achieve reasonable palliation and probably

increases survival in poor-prognosis thyroid cancers

CVD regimenbull Schedule

bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks

bull Cell typebull Medullary thyroid carcinoma

bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in

patients with advanced MTC

Dacarbazine and 5-fluorouracil

bull Schedule

bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and

12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks

Six cycles

bull Cell type

bull MTC

bull Effectiveness

bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to

have significant activity and was well tolerated

Target therapy

Take home messagesbull FNAC is not adequate for definite diagnosis of follicular

carcinomabull Because the mixed papillary-follicular variant tends to

behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis

bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer

bull Once medullary carcinoma is diagnosed familial predisposition should be checked up

bull If I131 is indicated stunning effect should be avoided

Take home messages

All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary

Stage I and II Papillary and FollicularI-Total thyroidectomy bull Rationale1048708 Bilateral cancers are common (30-85)1048708 improved effectiveness for I131 ablation1048708 lowers dose needed for I131 ablation1048708 allows fu with thyroglobulin levels1048708 decreased recurrence in all groups1048708 improved survival in high risk pts1048708 Decreased risk of pulmonary metsbull Disadvantage higher incidence of hypoparathyroidism but this

complication may be reduced when a small amount of tissue remains on the contralateral side

II-Lobectomy

bull Rationale

1048708 Most patients are low risk and excellent prognosis

1048708 Role of adjuvant treatment not defined

1048708 Complications of Total

1048708 Occult multicentric tumor not clinically significant

1048708 Most local recurrences treated with surgery

1048708 Excellent outcome with lobectomy in low risk patients

bull Disadvantage

bull approximately 5 to 10 of patients will have a recurrence

Indications for total Thyroidectomy OR lobectomy (all present)

bull Age 15 y - 45 ybull No prior radiationbull No distant metastasesbull No cervical lymph node metastasesbull No extrathyroidal extensionbull Tumor lt 4 cm in diameterbull No aggressive variant

When complete total thyroidectomy after lobectomybull Aggressive variantbull Macroscopic multifocal diseasebull Positive isthmus marginsbull Cervical lymph node metastasesbull Extrathyroidal extension

Aggressive=Tall cell columnar cell insular oxyphilic or poorly differentiated features

bull Node removal

bull Selective node removal can be performed and radical

neck dissection is usually not required

bull This results in a decreased recurrence rate but has not

been shown to improve survival

Thyroid carcinoma after lobectomy for benign lesions

I-Completion of thyroidectomy

bull gt 4 cm

bull Positive margins

bull Extra-thyroidal invasion (T3 or T4(

II- Completion of Thyroidectomy or follow

up

bull Clinically suspicious lymph node

contralateral lesion or perithyroidal node

bull Aggressive variant

bull Macroscopic multifocal disease

bull ge1 cm in diameter

III- follow up

bull Negative margins

bull No contralateral lesion

bull lt 1 cm in diameter

bull No suspicious lymph

node

POSTSURGICAL EVALUATION AFTER THYROIDECTOMY

I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +

antithyroglobulin antibodies)

II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan

Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT

bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)

Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas

Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant

Pretherapy whole body iodine scan

bullIf performed a pretherapy scan should use a low dose of 131I

(1 to 5 mCi) or 123I

bull To detect residual thyroid tissue thyroid cancer and metastatic foci

bull To reduce the potential for sublethal radiation stunning of thyroid tissue that

prevents optimal uptake of future 131I therapy

bullStunning is defined as a reduction in uptake of the 131I

therapy dose induced by a pretreatment diagnostic dose

Dose of RAI

bullThe dosing of 131I for ablation is somewhat controversial

bullLow-dose ablation with less than 30 mCi administered on

an outpatient basis

bull For low-risk young patients

bullHigh-dose ablation with100 to 200 mCi

bull For high-risk patients

bull300 mCi

bull For all patients with metastatic disease that treated with repeated

therapeutic doses of 131I

Replacement therapy

bullPostoperative treatment with exogenous thyroid hormone

in doses sufficient to suppress thyroid-stimulating hormone

(TSH) with development of thyrotoxic manifestations

decreases incidence of recurrence

bullAdministration of Thyroid Hormone

To suppress TSH and growth of any residual thyroid

To maintain patient euthyroid

o Maintain TSH level 01uUml in low risk pts

o Maintain TSH Level lt 01uUml in high risk pts

Stage III Papillary and Follicular

A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease

B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients

Stage IV Papillary and Follicular 1) Adequate uptake of I131

bull I131

1) Inadequate uptake or not sensitive to I131

i Localized lesions

1) Radiation therapy

2) Resection of limited metastases dont uptake of I131

iiDisseminated disease

1) TSH suppression with thyroxine is effective

2) Chemotherapy has been reported to produce occasional complete

responses of long duration

3) Clinical trials testing new approaches to this disease

Medullary Thyroid Cancer treatment

bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck

dissections Why

bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival

advantage

bull Radioactive iodine has no place in the treatment of patients with MTC

bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in

patients with metastatic disease

bull No single drug regimen can be considered standard

bull Some patients with distant metastases will experience prolonged survival and can

be observed until they become symptomatic

Anaplastic Thyroid Cancer bull Surgery

bull Tracheostomy is frequently necessary

bull If the disease is confined to the local area which is rare total

thyroidectomy is warranted to reduce symptoms caused by the

tumor mass

bull Radiation therapy

bull Used in patients who are not surgical candidates or whose tumor

cannot be surgically excised

Anaplastic Thyroid Cancer bull Chemotherapy

bull Produce partial remissions in some patients

bull Approximately 30 of patients achieve a partial remission with

doxorubicin

bull The combination of doxorubicin plus cisplatin appears to be more

active than doxorubicin alone and has been reported to produce

more complete responses

Treatment options under clinical evaluation

bull The combination of chemotherapy plus radiation therapy in patients following

complete resection may provide prolonged survival but has not been compared to

any one modality alone

Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30

bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common

site of distant metastasis is the lung

bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type

Treatment of recurrent thyroid cancer

The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations

bull Adequate I131 uptake

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull I131 ablation

bull RT

bull Disseminated

bull I131 ablation

bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has

been reported to produce occasional objective responses usually of short

duration

Treatment of recurrent thyroid cancer

bull Inadequate I131 uptake or insensitive to I131

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull RT

bull Disseminated

bull Systemic chemotherapy

Treatment of recurrent thyroid cancer

Systemic chemotherapy

bull Doxorubicin alone

bull Cisplatin and doxorubicin (better)

bull BAP Cisplatin doxorubicin and bleomycin

bull CVD cyclophosphamide vincristine and dacarbazine

bull Dacarbazine and 5-fluorouracil

bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy

bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT

bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)

bull Improve OS and decrease RR

BAP regimenbull Schedule

bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5

bull Cell typebull Several histologic types of thyroid carcinoma responded but the

best responses were observed in medullary and anaplastic giant-cell carcinomas

bull Effectivenessbull BAP regime can achieve reasonable palliation and probably

increases survival in poor-prognosis thyroid cancers

CVD regimenbull Schedule

bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks

bull Cell typebull Medullary thyroid carcinoma

bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in

patients with advanced MTC

Dacarbazine and 5-fluorouracil

bull Schedule

bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and

12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks

Six cycles

bull Cell type

bull MTC

bull Effectiveness

bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to

have significant activity and was well tolerated

Target therapy

Take home messagesbull FNAC is not adequate for definite diagnosis of follicular

carcinomabull Because the mixed papillary-follicular variant tends to

behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis

bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer

bull Once medullary carcinoma is diagnosed familial predisposition should be checked up

bull If I131 is indicated stunning effect should be avoided

Take home messages

All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary

II-Lobectomy

bull Rationale

1048708 Most patients are low risk and excellent prognosis

1048708 Role of adjuvant treatment not defined

1048708 Complications of Total

1048708 Occult multicentric tumor not clinically significant

1048708 Most local recurrences treated with surgery

1048708 Excellent outcome with lobectomy in low risk patients

bull Disadvantage

bull approximately 5 to 10 of patients will have a recurrence

Indications for total Thyroidectomy OR lobectomy (all present)

bull Age 15 y - 45 ybull No prior radiationbull No distant metastasesbull No cervical lymph node metastasesbull No extrathyroidal extensionbull Tumor lt 4 cm in diameterbull No aggressive variant

When complete total thyroidectomy after lobectomybull Aggressive variantbull Macroscopic multifocal diseasebull Positive isthmus marginsbull Cervical lymph node metastasesbull Extrathyroidal extension

Aggressive=Tall cell columnar cell insular oxyphilic or poorly differentiated features

bull Node removal

bull Selective node removal can be performed and radical

neck dissection is usually not required

bull This results in a decreased recurrence rate but has not

been shown to improve survival

Thyroid carcinoma after lobectomy for benign lesions

I-Completion of thyroidectomy

bull gt 4 cm

bull Positive margins

bull Extra-thyroidal invasion (T3 or T4(

II- Completion of Thyroidectomy or follow

up

bull Clinically suspicious lymph node

contralateral lesion or perithyroidal node

bull Aggressive variant

bull Macroscopic multifocal disease

bull ge1 cm in diameter

III- follow up

bull Negative margins

bull No contralateral lesion

bull lt 1 cm in diameter

bull No suspicious lymph

node

POSTSURGICAL EVALUATION AFTER THYROIDECTOMY

I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +

antithyroglobulin antibodies)

II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan

Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT

bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)

Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas

Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant

Pretherapy whole body iodine scan

bullIf performed a pretherapy scan should use a low dose of 131I

(1 to 5 mCi) or 123I

bull To detect residual thyroid tissue thyroid cancer and metastatic foci

bull To reduce the potential for sublethal radiation stunning of thyroid tissue that

prevents optimal uptake of future 131I therapy

bullStunning is defined as a reduction in uptake of the 131I

therapy dose induced by a pretreatment diagnostic dose

Dose of RAI

bullThe dosing of 131I for ablation is somewhat controversial

bullLow-dose ablation with less than 30 mCi administered on

an outpatient basis

bull For low-risk young patients

bullHigh-dose ablation with100 to 200 mCi

bull For high-risk patients

bull300 mCi

bull For all patients with metastatic disease that treated with repeated

therapeutic doses of 131I

Replacement therapy

bullPostoperative treatment with exogenous thyroid hormone

in doses sufficient to suppress thyroid-stimulating hormone

(TSH) with development of thyrotoxic manifestations

decreases incidence of recurrence

bullAdministration of Thyroid Hormone

To suppress TSH and growth of any residual thyroid

To maintain patient euthyroid

o Maintain TSH level 01uUml in low risk pts

o Maintain TSH Level lt 01uUml in high risk pts

Stage III Papillary and Follicular

A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease

B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients

Stage IV Papillary and Follicular 1) Adequate uptake of I131

bull I131

1) Inadequate uptake or not sensitive to I131

i Localized lesions

1) Radiation therapy

2) Resection of limited metastases dont uptake of I131

iiDisseminated disease

1) TSH suppression with thyroxine is effective

2) Chemotherapy has been reported to produce occasional complete

responses of long duration

3) Clinical trials testing new approaches to this disease

Medullary Thyroid Cancer treatment

bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck

dissections Why

bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival

advantage

bull Radioactive iodine has no place in the treatment of patients with MTC

bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in

patients with metastatic disease

bull No single drug regimen can be considered standard

bull Some patients with distant metastases will experience prolonged survival and can

be observed until they become symptomatic

Anaplastic Thyroid Cancer bull Surgery

bull Tracheostomy is frequently necessary

bull If the disease is confined to the local area which is rare total

thyroidectomy is warranted to reduce symptoms caused by the

tumor mass

bull Radiation therapy

bull Used in patients who are not surgical candidates or whose tumor

cannot be surgically excised

Anaplastic Thyroid Cancer bull Chemotherapy

bull Produce partial remissions in some patients

bull Approximately 30 of patients achieve a partial remission with

doxorubicin

bull The combination of doxorubicin plus cisplatin appears to be more

active than doxorubicin alone and has been reported to produce

more complete responses

Treatment options under clinical evaluation

bull The combination of chemotherapy plus radiation therapy in patients following

complete resection may provide prolonged survival but has not been compared to

any one modality alone

Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30

bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common

site of distant metastasis is the lung

bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type

Treatment of recurrent thyroid cancer

The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations

bull Adequate I131 uptake

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull I131 ablation

bull RT

bull Disseminated

bull I131 ablation

bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has

been reported to produce occasional objective responses usually of short

duration

Treatment of recurrent thyroid cancer

bull Inadequate I131 uptake or insensitive to I131

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull RT

bull Disseminated

bull Systemic chemotherapy

Treatment of recurrent thyroid cancer

Systemic chemotherapy

bull Doxorubicin alone

bull Cisplatin and doxorubicin (better)

bull BAP Cisplatin doxorubicin and bleomycin

bull CVD cyclophosphamide vincristine and dacarbazine

bull Dacarbazine and 5-fluorouracil

bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy

bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT

bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)

bull Improve OS and decrease RR

BAP regimenbull Schedule

bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5

bull Cell typebull Several histologic types of thyroid carcinoma responded but the

best responses were observed in medullary and anaplastic giant-cell carcinomas

bull Effectivenessbull BAP regime can achieve reasonable palliation and probably

increases survival in poor-prognosis thyroid cancers

CVD regimenbull Schedule

bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks

bull Cell typebull Medullary thyroid carcinoma

bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in

patients with advanced MTC

Dacarbazine and 5-fluorouracil

bull Schedule

bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and

12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks

Six cycles

bull Cell type

bull MTC

bull Effectiveness

bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to

have significant activity and was well tolerated

Target therapy

Take home messagesbull FNAC is not adequate for definite diagnosis of follicular

carcinomabull Because the mixed papillary-follicular variant tends to

behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis

bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer

bull Once medullary carcinoma is diagnosed familial predisposition should be checked up

bull If I131 is indicated stunning effect should be avoided

Take home messages

All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary

Indications for total Thyroidectomy OR lobectomy (all present)

bull Age 15 y - 45 ybull No prior radiationbull No distant metastasesbull No cervical lymph node metastasesbull No extrathyroidal extensionbull Tumor lt 4 cm in diameterbull No aggressive variant

When complete total thyroidectomy after lobectomybull Aggressive variantbull Macroscopic multifocal diseasebull Positive isthmus marginsbull Cervical lymph node metastasesbull Extrathyroidal extension

Aggressive=Tall cell columnar cell insular oxyphilic or poorly differentiated features

bull Node removal

bull Selective node removal can be performed and radical

neck dissection is usually not required

bull This results in a decreased recurrence rate but has not

been shown to improve survival

Thyroid carcinoma after lobectomy for benign lesions

I-Completion of thyroidectomy

bull gt 4 cm

bull Positive margins

bull Extra-thyroidal invasion (T3 or T4(

II- Completion of Thyroidectomy or follow

up

bull Clinically suspicious lymph node

contralateral lesion or perithyroidal node

bull Aggressive variant

bull Macroscopic multifocal disease

bull ge1 cm in diameter

III- follow up

bull Negative margins

bull No contralateral lesion

bull lt 1 cm in diameter

bull No suspicious lymph

node

POSTSURGICAL EVALUATION AFTER THYROIDECTOMY

I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +

antithyroglobulin antibodies)

II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan

Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT

bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)

Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas

Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant

Pretherapy whole body iodine scan

bullIf performed a pretherapy scan should use a low dose of 131I

(1 to 5 mCi) or 123I

bull To detect residual thyroid tissue thyroid cancer and metastatic foci

bull To reduce the potential for sublethal radiation stunning of thyroid tissue that

prevents optimal uptake of future 131I therapy

bullStunning is defined as a reduction in uptake of the 131I

therapy dose induced by a pretreatment diagnostic dose

Dose of RAI

bullThe dosing of 131I for ablation is somewhat controversial

bullLow-dose ablation with less than 30 mCi administered on

an outpatient basis

bull For low-risk young patients

bullHigh-dose ablation with100 to 200 mCi

bull For high-risk patients

bull300 mCi

bull For all patients with metastatic disease that treated with repeated

therapeutic doses of 131I

Replacement therapy

bullPostoperative treatment with exogenous thyroid hormone

in doses sufficient to suppress thyroid-stimulating hormone

(TSH) with development of thyrotoxic manifestations

decreases incidence of recurrence

bullAdministration of Thyroid Hormone

To suppress TSH and growth of any residual thyroid

To maintain patient euthyroid

o Maintain TSH level 01uUml in low risk pts

o Maintain TSH Level lt 01uUml in high risk pts

Stage III Papillary and Follicular

A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease

B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients

Stage IV Papillary and Follicular 1) Adequate uptake of I131

bull I131

1) Inadequate uptake or not sensitive to I131

i Localized lesions

1) Radiation therapy

2) Resection of limited metastases dont uptake of I131

iiDisseminated disease

1) TSH suppression with thyroxine is effective

2) Chemotherapy has been reported to produce occasional complete

responses of long duration

3) Clinical trials testing new approaches to this disease

Medullary Thyroid Cancer treatment

bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck

dissections Why

bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival

advantage

bull Radioactive iodine has no place in the treatment of patients with MTC

bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in

patients with metastatic disease

bull No single drug regimen can be considered standard

bull Some patients with distant metastases will experience prolonged survival and can

be observed until they become symptomatic

Anaplastic Thyroid Cancer bull Surgery

bull Tracheostomy is frequently necessary

bull If the disease is confined to the local area which is rare total

thyroidectomy is warranted to reduce symptoms caused by the

tumor mass

bull Radiation therapy

bull Used in patients who are not surgical candidates or whose tumor

cannot be surgically excised

Anaplastic Thyroid Cancer bull Chemotherapy

bull Produce partial remissions in some patients

bull Approximately 30 of patients achieve a partial remission with

doxorubicin

bull The combination of doxorubicin plus cisplatin appears to be more

active than doxorubicin alone and has been reported to produce

more complete responses

Treatment options under clinical evaluation

bull The combination of chemotherapy plus radiation therapy in patients following

complete resection may provide prolonged survival but has not been compared to

any one modality alone

Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30

bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common

site of distant metastasis is the lung

bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type

Treatment of recurrent thyroid cancer

The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations

bull Adequate I131 uptake

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull I131 ablation

bull RT

bull Disseminated

bull I131 ablation

bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has

been reported to produce occasional objective responses usually of short

duration

Treatment of recurrent thyroid cancer

bull Inadequate I131 uptake or insensitive to I131

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull RT

bull Disseminated

bull Systemic chemotherapy

Treatment of recurrent thyroid cancer

Systemic chemotherapy

bull Doxorubicin alone

bull Cisplatin and doxorubicin (better)

bull BAP Cisplatin doxorubicin and bleomycin

bull CVD cyclophosphamide vincristine and dacarbazine

bull Dacarbazine and 5-fluorouracil

bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy

bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT

bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)

bull Improve OS and decrease RR

BAP regimenbull Schedule

bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5

bull Cell typebull Several histologic types of thyroid carcinoma responded but the

best responses were observed in medullary and anaplastic giant-cell carcinomas

bull Effectivenessbull BAP regime can achieve reasonable palliation and probably

increases survival in poor-prognosis thyroid cancers

CVD regimenbull Schedule

bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks

bull Cell typebull Medullary thyroid carcinoma

bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in

patients with advanced MTC

Dacarbazine and 5-fluorouracil

bull Schedule

bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and

12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks

Six cycles

bull Cell type

bull MTC

bull Effectiveness

bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to

have significant activity and was well tolerated

Target therapy

Take home messagesbull FNAC is not adequate for definite diagnosis of follicular

carcinomabull Because the mixed papillary-follicular variant tends to

behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis

bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer

bull Once medullary carcinoma is diagnosed familial predisposition should be checked up

bull If I131 is indicated stunning effect should be avoided

Take home messages

All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary

When complete total thyroidectomy after lobectomybull Aggressive variantbull Macroscopic multifocal diseasebull Positive isthmus marginsbull Cervical lymph node metastasesbull Extrathyroidal extension

Aggressive=Tall cell columnar cell insular oxyphilic or poorly differentiated features

bull Node removal

bull Selective node removal can be performed and radical

neck dissection is usually not required

bull This results in a decreased recurrence rate but has not

been shown to improve survival

Thyroid carcinoma after lobectomy for benign lesions

I-Completion of thyroidectomy

bull gt 4 cm

bull Positive margins

bull Extra-thyroidal invasion (T3 or T4(

II- Completion of Thyroidectomy or follow

up

bull Clinically suspicious lymph node

contralateral lesion or perithyroidal node

bull Aggressive variant

bull Macroscopic multifocal disease

bull ge1 cm in diameter

III- follow up

bull Negative margins

bull No contralateral lesion

bull lt 1 cm in diameter

bull No suspicious lymph

node

POSTSURGICAL EVALUATION AFTER THYROIDECTOMY

I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +

antithyroglobulin antibodies)

II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan

Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT

bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)

Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas

Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant

Pretherapy whole body iodine scan

bullIf performed a pretherapy scan should use a low dose of 131I

(1 to 5 mCi) or 123I

bull To detect residual thyroid tissue thyroid cancer and metastatic foci

bull To reduce the potential for sublethal radiation stunning of thyroid tissue that

prevents optimal uptake of future 131I therapy

bullStunning is defined as a reduction in uptake of the 131I

therapy dose induced by a pretreatment diagnostic dose

Dose of RAI

bullThe dosing of 131I for ablation is somewhat controversial

bullLow-dose ablation with less than 30 mCi administered on

an outpatient basis

bull For low-risk young patients

bullHigh-dose ablation with100 to 200 mCi

bull For high-risk patients

bull300 mCi

bull For all patients with metastatic disease that treated with repeated

therapeutic doses of 131I

Replacement therapy

bullPostoperative treatment with exogenous thyroid hormone

in doses sufficient to suppress thyroid-stimulating hormone

(TSH) with development of thyrotoxic manifestations

decreases incidence of recurrence

bullAdministration of Thyroid Hormone

To suppress TSH and growth of any residual thyroid

To maintain patient euthyroid

o Maintain TSH level 01uUml in low risk pts

o Maintain TSH Level lt 01uUml in high risk pts

Stage III Papillary and Follicular

A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease

B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients

Stage IV Papillary and Follicular 1) Adequate uptake of I131

bull I131

1) Inadequate uptake or not sensitive to I131

i Localized lesions

1) Radiation therapy

2) Resection of limited metastases dont uptake of I131

iiDisseminated disease

1) TSH suppression with thyroxine is effective

2) Chemotherapy has been reported to produce occasional complete

responses of long duration

3) Clinical trials testing new approaches to this disease

Medullary Thyroid Cancer treatment

bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck

dissections Why

bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival

advantage

bull Radioactive iodine has no place in the treatment of patients with MTC

bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in

patients with metastatic disease

bull No single drug regimen can be considered standard

bull Some patients with distant metastases will experience prolonged survival and can

be observed until they become symptomatic

Anaplastic Thyroid Cancer bull Surgery

bull Tracheostomy is frequently necessary

bull If the disease is confined to the local area which is rare total

thyroidectomy is warranted to reduce symptoms caused by the

tumor mass

bull Radiation therapy

bull Used in patients who are not surgical candidates or whose tumor

cannot be surgically excised

Anaplastic Thyroid Cancer bull Chemotherapy

bull Produce partial remissions in some patients

bull Approximately 30 of patients achieve a partial remission with

doxorubicin

bull The combination of doxorubicin plus cisplatin appears to be more

active than doxorubicin alone and has been reported to produce

more complete responses

Treatment options under clinical evaluation

bull The combination of chemotherapy plus radiation therapy in patients following

complete resection may provide prolonged survival but has not been compared to

any one modality alone

Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30

bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common

site of distant metastasis is the lung

bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type

Treatment of recurrent thyroid cancer

The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations

bull Adequate I131 uptake

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull I131 ablation

bull RT

bull Disseminated

bull I131 ablation

bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has

been reported to produce occasional objective responses usually of short

duration

Treatment of recurrent thyroid cancer

bull Inadequate I131 uptake or insensitive to I131

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull RT

bull Disseminated

bull Systemic chemotherapy

Treatment of recurrent thyroid cancer

Systemic chemotherapy

bull Doxorubicin alone

bull Cisplatin and doxorubicin (better)

bull BAP Cisplatin doxorubicin and bleomycin

bull CVD cyclophosphamide vincristine and dacarbazine

bull Dacarbazine and 5-fluorouracil

bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy

bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT

bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)

bull Improve OS and decrease RR

BAP regimenbull Schedule

bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5

bull Cell typebull Several histologic types of thyroid carcinoma responded but the

best responses were observed in medullary and anaplastic giant-cell carcinomas

bull Effectivenessbull BAP regime can achieve reasonable palliation and probably

increases survival in poor-prognosis thyroid cancers

CVD regimenbull Schedule

bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks

bull Cell typebull Medullary thyroid carcinoma

bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in

patients with advanced MTC

Dacarbazine and 5-fluorouracil

bull Schedule

bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and

12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks

Six cycles

bull Cell type

bull MTC

bull Effectiveness

bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to

have significant activity and was well tolerated

Target therapy

Take home messagesbull FNAC is not adequate for definite diagnosis of follicular

carcinomabull Because the mixed papillary-follicular variant tends to

behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis

bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer

bull Once medullary carcinoma is diagnosed familial predisposition should be checked up

bull If I131 is indicated stunning effect should be avoided

Take home messages

All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary

bull Node removal

bull Selective node removal can be performed and radical

neck dissection is usually not required

bull This results in a decreased recurrence rate but has not

been shown to improve survival

Thyroid carcinoma after lobectomy for benign lesions

I-Completion of thyroidectomy

bull gt 4 cm

bull Positive margins

bull Extra-thyroidal invasion (T3 or T4(

II- Completion of Thyroidectomy or follow

up

bull Clinically suspicious lymph node

contralateral lesion or perithyroidal node

bull Aggressive variant

bull Macroscopic multifocal disease

bull ge1 cm in diameter

III- follow up

bull Negative margins

bull No contralateral lesion

bull lt 1 cm in diameter

bull No suspicious lymph

node

POSTSURGICAL EVALUATION AFTER THYROIDECTOMY

I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +

antithyroglobulin antibodies)

II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan

Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT

bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)

Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas

Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant

Pretherapy whole body iodine scan

bullIf performed a pretherapy scan should use a low dose of 131I

(1 to 5 mCi) or 123I

bull To detect residual thyroid tissue thyroid cancer and metastatic foci

bull To reduce the potential for sublethal radiation stunning of thyroid tissue that

prevents optimal uptake of future 131I therapy

bullStunning is defined as a reduction in uptake of the 131I

therapy dose induced by a pretreatment diagnostic dose

Dose of RAI

bullThe dosing of 131I for ablation is somewhat controversial

bullLow-dose ablation with less than 30 mCi administered on

an outpatient basis

bull For low-risk young patients

bullHigh-dose ablation with100 to 200 mCi

bull For high-risk patients

bull300 mCi

bull For all patients with metastatic disease that treated with repeated

therapeutic doses of 131I

Replacement therapy

bullPostoperative treatment with exogenous thyroid hormone

in doses sufficient to suppress thyroid-stimulating hormone

(TSH) with development of thyrotoxic manifestations

decreases incidence of recurrence

bullAdministration of Thyroid Hormone

To suppress TSH and growth of any residual thyroid

To maintain patient euthyroid

o Maintain TSH level 01uUml in low risk pts

o Maintain TSH Level lt 01uUml in high risk pts

Stage III Papillary and Follicular

A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease

B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients

Stage IV Papillary and Follicular 1) Adequate uptake of I131

bull I131

1) Inadequate uptake or not sensitive to I131

i Localized lesions

1) Radiation therapy

2) Resection of limited metastases dont uptake of I131

iiDisseminated disease

1) TSH suppression with thyroxine is effective

2) Chemotherapy has been reported to produce occasional complete

responses of long duration

3) Clinical trials testing new approaches to this disease

Medullary Thyroid Cancer treatment

bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck

dissections Why

bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival

advantage

bull Radioactive iodine has no place in the treatment of patients with MTC

bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in

patients with metastatic disease

bull No single drug regimen can be considered standard

bull Some patients with distant metastases will experience prolonged survival and can

be observed until they become symptomatic

Anaplastic Thyroid Cancer bull Surgery

bull Tracheostomy is frequently necessary

bull If the disease is confined to the local area which is rare total

thyroidectomy is warranted to reduce symptoms caused by the

tumor mass

bull Radiation therapy

bull Used in patients who are not surgical candidates or whose tumor

cannot be surgically excised

Anaplastic Thyroid Cancer bull Chemotherapy

bull Produce partial remissions in some patients

bull Approximately 30 of patients achieve a partial remission with

doxorubicin

bull The combination of doxorubicin plus cisplatin appears to be more

active than doxorubicin alone and has been reported to produce

more complete responses

Treatment options under clinical evaluation

bull The combination of chemotherapy plus radiation therapy in patients following

complete resection may provide prolonged survival but has not been compared to

any one modality alone

Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30

bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common

site of distant metastasis is the lung

bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type

Treatment of recurrent thyroid cancer

The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations

bull Adequate I131 uptake

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull I131 ablation

bull RT

bull Disseminated

bull I131 ablation

bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has

been reported to produce occasional objective responses usually of short

duration

Treatment of recurrent thyroid cancer

bull Inadequate I131 uptake or insensitive to I131

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull RT

bull Disseminated

bull Systemic chemotherapy

Treatment of recurrent thyroid cancer

Systemic chemotherapy

bull Doxorubicin alone

bull Cisplatin and doxorubicin (better)

bull BAP Cisplatin doxorubicin and bleomycin

bull CVD cyclophosphamide vincristine and dacarbazine

bull Dacarbazine and 5-fluorouracil

bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy

bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT

bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)

bull Improve OS and decrease RR

BAP regimenbull Schedule

bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5

bull Cell typebull Several histologic types of thyroid carcinoma responded but the

best responses were observed in medullary and anaplastic giant-cell carcinomas

bull Effectivenessbull BAP regime can achieve reasonable palliation and probably

increases survival in poor-prognosis thyroid cancers

CVD regimenbull Schedule

bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks

bull Cell typebull Medullary thyroid carcinoma

bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in

patients with advanced MTC

Dacarbazine and 5-fluorouracil

bull Schedule

bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and

12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks

Six cycles

bull Cell type

bull MTC

bull Effectiveness

bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to

have significant activity and was well tolerated

Target therapy

Take home messagesbull FNAC is not adequate for definite diagnosis of follicular

carcinomabull Because the mixed papillary-follicular variant tends to

behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis

bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer

bull Once medullary carcinoma is diagnosed familial predisposition should be checked up

bull If I131 is indicated stunning effect should be avoided

Take home messages

All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary

Thyroid carcinoma after lobectomy for benign lesions

I-Completion of thyroidectomy

bull gt 4 cm

bull Positive margins

bull Extra-thyroidal invasion (T3 or T4(

II- Completion of Thyroidectomy or follow

up

bull Clinically suspicious lymph node

contralateral lesion or perithyroidal node

bull Aggressive variant

bull Macroscopic multifocal disease

bull ge1 cm in diameter

III- follow up

bull Negative margins

bull No contralateral lesion

bull lt 1 cm in diameter

bull No suspicious lymph

node

POSTSURGICAL EVALUATION AFTER THYROIDECTOMY

I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +

antithyroglobulin antibodies)

II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan

Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT

bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)

Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas

Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant

Pretherapy whole body iodine scan

bullIf performed a pretherapy scan should use a low dose of 131I

(1 to 5 mCi) or 123I

bull To detect residual thyroid tissue thyroid cancer and metastatic foci

bull To reduce the potential for sublethal radiation stunning of thyroid tissue that

prevents optimal uptake of future 131I therapy

bullStunning is defined as a reduction in uptake of the 131I

therapy dose induced by a pretreatment diagnostic dose

Dose of RAI

bullThe dosing of 131I for ablation is somewhat controversial

bullLow-dose ablation with less than 30 mCi administered on

an outpatient basis

bull For low-risk young patients

bullHigh-dose ablation with100 to 200 mCi

bull For high-risk patients

bull300 mCi

bull For all patients with metastatic disease that treated with repeated

therapeutic doses of 131I

Replacement therapy

bullPostoperative treatment with exogenous thyroid hormone

in doses sufficient to suppress thyroid-stimulating hormone

(TSH) with development of thyrotoxic manifestations

decreases incidence of recurrence

bullAdministration of Thyroid Hormone

To suppress TSH and growth of any residual thyroid

To maintain patient euthyroid

o Maintain TSH level 01uUml in low risk pts

o Maintain TSH Level lt 01uUml in high risk pts

Stage III Papillary and Follicular

A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease

B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients

Stage IV Papillary and Follicular 1) Adequate uptake of I131

bull I131

1) Inadequate uptake or not sensitive to I131

i Localized lesions

1) Radiation therapy

2) Resection of limited metastases dont uptake of I131

iiDisseminated disease

1) TSH suppression with thyroxine is effective

2) Chemotherapy has been reported to produce occasional complete

responses of long duration

3) Clinical trials testing new approaches to this disease

Medullary Thyroid Cancer treatment

bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck

dissections Why

bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival

advantage

bull Radioactive iodine has no place in the treatment of patients with MTC

bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in

patients with metastatic disease

bull No single drug regimen can be considered standard

bull Some patients with distant metastases will experience prolonged survival and can

be observed until they become symptomatic

Anaplastic Thyroid Cancer bull Surgery

bull Tracheostomy is frequently necessary

bull If the disease is confined to the local area which is rare total

thyroidectomy is warranted to reduce symptoms caused by the

tumor mass

bull Radiation therapy

bull Used in patients who are not surgical candidates or whose tumor

cannot be surgically excised

Anaplastic Thyroid Cancer bull Chemotherapy

bull Produce partial remissions in some patients

bull Approximately 30 of patients achieve a partial remission with

doxorubicin

bull The combination of doxorubicin plus cisplatin appears to be more

active than doxorubicin alone and has been reported to produce

more complete responses

Treatment options under clinical evaluation

bull The combination of chemotherapy plus radiation therapy in patients following

complete resection may provide prolonged survival but has not been compared to

any one modality alone

Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30

bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common

site of distant metastasis is the lung

bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type

Treatment of recurrent thyroid cancer

The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations

bull Adequate I131 uptake

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull I131 ablation

bull RT

bull Disseminated

bull I131 ablation

bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has

been reported to produce occasional objective responses usually of short

duration

Treatment of recurrent thyroid cancer

bull Inadequate I131 uptake or insensitive to I131

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull RT

bull Disseminated

bull Systemic chemotherapy

Treatment of recurrent thyroid cancer

Systemic chemotherapy

bull Doxorubicin alone

bull Cisplatin and doxorubicin (better)

bull BAP Cisplatin doxorubicin and bleomycin

bull CVD cyclophosphamide vincristine and dacarbazine

bull Dacarbazine and 5-fluorouracil

bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy

bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT

bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)

bull Improve OS and decrease RR

BAP regimenbull Schedule

bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5

bull Cell typebull Several histologic types of thyroid carcinoma responded but the

best responses were observed in medullary and anaplastic giant-cell carcinomas

bull Effectivenessbull BAP regime can achieve reasonable palliation and probably

increases survival in poor-prognosis thyroid cancers

CVD regimenbull Schedule

bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks

bull Cell typebull Medullary thyroid carcinoma

bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in

patients with advanced MTC

Dacarbazine and 5-fluorouracil

bull Schedule

bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and

12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks

Six cycles

bull Cell type

bull MTC

bull Effectiveness

bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to

have significant activity and was well tolerated

Target therapy

Take home messagesbull FNAC is not adequate for definite diagnosis of follicular

carcinomabull Because the mixed papillary-follicular variant tends to

behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis

bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer

bull Once medullary carcinoma is diagnosed familial predisposition should be checked up

bull If I131 is indicated stunning effect should be avoided

Take home messages

All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary

POSTSURGICAL EVALUATION AFTER THYROIDECTOMY

I-No gross Residual Disease in neckbull Follow up (TSH + thyroglobulin measurement +

antithyroglobulin antibodies)

II- Gross Residual Disease in neckbull Resectable gtgtgtgtgtgtgtgt Surgery bull Irresectable gtgtgtgtgtgtgtgt Total body radioiodine scan

Inadequate uptake gtgtgtgtgtgtRTAdequate uptake gtgtgtgtgt Radioiodine treatment or RTNo scan performed gtgtgtgtgtRadioiodine treatment or RT

bull Total body radioiodine scan is done after adequate TSH stimulation (thyroid withdrawal or recombinant rhTSH stimulation)

Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas

Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant

Pretherapy whole body iodine scan

bullIf performed a pretherapy scan should use a low dose of 131I

(1 to 5 mCi) or 123I

bull To detect residual thyroid tissue thyroid cancer and metastatic foci

bull To reduce the potential for sublethal radiation stunning of thyroid tissue that

prevents optimal uptake of future 131I therapy

bullStunning is defined as a reduction in uptake of the 131I

therapy dose induced by a pretreatment diagnostic dose

Dose of RAI

bullThe dosing of 131I for ablation is somewhat controversial

bullLow-dose ablation with less than 30 mCi administered on

an outpatient basis

bull For low-risk young patients

bullHigh-dose ablation with100 to 200 mCi

bull For high-risk patients

bull300 mCi

bull For all patients with metastatic disease that treated with repeated

therapeutic doses of 131I

Replacement therapy

bullPostoperative treatment with exogenous thyroid hormone

in doses sufficient to suppress thyroid-stimulating hormone

(TSH) with development of thyrotoxic manifestations

decreases incidence of recurrence

bullAdministration of Thyroid Hormone

To suppress TSH and growth of any residual thyroid

To maintain patient euthyroid

o Maintain TSH level 01uUml in low risk pts

o Maintain TSH Level lt 01uUml in high risk pts

Stage III Papillary and Follicular

A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease

B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients

Stage IV Papillary and Follicular 1) Adequate uptake of I131

bull I131

1) Inadequate uptake or not sensitive to I131

i Localized lesions

1) Radiation therapy

2) Resection of limited metastases dont uptake of I131

iiDisseminated disease

1) TSH suppression with thyroxine is effective

2) Chemotherapy has been reported to produce occasional complete

responses of long duration

3) Clinical trials testing new approaches to this disease

Medullary Thyroid Cancer treatment

bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck

dissections Why

bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival

advantage

bull Radioactive iodine has no place in the treatment of patients with MTC

bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in

patients with metastatic disease

bull No single drug regimen can be considered standard

bull Some patients with distant metastases will experience prolonged survival and can

be observed until they become symptomatic

Anaplastic Thyroid Cancer bull Surgery

bull Tracheostomy is frequently necessary

bull If the disease is confined to the local area which is rare total

thyroidectomy is warranted to reduce symptoms caused by the

tumor mass

bull Radiation therapy

bull Used in patients who are not surgical candidates or whose tumor

cannot be surgically excised

Anaplastic Thyroid Cancer bull Chemotherapy

bull Produce partial remissions in some patients

bull Approximately 30 of patients achieve a partial remission with

doxorubicin

bull The combination of doxorubicin plus cisplatin appears to be more

active than doxorubicin alone and has been reported to produce

more complete responses

Treatment options under clinical evaluation

bull The combination of chemotherapy plus radiation therapy in patients following

complete resection may provide prolonged survival but has not been compared to

any one modality alone

Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30

bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common

site of distant metastasis is the lung

bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type

Treatment of recurrent thyroid cancer

The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations

bull Adequate I131 uptake

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull I131 ablation

bull RT

bull Disseminated

bull I131 ablation

bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has

been reported to produce occasional objective responses usually of short

duration

Treatment of recurrent thyroid cancer

bull Inadequate I131 uptake or insensitive to I131

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull RT

bull Disseminated

bull Systemic chemotherapy

Treatment of recurrent thyroid cancer

Systemic chemotherapy

bull Doxorubicin alone

bull Cisplatin and doxorubicin (better)

bull BAP Cisplatin doxorubicin and bleomycin

bull CVD cyclophosphamide vincristine and dacarbazine

bull Dacarbazine and 5-fluorouracil

bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy

bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT

bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)

bull Improve OS and decrease RR

BAP regimenbull Schedule

bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5

bull Cell typebull Several histologic types of thyroid carcinoma responded but the

best responses were observed in medullary and anaplastic giant-cell carcinomas

bull Effectivenessbull BAP regime can achieve reasonable palliation and probably

increases survival in poor-prognosis thyroid cancers

CVD regimenbull Schedule

bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks

bull Cell typebull Medullary thyroid carcinoma

bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in

patients with advanced MTC

Dacarbazine and 5-fluorouracil

bull Schedule

bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and

12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks

Six cycles

bull Cell type

bull MTC

bull Effectiveness

bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to

have significant activity and was well tolerated

Target therapy

Take home messagesbull FNAC is not adequate for definite diagnosis of follicular

carcinomabull Because the mixed papillary-follicular variant tends to

behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis

bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer

bull Once medullary carcinoma is diagnosed familial predisposition should be checked up

bull If I131 is indicated stunning effect should be avoided

Take home messages

All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary

Postoberative I131 a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas

Indications (any present)bull Age lt 15 y or gt 45 ybull Radiation historybull Known distant metastasesbull Bilateral nodularitybull Extrathyroidal extensionbull Tumor gt 4 cm in diameterbull Cervical lymph node metastasesbull Aggressive variant

Pretherapy whole body iodine scan

bullIf performed a pretherapy scan should use a low dose of 131I

(1 to 5 mCi) or 123I

bull To detect residual thyroid tissue thyroid cancer and metastatic foci

bull To reduce the potential for sublethal radiation stunning of thyroid tissue that

prevents optimal uptake of future 131I therapy

bullStunning is defined as a reduction in uptake of the 131I

therapy dose induced by a pretreatment diagnostic dose

Dose of RAI

bullThe dosing of 131I for ablation is somewhat controversial

bullLow-dose ablation with less than 30 mCi administered on

an outpatient basis

bull For low-risk young patients

bullHigh-dose ablation with100 to 200 mCi

bull For high-risk patients

bull300 mCi

bull For all patients with metastatic disease that treated with repeated

therapeutic doses of 131I

Replacement therapy

bullPostoperative treatment with exogenous thyroid hormone

in doses sufficient to suppress thyroid-stimulating hormone

(TSH) with development of thyrotoxic manifestations

decreases incidence of recurrence

bullAdministration of Thyroid Hormone

To suppress TSH and growth of any residual thyroid

To maintain patient euthyroid

o Maintain TSH level 01uUml in low risk pts

o Maintain TSH Level lt 01uUml in high risk pts

Stage III Papillary and Follicular

A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease

B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients

Stage IV Papillary and Follicular 1) Adequate uptake of I131

bull I131

1) Inadequate uptake or not sensitive to I131

i Localized lesions

1) Radiation therapy

2) Resection of limited metastases dont uptake of I131

iiDisseminated disease

1) TSH suppression with thyroxine is effective

2) Chemotherapy has been reported to produce occasional complete

responses of long duration

3) Clinical trials testing new approaches to this disease

Medullary Thyroid Cancer treatment

bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck

dissections Why

bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival

advantage

bull Radioactive iodine has no place in the treatment of patients with MTC

bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in

patients with metastatic disease

bull No single drug regimen can be considered standard

bull Some patients with distant metastases will experience prolonged survival and can

be observed until they become symptomatic

Anaplastic Thyroid Cancer bull Surgery

bull Tracheostomy is frequently necessary

bull If the disease is confined to the local area which is rare total

thyroidectomy is warranted to reduce symptoms caused by the

tumor mass

bull Radiation therapy

bull Used in patients who are not surgical candidates or whose tumor

cannot be surgically excised

Anaplastic Thyroid Cancer bull Chemotherapy

bull Produce partial remissions in some patients

bull Approximately 30 of patients achieve a partial remission with

doxorubicin

bull The combination of doxorubicin plus cisplatin appears to be more

active than doxorubicin alone and has been reported to produce

more complete responses

Treatment options under clinical evaluation

bull The combination of chemotherapy plus radiation therapy in patients following

complete resection may provide prolonged survival but has not been compared to

any one modality alone

Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30

bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common

site of distant metastasis is the lung

bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type

Treatment of recurrent thyroid cancer

The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations

bull Adequate I131 uptake

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull I131 ablation

bull RT

bull Disseminated

bull I131 ablation

bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has

been reported to produce occasional objective responses usually of short

duration

Treatment of recurrent thyroid cancer

bull Inadequate I131 uptake or insensitive to I131

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull RT

bull Disseminated

bull Systemic chemotherapy

Treatment of recurrent thyroid cancer

Systemic chemotherapy

bull Doxorubicin alone

bull Cisplatin and doxorubicin (better)

bull BAP Cisplatin doxorubicin and bleomycin

bull CVD cyclophosphamide vincristine and dacarbazine

bull Dacarbazine and 5-fluorouracil

bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy

bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT

bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)

bull Improve OS and decrease RR

BAP regimenbull Schedule

bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5

bull Cell typebull Several histologic types of thyroid carcinoma responded but the

best responses were observed in medullary and anaplastic giant-cell carcinomas

bull Effectivenessbull BAP regime can achieve reasonable palliation and probably

increases survival in poor-prognosis thyroid cancers

CVD regimenbull Schedule

bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks

bull Cell typebull Medullary thyroid carcinoma

bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in

patients with advanced MTC

Dacarbazine and 5-fluorouracil

bull Schedule

bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and

12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks

Six cycles

bull Cell type

bull MTC

bull Effectiveness

bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to

have significant activity and was well tolerated

Target therapy

Take home messagesbull FNAC is not adequate for definite diagnosis of follicular

carcinomabull Because the mixed papillary-follicular variant tends to

behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis

bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer

bull Once medullary carcinoma is diagnosed familial predisposition should be checked up

bull If I131 is indicated stunning effect should be avoided

Take home messages

All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary

Pretherapy whole body iodine scan

bullIf performed a pretherapy scan should use a low dose of 131I

(1 to 5 mCi) or 123I

bull To detect residual thyroid tissue thyroid cancer and metastatic foci

bull To reduce the potential for sublethal radiation stunning of thyroid tissue that

prevents optimal uptake of future 131I therapy

bullStunning is defined as a reduction in uptake of the 131I

therapy dose induced by a pretreatment diagnostic dose

Dose of RAI

bullThe dosing of 131I for ablation is somewhat controversial

bullLow-dose ablation with less than 30 mCi administered on

an outpatient basis

bull For low-risk young patients

bullHigh-dose ablation with100 to 200 mCi

bull For high-risk patients

bull300 mCi

bull For all patients with metastatic disease that treated with repeated

therapeutic doses of 131I

Replacement therapy

bullPostoperative treatment with exogenous thyroid hormone

in doses sufficient to suppress thyroid-stimulating hormone

(TSH) with development of thyrotoxic manifestations

decreases incidence of recurrence

bullAdministration of Thyroid Hormone

To suppress TSH and growth of any residual thyroid

To maintain patient euthyroid

o Maintain TSH level 01uUml in low risk pts

o Maintain TSH Level lt 01uUml in high risk pts

Stage III Papillary and Follicular

A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease

B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients

Stage IV Papillary and Follicular 1) Adequate uptake of I131

bull I131

1) Inadequate uptake or not sensitive to I131

i Localized lesions

1) Radiation therapy

2) Resection of limited metastases dont uptake of I131

iiDisseminated disease

1) TSH suppression with thyroxine is effective

2) Chemotherapy has been reported to produce occasional complete

responses of long duration

3) Clinical trials testing new approaches to this disease

Medullary Thyroid Cancer treatment

bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck

dissections Why

bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival

advantage

bull Radioactive iodine has no place in the treatment of patients with MTC

bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in

patients with metastatic disease

bull No single drug regimen can be considered standard

bull Some patients with distant metastases will experience prolonged survival and can

be observed until they become symptomatic

Anaplastic Thyroid Cancer bull Surgery

bull Tracheostomy is frequently necessary

bull If the disease is confined to the local area which is rare total

thyroidectomy is warranted to reduce symptoms caused by the

tumor mass

bull Radiation therapy

bull Used in patients who are not surgical candidates or whose tumor

cannot be surgically excised

Anaplastic Thyroid Cancer bull Chemotherapy

bull Produce partial remissions in some patients

bull Approximately 30 of patients achieve a partial remission with

doxorubicin

bull The combination of doxorubicin plus cisplatin appears to be more

active than doxorubicin alone and has been reported to produce

more complete responses

Treatment options under clinical evaluation

bull The combination of chemotherapy plus radiation therapy in patients following

complete resection may provide prolonged survival but has not been compared to

any one modality alone

Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30

bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common

site of distant metastasis is the lung

bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type

Treatment of recurrent thyroid cancer

The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations

bull Adequate I131 uptake

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull I131 ablation

bull RT

bull Disseminated

bull I131 ablation

bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has

been reported to produce occasional objective responses usually of short

duration

Treatment of recurrent thyroid cancer

bull Inadequate I131 uptake or insensitive to I131

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull RT

bull Disseminated

bull Systemic chemotherapy

Treatment of recurrent thyroid cancer

Systemic chemotherapy

bull Doxorubicin alone

bull Cisplatin and doxorubicin (better)

bull BAP Cisplatin doxorubicin and bleomycin

bull CVD cyclophosphamide vincristine and dacarbazine

bull Dacarbazine and 5-fluorouracil

bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy

bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT

bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)

bull Improve OS and decrease RR

BAP regimenbull Schedule

bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5

bull Cell typebull Several histologic types of thyroid carcinoma responded but the

best responses were observed in medullary and anaplastic giant-cell carcinomas

bull Effectivenessbull BAP regime can achieve reasonable palliation and probably

increases survival in poor-prognosis thyroid cancers

CVD regimenbull Schedule

bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks

bull Cell typebull Medullary thyroid carcinoma

bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in

patients with advanced MTC

Dacarbazine and 5-fluorouracil

bull Schedule

bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and

12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks

Six cycles

bull Cell type

bull MTC

bull Effectiveness

bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to

have significant activity and was well tolerated

Target therapy

Take home messagesbull FNAC is not adequate for definite diagnosis of follicular

carcinomabull Because the mixed papillary-follicular variant tends to

behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis

bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer

bull Once medullary carcinoma is diagnosed familial predisposition should be checked up

bull If I131 is indicated stunning effect should be avoided

Take home messages

All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary

Dose of RAI

bullThe dosing of 131I for ablation is somewhat controversial

bullLow-dose ablation with less than 30 mCi administered on

an outpatient basis

bull For low-risk young patients

bullHigh-dose ablation with100 to 200 mCi

bull For high-risk patients

bull300 mCi

bull For all patients with metastatic disease that treated with repeated

therapeutic doses of 131I

Replacement therapy

bullPostoperative treatment with exogenous thyroid hormone

in doses sufficient to suppress thyroid-stimulating hormone

(TSH) with development of thyrotoxic manifestations

decreases incidence of recurrence

bullAdministration of Thyroid Hormone

To suppress TSH and growth of any residual thyroid

To maintain patient euthyroid

o Maintain TSH level 01uUml in low risk pts

o Maintain TSH Level lt 01uUml in high risk pts

Stage III Papillary and Follicular

A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease

B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients

Stage IV Papillary and Follicular 1) Adequate uptake of I131

bull I131

1) Inadequate uptake or not sensitive to I131

i Localized lesions

1) Radiation therapy

2) Resection of limited metastases dont uptake of I131

iiDisseminated disease

1) TSH suppression with thyroxine is effective

2) Chemotherapy has been reported to produce occasional complete

responses of long duration

3) Clinical trials testing new approaches to this disease

Medullary Thyroid Cancer treatment

bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck

dissections Why

bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival

advantage

bull Radioactive iodine has no place in the treatment of patients with MTC

bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in

patients with metastatic disease

bull No single drug regimen can be considered standard

bull Some patients with distant metastases will experience prolonged survival and can

be observed until they become symptomatic

Anaplastic Thyroid Cancer bull Surgery

bull Tracheostomy is frequently necessary

bull If the disease is confined to the local area which is rare total

thyroidectomy is warranted to reduce symptoms caused by the

tumor mass

bull Radiation therapy

bull Used in patients who are not surgical candidates or whose tumor

cannot be surgically excised

Anaplastic Thyroid Cancer bull Chemotherapy

bull Produce partial remissions in some patients

bull Approximately 30 of patients achieve a partial remission with

doxorubicin

bull The combination of doxorubicin plus cisplatin appears to be more

active than doxorubicin alone and has been reported to produce

more complete responses

Treatment options under clinical evaluation

bull The combination of chemotherapy plus radiation therapy in patients following

complete resection may provide prolonged survival but has not been compared to

any one modality alone

Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30

bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common

site of distant metastasis is the lung

bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type

Treatment of recurrent thyroid cancer

The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations

bull Adequate I131 uptake

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull I131 ablation

bull RT

bull Disseminated

bull I131 ablation

bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has

been reported to produce occasional objective responses usually of short

duration

Treatment of recurrent thyroid cancer

bull Inadequate I131 uptake or insensitive to I131

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull RT

bull Disseminated

bull Systemic chemotherapy

Treatment of recurrent thyroid cancer

Systemic chemotherapy

bull Doxorubicin alone

bull Cisplatin and doxorubicin (better)

bull BAP Cisplatin doxorubicin and bleomycin

bull CVD cyclophosphamide vincristine and dacarbazine

bull Dacarbazine and 5-fluorouracil

bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy

bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT

bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)

bull Improve OS and decrease RR

BAP regimenbull Schedule

bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5

bull Cell typebull Several histologic types of thyroid carcinoma responded but the

best responses were observed in medullary and anaplastic giant-cell carcinomas

bull Effectivenessbull BAP regime can achieve reasonable palliation and probably

increases survival in poor-prognosis thyroid cancers

CVD regimenbull Schedule

bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks

bull Cell typebull Medullary thyroid carcinoma

bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in

patients with advanced MTC

Dacarbazine and 5-fluorouracil

bull Schedule

bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and

12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks

Six cycles

bull Cell type

bull MTC

bull Effectiveness

bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to

have significant activity and was well tolerated

Target therapy

Take home messagesbull FNAC is not adequate for definite diagnosis of follicular

carcinomabull Because the mixed papillary-follicular variant tends to

behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis

bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer

bull Once medullary carcinoma is diagnosed familial predisposition should be checked up

bull If I131 is indicated stunning effect should be avoided

Take home messages

All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary

Replacement therapy

bullPostoperative treatment with exogenous thyroid hormone

in doses sufficient to suppress thyroid-stimulating hormone

(TSH) with development of thyrotoxic manifestations

decreases incidence of recurrence

bullAdministration of Thyroid Hormone

To suppress TSH and growth of any residual thyroid

To maintain patient euthyroid

o Maintain TSH level 01uUml in low risk pts

o Maintain TSH Level lt 01uUml in high risk pts

Stage III Papillary and Follicular

A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease

B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients

Stage IV Papillary and Follicular 1) Adequate uptake of I131

bull I131

1) Inadequate uptake or not sensitive to I131

i Localized lesions

1) Radiation therapy

2) Resection of limited metastases dont uptake of I131

iiDisseminated disease

1) TSH suppression with thyroxine is effective

2) Chemotherapy has been reported to produce occasional complete

responses of long duration

3) Clinical trials testing new approaches to this disease

Medullary Thyroid Cancer treatment

bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck

dissections Why

bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival

advantage

bull Radioactive iodine has no place in the treatment of patients with MTC

bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in

patients with metastatic disease

bull No single drug regimen can be considered standard

bull Some patients with distant metastases will experience prolonged survival and can

be observed until they become symptomatic

Anaplastic Thyroid Cancer bull Surgery

bull Tracheostomy is frequently necessary

bull If the disease is confined to the local area which is rare total

thyroidectomy is warranted to reduce symptoms caused by the

tumor mass

bull Radiation therapy

bull Used in patients who are not surgical candidates or whose tumor

cannot be surgically excised

Anaplastic Thyroid Cancer bull Chemotherapy

bull Produce partial remissions in some patients

bull Approximately 30 of patients achieve a partial remission with

doxorubicin

bull The combination of doxorubicin plus cisplatin appears to be more

active than doxorubicin alone and has been reported to produce

more complete responses

Treatment options under clinical evaluation

bull The combination of chemotherapy plus radiation therapy in patients following

complete resection may provide prolonged survival but has not been compared to

any one modality alone

Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30

bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common

site of distant metastasis is the lung

bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type

Treatment of recurrent thyroid cancer

The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations

bull Adequate I131 uptake

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull I131 ablation

bull RT

bull Disseminated

bull I131 ablation

bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has

been reported to produce occasional objective responses usually of short

duration

Treatment of recurrent thyroid cancer

bull Inadequate I131 uptake or insensitive to I131

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull RT

bull Disseminated

bull Systemic chemotherapy

Treatment of recurrent thyroid cancer

Systemic chemotherapy

bull Doxorubicin alone

bull Cisplatin and doxorubicin (better)

bull BAP Cisplatin doxorubicin and bleomycin

bull CVD cyclophosphamide vincristine and dacarbazine

bull Dacarbazine and 5-fluorouracil

bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy

bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT

bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)

bull Improve OS and decrease RR

BAP regimenbull Schedule

bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5

bull Cell typebull Several histologic types of thyroid carcinoma responded but the

best responses were observed in medullary and anaplastic giant-cell carcinomas

bull Effectivenessbull BAP regime can achieve reasonable palliation and probably

increases survival in poor-prognosis thyroid cancers

CVD regimenbull Schedule

bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks

bull Cell typebull Medullary thyroid carcinoma

bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in

patients with advanced MTC

Dacarbazine and 5-fluorouracil

bull Schedule

bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and

12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks

Six cycles

bull Cell type

bull MTC

bull Effectiveness

bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to

have significant activity and was well tolerated

Target therapy

Take home messagesbull FNAC is not adequate for definite diagnosis of follicular

carcinomabull Because the mixed papillary-follicular variant tends to

behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis

bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer

bull Once medullary carcinoma is diagnosed familial predisposition should be checked up

bull If I131 is indicated stunning effect should be avoided

Take home messages

All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary

Stage III Papillary and Follicular

A Surgery bullTotal thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease

B Adjuvant therapy bullI131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope bullExternal-beam radiation therapy if I131 uptake is minimalbullReplacement therapy for all patients

Stage IV Papillary and Follicular 1) Adequate uptake of I131

bull I131

1) Inadequate uptake or not sensitive to I131

i Localized lesions

1) Radiation therapy

2) Resection of limited metastases dont uptake of I131

iiDisseminated disease

1) TSH suppression with thyroxine is effective

2) Chemotherapy has been reported to produce occasional complete

responses of long duration

3) Clinical trials testing new approaches to this disease

Medullary Thyroid Cancer treatment

bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck

dissections Why

bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival

advantage

bull Radioactive iodine has no place in the treatment of patients with MTC

bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in

patients with metastatic disease

bull No single drug regimen can be considered standard

bull Some patients with distant metastases will experience prolonged survival and can

be observed until they become symptomatic

Anaplastic Thyroid Cancer bull Surgery

bull Tracheostomy is frequently necessary

bull If the disease is confined to the local area which is rare total

thyroidectomy is warranted to reduce symptoms caused by the

tumor mass

bull Radiation therapy

bull Used in patients who are not surgical candidates or whose tumor

cannot be surgically excised

Anaplastic Thyroid Cancer bull Chemotherapy

bull Produce partial remissions in some patients

bull Approximately 30 of patients achieve a partial remission with

doxorubicin

bull The combination of doxorubicin plus cisplatin appears to be more

active than doxorubicin alone and has been reported to produce

more complete responses

Treatment options under clinical evaluation

bull The combination of chemotherapy plus radiation therapy in patients following

complete resection may provide prolonged survival but has not been compared to

any one modality alone

Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30

bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common

site of distant metastasis is the lung

bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type

Treatment of recurrent thyroid cancer

The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations

bull Adequate I131 uptake

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull I131 ablation

bull RT

bull Disseminated

bull I131 ablation

bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has

been reported to produce occasional objective responses usually of short

duration

Treatment of recurrent thyroid cancer

bull Inadequate I131 uptake or insensitive to I131

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull RT

bull Disseminated

bull Systemic chemotherapy

Treatment of recurrent thyroid cancer

Systemic chemotherapy

bull Doxorubicin alone

bull Cisplatin and doxorubicin (better)

bull BAP Cisplatin doxorubicin and bleomycin

bull CVD cyclophosphamide vincristine and dacarbazine

bull Dacarbazine and 5-fluorouracil

bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy

bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT

bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)

bull Improve OS and decrease RR

BAP regimenbull Schedule

bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5

bull Cell typebull Several histologic types of thyroid carcinoma responded but the

best responses were observed in medullary and anaplastic giant-cell carcinomas

bull Effectivenessbull BAP regime can achieve reasonable palliation and probably

increases survival in poor-prognosis thyroid cancers

CVD regimenbull Schedule

bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks

bull Cell typebull Medullary thyroid carcinoma

bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in

patients with advanced MTC

Dacarbazine and 5-fluorouracil

bull Schedule

bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and

12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks

Six cycles

bull Cell type

bull MTC

bull Effectiveness

bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to

have significant activity and was well tolerated

Target therapy

Take home messagesbull FNAC is not adequate for definite diagnosis of follicular

carcinomabull Because the mixed papillary-follicular variant tends to

behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis

bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer

bull Once medullary carcinoma is diagnosed familial predisposition should be checked up

bull If I131 is indicated stunning effect should be avoided

Take home messages

All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary

Stage IV Papillary and Follicular 1) Adequate uptake of I131

bull I131

1) Inadequate uptake or not sensitive to I131

i Localized lesions

1) Radiation therapy

2) Resection of limited metastases dont uptake of I131

iiDisseminated disease

1) TSH suppression with thyroxine is effective

2) Chemotherapy has been reported to produce occasional complete

responses of long duration

3) Clinical trials testing new approaches to this disease

Medullary Thyroid Cancer treatment

bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck

dissections Why

bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival

advantage

bull Radioactive iodine has no place in the treatment of patients with MTC

bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in

patients with metastatic disease

bull No single drug regimen can be considered standard

bull Some patients with distant metastases will experience prolonged survival and can

be observed until they become symptomatic

Anaplastic Thyroid Cancer bull Surgery

bull Tracheostomy is frequently necessary

bull If the disease is confined to the local area which is rare total

thyroidectomy is warranted to reduce symptoms caused by the

tumor mass

bull Radiation therapy

bull Used in patients who are not surgical candidates or whose tumor

cannot be surgically excised

Anaplastic Thyroid Cancer bull Chemotherapy

bull Produce partial remissions in some patients

bull Approximately 30 of patients achieve a partial remission with

doxorubicin

bull The combination of doxorubicin plus cisplatin appears to be more

active than doxorubicin alone and has been reported to produce

more complete responses

Treatment options under clinical evaluation

bull The combination of chemotherapy plus radiation therapy in patients following

complete resection may provide prolonged survival but has not been compared to

any one modality alone

Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30

bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common

site of distant metastasis is the lung

bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type

Treatment of recurrent thyroid cancer

The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations

bull Adequate I131 uptake

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull I131 ablation

bull RT

bull Disseminated

bull I131 ablation

bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has

been reported to produce occasional objective responses usually of short

duration

Treatment of recurrent thyroid cancer

bull Inadequate I131 uptake or insensitive to I131

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull RT

bull Disseminated

bull Systemic chemotherapy

Treatment of recurrent thyroid cancer

Systemic chemotherapy

bull Doxorubicin alone

bull Cisplatin and doxorubicin (better)

bull BAP Cisplatin doxorubicin and bleomycin

bull CVD cyclophosphamide vincristine and dacarbazine

bull Dacarbazine and 5-fluorouracil

bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy

bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT

bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)

bull Improve OS and decrease RR

BAP regimenbull Schedule

bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5

bull Cell typebull Several histologic types of thyroid carcinoma responded but the

best responses were observed in medullary and anaplastic giant-cell carcinomas

bull Effectivenessbull BAP regime can achieve reasonable palliation and probably

increases survival in poor-prognosis thyroid cancers

CVD regimenbull Schedule

bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks

bull Cell typebull Medullary thyroid carcinoma

bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in

patients with advanced MTC

Dacarbazine and 5-fluorouracil

bull Schedule

bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and

12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks

Six cycles

bull Cell type

bull MTC

bull Effectiveness

bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to

have significant activity and was well tolerated

Target therapy

Take home messagesbull FNAC is not adequate for definite diagnosis of follicular

carcinomabull Because the mixed papillary-follicular variant tends to

behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis

bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer

bull Once medullary carcinoma is diagnosed familial predisposition should be checked up

bull If I131 is indicated stunning effect should be avoided

Take home messages

All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary

Medullary Thyroid Cancer treatment

bull Thyroidectomy bull total thyroidectomy + routine central and bilateral modified neck

dissections Why

bull External radiation therapy bull palliation of locally recurrent tumors without evidence that it provides any survival

advantage

bull Radioactive iodine has no place in the treatment of patients with MTC

bull Palliative chemotherapy bull Palliative chemotherapy has been reported to produce occasional responses in

patients with metastatic disease

bull No single drug regimen can be considered standard

bull Some patients with distant metastases will experience prolonged survival and can

be observed until they become symptomatic

Anaplastic Thyroid Cancer bull Surgery

bull Tracheostomy is frequently necessary

bull If the disease is confined to the local area which is rare total

thyroidectomy is warranted to reduce symptoms caused by the

tumor mass

bull Radiation therapy

bull Used in patients who are not surgical candidates or whose tumor

cannot be surgically excised

Anaplastic Thyroid Cancer bull Chemotherapy

bull Produce partial remissions in some patients

bull Approximately 30 of patients achieve a partial remission with

doxorubicin

bull The combination of doxorubicin plus cisplatin appears to be more

active than doxorubicin alone and has been reported to produce

more complete responses

Treatment options under clinical evaluation

bull The combination of chemotherapy plus radiation therapy in patients following

complete resection may provide prolonged survival but has not been compared to

any one modality alone

Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30

bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common

site of distant metastasis is the lung

bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type

Treatment of recurrent thyroid cancer

The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations

bull Adequate I131 uptake

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull I131 ablation

bull RT

bull Disseminated

bull I131 ablation

bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has

been reported to produce occasional objective responses usually of short

duration

Treatment of recurrent thyroid cancer

bull Inadequate I131 uptake or insensitive to I131

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull RT

bull Disseminated

bull Systemic chemotherapy

Treatment of recurrent thyroid cancer

Systemic chemotherapy

bull Doxorubicin alone

bull Cisplatin and doxorubicin (better)

bull BAP Cisplatin doxorubicin and bleomycin

bull CVD cyclophosphamide vincristine and dacarbazine

bull Dacarbazine and 5-fluorouracil

bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy

bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT

bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)

bull Improve OS and decrease RR

BAP regimenbull Schedule

bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5

bull Cell typebull Several histologic types of thyroid carcinoma responded but the

best responses were observed in medullary and anaplastic giant-cell carcinomas

bull Effectivenessbull BAP regime can achieve reasonable palliation and probably

increases survival in poor-prognosis thyroid cancers

CVD regimenbull Schedule

bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks

bull Cell typebull Medullary thyroid carcinoma

bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in

patients with advanced MTC

Dacarbazine and 5-fluorouracil

bull Schedule

bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and

12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks

Six cycles

bull Cell type

bull MTC

bull Effectiveness

bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to

have significant activity and was well tolerated

Target therapy

Take home messagesbull FNAC is not adequate for definite diagnosis of follicular

carcinomabull Because the mixed papillary-follicular variant tends to

behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis

bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer

bull Once medullary carcinoma is diagnosed familial predisposition should be checked up

bull If I131 is indicated stunning effect should be avoided

Take home messages

All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary

Anaplastic Thyroid Cancer bull Surgery

bull Tracheostomy is frequently necessary

bull If the disease is confined to the local area which is rare total

thyroidectomy is warranted to reduce symptoms caused by the

tumor mass

bull Radiation therapy

bull Used in patients who are not surgical candidates or whose tumor

cannot be surgically excised

Anaplastic Thyroid Cancer bull Chemotherapy

bull Produce partial remissions in some patients

bull Approximately 30 of patients achieve a partial remission with

doxorubicin

bull The combination of doxorubicin plus cisplatin appears to be more

active than doxorubicin alone and has been reported to produce

more complete responses

Treatment options under clinical evaluation

bull The combination of chemotherapy plus radiation therapy in patients following

complete resection may provide prolonged survival but has not been compared to

any one modality alone

Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30

bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common

site of distant metastasis is the lung

bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type

Treatment of recurrent thyroid cancer

The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations

bull Adequate I131 uptake

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull I131 ablation

bull RT

bull Disseminated

bull I131 ablation

bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has

been reported to produce occasional objective responses usually of short

duration

Treatment of recurrent thyroid cancer

bull Inadequate I131 uptake or insensitive to I131

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull RT

bull Disseminated

bull Systemic chemotherapy

Treatment of recurrent thyroid cancer

Systemic chemotherapy

bull Doxorubicin alone

bull Cisplatin and doxorubicin (better)

bull BAP Cisplatin doxorubicin and bleomycin

bull CVD cyclophosphamide vincristine and dacarbazine

bull Dacarbazine and 5-fluorouracil

bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy

bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT

bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)

bull Improve OS and decrease RR

BAP regimenbull Schedule

bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5

bull Cell typebull Several histologic types of thyroid carcinoma responded but the

best responses were observed in medullary and anaplastic giant-cell carcinomas

bull Effectivenessbull BAP regime can achieve reasonable palliation and probably

increases survival in poor-prognosis thyroid cancers

CVD regimenbull Schedule

bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks

bull Cell typebull Medullary thyroid carcinoma

bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in

patients with advanced MTC

Dacarbazine and 5-fluorouracil

bull Schedule

bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and

12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks

Six cycles

bull Cell type

bull MTC

bull Effectiveness

bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to

have significant activity and was well tolerated

Target therapy

Take home messagesbull FNAC is not adequate for definite diagnosis of follicular

carcinomabull Because the mixed papillary-follicular variant tends to

behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis

bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer

bull Once medullary carcinoma is diagnosed familial predisposition should be checked up

bull If I131 is indicated stunning effect should be avoided

Take home messages

All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary

Anaplastic Thyroid Cancer bull Chemotherapy

bull Produce partial remissions in some patients

bull Approximately 30 of patients achieve a partial remission with

doxorubicin

bull The combination of doxorubicin plus cisplatin appears to be more

active than doxorubicin alone and has been reported to produce

more complete responses

Treatment options under clinical evaluation

bull The combination of chemotherapy plus radiation therapy in patients following

complete resection may provide prolonged survival but has not been compared to

any one modality alone

Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30

bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common

site of distant metastasis is the lung

bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type

Treatment of recurrent thyroid cancer

The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations

bull Adequate I131 uptake

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull I131 ablation

bull RT

bull Disseminated

bull I131 ablation

bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has

been reported to produce occasional objective responses usually of short

duration

Treatment of recurrent thyroid cancer

bull Inadequate I131 uptake or insensitive to I131

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull RT

bull Disseminated

bull Systemic chemotherapy

Treatment of recurrent thyroid cancer

Systemic chemotherapy

bull Doxorubicin alone

bull Cisplatin and doxorubicin (better)

bull BAP Cisplatin doxorubicin and bleomycin

bull CVD cyclophosphamide vincristine and dacarbazine

bull Dacarbazine and 5-fluorouracil

bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy

bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT

bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)

bull Improve OS and decrease RR

BAP regimenbull Schedule

bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5

bull Cell typebull Several histologic types of thyroid carcinoma responded but the

best responses were observed in medullary and anaplastic giant-cell carcinomas

bull Effectivenessbull BAP regime can achieve reasonable palliation and probably

increases survival in poor-prognosis thyroid cancers

CVD regimenbull Schedule

bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks

bull Cell typebull Medullary thyroid carcinoma

bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in

patients with advanced MTC

Dacarbazine and 5-fluorouracil

bull Schedule

bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and

12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks

Six cycles

bull Cell type

bull MTC

bull Effectiveness

bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to

have significant activity and was well tolerated

Target therapy

Take home messagesbull FNAC is not adequate for definite diagnosis of follicular

carcinomabull Because the mixed papillary-follicular variant tends to

behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis

bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer

bull Once medullary carcinoma is diagnosed familial predisposition should be checked up

bull If I131 is indicated stunning effect should be avoided

Take home messages

All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary

Recurrent Thyroid Cancer bull Recurrence rate for differentiated thyroidis about 10-30

bull 80 develop recurrence with disease in the neck alone andbull 20 develop recurrence with distant metastases The most common

site of distant metastasis is the lung

bull The prognosis for patients with clinically detectable recurrences is generally poor regardless of cell type

Treatment of recurrent thyroid cancer

The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations

bull Adequate I131 uptake

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull I131 ablation

bull RT

bull Disseminated

bull I131 ablation

bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has

been reported to produce occasional objective responses usually of short

duration

Treatment of recurrent thyroid cancer

bull Inadequate I131 uptake or insensitive to I131

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull RT

bull Disseminated

bull Systemic chemotherapy

Treatment of recurrent thyroid cancer

Systemic chemotherapy

bull Doxorubicin alone

bull Cisplatin and doxorubicin (better)

bull BAP Cisplatin doxorubicin and bleomycin

bull CVD cyclophosphamide vincristine and dacarbazine

bull Dacarbazine and 5-fluorouracil

bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy

bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT

bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)

bull Improve OS and decrease RR

BAP regimenbull Schedule

bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5

bull Cell typebull Several histologic types of thyroid carcinoma responded but the

best responses were observed in medullary and anaplastic giant-cell carcinomas

bull Effectivenessbull BAP regime can achieve reasonable palliation and probably

increases survival in poor-prognosis thyroid cancers

CVD regimenbull Schedule

bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks

bull Cell typebull Medullary thyroid carcinoma

bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in

patients with advanced MTC

Dacarbazine and 5-fluorouracil

bull Schedule

bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and

12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks

Six cycles

bull Cell type

bull MTC

bull Effectiveness

bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to

have significant activity and was well tolerated

Target therapy

Take home messagesbull FNAC is not adequate for definite diagnosis of follicular

carcinomabull Because the mixed papillary-follicular variant tends to

behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis

bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer

bull Once medullary carcinoma is diagnosed familial predisposition should be checked up

bull If I131 is indicated stunning effect should be avoided

Take home messages

All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary

Treatment of recurrent thyroid cancer

The selection of further treatment depends on many factors including Cell type Uptake of I131 Prior treatment Site of recurrence Individual patient considerations

bull Adequate I131 uptake

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull I131 ablation

bull RT

bull Disseminated

bull I131 ablation

bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has

been reported to produce occasional objective responses usually of short

duration

Treatment of recurrent thyroid cancer

bull Inadequate I131 uptake or insensitive to I131

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull RT

bull Disseminated

bull Systemic chemotherapy

Treatment of recurrent thyroid cancer

Systemic chemotherapy

bull Doxorubicin alone

bull Cisplatin and doxorubicin (better)

bull BAP Cisplatin doxorubicin and bleomycin

bull CVD cyclophosphamide vincristine and dacarbazine

bull Dacarbazine and 5-fluorouracil

bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy

bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT

bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)

bull Improve OS and decrease RR

BAP regimenbull Schedule

bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5

bull Cell typebull Several histologic types of thyroid carcinoma responded but the

best responses were observed in medullary and anaplastic giant-cell carcinomas

bull Effectivenessbull BAP regime can achieve reasonable palliation and probably

increases survival in poor-prognosis thyroid cancers

CVD regimenbull Schedule

bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks

bull Cell typebull Medullary thyroid carcinoma

bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in

patients with advanced MTC

Dacarbazine and 5-fluorouracil

bull Schedule

bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and

12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks

Six cycles

bull Cell type

bull MTC

bull Effectiveness

bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to

have significant activity and was well tolerated

Target therapy

Take home messagesbull FNAC is not adequate for definite diagnosis of follicular

carcinomabull Because the mixed papillary-follicular variant tends to

behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis

bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer

bull Once medullary carcinoma is diagnosed familial predisposition should be checked up

bull If I131 is indicated stunning effect should be avoided

Take home messages

All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary

bull Adequate I131 uptake

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull I131 ablation

bull RT

bull Disseminated

bull I131 ablation

bull Systemic chemotherapy for tumor not sensitive to I131 Chemotherapy has

been reported to produce occasional objective responses usually of short

duration

Treatment of recurrent thyroid cancer

bull Inadequate I131 uptake or insensitive to I131

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull RT

bull Disseminated

bull Systemic chemotherapy

Treatment of recurrent thyroid cancer

Systemic chemotherapy

bull Doxorubicin alone

bull Cisplatin and doxorubicin (better)

bull BAP Cisplatin doxorubicin and bleomycin

bull CVD cyclophosphamide vincristine and dacarbazine

bull Dacarbazine and 5-fluorouracil

bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy

bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT

bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)

bull Improve OS and decrease RR

BAP regimenbull Schedule

bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5

bull Cell typebull Several histologic types of thyroid carcinoma responded but the

best responses were observed in medullary and anaplastic giant-cell carcinomas

bull Effectivenessbull BAP regime can achieve reasonable palliation and probably

increases survival in poor-prognosis thyroid cancers

CVD regimenbull Schedule

bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks

bull Cell typebull Medullary thyroid carcinoma

bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in

patients with advanced MTC

Dacarbazine and 5-fluorouracil

bull Schedule

bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and

12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks

Six cycles

bull Cell type

bull MTC

bull Effectiveness

bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to

have significant activity and was well tolerated

Target therapy

Take home messagesbull FNAC is not adequate for definite diagnosis of follicular

carcinomabull Because the mixed papillary-follicular variant tends to

behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis

bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer

bull Once medullary carcinoma is diagnosed familial predisposition should be checked up

bull If I131 is indicated stunning effect should be avoided

Take home messages

All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary

bull Inadequate I131 uptake or insensitive to I131

bull Localized

bull Surgery with or without I131 ablation can be useful in controlling local

recurrences regional node metastases or occasionally metastases at other

localized sites

bull RT

bull Disseminated

bull Systemic chemotherapy

Treatment of recurrent thyroid cancer

Systemic chemotherapy

bull Doxorubicin alone

bull Cisplatin and doxorubicin (better)

bull BAP Cisplatin doxorubicin and bleomycin

bull CVD cyclophosphamide vincristine and dacarbazine

bull Dacarbazine and 5-fluorouracil

bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy

bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT

bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)

bull Improve OS and decrease RR

BAP regimenbull Schedule

bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5

bull Cell typebull Several histologic types of thyroid carcinoma responded but the

best responses were observed in medullary and anaplastic giant-cell carcinomas

bull Effectivenessbull BAP regime can achieve reasonable palliation and probably

increases survival in poor-prognosis thyroid cancers

CVD regimenbull Schedule

bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks

bull Cell typebull Medullary thyroid carcinoma

bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in

patients with advanced MTC

Dacarbazine and 5-fluorouracil

bull Schedule

bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and

12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks

Six cycles

bull Cell type

bull MTC

bull Effectiveness

bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to

have significant activity and was well tolerated

Target therapy

Take home messagesbull FNAC is not adequate for definite diagnosis of follicular

carcinomabull Because the mixed papillary-follicular variant tends to

behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis

bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer

bull Once medullary carcinoma is diagnosed familial predisposition should be checked up

bull If I131 is indicated stunning effect should be avoided

Take home messages

All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary

Systemic chemotherapy

bull Doxorubicin alone

bull Cisplatin and doxorubicin (better)

bull BAP Cisplatin doxorubicin and bleomycin

bull CVD cyclophosphamide vincristine and dacarbazine

bull Dacarbazine and 5-fluorouracil

bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy

bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT

bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)

bull Improve OS and decrease RR

BAP regimenbull Schedule

bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5

bull Cell typebull Several histologic types of thyroid carcinoma responded but the

best responses were observed in medullary and anaplastic giant-cell carcinomas

bull Effectivenessbull BAP regime can achieve reasonable palliation and probably

increases survival in poor-prognosis thyroid cancers

CVD regimenbull Schedule

bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks

bull Cell typebull Medullary thyroid carcinoma

bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in

patients with advanced MTC

Dacarbazine and 5-fluorouracil

bull Schedule

bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and

12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks

Six cycles

bull Cell type

bull MTC

bull Effectiveness

bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to

have significant activity and was well tolerated

Target therapy

Take home messagesbull FNAC is not adequate for definite diagnosis of follicular

carcinomabull Because the mixed papillary-follicular variant tends to

behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis

bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer

bull Once medullary carcinoma is diagnosed familial predisposition should be checked up

bull If I131 is indicated stunning effect should be avoided

Take home messages

All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary

bull Combined treatment of anaplastic thyroid carcinoma with surgery chemotherapy and hyperfractionated accelerated external radiotherapy

bull Two cycles of doxorubicin (60 mgm(2)) and cisplatin (120 mgm(2)) were delivered before RT and four cycles after RT

bull RT consisted of two daily fractions of 125 Gy 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum)

bull Improve OS and decrease RR

BAP regimenbull Schedule

bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5

bull Cell typebull Several histologic types of thyroid carcinoma responded but the

best responses were observed in medullary and anaplastic giant-cell carcinomas

bull Effectivenessbull BAP regime can achieve reasonable palliation and probably

increases survival in poor-prognosis thyroid cancers

CVD regimenbull Schedule

bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks

bull Cell typebull Medullary thyroid carcinoma

bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in

patients with advanced MTC

Dacarbazine and 5-fluorouracil

bull Schedule

bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and

12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks

Six cycles

bull Cell type

bull MTC

bull Effectiveness

bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to

have significant activity and was well tolerated

Target therapy

Take home messagesbull FNAC is not adequate for definite diagnosis of follicular

carcinomabull Because the mixed papillary-follicular variant tends to

behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis

bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer

bull Once medullary carcinoma is diagnosed familial predisposition should be checked up

bull If I131 is indicated stunning effect should be avoided

Take home messages

All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary

BAP regimenbull Schedule

bull BAP regimen which consisted of bleomycin (B) 30 mg a day for three days adriamycin (A) 60 mgm2 iv in day 5 and cisplatinum (P) 60 to mgm2 iv in day 5

bull Cell typebull Several histologic types of thyroid carcinoma responded but the

best responses were observed in medullary and anaplastic giant-cell carcinomas

bull Effectivenessbull BAP regime can achieve reasonable palliation and probably

increases survival in poor-prognosis thyroid cancers

CVD regimenbull Schedule

bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks

bull Cell typebull Medullary thyroid carcinoma

bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in

patients with advanced MTC

Dacarbazine and 5-fluorouracil

bull Schedule

bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and

12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks

Six cycles

bull Cell type

bull MTC

bull Effectiveness

bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to

have significant activity and was well tolerated

Target therapy

Take home messagesbull FNAC is not adequate for definite diagnosis of follicular

carcinomabull Because the mixed papillary-follicular variant tends to

behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis

bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer

bull Once medullary carcinoma is diagnosed familial predisposition should be checked up

bull If I131 is indicated stunning effect should be avoided

Take home messages

All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary

CVD regimenbull Schedule

bull cyclophosphamide (750 mgm2) vincristine (14 mgm2) and dacarbazine (600 mgm2 daily for 2 days in each cycle) every 3 weeks

bull Cell typebull Medullary thyroid carcinoma

bull Effecetivenessbull CVD chemotherapy has moderate activity and is well tolerated in

patients with advanced MTC

Dacarbazine and 5-fluorouracil

bull Schedule

bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and

12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks

Six cycles

bull Cell type

bull MTC

bull Effectiveness

bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to

have significant activity and was well tolerated

Target therapy

Take home messagesbull FNAC is not adequate for definite diagnosis of follicular

carcinomabull Because the mixed papillary-follicular variant tends to

behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis

bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer

bull Once medullary carcinoma is diagnosed familial predisposition should be checked up

bull If I131 is indicated stunning effect should be avoided

Take home messages

All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary

Dacarbazine and 5-fluorouracil

bull Schedule

bull 5 day intravenous courses of dacarbazine (DTIC) (250 mgsqm) and

12 hour infusion 5-fluorouracil (450 mgsqm) given every 4 weeks

Six cycles

bull Cell type

bull MTC

bull Effectiveness

bull Treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to

have significant activity and was well tolerated

Target therapy

Take home messagesbull FNAC is not adequate for definite diagnosis of follicular

carcinomabull Because the mixed papillary-follicular variant tends to

behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis

bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer

bull Once medullary carcinoma is diagnosed familial predisposition should be checked up

bull If I131 is indicated stunning effect should be avoided

Take home messages

All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary

Target therapy

Take home messagesbull FNAC is not adequate for definite diagnosis of follicular

carcinomabull Because the mixed papillary-follicular variant tends to

behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis

bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer

bull Once medullary carcinoma is diagnosed familial predisposition should be checked up

bull If I131 is indicated stunning effect should be avoided

Take home messages

All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary

Take home messagesbull FNAC is not adequate for definite diagnosis of follicular

carcinomabull Because the mixed papillary-follicular variant tends to

behave like a pure papillary cancer it is treated in the same manner and has a similar prognosis

bull Thyroglobulin as a marker of follow up is useful only in absence of any thyroid tissue in differentiated thyroid cancer

bull Once medullary carcinoma is diagnosed familial predisposition should be checked up

bull If I131 is indicated stunning effect should be avoided

Take home messages

All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary

Take home messages

All except rulebullAll risk factors of differentiated thyroid cancers are not established except RadiotherapybullAll types are caused by RT except medullarybullAll types commonly occur before age of 50y except anaplasticbullAll types are commoner in females than in males except anaplastic (M gt F) and familial MTC (M=F)bullAll types rarely associated with genetic syndrome except medullary