03/12/2019

1

Oxford

Endocrine Surgery

Management of thyroid cancer

- progress, hopes, challenges -

Radu Mihai MD PhD FRCS

Consultant Surgeon, Honorary Senior Clinical Lecturer

Department of Endocrine Surgery, Churchill Cancer Centre, Oxford, UK

Nuffield Department of Surgical Sciences, Oxford University, UK

Sobel House, 22nd November 2019

Oxford

Endocrine Surgery

two setons were inserted at right angles, with the help of a hot iron, and manipulated towards the surface twice daily until they had cut through the flesh

1170, Roger Frugardi Italian School of Salerno .. the first thyroidectomy using scalpels …the

patient died and the surgeon was imprisoned 1646, Wilhelm Fabricus

The French Academy of Medicine condemns any operative procedures on the thyroid gland

19th century

“No honest and sensible surgeons would ever engage in it!”

1866, Samuel David Gross, USA

… setons … jail sentence … prohibited

03/12/2019

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Oxford

Endocrine Surgery

History of thyroid surgery

Misadventures Experimental procedures

Anatomical knowledge

Functional relationships

Bootlaces

Wires

Ligation of

superior

thyroid artery

Theodor Kocher

Crille doctrine

‘never see the nerve’

Lahey: ‘always see the nerve’

Voice studies

Nerve monitoring

1st-16th century 18-19th century 20th century 21st century

Oxford

Endocrine Surgery

Outside the UK the world of thyroid surgery is changing

MIVAT – minimally invasive video-assisted

Periareolar approach

Face-lift approach

R

O

B

O

T

I

C

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Oxford

Endocrine Surgery

Trans-oral thyroidectomy

Oxford

Endocrine Surgery

WHO ?

03/12/2019

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Oxford

Endocrine Surgery

Thyroid surgery in USA

• 5860 Maryland patients ‘91-’96:

“non-expert” surgeons do 86% of thyroid surgery

Udelsman Ann Surg 1998

• 57,000 National Inpatient Sample 88-2000:

– “non-expert” surgeons do 82% thyroid surgery

– In USA 50% patients undergoing thyroid surgery have it done

by surgeons doing less than 5/year

Gauger Surgery 2003

Oxford

Endocrine Surgery

UK - HES data: Activity volume patterns

03/12/2019

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Oxford

Endocrine Surgery

Surgery for TC in centers with >20-50 thyroidectomies /yr

Oxford

Endocrine Surgery

Thyroid Cancer

1% of all cancers, 0.5% of all cancer deaths

Poorly differentiated TC

Anaplastic TC

Papillary

TC

Follicular

TC

Medullary TC

1959 Hazar J et al. Medulary (solid) carcinoma

of the thyroid - a clinicopathologic entity

03/12/2019

6

Oxford

Endocrine Surgery

Thyroid cancer – an increasing incidence

80%

85%

90%

95%

100%

> 1-yr > 5-yrs > 10-yrs

Overall survival

Oxford

Endocrine Surgery

A spectrum of disease

Micropapillary thyroid cancers

< 1cm

majority of patients

Clinically-apparent TC

respond very well to surgery

and I131 ablation

10% of TC recur within 10 years

after initial treatment

Should all incidental PTC

be operated ?

Dynamic risk stratification

based on initial response

to therapy

How to predict ?

How to diagnose?

What treatment is available?

What is the impact on survival?

Current debates

03/12/2019

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Oxford

Endocrine Surgery

Risk-adapted treatment for TC

• Extent of surgery

• Use of RIA

• Need for TSH suppression

• Follow-up recommendations

High-intensity treatment

Upfront aggressive treatment

and early detection of small

volume residual disease would

lead to improved outcomes

Low intensity treatment paradigm

• Low risk TC have excellent prognosis,

disease-specific survival 99%

• Delayed intervention is effective and has

no impact on disease-specific survival

• Early detection of small volume primary

tumours or residual disease has little

clinical benefit

Cultural differences, personal views, patients’ views

Oxford

Endocrine Surgery

Low-risk papillary microcarcinomas

• Definition: ≤1cm , irrespective of and high-risk features (e.g. LN mets)

• Autopsies studies showed PMC 3-10 mm in up to 5%

• Korea: incidence of TC increase 15 folds (US screening)

Active surveillance (Japan data)

• Patients asked what option they prefer but clinicians offer surveillance as first-line

• US at 6 months and yearly afterwards

• 2014 report: over 1200 patients

• Tumour size enlargement in 8%

• Appearance of LN mets in 4%

• TSH values not linked to progression

• PMC in young patient more likely to progress

Japan: diagnose small

nodules but offer

surveillance only

ATA 2015 guidelines:

discourage FNA for nodules <10 mm

TR5 nodules: biopsy of >10 mm and FU if >5 mm

vs.

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Oxford

Endocrine Surgery

Similar finding reported from the western world

Tuttle M, et al JAMA Otolaryngol Head Neck Surg.2017;143(10):1015-102

291 patients

• PTC (Bethesda category VI), or

• suspicious for PTC (Bethesda category V)

• suspicious ultrasonographic characteristics

• Tumor size 15 mm or less in max dimension

Patients younger than 50years at diagnosis had

an early 5-fold likelihood of experiencing tumour

growth compared with patients 50 years or older

(27.3% vs 4.6% at 5 years; HR, 4.5; 95% CI, 1.2-17.0; P=.03)

Oxford

Endocrine Surgery

Management of micro PTC in UK in 2020

• No database, no published series

• No consensus

• Likely to be (very) variable

• Not part of the current ‘conversation’

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Oxford

Endocrine Surgery

Reducing the intensity of treatment for low-risk tumours

• No surgery for tumours <1 cm

• Less extensive surgery

(lobectomy vs. total thyroidectomy for tumours <4cm)

• Less radioactive iodine ablation

• Shorter follow-up based on dynamic risk stratification

Oxford

Endocrine Surgery

Total thyroidectomy

for all cancers

> 1 cm

Lobectomy for

low risk cancers

Thyroid cancers - Guidelines

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Oxford

Endocrine Surgery

2

Extent of Surgery for Papillary Thyroid Cancer Is Not Associated With Survival: An Analysis of 61,775 Patients. Adam M, Pura J, Gu L, Dinan M, Tyler D, Reed S, Scheri R, Roman S, Sosa J; Annals of Surgery. 260(4):601-607, October 2014.

Population studies – National Cancer Database, US, 1998-2011

61775 patients with tumours < 4cm

Lobectomy 11% (6849)

TT 89% (54,926)

Median FU 7 years (5-15 yrs)

No difference in overall survival

No significant difference for tumours up to 4 cm

Oxford

Endocrine Surgery

IJ. Nixon , I Ganly , SG. Patel , FL. Palmer , MM. Whitcher ,

RM. Tuttle , A Shaha. Thyroid lobectomy for treatment of well

differentiated intrathyroid malignancy Surgery, 2012, 151(4) 571-9

Memorial Sloan Kettering, 1986-2005 Lobectomy Total

thyroidectomy

N=361 N=528

pT1

PT2

69%

31%

73%

27%

10 years

Local recurrence

Neck recurrence

Distant recurrence

0

0

0

0

0.8%

3%

Low risk Intermediate

risk

High risk

<45 years

pT1/pT2

>45 years

pT3/pT4

Distant metastases

High grade tumours

Lobectomy Case-by-case

decision

Total thyroidectomy

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Oxford

Endocrine Surgery

Cause-specific survival (%) Disease-free survival (%)

Ebina A, et al. Surgery, 2014, 156(6):1579 - 89

Japan – redefining risk groups

Nippon Medical School, Tokyo

1993-2010

1187 patients, PTC, >1cm

High risk

Distant metastases

>50 years with

Massive extrathyroidal invasion

Large LN mets (>3cm) 967 (82%) low risk patients

Risk of recurrence: Age > 60, Tumour > 3 cm, LNM > 2 cm

Oxford

Endocrine Surgery

Thames Valley Thyroid MDT 2015-2019 early adoption of lobectomy-only

BAETS 2019 meeting – poster presentation

2015-2018, 300 patients offered lobectomy

Thy 2 Thy 3a Thy 3F Thy 4 Thy 5

66%

34%

No Completion Completion thyroidectomy

Malignancy in completetion specimen No cases would indicate further treatment

Benign Malignant

0

10

20

30

40

50

60

70

THY3A THY3F THY4 THY5

lobectomy

TT

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Oxford

Endocrine Surgery

World-wide trend in reducing the use of radioactive iodine

Oxford

Endocrine Surgery

Goals of RIA in treatment of TC

Remnant ablation Destroy normal thyroid

tissue remaining after TT

Improve initial staging,

facilitate high sensitivity FU

Adjuvant treatment Destroy subclinical

microscopic tumour

deposits

Decrease recurrence,

increase survival

Treatment of known

residual or

recurrent disease

Destroy known

residual/recurrent disease

Remission, improve

progression-free survival

Limitations

• Lack of randomized trials (IoN ongoing)

• Definition of ‘low-risk’ variable

• Negative outcome/events are rare, can occur decades after diagnosis

• Current info based on previous cohorts treated at the time when imaging was of

lower quality and TG measurements were less sensitive

03/12/2019

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Oxford

Endocrine Surgery

Methods

2000-2014 416 patients underwent RIA following thyroid surgery

A prospective database recorded details of patients treated for thyroid

cancer in a tertiary referral centre.

Oxford

Endocrine Surgery

Methods

2000-2014

290 patients had TG measured BEFORE I131 administration

Immediate

outcome analysis I* cervical uptake

I123 uptake 5 months after ablation

A prospective database recorded details of patients treated for thyroid

cancer in a tertiary referral centre.

416 patients underwent RIA following thyroid surgery

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Oxford

Endocrine Surgery

Methods

2000-2014

290 patients had TG measured BEFORE I131 administration

Disease-free Unmeasurable TG

Biochemical

evidence of

disease

Raising TG / normal

radiological assessment

Radiological

evidence of

disease

High TG, positive cross-

sectional imaging or I*uptake

Final outcome

Immediate

outcome analysis I* cervical uptake

I123 uptake 5 months after ablation

416 patients underwent RIA following thyroid surgery

A prospective database recorded details of patients treated for thyroid

cancer in a tertiary referral centre.

Oxford

Endocrine Surgery

Pre-ablation stimulated thyroglobulin

0.1

1

10

100

1000

10000

100000

0 25 50 75 100 125 150

Se

rum

th

yro

glo

bu

lin

(n

g/m

L)

Serum TSH (mU/L)

Undetectable TG

116/290 (40%)

<5 ng/mL (before Sept 2012): 99/227 (44%)

<0.2 ng/mL (after Sept 2012): 17/63 (27%)

Very low TG (0.2-5 ng/mL)

21/63 (33%)

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Oxford

Endocrine Surgery

Sumarry

• At least a third of patients operated for well-differentiated thyroid

carcinoma have unmeasurable stimulated-TG hence they could be

spared radioactive iodine ablation and offered long term monitoring.

• Selection for radioactive iodine ablation relying on risk stratification

based on postoperative sTG could/should be the basis of a multicentre

randomized trial.

Oxford

Endocrine Surgery

TT + central compartment + lateral radical neck dissection

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Oxford

Endocrine Surgery

Radical neck dissection for thyroid cancer

0

10

20

30

40

50

1 11 21 31 41 51 61 71 81

LN-ve LN+ve

Index patient

Lym

ph n

ode y

ield

50 31

F M

Papillary (n=74)

Follicular (n=3)

Anaplastic (n=4)

unilateral(n=73) or

bilateral (n=8)

age 16-90 yrs

(median 56 yrs)

At the time of presentation

(n=62) or at median 3-years

after initial treatment.

Oxford

Endocrine Surgery

Radical neck dissection for thyroid cancer

0

10

20

30

40

50

1 11 21 31 41 51 61 71 81

LN-ve LN+ve

Index patient

Lym

ph n

ode y

ield

50 31

F M

Papillary (n=74)

Follicular (n=3)

Anaplastic (n=4)

unilateral(n=73) or

bilateral (n=8)

age 16-90 yrs

(median 56 yrs)

At the time of presentation

(n=62) or at median 3-years

after initial treatment.

0.1

1

10

100

1000

10000

0 12 24 36 48 60 72 84 96 108120132144156168180

cured

biochemical recurrence

radiological disease

Follow-up (months)

thyro

glo

bulin

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Oxford

Endocrine Surgery

Radical neck dissection for thyroid cancer

0

10

20

30

40

50

1 11 21 31 41 51 61 71 81

LN-ve LN+ve

Index patient

Lym

ph n

ode y

ield

50 31

F M

Papillary (n=74)

Follicular (n=3)

Anaplastic (n=4)

unilateral(n=73) or

bilateral (n=8)

age 16-90 yrs

(median 56 yrs)

At the time of presentation

(n=62) or at median 3-years

after initial treatment.

0.1

1

10

100

1000

10000

0 12 24 36 48 60 72 84 96 108120132144156168180

cured

biochemical recurrence

radiological disease

After 48-months median follow-up (range 2-169months),

• 52(64%) patients were cured,

• 4 had biochemical recurrence and

• 6 had structural recurrence

• (4 lost to follow-up).

14 patients died within 2-56 months either with

local/metastatic disease (n=11) or from another

cause(n=3). Follow-up (months)

thyro

glo

bulin

Oxford

Endocrine Surgery

Radical neck dissection for thyroid cancer

0

10

20

30

40

50

1 11 21 31 41 51 61 71 81

LN-ve LN+ve

Index patient

Lym

ph n

ode y

ield

50 31

F M

Papillary (n=74)

Follicular (n=3)

Anaplastic (n=4)

unilateral(n=73) or

bilateral (n=8)

age 16-90 yrs

(median 56 yrs)

At the time of presentation

(n=62) or at median 3-years

after initial treatment.

0.1

1

10

100

1000

10000

0 12 24 36 48 60 72 84 96 108120132144156168180

cured

biochemical recurrence

radiological disease

After 48-months median follow-up (range 2-169months),

• 52(64%) patients were cured,

• 4 had biochemical recurrence and

• 6 had structural recurrence

• (4 lost to follow-up).

14 patients died within 2-56 months either with

local/metastatic disease (n=11) or from another cause

Dynamic risk stratification based on thyroglobulin levels at 12 months postoperatively is a more accurate predictor of long-term recurrence.

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Oxford

Endocrine Surgery

Risk of recurrence vs. survival rates

Patient Tumour Treatment

older age at diagnosis

(possibly) male sex

larger size,

capsular invasion,

vascular invasion,

extrathyroidal extension,

metastatic disease, and

BRAF(V600E) mutation

lobectomy vs total thyroidectomy

use of radioiodine ablation (RIA)

AGES

Mayo Clinic

AMES

Lahey clinic

MACIS

Mayo Clinic

DAMES

Karolynska Institute

GAMES

MSKH, NY

Age

Grade

Extent

Size

Age

Metastases

Extent

Size

Metastasis

Age

Complete resection

Invasion

Size

DNA ploidy

Age

Metastases

Extent

Size

Grade

Age

Metastases

Extent

Size

Oxford

Endocrine Surgery

50% of recurrences occur in first 5 yrs

Recurrence vs. persistent disease ?

• Local

• LocoRegional

• Metastatic disease

TG monitoring

USS

USS-guided Bx of LN

CT

PET-CT

Total-body scan

1. Observation

2. Radioactive Iodine 131I Ablation (RAI)

3. Surgical resection of the involved regions

4. External Beam Radiation Therapy (EBRT)

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Oxford

Endocrine Surgery

Risk of recurrence after initial treatment

• large tumours

• macroscopic local invasion

• extension beyond thyroid capsule

• lymph node metastases (bulky)

• aggressive histological types

LN ratio >0.3

1 +ve LN out of three total

LNR of 0.30 or higher have a 3.4 times higher

risk of persistent or recurrent disease

LNR of 0.11 or lower have an 80% chance of

remaining disease free during 5 yrs of follow-up

Van Nunes JH et al., Thyroid. 2013;23(7):811-6

LNR ≥0.7 or a cLNR ≥0.86 have significantly

worse disease-free survival rates

Schneider DF, et al. Oncologist 2013;18(2):157-62

Oxford

Endocrine Surgery

Dynamic Risk Stratification

Response to initial therapy

Excellent

response

Acceptable

response

Incomplete

response

sTG <1ng/ml

Neck USS NAD

Nuclear scans -ve

1 < sTG <10 ng/ml

USS: LN<1cm, stable

Nuclear scans with

nonspecific changes

sTG>10 ng/ml

Raising TG

Persistent or new

disease on cross-

sectional or

nuclear imaging

Tuttle M. et al, Thyroid 2010, 20(12):1341; 2011, 21(12)1317

Patients with excellent response have only 4% risk of recurrence.

Only patients with structural incomplete response had a risk of dying of their disease.

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Oxford

Endocrine Surgery

Anaplastic Thyroid Cancer

• Rapidly enlarging neck mass

• Most arise from pre-existing differentiated tumours

• Associated with symptoms

– vocal cord palsy / dyspnea / dysphagia

• F:M ratio 2:1 (8:1)

• Peak incidence 60s-70s

• Advanced on presentation

• 50% distant metastasis (lung)

Oxford

Endocrine Surgery

Recent trends: multimodal therapy

• Surgical debulking followed by chemoradiotherapy

• Sweden: chemoradiotherapy before surgery

• Need for correct diagnosis

World J Surgery, 2008

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Oxford

Endocrine Surgery

Results

• 25 patients (6M:19F), mean age 72y (47-90y)

• Diagnosis

– 16 anaplastic

– 8 poorly differentiated

– 1 anaplastic/poorly differentiated

• Diagnostic modality

– 22 FNA

– 2 core biopsy

– anaplastic areas in a Hurthle cell cancer

• 4 specimens where upgraded to anaplastic

Oxford

Endocrine Surgery

Treatment

• 8 total thyroidectomy lymph node dissection

– 6 : poorly differentiated

– 1 : areas of anaplastic in Hurtle cell carcinoma

– 2 : anaplastic (debulking of tumour)

• 16 palliative radiotherapy

• 1 not for surgery/radiotherapy on diagnosis. Presented months later

with airway compromised and too large tumour for radiotherapy

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Oxford

Endocrine Surgery

well

differentiated

LN metastases -

well differentiated

moderately

differentiated

poorly

differentiated

p53

+++

+

-/+

-/+

Oxford

Endocrine Surgery

Airway management

• 10 airway compromised

– 2 poorly differentiated

– 7 anaplastic

– 1 poorly differentiated/anaplastic

• Management of airway obstruction

– 7/10 stented

– 1/10 failed stent

– 2/10 tracheostomies

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Oxford

Endocrine Surgery

Endo-tracheal stenting

Oxford

Endocrine Surgery

Outcome of airway obstruction

• 1 patient alive at 24 months after stenting

• 9 patients died within 0-9 weeks (median 6 weeks)

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Oxford

Endocrine Surgery

Current arrangements within TVCN

• Cases discussed (?timely decisions?)

• Imaging and cytology

• Two surgeons nominated for neck dissections

• Tracheal stenting/debulking (ENT/thoracic surgery)

• New chemotherapy regimes ?

Oxford

Endocrine Surgery

Medullary Thyroid Cancer – summary facts

• < 5% of all thyroid cancers

• 25% are familial - virtually all familial MTC have RET mutations

• Sporadic form more common in 4th-6th decade

• Surgery the only curative therapy

• 70% of MTC patients with palpable nodule have cervical lymph nodes

• The clinical behavior of sporadic MTC is unpredictable; however, and

some patients with distant metastases may live for several years

• Overall 10 years prognosis of 60-75%

• Distant metastases are the main cause of death

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Oxford

Endocrine Surgery

Diagnosis of MTC

• History

– Change in bowel habits

– Family history of ‘thyroid cancer’

– Symptoms of phaeochromocytoma

• Examination

– Thyroid nodule

– Local lymph nodes (painful)

• Thyroid/LN FNA

• Calcitonin/CEA

• urinary metanephrines

Oxford

Endocrine Surgery

Positive predictive value of calcitonin

Calcitonin concentration Predictive value

20-50 10%

50-100 25%

>100 100%

Routine screening with calcitonin assay in patients with nodular

thyroid disease is standard practice in some countries but not in UK

False positives: chronic renal failure, autoimmune thyroiditis, lung or

prostate cancer, enteric or pulmonary neuroendocrine tumours

Diagnosis

30-60 pg/ml possible LN disease

200 intrathyroidal disease

300 only 50% will become acalcitoninaemic

2000 likely metastatic disease

3000 NOBODY will become acalcitoninaemic

Staging

Normal values

F: 5.2 ng/L

M: 11.7 ng/L

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Oxford

Endocrine Surgery

Surgery with curative intent

NO M0

Total thyroidectomy + bilateral

central compartment dissection

N1 M0

Total thyroidectomy + bilateral

central compartment dissection +

uni/bi-lateral node dissection

Tumors in the upper pole of the gland, involving the lateral compartment nodes on

the ipsilateral side, skip the central compartment in approximately 25% of cases

Oxford

Endocrine Surgery

Surgery with curative intent

NO M0

Total thyroidectomy + bilateral

central compartment dissection

N1 M0

Total thyroidectomy + bilateral

central compartment dissection +

uni/bi-lateral node dissection

Tumors in the upper pole of the gland, involving the lateral compartment nodes on

the ipsilateral side, skip the central compartment in approximately 25% of cases

No LN

1-3 LN+ve

4 or > LN+ve

Central compartment

10%

80%

98%

Ipsilateral

lateral compartment

Contralateral

lateral compartment

5%

40%

75%

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Oxford

Endocrine Surgery

Surgery with curative intent

NO M0

Total thyroidectomy + bilateral

central compartment dissection

N1 M0

Total thyroidectomy + bilateral

central compartment dissection +

lateral node dissection

Palliative surgery

Advanced local or distant disease: less aggressive surgery aiming at

preserving speech, swallowing and parathyroid function

Oxford

Endocrine Surgery

10-years survival in sporadic MTC

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Oxford

Endocrine Surgery

Familial forms of MTC

syndrome %

of cases MTC Phaeo associated

MEN 2 (2A) 50-60 100% 50% Hirshprung’s, cutaneous lichen amyloidosis

MEN 3 (2B) 10 100% 50% Marfanoid habitus, ganglioneuromas

Familial

MTC

35 95% v rare

Oxford

Endocrine Surgery

The diagnosis could explain many previously

mysterious characteristics:

Lincoln was about 7.5 inches taller than average.

His height came from his legs. Sitting, he was no

taller than the average man.

Lincoln's body shape, i.e. his height, long limbs,

loose-joints, big feet, leanness, high voice, flat

feet, sunken chest are typical of persons with

Marfan syndrome

Abraham Lincoln – first known MEN-2B patient ?

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Oxford

Endocrine Surgery

An 1860 cast of Abraham Lincoln's face suggests a

lump in his right lower lip. (National Portrait Gallery)

The death of three of Lincoln's sons before age 20,

and, probably, his mother's death at 34.

Oxford

Endocrine Surgery

RET gene

RET is expressed in cells derived from the neural crest, the

branchial arches, and the urogenital system

Chromosomal translocations activating RET occur in 20-30% of

patients with PTC (27).

Activating RET translocations also occur in patients with lung

adenocarcinoma and chronic myelomonocytic leukemia

Inactivating mutations occur throughout the RET oncogene in

patients with hereditary and sporadic Hirschsprung’s Disease

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Oxford

Endocrine Surgery

Phenotype-genotype correlation

• Age of screening

• Age of surgical intervention

Oxford

Endocrine Surgery

Codon mutation influences timing of screening and intervention

A B C D

codon 768,790, 791, 804,

649, 891

609, 611, 618, 620,

630, 631

634 918, 883

MTC

aggressiveness

HIGH HIGHER HIGHER HIGHEST

MTC age of

onset

ADULTS 5 YRS Before age

5 yrs

First year of

life

Familial Cancer 2010; 9:449-457

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Oxford

Endocrine Surgery

Codon mutation influences timing of screening and intervention

A B C D

codon 768,790, 791, 804,

649, 891

609, 611, 618, 620,

630, 631

634 918, 883

MTC

aggressiveness

HIGH HIGHER HIGHER HIGHEST

MTC age of

onset

ADULTS 5 YRS Before age

5 yrs

First year of

life

Timing of

prophylactic

thyroidectomy

AGE 5-10 5 YRS Before age

5 yrs

First months

!?

Familial Cancer 2010; 9:449-457

Oxford

Endocrine Surgery

Codon mutation influences timing of screening and intervention

A B C D

codon 768,790, 791, 804,

649, 891

609, 611, 618, 620,

630, 631

634 918, 883

MTC

aggressiveness

HIGH HIGHER HIGHER HIGHEST

MTC age of

onset

ADULTS 5 YRS Before age

5 yrs

First year of

life

Timing of

prophylactic

thyroidectomy

AGE 5-10 5 YRS Before age

5 yrs

First months

!?

Screening for

Phaeo

Start at 20 yrs Start at 20 yrs Start at

8 yrs

Start at

8 yrs

Screening for

HPT

Start at 20 yrs Start at 20 yrs Start at

8 yrs

Familial Cancer 2010; 9:449-457

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Oxford

Endocrine Surgery

Risk-stratified management in familial MTC

3 distinct scenarios

- New patient presenting with MTC

- Screen-detected MTC

- First degree relatives of patients with MTC

Oxford

Endocrine Surgery

Surgery for screen-detected familial MTC

Specific consideration

• Patients are well, unaware of any disease

• You may have to operate more than one member of the same

family

Who should do it

• >75 thyroid operations/year

• Working in a MDT environment:

endocrinology/pathology/genetics/oncology

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Oxford

Endocrine Surgery

MEN-2 family (620 codon)

70 yr

56 yr

33yr 30yr 28 yr

2008

2010

1975

Oxford

Endocrine Surgery

Calcitonin 780

USS: 1cm L nodule,

supraclavicular LN

70 yr

56 yr

33yr 30yr 28 yr

Calcitonin

N

USS normal

MEN-2 family (620 codon)

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Oxford

Endocrine Surgery

Calcitonin 780

USS: 1cm L nodule,

supraclavicular LN

70 yr

56 yr

33yr 30yr 28 yr

Calcitonin N

10 mm

MTC

+ve

3/11 LN+ve

4/6 LN+ve

2 mm

MTC

C-cell

hppl

3mm and 5 mm MTC 0/7 LN involved

MEN-2 family (620 codon)

Oxford

Endocrine Surgery

MEN-2 family (620 codon) – follow-up data 2018

70 yr

66 yr

43yr 40yr 28 yr

1975

Calcitonin 1400

No radiological disease

Calcitonin 4300

Stable radiological disease

Calcitonin

< 2.00

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Oxford

Endocrine Surgery

MEN2 - prophylactic thyroidectomy

• 4 years old girl

• Step sister diagnosed with MTC in Australia in early 20s, had genetic testing

and found to have RET gene mutation

• Mother tested negative for mutation so ‘absent father’ considered to be the

carrier hence step sister referred for genetic testing

• Calcitonin normal / mutation

• Total thyroidectomy Oct 2017 – normal thyroid

Oxford

Endocrine Surgery

Summary - MTC

• Is a different disease

• Is an excellent example of translation from

laboratory research to clinical decision making

• Thank you to all colleagues who referred such

patients to OUH