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7/28/2019 Thyroid Cancer 2009
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Thyroid Cancer 2009
Megan R. Haymart, MD
Endocrinology
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Overview
1) Thyroid Cancera) PTC
b) FTCc) MTC
d) Anaplastic
2) Oncologist Role
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Case 1: Papillary Thyroid Cancer
38 yo woman has 3 right sided thyroidnodules detected during her first pregnancy.
1/07 US guided FNA of all 3 nodulesconsistent with benign colloid nodules.
Minimal nodule growth during her second
pregnancy. 10/08 US guided FNA of 2nodules benign colloid and one suspiciousfor PTC.
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Case 1: PTC
Patient was informed
FNA is 97% accurate if
diagnostic for PTC and
57% accurate if
suspicious for PTC.
Haymart MR et al. Thyroid 18(4): 419-423, 2008.
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Case 1: PTC
The patient underwent right lobectomy,isthmusectomy, and intraoperative frozen sectionfollowed by left thyroid lobectomy completingtotal thyroidectomy.
Pathology with a 1.0 x 0.8 x 0.6 cm PTC in the
right thyroid lobe.
Post-op Thyroglobulin= 0.9.
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Papillary Thyroid Cancer
Estimated 37,340 new cases of thyroid cancer in
2008
At least 80% of thyroid cancer PTC
Three out of four cases of PTC in women
Two thirds of PTC in patients age 20-55
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Jonklaas et al. Thyroid 2006 (16): 1229-42.
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Age is a Prognostic IndicatorTNM Staging for Differentiated Thyroid
Cancer
Age
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Risk Factors for Increased
Mortality1) Age
2) Extrathyroidal extension
3) Size over 4 cm
4) Distant Mets
5) +/- LN Mets6) Cell type (ie. Tall cell variant of PTC)
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Case 1: PTC
Standard Therapy:
1) Surgery
2) RAI
3) Suppressive doses of
LT4
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RAI
RAI is taken up by the sodium-iodine symporter(Na/I S) and concentrated in the thyroid follicularcells.
Compared to normal thyrocytes, cancer cells havedecreased expression of the Na/I symporter thus
leading to decreased iodine uptake in the tumor.
In vivo models, have shown upregulation of theNa/I S with TSH stimulation.
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Case 2: Follicular Thyroid
Cancer 78 yo man with a history of back pain for 5
years has an MRI revealing a 5 cm
expansile L1 vertebral body mass. Follow-up CT shows an 8 cm mass at T7, invasionof the posterior wall, invasion of theadjacent thoracic vertebrae and rib, possible
left neuroforaminal involvement, a secondlesion at T12-L1, and hypodense nodularlesions in both lobes of the thyroid.
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Case 2: FTC
8/07 he undergoes total
thyroidectomy and left
thoracotomy with chest
wall resection.
Pathology revealed a 2.1 x
1.4 x 1.4 cm FTC limited
to the thyroid and chest
wall excision showedmetastatic FTC invading
skeletal muscles and rib.
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Case 2: FTC
10/07 Patient receives 149 mCi I-131. Post treatment scanshows radiotracer uptake in hyoid bone, posterior leftaspect of thyroid resection bed, region of left posterior 7th
rib, and patients L1 metastases 12/07 Patient receives 10 doses of external beam radiation
to T12-L2
2/08 Patients back pain improves. Patient gains weight,spirits good
8/08 He starts Zolendronic Acid. Calcium and vitamin Dmonitored
12/08 Patient receives 202 mCi I-131. There is persistentuptake in the 7th rib and L1 vertebral body
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Case 2: FTC
Tumor Marker
0
5000
10000
15000
20000
preop post RAI 1 post RAI 2ThyroglobulinLevel(ng/mL)
Preoperative Tgb= 16,478 ng/mL
Post 149 mCi I-131= 597 ng/mL,
Post 202 mCi I=-131= 101.5 ng/mL
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Follicular Thyroid Cancer
Less than 10% of all thyroid cancer. Morecommon in iodine deficient countries
Also considered well-differentiated withsurgery, RAI, and suppressive doses of LT4 asstandard therapy
PTC more likely to metastasize to local LNs first.
FTC can metastasize to distant sites without LNspread
Hurthle cell carcinoma is a subtype of FTC
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FNA would show follicular neoplasm. On final pathology,
80% of FN are benign follicular adenomas and 20% are follicular
carcinoma.
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Case 3: Medullary Thyroid Cancer
40 yo woman who presented 14 years ago with
hypertension and hypercalcemia. At time of
parathyroidectomy, a thyroid nodule was biopsiedand consistent with MTC. She was subsequently
diagnosed with a pheochromocytoma and
underwent right adrenalectomy.
Genetic testing revealed a mutation in codon 634
of RET- diagnosis MEN2A.
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Pap stain Congo Red Stain
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Family History
Her father hadhypertension, stroke, anddied of an infection at age
57. He also had a h/o ?PTC.
1 of her 2 sisters carriedthe RET mutation and hadMTC diagnosed. Herniece had c-cellhyperplasia when totalthyroidectomy was
performed at age 5.
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MEDULLARY THYROID
CANCER: MTC accounts for 5 to 10% of all thyroid
cancers
The clinical course ranges from indolent toaggressive
Most cases are sporadic but 20% are the
result of a germline mutation in ret proto-oncogene
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Evans et al. Surgery2007; Kouvaraki et al. Thyroid. 2005.
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Familial MTC
MEN2A- MTC>95%, Pheo 50%, hyperparathyroidism20-35%
MEN2B- MTC 100%, Pheo 50%, marfanoid,ganglioneuromas
FMTC- no evidence of pheo or hyperpara in >10carriers and multiple members must be affected after age
50
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Best Initial Operation for MTC
Hereditary MTC: Prophylactic total thyroidectomy
Sporadic MTC:
Total thyroidectomy
+ central lymph node
dissection (CLND) +/- modified radical
neck dissection
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Case 4: Anaplastic
72 yo man with h/o multiple medical
problems presents with 1 year history of
dysphagia requiring EGD and balloondilatation. CT reveals a 10 x 9 x 4.5 cm
mass in the thyroid and LNs in level II, III,
IV.
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Anaplastic Thyroid Cancer
FNA revealsanaplastic thyroidcancer with areas of
low grade papillarythyroid cancer.
Staging CT showsmetastases in the lung,liver, adrenal, spleen,and multiple lymphnodes.
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Anaplastic Thyroid Cancer
Undifferentiated
thyroid cancer
2% of all thyroidcancer
Thought to develop
from existing PTC or
FTC
Aggressive course
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BRAF Mutation
Most common mutation in papillary cancer Fugazzola, et al,Clinical Endocrinology 2004
Codes for serinethreonine kinase
Higher incidence of extrathyroidal extension, nodalmetastases, and recurrence Xing, et al JCEM 90, 2005; Lee, et al, Cancer, 2007
Inhibit genes involved with iodine metabolism, includingNIS, AIT-B, TG, TPO Durante, et al JCEM 92, 2007
Co-existence of BRAF and PI3K/Akt pathway mutations
may facilitate progression of PTC to ATC Hou Clinical CancerResearch, 2007; Santarpia, et al, JCEM, 93, 2008
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Therapeutic Options in Poorly
Differentiated Thyroid Cancer Surgery
I-131limited effect in poorly or un-differentiated tumors
XRTmost useful in management of distantmetastases (skeleton, brain)
Chemotherapyadriamycin not effective,
adriamycin + cisplatin more toxic and noteffectiveShimaoka, Cancer 1985
Arterial embolization for local disease Dedecjus, Endocr RelatCancer 2007
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Role of the Oncologist: Case #3:
MTC 14 years after her original diagnosis, patient
presents with rising calcitonin. FNA of right levelIII and level IV LNs consistent with MTC. 2/09
MRI with 2 hypervascular liver lesions concerningfor MTC mets.
Patient requiring increasing # of antihypertensives.Urine metanepherines elevated. MRI and thenMIBG localize pheochromocytoma to remainingleft adrenal gland.
C l it i D bli Ti
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Calcitonin Doubling Time
Prognostic Indicator
Case 3:
In 1 mo.
Calcitonin increased
From 821 to 1320.
Prognostic Impact of Serum
Calcitonin and
Carcinoembryonic Antigen
Doubling-Times in Patients
With Medullary Thyroid
Cancer. Barbet JCEM 2005;
90:6077-6084.
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Case #3: Role of the Oncologist
4/09 Laparoscopic left adrenalectomy forpheochromocytoma and liver viewed at time ofsurgery. Op note: large number of small,
white miliary lesions present through the liverdiffusely. This was consistent with metastaticdisease.
Treatment options: Given distant mets.surgical resection of level III and IV neck LNsnot beneficial. Consider octreotide LAR forsymptomatic relief of flushing; clinical trial forMTC. Patient referred to oncology.
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Advanced Thyroid Cancer: Need
an Oncologist? Multidisciplinary approach to thyroid
cancer
Surgeon, Endocrinologist, NuclearMedicine, and Oncologist
Selection of patients for trials/uniqueaspects of thyroid cancer
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Targeted Therapy
Decreased cellular proliferation
Decreased angiogenesis
Increased apoptosis
Re-differentiation
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Next
Motesanib Diphosphate in Progressive Differentiated Thyroid Cancer
Steven I. Sherman, M.D., Lori J. Wirth, M.D., Jean-Pierre Droz, M.D., Michael Hofmann, M.D., Ph.D., Lars Bastholt, M.D.,
Renato G. Martins, M.D., Lisa Licitra, M.D., Michael J. Eschenberg, M.S., Yu-Nien Sun, Ph.D., Todd Juan, Ph.D., Daniel E.
Stepan, M.D., Martin J. Schlumberger, M.D., for the Motesanib Thyroid Cancer Study Group NEJM 2008
http://content.nejm.org/content/vol359/issue1/images/large/06f1.jpeghttp://content.nejm.org/content/vol359/issue1/images/large/06f1.jpeghttp://content.nejm.org/content/vol359/issue1/images/large/06f1.jpeghttp://content.nejm.org/content/vol359/issue1/images/large/06f1.jpeghttp://content.nejm.org/cgi/content/short/359/1/43?query=nextarrowhttp://content.nejm.org/cgi/content/short/359/1/43?query=nextarrowhttp://content.nejm.org/cgi/content/short/359/1/43?query=nextarrow7/28/2019 Thyroid Cancer 2009
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Emphasis on Tyrosine Kinase
Inhibitors Over-expression of VEGFR, EGFR, c-MET in thyroid
cancer
Sorafenibinhibits both Raf kinase and multiple tyrosine
kinase receptors (VEGF, PDGF, RET) signaling Carlomagno, et al JNatl Cancer Inst, 2006 VEGFR over-expression in angiogenesis
VEGF blocked by Vandetinib (also blocks EGFR andRET) Carlomagno, et al, Cancer Res 2002
EGFR activates both MAPK and PI3K pathways, blockedby gefitinibSchiff, et al Clin Cancer Res 2004
Imatinib inhibited cell proliferation of ATC in culturePodtcheko, et al JCEM, 2003
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Each a Unique Cancer
All thyroid cancers not equal
MTC more similar to neuroendocrine tumors. ie.carcinoid
WDTC (ie FTC and PTC) more similar
Chemotherapy with more of a role for anaplastic
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Summary:
Initial management of low risk thyroid cancer
should be addressed by endocrinologists.
Advanced disease needs a multidisciplinaryapproach including endocrinologists, surgeons,
nuclear medicine (PTC/FTC), and oncologists.
There is a window of opportunity for oncologists
interested in thyroid cancer because relative toother malignancies, thyroid cancer is a late entry
in the world of clinical trials.
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Thanks and Good Luck!!
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