thyroid cancer 2009

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=nextarrow


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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!!

thyroid cancer 2009

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