TREATMENT OF DIFF THYROID

CANCERS
DR SAMEER FASIH
Case 1: Papillary Thyroid Cancer
38 yo woman has 3 right sided thyroid
nodules detected during her first pregnancy.
US guided FNA of all 3 nodules consistent with
benign colloid nodules.
Minimal nodule growth during her second
pregnancy.
US guided FNA of 2 nodules benign colloid and
one suspicious for PTC.
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.
Case 1: PTC
The patient underwent right lobectomy,
isthmusectomy, and intraoperative frozen section
followed by left thyroid lobectomy completing total
thyroidectomy.

Pathology with a 1.0 x 0.8 x 0.6 cm PTC in the right
thyroid lobe.

Post-op Thyroglobulin= 0.9.


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, invasion of the posterior wall,
invasion of the adjacent thoracic vertebrae
and rib, possible left neuroforaminal
involvement, a second lesion at T12-L1, and
hypodense nodular lesions in both lobes of
the thyroid.
Case 2: FTC
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 showed metastatic
FTC invading skeletal
muscles and rib.
Case 2: FTC
Patient receives 149 mCi I-131. Post treatment scan shows
radiotracer uptake in hyoid bone, posterior left aspect of
thyroid resection bed, region of left posterior 7
th
rib, and
patients L1 metastases
Patient receives 10 doses of external beam radiation to T12-L2
Patients back pain improves. Patient gains weight, spirits
good
He starts Zolendronic Acid. Calcium and vitamin D monitored
Patient receives 202 mCi I-131. There is persistent uptake in
the 7
th
rib and L1 vertebral body

Case 2: FTC
Tumor Marker
0
5000
10000
15000
20000
preop post RAI 1 post RAI 2
T
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L
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(
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Preoperative Tgb= 16,478 ng/mL
Post 149 mCi I-131= 597 ng/mL,
Post 202 mCi I=-131= 101.5 ng/mL
DTC
Differentiated thyroid carcinomas 94% of all
thyroid cancers
Papillary carcinoma 80%
Follicular cell carcinomas 11%
Hrthle cell carcinomas (often considered to
be a subgroup of follicular carcinoma) account
for approximately 3%.
Thyroid. 2010 Jul;20(7):707-13. doi: 10.1089/thy.2010.1641.
10-year survival rates are 93%, 85%, and 76%
for papillary, follicular, and Hrthle cell
carcinomas, respectively.
Cancer. 1998 Dec 15;83(12):2638-48
Differentiated thyroid cancers retain
characteristics of normal thyroid follicular
cells, including the presence of a unique
sodium iodide symporter, which concentrates
iodine in the cells.
Thus, radioactive iodine (RAI) is a mainstay of
the diagnosis, treatment, and management of
differentiated thyroid cancers.
INITIAL TREATMENT
Total thyroidectomy is recommended for all
but a few cases of differentiated thyroid
cancer.
This surgery is often definitive, and the patient
may require no further treatment.
The surgery should include removal of all
involved lymph nodes identified by
preoperative neck ultrasonography, where
possible.
Radioactive iodine (RAI) should be given as
part of the immediate posttreatment workup
for patients with
Tumors > 4 cm,
Residual thyroid tissue
Known metastases to ablate any remnants of
carcinoma and
To improve survival.
Thyroid. 2009 Nov;19(11):1167-214. doi: 10.1089/thy.2009.0110.
Recurrent disease and distant metastases are often
associated with an increase in serum thyroglobulin.
Serum thyroglobulin may not be reliable when an anti-
thyroglobulin antibody is detected.
RAI is usually administered at treatment doses of more
than 100 mCi,
Once RAI is completed, patients start replacement
therapy with levothyroxine, which also acts as
suppressive therapy, because feedback inhibition of
thyroid stimulating hormone by this agent, at this
point, can help suppress growth of differentiated
cancer.
ADVANCE DISEASE
Recurrent or metastatic lesions either no
longer take up radioactive iodine (RAI) or
Grown in the setting of recent treatment with
RAI (ie, RAI refractory)
If the recommended lifetime dose of RAI (600
mci) has been exceeded.
Loss of RAI uptake is often associated with the
increased uptake of fluoro-deoxyglucose on
positron emission tomography (PET) scanning;
thus, additional sites of disease are often
detected with this imaging modality.
Once the carcinoma no longer responds to RAI
therapy and is PET positive, the survival drops
to an average of 2.5-3.5 years.

Robbins RJ, wan Q, grewal RK, reibke R, gonen M, strauss HW, tuttle RM, drucker W, larson SM. J clin
endocrinol metab. 2006 feb;91(2):498-505. Epub 2005 nov 22.

Exception: in rare patients, there is a solitary
focus of PET-positive carcinoma that is
amenable to surgery.
BRAF Mutation
Most common mutation in papillary cancer
Fugazzola, et al, Clinical Endocrinology 2004
Codes for serine threonine kinase
Higher incidence of extrathyroidal extension,
nodal metastases, and recurrence Xing, et al JCEM 90,
2005; Lee, et al, Cancer, 2007
Inhibit genes involved with iodine metabolism,
including NIS, 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 Cancer Research, 2007; Santarpia, et al, JCEM, 93, 2008
Several tyrosine kinase inhibitors have shown
activity in this setting, exploiting the vascular
nature of these tumors and/or the strong
association with genetic mutations that lead
to aberrant intracellular signaling.
The majority (Motesanib, Sunitinib, Sorafenib,
and Pazopanib) target the mitogen-activated
protein kinase and anti-angiogenic pathways.

Eur J Endocrinol. 2011 Aug;165(2):315-22.
J Clin Endocrinol Metab. 2011 Apr;96(4):997-1005.
Clin Cancer Res. 2010 Nov 1;16(21):5260-8.
J Clin Oncol. 2010 May 10;28(14):2323-30.
Emphasis on Tyrosine Kinase Inhibitors
Over-expression of VEGFR, EGFR, c-MET in thyroid
cancer
Sorafenib inhibits both Raf kinase and multiple
tyrosine kinase receptors (VEGF, PDGF, RET) signaling
Carlomagno, et al J Natl Cancer Inst, 2006
VEGFR over-expression in angiogenesis
VEGF blocked by Vandetinib (also blocks EGFR and
RET) Carlomagno, et al, Cancer Res 2002
EGFR activates both MAPK and PI3K pathways,
blocked by gefitinib Schiff, et al Clin Cancer Res 2004
Imatinib inhibited cell proliferation of ATC in culture
Podtcheko, et al JCEM, 2003

In a small study (N = 17), sorafenib was
associated with a partial response in 30% and
stable disease in 41% of patients with RAI-
refractory DTC.
Sorafenib in advanced iodine-refractory differentiated thyroid cancer: efficacy, safety and
exploratory analysis of role of serum thyroglobulin and FDG-PET. Clin Endocrinol (Oxf).
2013 May;78(5):760-7
Phase III DECISION trial
(N = 417) patients treated with sorafenib.
Significantly longer median progression-free
survival vs placebo 10.8 vs 5.8 months (HR: 0.58;
95% CI: 0.45-0.75; P < .0001),
Higher response rate (12.2% vs 0.5%; P < .0001),
and stable disease 6 months (42% and 33%,
respectively).
Based on these results, the US Food and Drug
Administration approved sorafenib for the
treatment of locally recurrent or metastatic,
progressive, DTC refractory to radioactive iodine
treatment.
Phase III DECISION trial. Program and abstracts of the 2013 Annual Meeting of the
American Society of Clinical Oncology; May 31 - June 4, 2013; Chicago, Illinois. Abstract 4.