2012 EDUCATIONAL BOOK - American Society of Clinical Oncology

EVALUATION OF ADVANCED THYROID CANCER
refractory DTC and the options discussed here have been
exhausted, use of targeted agents can be considered. Three
questions to answer are (1.) Does the patient currently have
symptoms from DTC that would be relieved from reduction
of the tumor? (2.) Based on the clinical history and imaging
studies, are there lesions, although asymptomatic now, that
pose an imminent threat? (3.) Is there evidence from the
patient history, imaging studies, or thyroglobulin levels that
the velocity of tumor progression is such that deferred
treatment might result in a rapid decline in performance
status? Some clinical features can be useful guides for
predicting which patients are likely to have more aggressive
disease (Table 1). As is the case with many common solid
tumors such as lung, colorectal, and breast cancers, often
the decision to treat in the metastatic or recurrent setting is
made on the basis of the extent of disease without knowledge
of the progression velocity. DTC, on the other hand, even in
patients with widely disseminated disease or a high thyroglobulin
level, can be indolent, and the timing of treatment
initiation can be challenging in an asymptomatic patient. As
analogies, one can think of patients with prostate cancer and
a high prostate-specific antigen level but no symptoms or
measurable disease or patients with low-grade neuroendocrine
tumors with high volume but minimally symptomatic
disease; the art of deciding whom and when to treat remains
a challenge.
Once the decision has been made that a patient with DTC
is appropriate for systemic drug treatment, ample data
support the use of several tyrosine kinase inhibitors (TKIs).
Medullary Thyroid Carcinoma
Unlike DTC, medullary thyroid carcinoma (MTC) is a rare
type of thyroid cancer and accounts for approximately 2% to
8% of all thyroid cancer. However, it is one of the best
characterized solid tumors. MTC is derived from parafollicular
cells of the thyroid and exhibit well-differentiated neuroendocrine
carcinoma histology. Given that MTC does not
originate from follicular cells of the thyroid, it is not iodine
avid and does not secrete thyroglobulin. MTC occurs in the
sporadic (75%) and hereditary (25%) setting. Germline mutation
in the RET proto-oncogene is a critical pathogenetic
defect associated with nearly 95% of all cases of the hereditary
type of MTC (MEN-2A, MEN-2B, or familial MTC).
Somatic mutation in the RET proto-oncogene is observed in
30% to 40% of tumors of sporadic MTC. Serum calcitonin
and carcinoembryonic antigen (CEA) are reliable tumor
markers with prognostic significance. Patients with MTC may
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have hormone-associated symptoms of flushing and diarrhea.
MTC is typically a systemic disease and is known to spread in
the setting of small primary tumors. In addition to lymph
nodes in the neck, common sites of metastasis include the
lung, mediastinal lymph nodes, liver, and bones. While cytotoxic
chemotherapies are ineffective, systemic therapies with
TKIs are promising. Over last decade, numerous clinical trials
ranging from phase I and phase III trials have been conducted
in patients with advanced MTC. Vandetanib is approved by
FDA in 2011 for patients with progressive advanced MTC. We
summarize the principles of diagnosis and management in
Table 2.
Anaplastic Thyroid Carcinoma
Anaplastic thyroid cancer (ATC) accounts for 2% of all
thyroid cancer. It is one of the most aggressive cancers among
all solid tumors and its progression can be clinically evident in
a matter of days to weeks. ATC is classified only as stage IV
and is divided into stage IVA, IVB, and IVC. Despite multimodality
aggressive therapy, the prognosis for patients with
ATC is poor, with a median survival of 6 months. Treatment
options usually include combinations of surgery, cytotoxic
chemotherapy, and radiation therapy. Cytotoxic chemotherapy
agents such as taxanes, platinums, or doxorubicin can be
used. Concurrent or sequential chemoradiation treatment is
an option. Supportive care and hospice should be mentioned
to the patient when discussing management of the disease.
In addition to multimodality therapy, other topics that
should be addressed are airway management and nutritional
status, with consideration of a percutaneous endoscopic
gastrostomy tube. Despite recent advances in the understanding
of the pathogenetics of ATC, novel targeted therapies
tested to date have proved to be ineffective. Patients should be
encouraged to participate in clinical trials.
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Sidebar 3. Guidelines for Management of Thyroid
Cancer
The following organizations provide guidelines for
the management of various types of thyroid cancer.
● National Comprehensive Cancer Network (NCCN):
www.nccn.org
● American Thyroid Association (ATA): http://thyroid
guidelines.com
● British Thyroid Association (BTA): www.britishthyroid-association.org/Guidelines
Research
Funding
A. Dimitrios Colevas ActoGeniX;
Bayer/Onyx;
Boehringer
Ingelheim;
Exelixis;
GlaxoSmithKline;
Roche
Manisha H. Shah Bayer Daiichi Sankyo;
Eisai; Exelixis
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