Natural History Study of Children and Adults With Medullary Thyroid Cancer

Background:

- Medullary Thyroid Carcinoma (MTC) is a calcitonin producing tumor arising from the

parafollicular C cells of thyroid. In children and adults, MTC is usually seen in

association with Multiple Endocrine Neoplasia (MEN) 2A and 2B, which are rare cancer

syndromes resulting from germline mutations of Rearranged during Transfection (RET)

proto-oncogene. MTC develops in virtually all patients with MEN 2, and is the

leading cause of death in these patients. Patients with MEN 2 may have other

characteristic manifestations such as pheochromocytoma and hyperparathyroidism in

MEN 2A and pheochromocytoma, ganglioneuromatosis, and skeletal deformities in MEN

2B.

- Complete surgical resection is the only current curative treatment for MTC, and the

tumor is unresponsive to standard chemotherapy and conventional doses of radiation

therapy. However, more than half the patients present with advanced or metastatic

disease and cannot be cured surgically. Novel agents are currently under

investigation for treatment of MTC, and vandetanib, an oral RET and receptor

tyrosine kinase (RTK) inhibitor was recently approved by the FDA for adults with

advanced or metastatic MTC. Vandetanib also has activity in children with hereditary

MTC.

- However, complete responses to RTKs have not been observed, and some patients

develop resistance to the treatment with RET and RTK inhibitors or have primary

refractory disease. The natural history of MTC, particularly in patients with MEN 2,

the molecular pathways involved in tumorigenesis, and the development of resistance

to targeted therapies are not well understood.

Objectives:

-The overall objective of this longitudinal study is to develop a better understanding of

the biology and natural history of MEN2 with or without MTC, particularly in children and

adults with MEN 2A and 2B, as well as study non-tumor manifestations of MEN 2. This will

hopefully allow for developing more effective treatment interventions for tumor and

non-tumor related manifestations, and more sensitive endpoints in clinical trials.

Eligibility:

- Patients, must have histologically or cytologically confirmed MTC, confirmed by the

Laboratory of Pathology, NCI or who have MEN2 (regardless of MTC status).

- Parent or primary caregiver of patient participant (<= 21)

- Participants may be undergoing standard care or receiving treatment on a clinical

trial while participating in this study.

Design:

This study will allow for longitudinal evaluations of MTC and MEN2 and non-tumor related

manifestations of MEN 2A and 2B in children and adults. Evaluations will consist of the

following (summarized):

1. Clinical and radiological evaluations

2. Detailed pathologic and molecular analysis of tumor specimens will be performed,

including immunohistochemistry (IHC), comparative genomic hybridization (CGH), and

genome sequencing. CGH and genome sequencing will be performd with co-enrollment on

protocol 10-C-0086 Comprehensive Omics Analysis of Pediatric Solid Tumors and

Establishment of a Repository for Related Biological Studies.