Dr. Deb Talukdar is a medical doctor from New Delhi, India. His research interest includes cancer therapeutics, Parkinson’s Disease, inflammatory and immunosuppressive drugs, COVID-19 predictive modeling and vaccination program, public health research associated with DHS and rare diseases such Pulmonary arterial hypertension (PAH). Previously, he was involved in AI research at Yale University. Currently, he is affiliated with All Saints University School of Medicine in Dominica.
Medullary thyroid cancer (MTC) produces excess calcitonin, which is the essential feature of this tumor. It arises from parafollicular or C cells. Patient education is critical because patients require lifelong thyroxine therapy after total thyroidectomy. With high calcitonin levels, susceptible patients undergo neck ultrasound and other non-invasive radiological investigations such as computed tomography (CT) scans. Physical examination is advised for patients twice a year for the first 2 years, and then once a year afterwards. Similarly, to evaluate recurrence or distant metastasis, serum calcitonin and carcinoembryonic antigen (CEA) levels should be monitored twice a year for the first 2 years, and then once a year afterwards.¹
Why is Patient Education Important?
Patients diagnosed with MTC undergo total thyroidectomy and prophylactic central lymph node dissection. They may have detectable calcitonin levels after surgery. Physical examination, cervical ultrasound, and other imaging techniques are conducted to detect metastatic disease. Also, patients may have elevated calcitonin levels without evidence of the disease. In case distant metastasis occurs, patients may initially present with a large tumor with lymph node involvement. It may affect multiple organs including the bones, liver, and lungs, and rarely the skin, brain, and breasts. Hence, it is important to address patients’ core concerns regarding various preliminary evidences, imaging studies, pre- and postoperative procedures, medications, and recovery.²
Educating Patients on the Diagnosis and Treatment of MTC
Early treatment of MTC can reduce mortality and improve prognosis. It is a cancer of non-thyroid cells that are normally present in the thyroid gland. Approximately 3% of thyroid cancers are associated with multiple endocrine neoplasia (MEN) 2 syndrome. Excess calcitonin in medullary carcinoma acts as a tumor marker. Clinically, thyroid cancers are divided into 2 categories – well-differentiated and poorly differentiated. Medullary cancer falls under the category of poorly differentiated.
After the diagnosis of MTC, patients must be aware of the preoperative staging and imaging procedures as they have the potential to alter a patient’s prognosis and treatment course.³ There are 4 different types of clinical MTC – MEN2A, MEN2B, sporadic MTC, and familial MTC. Lymph node metastasis is detected in 50% of patients, which indicates progression of the disease. Between 10% and 20% of MTC cases can have liver, lung, or bone metastasis. Certain features like flushes, diarrheal syndrome, family history of MTC, and pheochromocytoma may allow a physician to suspect and diagnose MTC. Physicians may even order plain radiographic films of the neck, which may reveal a dense, coarse calcification pattern. Patients must be educated about fine needle aspiration (FNA), which has the potential to diagnose MTC before surgery.⁴
Family History of MTC
Patients diagnosed with MTC need to be informed about the type of medullary thyroid cancer they were diagnosed with along with the treatment plan. For those with sporadic cases of MTC, total thyroidectomy and cervical lymph node dissection must be performed. Patients who are known carriers of RET mutations are recommended for surgery before the development of cancer as it can turn aggressive. Delaying the surgery can significantly increase the risk of distant metastasis and local recurrence. Surgery is considered if there are no distant metastases. If there are metastases, a physician may decide to reoperate based on the extent of metastatic disease.
Patients with a family history of mutated RET genes are susceptible. The RET gene is responsible for the growth and differentiation of neural crest cells from which MTC is derived. It is a member of the proto-oncogene cadherin family that undergoes oncogenic activation, and it is cytogenetically rearranged.⁵
Understanding the Management of MTC
Early detection of MTC can significantly improve a patient’s outcome. As per the American Thyroid Association (ATA), the risk of aggressive medullary thyroid cancer is based on RET mutations. The ATA recommends screening for pheochromocytoma at the age of 8 years for patients with codon 883 and 918 mutations or dual mutations in 804/805, 804/806, and 804/904. The ATA terms them as patients with the highest risk (Level D).
Prophylactic surgery is recommended for patients before the clinical onset of the disease. Physicians must determine whether the risk of clinically significant disease outweighs the risk of prophylactic intervention. In hereditary MTC, it should be noted that patients can show a strong age-related progression from C-cell hyperplasia to MTC, and progression to nodal disease. External beam radiation therapy (EBRT) can improve survivability, quality of life, and symptoms, but it is not considered an effective treatment option for MTC. Conventional chemotherapy has limited efficacy in patients diagnosed with MTC. Single-agent regimens with capecitabine, dacarbazine, 5-fluorouracil, and doxorubicin have a partial response rate of 24% to 29%.⁶
Potential MTC Therapies for Susceptible Patients
Current research studies show that signal transduction can contribute to tumor growth and hormone production in MTC. Sporadic and MEN2B-associated MTCs are the most aggressive forms as compared to MEN2A-associated MTC. They present at an advanced stage with a worse prognosis. Almost 80% of these cases present with metastatic disease, which means that conventional therapies like surgery alone cannot cure MTC. As per the current recommendation of the ATA, EBRT and/or chemotherapy are recommended for patients with advanced regional or metastatic disease. High-risk patients with postoperative recurrence are also recommended for EBRT.⁷
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Reviewed by Harshi Dhingra, MD, on 7/8/2021.