Abstract

Introduction: Medullary thyroid cancers (MTC) constitute about 5% of all thyroid cancers. The 10-year overall survival (OS) rate of patients with localized disease in thyroid for this pathology is 80% to 90% which is comparable with differentiated thyroid cancers, figures drop to 75% for cases with nodal metastases. Only 20% of patients with distant metastases at diagnosis survive for 10 years. In metastatic disease there are variations with smoldering less active disease to progressive active disease. Surgery is cornerstone of the management with total thyroidectomy and nodal dissection as main treatment. Adjuvant treatment with radiotherapy is case selective, varies from case to case. The management of residual, recurrent disease is possible re-surgery with external beam radiation therapy. The development of targeted therapy has brought in a major advantage in management of metastatic disease. Two drugs -vandetanib and cabozantinib- have been approved for use in metastatic MTC. The optimum management in this group of patients is a challenge and long-term use of TKI needs to be balanced with monitoring side effects of TKI and dose adjustments of TKI.

Materials and methods: A retrospective review of cases with diagnosis of medullary thyroid cancers treated or registered at Kuwait Cancer Control Center was conducted. The data of patients registered between 1987 till 2017 was analyzed. The data was collected and analyzed using SPSS (version 20) software program. For analysis we considered date of surgery as the date of diagnosis. Final state of disease along with emphasis on prognostic factors was correlated with Kaplan Meyer survival curves.

Results: There were total 31 cases out of which 15(48.4%) were male and 16(51.6%) females. The median age at presentation was 51.6 years (range-28years-77years). MEN syndrome was diagnosed in 6(19.4%) patients. Staging revealed Stage I - 7/31 (22.58%), Stage II-3/31(9.67%), Stage III-7/31(22.58%), Stage IVA (nonmetastatic) -12/31 (38.70%), Stage IVC (metastatic) - 2/31 (6.45%). Total thyroidectomy and central compartment neck dissection was optimum surgery (29%). Total thyroidectomy with central compartment neck dissection and unilateral neck dissection was done in 38.7% patients, comprehensive neck dissection and total thyroidectomy was done in 32.2% patients. External beam radiotherapy (EBRT) with conformal or IMRT technique was used in 13 out of 31 patients. One patient was treated for bony metastasis with palliative intent. Four patients were treated by TKI for metastatic disease or at progression. Median follow up was 79 months. Median overall survival was 93 months. Median progression free survival irrespective of stage was 62 months. At the end of 5 years 61% patients were alive irrespective of stage of disease. Due to the small sample size and natural history of advanced MTC the observed p-value for several pathological variables in relation with survival was not significant.

Conclusion: Stage I and stage II cases of our study did well and were all alive and disease free till our last follow up. EBRT in our cohort of patient did not revealed any added benefits in survival. The use of TKI in metastatic disease was associated with many issues including availability of drug. Elevated serum calcitonin and CEA levels in absence of measurable disease should be dealt cautiously.