Predictors of Locoregional Failure in Resected Medullary Thyroid Cancer: Implications for Adjuvant Radiation.

Loco-regional Failure (LRF) can be an important cause of morbidity and mortality in patients with advanced medullary thyroid cancer (MTC), especially in the era of more effective systemic therapies. We sought to identify risk factors predictive of LRF and the role of radiation therapy in modifying this outcome. Patients with MTC treated with definitive surgical resection between 2004 and 2020 were identified in an IRB approved database. Patients who did not undergo definitive surgery, with or without metastatic disease, or those treated with radiation alone were excluded. Patients who underwent postoperative radiation (PORT) to a dose of >45Gy were included. LRF was defined as any failure in the thyroid bed, neck or mediastinum. Kaplan Meier analysis was performed to calculate rates of LRF and log rank analysis was used to identify associations of specific high-risk features with LRF. High-risk pathologic factors included in this analysis were positive surgical margins, multifocal disease, angiolymphatic and/or lymphovascular space invasion (LVI), extrathyroidal extension, nodal extracapsular extension, and rising CEA or calcitonin postoperatively. Of 68 patients who were included in this study, 36 (53%) were stage I/II and 32 (47%) were stage III/IV. MTC was co-incidental with a papillary thyroid cancer in 34 patients (50%). LRF occurred in 1 (3%) stage I/II and 12 (38%) stage III/IV patients. Among stage III/IV patients with known mutational analysis, 14/25 (56%) harbored RET mutations, 11 of whom received targeted therapies. Patients with these mutations had numerically lower rates of LRF compared to non-mutated tumors (18% vs. 43%; p=0.23). Patients with positive margin, LVI, or multifocal disease trended towards an increased risk of 3-yr LRF (36.2% vs 0%; p=0.22). No other pathologic risk factors were associated with LRF. PORT was used in 14 stage III/IV patients (44%), and was associated with a lower 3-yr LRF rate (7% vs. 38%; p=0.17). This was independent of known risk factors. Patients with stage III/IV MTC treated with definitive resection with either a positive margin, LVI and/or multifocal disease have high rates of LRF and may benefit from PORT. Further studies are needed to corroborate this finding, especially in RET mutated tumors in the era of targeted therapies. [ABSTRACT FROM AUTHOR]