BACKGROUND: Targeted kinase inhibitors have been increasingly utilized in the 
treatment of advanced medullary thyroid cancer (MTC) over the last decade. 
Recently, highly potent next generation selective RET inhibitors have been 
clinically validated, and selpercatinib was recently Food and Drug 
Administration (FDA)-approved for advanced MTC. The advent of highly selective, 
potent RET inhibitors is broadening the treatment options for patients with 
RET-mutated cancers.
METHODS: We report the first published case of neoadjuvant selpercatinib 
followed by surgery for a patient with initially unresectable, widely 
metastatic, RET-mutated MTC who was treated on a single patient protocol.
RESULTS: After greater than 50% RECIST response, the patient underwent complete 
surgical resection followed by selpercatinib resumption. He remains 
locoregionally disease-free 21 months after starting therapy with stable 
metastatic disease (after initial partial response); and calcitonin/CEA continue 
to decline.
CONCLUSION: This novel treatment strategy for locoregionally advanced 
RET-mutated MTC warrants further study in clinical trials.