A Novel Fusion in Pediatric Medullary Thyroid Carcinoma.

Medullary thyroid carcinoma (MTC) is most commonly associated with gene mutations. fusions have rarely been described, although not previously in pediatrics and not previously partnered with in MTC or any other cancer. A 10-year-old boy with progressive stridor was found to have metastatic MTC, including lung, lymph node, and adrenal metastases. Baseline calcitonin was 6703 pg/mL. While molecular testing was pending, he was treated empirically with the investigational selective RET inhibitor, LOXO-292, without improvement. Molecular testing revealed a novel - fusion. His therapy was changed to crizotinib and then to alectinib for improved tolerability. Calcitonin decreased to 663 pg/mL after 6 days of ALK inhibition. He remains on alectinib with ongoing response. A novel - fusion has now been implicated in a pediatric case of metastatic MTC. This fusion has profound clinical sensitivity to ALK inhibitors. This report expands the spectrum of fusions seen in MTC, including the first pediatric case of translocated MTC. This novel fusion with has not previously been reported in other human cancers. Given the dramatic response to ALK inhibition in this case, identifying patients with fusion MTC has important therapeutic implications.