We present the case of a gentleman who developed oligometastatic colon cancer in his brain one year after completing adjuvant chemotherapy. Subsequent dural metastasis necessitated whole brain radiation therapy (WBRT). Whole exome sequencing (WES) identified a NCOA4-RET fusion and high tumor mutation burden. Treatment with selpercatinib following WBRT for multifocal dural metastases led to an initial treatment response, interrupted by grade 3 transaminitis for two weeks, during which dural metastases progressed. Resuming selpercatinib at 50% dose led to a rapid treatment response and maintained for four months until further brain metastases. Our patient survived 21 months following initial diagnoses of metastatic recurrence including nine months of selpercatinib. This case underscores the importance of molecular tumor board meetings and the use of next-generation sequencing WES to detect rare and targetable mutations, ultimately improving patient outcomes.
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