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Pituitary adenomas are the commonest intracranial tumor, but metastases are rare (0.2% yearly incidence) and portend poor prognosis. CAPecitabine and TEMozolomide improved outcomes for neuroendocrine tumors. However, no chemotherapy is approved for refractory pituitary carcinomas. Next-generation sequencing revealed an actionable mTOR pathway STK11 mutation in a woman with adrenocorticotropic hormone-secreting pituitary carcinoma refractory to six resections, radiation and CAPecitabine and TEMozolomide. Given efficacy in preclinical pancreatic cancer models with STK11 mutations, she received radiation and everolimus leading to clinical improvement and stability on MRI and PET for &gt;6 months. She ultimately expired from widely metastatic disease. Next-generation sequencing can identify actionable mutations in rare or treatment refractory tumors. Earlier targeted therapy may improve outcomes.

Widely metastatic atypical pituitary adenoma with mTOR pathway STK11(F298L) mutation treated with everolimus therapy