Widely metastatic atypical pituitary adenoma with mTOR pathway STK11(F298L) mutation treated with everolimus therapy.
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 >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.
Columbia University Medical School, New York, NY, USA.
Laura E
LE
Donovan
Columbia University Medical School, New York, NY, USA.
Ashley V
AV
Arnal
Department of Pathology, Columbia University Medical Center/New York-Presbyterian Hospital, New York, NY, USA.
Shih-Hsiu
SH
Wang
Miami Cancer Institute, Baptist Health South Florida, Miami, FL, USA.
Yazmin
Y
Odia
D000091162:AMP-Activated Protein Kinase Kinases; D000236:Adenoma / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001921:Brain / Q000000981:diagnostic imaging; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000556:secondary / Q000601:surgery; D000069287:Capecitabine / Q000627:therapeutic use; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000068338:Everolimus / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010911:Pituitary Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D000077204:Temozolomide
D000970:Antineoplastic Agents; D019394:Ki-67 Antigen; D000069287:Capecitabine; D003606:Dacarbazine; D000324:Adrenocorticotropic Hormone; D000068338:Everolimus; D017346:Protein Serine-Threonine Kinases; C109790:STK11 protein, human; D000091162:AMP-Activated Protein Kinase Kinases; D000077204:Temozolomide
STK11; atypical pituitary adenoma; everolimus