Neoadjuvant Treatment of BRAFV600E Papillary Craniopharyngiomas: A Case Series

BACKGROUND AND OBJECTIVES: Craniopharyngiomas are locally invasive and frequently recurrent tumors of the sellar/suprasellar region. Historically, the mainstay of treatment has been surgical resection. The papillary type of craniopharyngiomas (PCP) frequently harbors a BRAFV600E mutation, rendering them amenable to targeted therapies. We present our institution's initial experience of using a minimally invasive endoscopic transventricular approach for biopsy, followed by neoadjuvant targeted BRAF/MEK inhibition. METHODS: We retrospectively reviewed 5 cases of patients with BRAFV600E-mutated PCP diagnosed by endoscopic transventricular biopsy between July 2018 and August 2023, who then received BRAF/MEK inhibitor therapy. Patient characteristics, symptoms, tumor volumes, and treatment outcomes were collected from the electronic medical record. Tumor volumes were collected from radiology reports. RESULTS: All 5 patients underwent endoscopic transventricular biopsy of a third ventricular tumor. The mean tumor volume postbiopsy was 23.8 ± 19.1 cm3 (range, 11.5-57.3 cm3). After confirmation of BRAFV600E mutation by biopsy, all patients received at least 1 cycle of BRAF/MEK inhibitor therapy (median, 5 cycles; range, 1-16 cycles). Two patients elected to undergo radiation treatment after 5 cycles of therapy. No patients experienced decline in endocrine function; notably, none of them developed arginine-vasopressin deficiency. Two patients with abnormal visual findings at baseline experienced improvement after treatment. At the last follow-up (mean, 5.1 ± 2.3 years after treatment initiation; range, 2.1-7.8 years), the mean tumor volume was 0.5 ± 0.4 cm3 (range, 0.07-1.2 cm3), corresponding to a mean reduction of 97.8% ± 1.2% (range, 96.2%-99.6%). CONCLUSION: When anatomically feasible, endoscopic transventricular biopsy appears to be a safe method for confirming BRAFV600E-mutated PCP. In our cohort, neoadjuvant BRAF/MEK inhibitor therapy after biopsy resulted in substantial, durable tumor shrinkage, visual improvement, and endocrine stability, without permanent treatment-related morbidity or need for more surgical management. The long-term follow-up reported here supports this novel, minimally invasive management pathway for BRAFV600E-mutated PCP.