Rapid response to BRAF/MEK inhibitor therapy within 2 weeks for high-grade glioma with leptomeningeal metastasis: illustrative case.

Abstract

Background: High-grade gliomas, particularly isocitrate dehydrogenase-wildtype glioblastomas (GBMs), are highly aggressive brain tumors with limited treatment options and poor outcomes. A subset of these tumors, including epithelioid GBM, can harbor the BRAF V600E mutation, which drives tumor growth via persistent activation of the RAS/MAPK signaling pathway. Recently, the combination of dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor) has been approved for treating inoperable solid tumors with this mutation.

Observations: The authors present the case of a 51-year-old man with epithelioid GBM harboring the BRAF V600E mutation who developed early leptomeningeal metastasis (LMM) following standard therapy with surgery, temozolomide, and radiotherapy. Owing to disease progression, he was treated with dabrafenib and trametinib. Remarkably, the patient showed rapid clinical and radiographic improvement within 2 weeks of treatment initiation. MR images demonstrated significant reduction in tumor-associated edema and contrast enhancement. At the 28-week follow-up, the patient achieved near-complete radiographic remission without notable adverse effects.

Lessons: This case highlights the potential of BRAF/MEK inhibitor therapy to significantly improve outcomes in patients with aggressive gliomas and LMM, conditions typically associated with extremely poor prognosis. Further studies are needed to validate the long-term efficacy and safety of this targeted therapeutic approach in similar cases. https://thejns.org/doi/10.3171/CASE25247.