OS06.4 Identification of novel NTRK fusion in glioneuronal tumors and radiographic response following therapy with an NTRK inhibitor

Glioneuronal tumors constitute a histologically diverse group of primary CNS neoplasms, with no effective systemic therapy after surgery has failed. To further characterize this group of tumors, we collected a cohort of 26 glioneuronal tumors and performed in-depth genomic analysis. We identified mutations in BRAF (34%) and oncogenic fusions (30%). In addition, we discovered novel oncogenic fusions involving members of the NTRK gene family in a subset of our cohort. One patient with BCAN exon 13 fused to NTRK1 exon 11 initially underwent a subtotal resection for a 4 th ventricular glioneuronal tumor but ultimately required additional therapy due to progressive, symptomatic disease. Given the patient’s targetable fusion, the patient was enrolled on a clinical trial with entrectinib, a pan-Trk, ROS1 and ALK inhibitor. The patient was treated for 11 months and during this time volumetric analysis of the lesion demonstrated a maximum reduction of 60% in the contrast-enhancing tumor compared to his pre-treatment MRI. The radiologic response was associated with resolution of his clinical symptoms and was maintained for eleven months on treatment. This represents the first report of BCAN-NTRK1 fusion in glioneuronal tumors and highlights its clinical importance as a novel, targetable alteration.