To study the natural history of FGFR fusions in glioma patients.

Glioma is a common subtype of adult primary brain tumors and despite therapeutic advances, it retains a deadly prognosis. Molecular profiling of gliomas has identified important subsets of gliomas that may benefit from targeted therapies, including FGFR fusions. Compiling natural histories of this subset could provide insight into differing survival rates in glioma patients and influence targeted drug development.   

We obtained a list of glioma patients with FGFR fusions from the pathology department’s molecular database. We then reviewed medical records to collect age, sex, FGFR fusion type, treatment, response, and additional molecular information. Kaplan Meier analysis was used to study overall survival (OS) and progression free survival (PFS).

Of the 16 patients with FGFR fusions, all 16 had the FGFR-TACC3 mutation except 1 with a FGFR3-PLEC mutation. Histology included: GBM (9), diffuse astrocytic gliomas (5), and glioneuronal tumors (2). Additional mutations in the GBM cases included: unmethylated MGMT promoter (5), methylated MGMT promoters (3), and no data (1). 7/9 GBM cases had a TERT promoter mutation, 8 had an additional FGFR3 mutation, and 4 had CDKN2A deletion.

 Of the patients with GBM, the median OS was 2.7 years, with a first PFS interval (PFS1) of 1.3 years, and second PFS interval of 0.63 years. Of the 4 patients with FGFR altered diffuse astrocytoma, the median OS was 5.0 years, with a PFS1 of 4.8 years. One patient with a diffuse astrocytic glioma was removed due to insufficient follow up time.

FGFR TACC3 Fusion patients with GBM had prolonged survival, even with an unmethylated MGMT promoter which is associated with a poorer prognosis. This suggests that patients with FGFR-TACC3 fusion mutations may have improved survival.