Long-term outcomes in IDH-wildtype (IDH-wt) gliomas with historical WHO grade 2 and 3 histology

PURPOSE: IDH-wt diffuse gliomas with histologic grade 2-3 features and distinct molecular characteristics are now classified as molecular glioblastoma, yet outcomes and optimal management remain incompletely defined in a contemporary cohort. METHODS: Adults with histologic grade 2-3 IDH-wt gliomas diagnosed from 1996 to 2019 were retrospectively identified. Overall survival (OS) and progression-free survival (PFS) were estimated using Kaplan-Meier methods, with Cox regression used to assess prognostic factors. To account for noncanonical IDH mutations, subgroup analyses were performed in those age > 55 or with next generation sequence (NGS) IDH testing. RESULTS: A total of 134 patients were included, with a median follow-up of 29.8 months. Median OS was 35 months (95% CI: 28.8-43), and median PFS was 20.9 months (95% CI: 14.5-27.4). Grade 2 tumors demonstrated significantly improved outcomes compared to grade 3 tumors (median OS 94.5 vs. 29.8 months; median PFS 50.6 vs. 15.3 months). Among grade 3 tumors, sequential radiation and chemotherapy yielded a median OS of 29.8 months versus 29.8 months with concurrent chemoradiation followed by chemotherapy (p = 0.17); median PFS was 22.2 months versus. CONCLUSION: IDH-wt gliomas with grade 2-3 histology have heterogeneous outcomes. Grade 3 tumors show survival comparable to molecular glioblastoma, while a subset of grade 2 tumors exhibit prolonged survival. Concurrent chemoradiation did not confer a survival advantage over sequential therapy in grade 3 tumors, supporting reevaluation of treatment intensity in selected patients.