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

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.

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.

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.

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.
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Carriere Carriere, Haisraely Haisraely, Aaroe Aaroe, Ahmed Ahmed, Lewis Lewis, Colson-Fearon Colson-Fearon, Bolden Bolden, Swanson Swanson, Beckham Beckham, Wang Wang, De De, Perni Perni, Tom Tom, Li Li, McGovern McGovern, McAleer McAleer, Ghia Ghia, Jiang Jiang, Chung Chung, Grosshans Grosshans, Ballester Ballester, Esquenazi Esquenazi, Kamiya-Matsuoka Kamiya-Matsuoka, Yeboa Yeboa
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