Abstract
PURPOSE: /Objectives: Older adults with WHO grade 4 glioma face distinct therapeutic challenges due to age-related comorbidities, treatment intolerance and tumor aggressiveness. This retrospective study evaluates the prognostic value of the Onco-Functional Outcome (OFO) classification, which integrates extent of resection and postoperative functional status, in the context of radiotherapy (RT) for patients with grade 4 glioma. MATERIALS: /Methods: 139 patients aged ≥ 60 years treated between 2001 and 2021 were included. Patients were grouped into four OFO categories based on Karnofsky Performance Status, National Institutes of Health Stroke Scale, and resection extent. Survival outcomes were assessed using Kaplan-Meier and compared by log-rank test. Univariate and multivariable analyses were performed using Cox proportional hazards model. RESULTS: Median OS decreased across OFO groups (OFO1-4: 22.6, 20.5, 12.6, and 11.2 months respectively, log-rank, p = 0.0026). PFS followed a similar pattern (12.2, 9.3, 6.7, and 5.7 months respectively; p = 0.0030). Among 119 patients with known MGMT status, methylation (n = 49) was associated with significantly prolonged OS (36.3 vs. 12.6 months, p < 0.00001) and PFS (14.1 vs 5.9 months, p < 0.00001). Survival advantage of NF-RT showed a a strong trend in both univariate (OS HR = 0.47, 95 % CI 0.28-0.82; p = 0.007) and multivariate models (OS HR = 0.57, 95 % CI 0.33-1.00, 0.051). In multivariable analysis, the OFO classification retained independent prognostic value, with OFO Group 4 associated with a significantly increased risk of both death (OS: HR = 2.91, p = 0.003) and disease progression (PFS: HR = 3.08, p = 0.0005) compared to OFO Group 1. CONCLUSIONS: OFO classification effectively stratifies survival in elderly grade 4 glioma patients. Its integration with MGMT methylation status and RT regimen refines risk assessment, supporting personalized treatment strategies in this vulnerable patient group.