LMAP-04 CHOOSING WISELY BETWEEN RADIOTHERAPY DOSE-FRACTIONATION SCHEDULES: THE MOLECULAR GRADED PROGNOSTIC ASSESSMENT (MOLGPA) FOR ELDERLY GLIOBLASTOMA (EGBM-MOLGPA)

This study aimed develop a prognostic model integrating genomic characteristics in patients with elderly glioblastoma (eGBM), and compare the efficacy between conventionally fractionated radiotherapy (CFRT) vs. hypofractionated radiotherapy (HFRT). Patients aged ≥65 years who underwent radiotherapy for IDH-wildtype eGBM between 2006 and 2021 were included. Patients planned for a ≥6-week or ≤4-week radiotherapy were regarded as being treated with CFRT (334 patients; median, 60 Gy in 30 fractions) or HFRT (239 patients; median, 45 Gy in 15 fractions), respectively. We developed the molecular graded prognostic assessment score for eGBM (eGBM-molGPA) and assigned 0.0, 0.5, and 1.0 points in proportion to the corresponding hazard ratio (HR) of each prognostic factor for overall survival (OS). Temozolomide-based chemoradiation was applied for 86% of patients. With a median follow-up of 17.4 months, the median OS was 18.7 months for CFRT plus temozolomide group, 15.1 months for HFRT plus temozolomide group, and 10.4 months for RT alone group. The eGBM-molGPAwas established based on prognostic factors from multivariate analysis (performance, extent of resection, temozolomide, methylation of the MGMT promoter, subventricular zone involvement, temporalis muscle thickness, and the mutation status of TERT promoter and TP53 gene) and patients were allocated to three risk groups (high risk, total score 3.0–4.5; intermediate risk, 1.5–2.5; low risk, 0.0–1.0). Patients treated with CFRT plus temozolomide had significantly improved OS compared to those treated with HFRT plus temozolomide or radiotherapy alone in the low and intermediate risk groups (p<0.001). However, in the high-risk group, there was no significant difference in OS between treatment options. CFRT plus temozolomide can be a more effective strategy for selected eGBM patients compared to HFRT. For high-risk patients, a protracted treatment schedule might not be beneficial. The novel eGBM-molGPA can be used as a clinical tool for choosing wisely among radiotherapy options.