Efficacy and safety of hypofractionated radiotherapy combined with temozolomide in patients with newly diagnosed glioblastoma with poor prognosis: a single-center retrospective analysis

Background The optimal management for newly diagnosed glioblastoma (GBM) patients with poor prognostic features, such as RPA class IV-VI or rapid early progression, remains debated. This study evaluated the efficacy and safety of postoperative hypofractionated radiotherapy (HFRT) with concurrent temozolomide in this population. Methods Single-institution retrospective analysis (Jan 2021-Aug 2025) included patients with histologically confirmed GBM and RPA class IV-VI or rapid early progression who completed postoperative HFRT (≥3 Gy/fraction) with concurrent temozolomide. Results Among 18 eligible patients, most had unfavorable characteristics (subtotal resection: 66.7%, biopsy-only: 33.3%). With a median follow-up of 22.3 months, the median progression-free survival was 8.4 months and median overall survival was 17.7 months. The disease control rate was 77.8%. Recurrence patterns were in-field (46.2%), marginal (38.5%), and out-of-field (15.4%). Acute grade ≥3 toxicities occurred in 16.7% of patients, all managed conservatively. No radiation necrosis was observed. Corticosteroid dependence occurred in 44.4% of patients but was manageable. Conclusion In this exploratory single-center retrospective study, individually tailored HFRT with concurrent temozolomide demonstrated promising survival outcomes and controllable toxicity in poor-prognosis GBM patients unsuitable for standard therapy. The recurrence pattern observed in this small sample cohort suggests a potential need for optimized target volume delineation for HFRT in this population. HFRT represents a potential viable therapeutic alternative in this challenging population, warranting further large-sample prospective validation.