BACKGROUND: Glioblastoma (GBM) is a common brain tumor with a poor prognosis. There is a paucity of knowledge regarding optimal treatment approaches for elderly patients with GBM who have a relatively good Karnofsky (KPS) or Eastern Cooperative Oncology Group (ECOG) performance status. This study compared treatment outcomes in older patients (≥65) with GBM based on their performance status, either high (KPS ≥ 70 and ECOG <
2) or low (KPS <
70 and ECOG ≥ 2), who underwent hypofractionated radiotherapy (HFRT) (40 Gy in 15 fractions) versus conventional fractionation (60 Gy in 30 fractions). METHODS AND MATERIALS: Fifty-six patients with newly diagnosed IDH-wildtype GBM were included in this single-institution retrospective analysis. Patient demographics, clinical features, and treatment outcomes were analyzed. Univariable and multivariable Cox regression analyses were used to analyze the association of treatments with overall survival (OS) and progression-free survival (PFS) and the impact of performance status. RESULTS: Twenty-six patients (46 %) received conventional RT and thirty (54 %) received HFRT. High or low performance status within this patient population did not impact either OS (p = 0.0532) or PFS (p = 0.3054). For conventionally fractionated RT vs. HFRT, median OS was 13.6 and 6.8 months, respectively, (p = 0.0034) and median PFS was 5.98 and 5.55 months respectively, (p = 0.0488). Adjuvant temozolomide was significantly associated with improved OS and PFS. CONCLUSIONS: High or low performance status did not affect patient outcomes in this population regardless of RT fractionation. Elderly patients with GBM who received conventionally fractionated RT had superior survival outcomes than those who underwent HFRT and were also more likely to receive concurrent and adjuvant temozolomide. Our findings underscore the impact of systemic therapy in this patient population.