Hypofractionated Radiotherapy Plus Temozolomide in Elderly Glioblastoma: A Systematic Review and Meta-analysis

Abstract

Background: Glioblastoma multiforme (GBM) has a poor prognosis in elderly patients, in whom standard multimodal therapy is often limited by comorbidities and treatment-related toxicity. Hypofractionated radiotherapy (HFRT) combined with temozolomide (TMZ) has been proposed as an alternative approach, but its effectiveness remains uncertain. Materials and methods: A systematic review and single-arm meta-analysis were conducted in accordance with PRISMA guidelines. PubMed, Embase, Scopus, Web of Science, and CENTRAL were searched from inception through February 2025. Prospective and retrospective studies evaluating moderate hypofractionated radiotherapy plus TMZ in patients aged ≥70 years with newly diagnosed GBM were included. Outcomes assessed were overall survival (OS), progression-free survival (PFS), radiographic tumor response, and treatment-related adverse events. Quantitative synthesis was performed using a random-effects model, and risk of bias was assessed with ROBINS-I. Results: Nine studies were included. Median OS ranged from 5.5 to 15.8 months. The longest OS (15.8 months) was reported with 40.05 Gy in 15 fractions plus TMZ, whereas the shortest OS (5.5 months) was observed in a study using variable hypofractionated schedules (30–45 Gy in 10–15 fractions). Median PFS ranged from 4.5 to 8.5 months, with the highest value reported for 45 Gy in 15 fractions and the lowest for 40 Gy in 15 fractions. Exploratory observations suggested variability in tumor response according to baseline Karnofsky Performance Status. Hematologic toxicity was the most common adverse event. Substantial heterogeneity was observed across studies. Conclusions: HFRT combined with TMZ may be a feasible option for selected elderly patients with GBM. However, given the heterogeneity, limited number of studies, and predominantly non-randomized designs, these findings should be interpreted as exploratory. Further well-designed prospective studies are needed.