Short-course radiotherapy with or without temozolomide in elderly patients with newly diagnosed glioblastoma: a time-to-event meta-analysis of overall and progression-free survival.

BACKGROUND

Glioblastoma is the most common and aggressive primary brain tumor in adults, with elderly patients facing particularly poor outcomes due to frailty and treatment intolerance. Short-course radiotherapy (SCRT) is a pragmatic approach, but the added benefit of temozolomide (TMZ) to SCRT is supported by limited evidence.

METHODS

We conducted a search of PubMed, SCOPUS and Embase for studies published from inception to July 9, 2025. Eligible studies directly compared SCRT to SCRT + TMZ in elderly adults (≥ 65years) with newly diagnosed, histologically confirmed glioblastoma, and provided Kaplan–Meier survival curves for overall survival (OS) or progression-free survival (PFS). Pseudo-individual patient data were digitized from published survival curves and survival curves were reconstructed. Hazard ratios (HRs) were estimated with a one stage Cox regression analyses and differences in restricted mean survival time (ΔRMST) were analyzed.

RESULTS

Initial search yielded 211 articles, out of which five studies (1,062 patients; 516 SCRT + TMZ, 546 SCRT) met inclusion for analysis. Mean age was 71.5 years with 53.2% of patients having Karnofsky Performance Status < 80. SCRT + TMZ significantly reduced the hazard of death (HR: 0.68, 95% CI: 0.70–0.77; p < 0.0001) and disease progression (HR 0.53, 95% CI 0.45–0.62, p < 0.0001). The median OS was longer with SCRT + TMZ than with SCRT alone (8.0 months vs. 6.1 months), as was the median PFS (5.1 months vs. 3.8 months). SCRT + TMZ showed increasing survival benefits with significant ΔRMST for OS of up to + 2.50 months at 30 months (95% CI: 1.74–3.31). PFS gains were also significant, with ΔRMST of up to + 1.58 months (95% CI: 1.16–2.01) at 10 months.

CONCLUSION

In elderly patients with newly diagnosed glioblastoma, SCRT + TMZ significantly improves OS and PFS compared with SCRT alone with increasing survival benefits over time. There is the need for more clinical trials to supplement the available evidence.