Hypofractionated versus standard radiation therapy in combination with temozolomide for glioblastoma in the elderly: a meta-analysis

Background: There is no clear consensus regarding the optimal treatment for glioblastoma (GBM) in the elderly. Hypofractionated radiation therapy (hRT) has emerged as a viable and comparable radiation regime compared to standard radiation therapy (sRT), however the survival effect of temozolomide (TMZ) with hRT is uncertain. The aim of this meta-analysis was to evaluate survival outcomes of hRT + TMZ vs sRT + TMZ in this specific demographic. Methods: Searches of 7 electronic databases from inception to January 2019 were conducted following the appropriate guidelines. Articles were screened against pre-specified criteria. The progression free survival (PFS) and overall survival (OS) metrics were then extracted and pooled by meta-analysis evaluating mean difference (MD). Results: A total of 7 individual comparative studies describing hRT + TMZ vs sRT + TMZ (n = 917) respectively satisfied inclusion criteria. Meta-analysis by random-effects modelling indicated that compared to sRT + TMZ, hRT + TMZ resulted in comparable PFS (MD 0.3 months; 95% CI − 2.4 to 2.9; I ² = 91.7%; P-effect = 0.85) and significantly shorter OS (MD − 3.5 months; 95% CI − 6.3 to − 0.6; I ² = 98.9%; P-effect = 0.02). Subgroup analysis between age definitions of elderly of > 65 vs > 70 years old both demonstrated the same significant trend with no statistical difference between the groups. Conclusion: The combination of hRT + TMZ is feasible in well-selected elderly GBM cases, and appears to confer a statistically comparable PFS compared to sRT + TMZ. However, expectations that the OS with hRT + TMZ is comparable to that of sRT + TMZ in all elderly GBM presentations should be tempered. It is likely a specific subgroup of elderly GBM patients will benefit greatly from the addition of TMZ to hRT, and greater investigation is needed to identify their characteristics.