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

BackgroundThere 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.MethodsSearches 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).ResultsA 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 0.3months; 95% CI -2.4 to 2.9; I-2=91.7%; P-effect=0.85) and significantly shorter OS (MD -3.5months; 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>70years old both demonstrated the same significant trend with no statistical difference between the groups.ConclusionThe 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.