Radiotherapy Plus Concurrent or Sequential Temozolomide for Glioblastoma in the Elderly: A Meta-Analysis

Abstract

BackgroundMany physicians are reluctant to treat elderly glioblastoma (GBM) patients as aggressively as younger patients, which is not evidence based due to the absence of validated data from primary studies. We conducted a meta-analysis to provide valid evidence for the use of the aggressive combination of radiotherapy (RT) and temozolomide (TMZ) in elderly GBM patients.MethodsA systematic literature search was conducted using the PubMed, EMBASE and Cochrane databases. Studies comparing combined RT/TMZ with RT alone in elderly patients (≥65 years) with newly diagnosed GBM were eligible for inclusion.ResultsNo eligible randomized trials were identified. Alternatively, a meta-analysis of nonrandomized studies (NRSs) was performed, with 16 studies eligible for overall survival (OS) analysis and nine for progression-free survival (PFS) analysis. Combined RT/TMZ was shown to reduce the risk of death and progression in elderly GBM patients compared with RT alone (OS hazard ratio [HR] 0.59, 95% confidence interval [CI] 0.48–0.72; PFS: HR 0.58, 95% CI 0.41–0.84). Evaluable patients were reported to tolerate combined treatment but certain toxicities, and especially hematological toxicities, were more frequently observed. Limited data on O6-methylguanine-DNA methyltransferase (MGMT) promoter status and quality of life were reported.ConclusionThe meta-analysis of NRSs provided level 2a evidence (Oxford Centre for Evidence-Based Medicine) that combined RT/TMZ conferred a clear survival benefit on a selection of elderly GBM patients who had a favorable prognosis (e.g., extensive resection, favorable KPS). Toxicities were more frequent but acceptable. Future randomized trials are warranted to justify a definitive conclusion.

A Surveillance, Epidemiology and End Results-Medicare data analysis of elderly patients with glioblastoma multiforme: Treatment patterns, outcomes and cost

“…In this analysis, treatment using SRT with concurrent TMZ correlated with an improved survival, which was also the trend for patients aged ≥75 years. This finding is supported by previously published studies reporting increased overall survival in elderly GBM patients since the TMZ era, as well as a recently published meta-analysis of non-randomized studies of elderly GBM patients treated with RT and concurrent TMZ or RT alone, who also exhibited improved survival (21)(22)(23).…”

Temozolomide with or without Radiotherapy in Patients with Newly Diagnosed Glioblastoma Multiforme: A Meta-Analysis

“…A recent meta-analysis revealed a clear survival benefit of RT + TMZ in elderly patients with glioblastoma, where it was shown that combined RT + TMZ reduced the risk of death and progression compared with RT-alone [31]. Although we did not perform a sub-group analysis based on patients' age in the present study, the results from Yin et al [31] reveal a clear beneficial effect of TMZ in elderly patients as well.…”

“…We were not able to perform a subgroup analysis based on the MGMT methylation status due to lack of reported data. Moreover, a subgroup analysis of the elderly was not performed, but there is enough evidence to support the survival benefit of TMZ in this population [31,37]. In addition, we did not perform analysis of toxicity due to incomplete reporting of adverse events, which further prevented the full consideration of TMZ as a concomitant treatment along with radiation.…”

Patient and treatment factors associated with survival among adult glioblastoma patients: A USA population-based study from 2000–2010

“…Given the increasing proportion of elderly GBM patients [28,29], it is important to focus on improving outcomes in this population and clarifying the standard of care. Recent studies have suggested the utility of aggressive multimodal treatment of elderly GBM patients [19,30].…”