Abstract
Older patients with glioblastoma (GBM) are underrepresented in clinical trials. Several abbreviated and standard chemoradiotherapy regimens are advocated with no consensus on the optimal approach. Our objective was to quantitatively evaluate which of these regimens would provide the most favorable survival outcomes in older patients with GBM using a network meta-analysis. MEDLINE, Embase, Google Scholar, and the Cochrane Library were searched. Patients >60 years of age with histologically confirmed GBM were included. Primary outcome of interest was the pooled HR from randomized controlled trials (RCTs). Secondary outcomes of interest included pooled HR from studies controlling for MGMT promoter methylation status, and safety. Fourteen studies, including 5 RCTs, reporting 4,561 patients were included. Using highest quality data from RCTs, our network-based approach demonstrated that standard radiotherapy (SRT) and temozolomide (TMZ) provided similar survival benefit when compared with hypofractionated radiotherapy (HRT) and TMZ [HR = 0.90; 95% confidence interval (CI), 0.43-1.87], TMZ alone (HR 1.25; 95% CI, 0.69-2.26), HRT alone (HR = 1.34; 95% CI, 0.73-2.45), or SRT alone (HR = 1.43; 95% CI, 0.87-2.36). HRT-TMZ had the highest probability (85%) of improving survival in older patients with GBM followed by SRT-TMZ (72%). Pooled analysis of trials controlling for MGMT promoter methylation status demonstrated that TMZ monotherapy confers similar survival benefit to combined chemoradiotherapy. Statistical comparisons using a network approach demonstrates that the common treatment regimens for older patients with GBM in previous RCTs confer similar survival benefits. Adjustments for MGMT promoter methylation status demonstrated that radiotherapy alone was inferior to TMZ-based approaches. Head-to-head comparison of TMZ monotherapy to combined TMZ and radiation is warranted.
Highlights
Glioblastoma (GBM) is the most common primary brain tumor in adults and its incidence increases with age
Using highest quality data from RCTs, our network-based approach demonstrated that standard radiotherapy (SRT) and temozolomide (TMZ) provided similar survival benefit when compared with hypofractionated radiotherapy (HRT) and TMZ [HR 1⁄4 0.90; 95% confidence interval (CI), 0.43–1.87], TMZ alone (HR 1.25; 95% CI, 0.69–2.26), HRT alone (HR 1⁄4 1.34; 95% CI, 0.73–2.45), or SRT alone (HR 1⁄4 1.43; 95% CI, 0.87–2.36)
Pooled analysis of trials controlling for MGMT promoter methylation status demonstrated that TMZ monotherapy confers similar survival benefit to combined chemoradiotherapy
Summary
Glioblastoma (GBM) is the most common primary brain tumor in adults and its incidence increases with age. In population-based studies, the median age at diagnosis is 65–67 years [1], while the median age of patients included in contemporary clinical trials is only 54–57 years This may limit the generalizability of trial results and fail to address the needs of a general GBM population. The current standard-of-care treatment protocol, commonly referred to as the “Stupp Protocol,” includes maximal safe tumor resection followed by daily temozolomide (TMZ; 75 mg/m2 orally) and concurrent radiotherapy (60 Gy in 30 fractions) followed by adjuvant TMZ (150–200 mg/m2) for 6 months [2] This approach prolonged survival with a HR of 0.62 [95% confidence interval (CI), 0.51–0.75], translating into an increase in median survival by 2.5 months and a 2-year survival.
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