e14087 Background: Tumor Treating Fields (TTFields) combined with temozolomide received FDA approval for newly diagnosed glioblastoma (ndGBM) in 2015. Since the last comprehensive meta-analysis (Ballo et al., 2023), substantial new evidence has emerged, including studies suggesting variable efficacy across geographic regions. No prior meta-analysis has provided pooled hazard ratios for progression-free survival (PFS). We conducted an updated systematic review and meta-analysis to evaluate overall survival (OS) and PFS outcomes with pre-specified geographic subgroup analyses. Methods: PubMed, SCOPUS, and EMBASE were searched through December 2025 following PRISMA guidelines (PROSPERO CRD420261292232). Comparative studies evaluating TTFields plus standard of care (SOC) versus SOC alone in ndGBM were included. Random-effects models estimated pooled hazard ratios. Geographic subgroups (Global, USA, Asia, Europe) were pre-specified. Publication bias was assessed using DOI plots with LFK index. Results: Twelve studies met inclusion criteria (n=5 new studies). TTFields significantly improved OS (HR 0.62, 95% CI 0.51–0.76, p<0.001; I²=70.7%) and PFS (HR 0.65, 95% CI 0.55–0.78, p<0.001; I²=62.7%). US-based studies demonstrated the most consistent benefit with minimal heterogeneity for both OS (HR 0.70, 95% CI 0.59–0.83; I²=0%) and PFS (HR 0.74, 95% CI 0.62–0.89; I²=10.7%). Asian studies showed significant but heterogeneous benefits (OS: HR 0.55, I²=88.2%; PFS: HR 0.59, I²=79.9%). LFK indices indicated no major publication bias (OS: −0.3; PFS: −1.6). Conclusions: This updated meta-analysis confirms TTFields survival benefit in ndGBM and provides the first pooled PFS hazard ratio estimate. US studies demonstrate highly consistent treatment effects. Regional heterogeneity in Asian populations warrants further investigation to optimize patient selection globally. Meta-analysis of overall survival and progression free survival by geographic subgroup. Subgroup N OS HR (95% CI) I² PFS HR (95% CI) I² Global 1 0.63 (0.53–0.76) — 0.63 (0.52–0.76) — USA 5 0.70 (0.59–0.83) 0% 0.74 (0.62–0.89) 10.7% Asia 5 0.55 (0.32–0.93) 88.2% 0.59 (0.41–0.86) 79.9% Europe 1 0.61 (0.39–0.95) — 0.64 (0.42–0.97) — Overall 12 0.62 (0.51–0.76) 70.7% 0.65 (0.55–0.78) 62.7% HR = hazard ratio; CI = confidence interval; OS = overall survival; PFS = progression free survival; N = number of studies. Test for subgroup differences: OS p=0.75; PFS p=0.55.
Krishnakumar et al. (Thu,) studied this question.