Tumor-Treating Fields Plus Temozolomide Versus Temozolomide Alone in Newly Diagnosed Glioblastoma: A Systematic Review and Bayesian Meta-Analysis with Meta-Regression

Introduction: Glioblastoma is the most aggressive primary brain tumor in adults, with limited survival despite multimodal therapy. Tumor-treating fields (TTFs) combined with temozolomide (TMZ) have emerged as a therapeutic option for newly diagnosed glioblastoma (nGBM), yet the magnitude, robustness, and generalizability of its benefit remain uncertain. This Bayesian meta-analysis aimed to determine whether the addition of TTFs to TMZ improves survival outcomes and safety profiles in patients with nGBM. Methods: We systematically searched PubMed, Scopus, and the Cochrane Library from inception to 5 April 2026, for studies comparing TTFs + TMZ with TMZ alone in nGBM (PROSPERO “CRD420261374813”). Outcomes included overall survival (OS; hazard ratio [HR]), progression-free survival (PFS; HR), and dermatologic adverse effects (proportions). A Bayesian random-effects model with vague priors for overall effects and informative/weakly informative priors for between-study heterogeneity was applied. Sensitivity analyses with alternative prior specifications were performed, and posterior probabilities (PPs), 95% credible intervals (CrIs), and posterior predictive probabilities (PPPs) were estimated. Results: Twelve studies (one randomized controlled trial and 11 observational studies) comprising 2797 patients were included (TTFs + TMZ: 1228; TMZ: 1569). TTFs + TMZ was associated with improved OS (HR 0.68; 95% CrI 0.57–0.80; 99% PP HR < 1) with a 96% PPP that future studies would also favor TTFs + TMZ. PFS was likewise improved (HR 0.67; 95% CrI 0.58–0.77; 99% PP HR < 1), with a 98% PPP favoring TTFs + TMZ in future studies. Subgroup analyses suggested that risk of bias contributed more to heterogeneity than study design. Among patients receiving TTFs + TMZ, the estimated proportion of dermatologic adverse effects was 57.8% (95% CrI 0.36–0.79), with high PPs of exceeding clinically meaningful thresholds. Conclusions: In this Bayesian meta-analysis, TTFs combined with TMZ was associated with improved OS and PFS in nGBM, although dermatologic toxicity was frequent. These findings support TTFs + TMZ as an effective adjunctive strategy, while emphasizing the importance of patient selection, adherence, and toxicity management.