Brain tumor volumes as assessed by magnetic resonance imaging (MRI) do not always spatially overlap with biological tumor volumes (BTV) measured by [¹⁸F]Fluoroethyltyrosine positron emission tomography ([¹⁸F]FET PET). We prospectively investigated volumetric patterns based on the extent of tumor volume overlap between the two modalities. Eighty-six patients with newly diagnosed glioma who had undergone MRI and [¹⁸F]FET PET between 2007 and 2009 were included in this prospective study and (re-)classified according to CNS WHO 2021 (Classification of Tumors of the Central Nervous System by the World Health Organization). Four different patterns of volume overlap were defined mathematically according to the extent of overlap between MRI-based T2 tumor volume (non-enhancing tumor volume, nCEV) and BTVs. Progression-free (PFS) and overall survival (OS) were determined. Seventy patients were diagnosed with isocitrate dehydrogenase wildtype (IDHwt) glioblastoma and 16 with IDH-mutant glioma, respectively. The most common pattern was characterized by a larger non-contrast-enhancing tumor volume (nCEV) that enclosed all or most of the BTV and was observed in 46 patients (54%) (pattern 1). This pattern was more frequent in IDH-mutant gliomas than in IDH-wildtype glioblastoma (81% versus 47%, p = 0.02). In multivariate analyses, pattern 1 was associated with prolonged PFS (HR 0.59; 95 CI 0.34-1.0; p = 0.05), but not OS (HR 0.66; 95 CI 0.4–1.08; p = 0.1). For OS, presence of an IDH mutation (p = 0.05) and lower age (p = 0.03) were associated with prolonged OS. The spatial relation between nCEV and BTV varies within and between glioma entities. Most frequently, a larger nCEV encases the BTV. Some patients show spatially dissociated nCEVs and BTVs. Not accounting for this phenomenon in surgery or radiotherapy planning might lead to undertreatment.

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.