Fractional tumor burden refines prognostic stratification beyond MGMT status in glioblastoma after chemoradiotherapy

Background and Purpose. Following standard-of-care treatment for glioblastoma, response to chemoradiotherapy is difficult to evaluate because changes on postcontrast T1WI may represent either treatment effect or tumor progression, particularly in the early posttreatment period. Although O6-methylguanine DNA methyltransferase promoter methylation is prognostic and informs treatment response, outcomes among patients remain heterogeneous. We hypothesized that combining advanced physiologic imaging with methylation status would improve early prognostic stratification. Materials and Methods. In this retrospective cohort study, patients with newly diagnosed glioblastoma who underwent surgical resection or biopsy followed by standard chemoradiotherapy and had diffusion- and perfusion-weighted MR imaging within 6 weeks after treatment completion were included. Imaging-derived metrics included mean apparent diffusion coefficient (ADC), mean standardized relative cerebral blood volume (sRCBV), change in contrast-enhancing volume on dT1, and the volume of fractional tumor burden (FTB), which is the volume of enhancing tissue with moderate-to-high probability of vascular tumor. Overall survival was evaluated using Kaplan-Meier analysis with log-rank testing. Results. Forty-three patients (21 male, 22 female) were included with a mean age of 57 years. Median overall survival was longer in patients with O6-methylguanine DNA methyltransferase-methylated tumors compared with unmethylated tumors (19.7 vs 10.6 months; P = .01). Stratification by mean sRCBV, mean ADC, or change in dT1 volumes was not associated with overall survival (P > .05 for all comparisons). Among unmethylated tumors, FTB <5 mL was associated with longer overall survival compared with ≥5 mL (14.5 vs 8.4 months; P = .006), whereas no survival difference, based on FTB volumes, was observed in methylated tumors (P = .50). Conclusions. Fractional tumor burden, measured within 6 weeks after chemoradiotherapy, refines prognostic stratification beyond methylation status in glioblastoma, identifying a subgroup of unmethylated tumors with longer overall survival. These findings support the use of spatially resolved perfusion imaging to improve interpretation of early posttreatment enhancement.