Prediction of Overall Survival in Glioblastoma Using Early Postoperative Reduction in FLAIR Lesion Volume After Gross...

Background/Objectives: Glioblastoma (GBM) comprises a contrast-enhancing (CE) mass and peritumoral hyperintensity on fluid-attenuated inversion recovery (FLAIR) on magnetic resonance imaging (MRI). Although a smaller residual FLAIR lesion volume (FLV) after gross total resection (GTR) is associated with longer survival, the clinical observation of rapid FLV reduction within the first postoperative month remains unknown. We evaluated the independent prognostic contributions of early and late FLV reduction in patients with newly diagnosed GBM, isocitrate dehydrogenase (IDH)-wildtype, who underwent GTR. Methods: In a retrospective cohort of 51 adults with GBM, IDH-wildtype, who underwent GTR and standard chemoradiotherapy, semi-automated FLV was measured on MRI preoperatively, immediately postoperatively (FLV0), at 1 month (FLV1), and at 3 months (FLV3). FLV changes were expressed as percentage changes relative to the preceding timepoint (ΔFLV0-1, ΔFLV1-3). Using a 3-month landmark analysis, multivariable Cox models for overall survival (OS) were fitted, adjusted for age, O6-methylguanine-DNA-methyltransferase promoter (pMGMT) methylation, and postoperative Karnofsky Performance Status (KPS). Results: In the multivariable 3-month landmark analysis, each 10-percentage-point early FLV reduction (∆FLV0-1^[10-pp]) was associated with lower mortality risk (hazard ratio [HR] 0.91, 95% confidence interval [CI] 0.82-0.99, p = 0.037) whereas a late FLV reduction (∆FLV1-3^[10-pp]) showed a smaller association with OS (HR 0.99, 95% CI 0.98-1.00, p = 0.043). In an exploratory dichotomized analysis at a 20% reduction threshold, early responders (∆FLV0-1 ≥ 20%) had markedly better OS (HR 0.33, p = 0.010). Conclusions: In selected patients with GBM, IDH-wildtype, who achieved radiographic GTR and received standard chemoradiotherapy, early postoperative FLV reduction at 1 month independently predicted longer OS, with a substantially larger effect than late reduction. Prospective multi-center validation is required before clinical implementation.