Spatial-temporal recurrence patterns of grade 4 glioma using deep learning integrated multiparametric MRI and molecular pathology

Grade 4 glioma is inherently lethal due to inevitable recurrence. Current radiotherapy guidelines recommend uniform target volume margins, disregarding molecular and clinical variables. We hypothesized that spatiotemporal recurrence may be predicted by molecular and phenotypic features present already at diagnosis. We analyzed 390 paired MRIs of grade 4 gliomas from Norwegian multi-centers and TCIA (2015-2025). Deep learning segmentation identified contrast-enhancing (CEcore) and non-enhancing (NE) tumor compartments and afflicted anatomical regions. We quantified primary CEcore/NE volume ratio, anatomical tumor trajectories, and spatiotemporal progression using Hausdorff-95-analyzed in relation to survival, MGMT, IDH, age, extent of resection, sex, and anatomical location, using machine learning and Cox regression. Primary tumor composition was independently prognostic: CEcore/NE volume ratio ≤0.324 predicted improved overall survival (adjusted HR = 0.56, 95% CI 0.37-0.84, p = 0.006), independent of age, MGMT-status, and individual compartments. Within IDH-wildtype, MGMT-unmethylated patients, low volume ratio ≤0.324 demonstrated a 4.3 months survival benefit (median 17.6 vs 13.3 months, p = 0.0209). Longer time to progression correlated with increased HD95 distances (p < 0.03). Tumors originating in occipital lobe had highest propensity to migrate to new sites (57.1%) and the shortest time to progression (adjusted HR = 1.90, p = 0.026). These findings support molecular-demographic-anatomical risk stratification that may inform personalized margin-determination in radiotherapy planning.