Contralateral DTI-ALPS index as a prognostic biomarker in IDH-wildtype glioblastoma: integrating extent of resection and sex-stratified analyses

Aim This study aimed to evaluate the independent prognostic value of the contralateral DTI-ALPS index in IDH-wildtype glioblastoma, incorporating tumor morphometry, extent of resection, and sex-stratified analyses within a multivariable framework.Methods A retrospective analysis was performed on 153 IDH-wildtype glioblastoma patients from the publicly available UPENN-GBM dataset. Contralateral DTI-ALPS was calculated using DSI Studio via manual ROI placement; tumor morphometry was derived from expert-annotated segmentation labels using 3D Slicer. Survival analyses included Kaplan-Meier estimation, multivariable Cox regression, time-dependent ROC, restricted cubic spline, and sequential C-index comparison with likelihood-ratio testing.Results The contralateral DTI-ALPS index independently predicted overall survival after adjustment for age, sex, tumor volume, and GTR status (HR = 0.405, 95% CI: 0.227-0.725, p = 0.002). Each one standard deviation increase in DTI-ALPS was associated with a 24.2% reduction in mortality risk. GTR >= 90% (HR = 0.651, p = 0.017) and age (HR = 1.021, p = 0.007) also retained independent significance. DTI-ALPS significantly improved model discrimination beyond age alone (C-index: 0.625 -> 0.653 -> 0.668; likelihood-ratio test p = 0.002). Time-dependent AUC reached 0.741 at 6 months. ALPS-based stratification was more pronounced in the subtotal resection subgroup. Sex-stratified analyses showed numerically stronger associations in females, but formal interaction testing did not confirm effect modification. In an exploratory MGMT subset (n = 57), DTI-ALPS did not retain independent significance after MGMT adjustment.Conclusion The contralateral DTI-ALPS index may provide complementary prognostic information beyond established clinical predictors in IDH-wildtype glioblastoma; however, given the incomplete MGMT methylation data and ongoing methodological debate regarding the biological validity of DTI-ALPS, these findings should be considered exploratory. Prospective validation in cohorts with complete molecular and treatment data is required.