Predicting the molecular subtypes of 2021 WHO grade 4 glioma by a multiparametric MRI-based machine learning model

Accurately distinguishing the different molecular subtypes of 2021 World Health Organization (WHO) grade 4 Central Nervous System (CNS) gliomas is highly relevant for prognostic stratification and personalized treatment.

To develop and validate a machine learning (ML) model using multiparametric MRI for the preoperative differentiation of astrocytoma, CNS WHO grade 4, and glioblastoma (GBM), isocitrate dehydrogenase-wild-type (IDH-wt) (WHO 2021) (Task 1:grade 4 vs. GBM); and to stratify astrocytoma, CNS WHO grade 4, by distinguish astrocytoma, IDH-mutant (IDH-mut), CNS WHO grade 4 from astrocytoma, IDH-wild-type (IDH-wt), CNS WHO grade 4 (Task 2:IDH-mut ^{grade 4} vs. IDH-wt ^{grade 4}). Additionally, to evaluate the model's prognostic value.

We retrospectively analyzed 320 glioma patients from three hospitals (training/testing, 7:3 ratio) and 99 patients from ‌The Cancer Genome Atlas (TCGA) database for external validation‌. Radiomic features were extracted from tumor and edema on contrast-enhanced T1-weighted imaging (CE-T1WI) and T2 fluid-attenuated inversion recovery (T2-FLAIR). Extreme gradient boosting (XGBoost) was utilized for constructing the ML, clinical, and combined models. Model performance was evaluated with receiver operating characteristic (ROC) curves, decision curves, and calibration curves. Stability was evaluated using six additional classifiers. Kaplan-Meier (KM) survival analysis and the log-rank test assessed the model's prognostic value.

In Task 1 and Task 2, the combined model (AUC = 0.907, 0.852 and 0.830 for Task 1; AUC = 0.899, 0.895 and 0.792 for Task 2) and the optimal ML model (AUC = 0.902, 0.854 and 0.832 for Task 1; AUC = 0.904, 0.899 and 0.783 for Task 2) significantly outperformed the clinical model (AUC = 0.671, 0.656, and 0.543 for Task 1; AUC = 0.619, 0.605 and 0.400 for Task 2) in both the training, testing and validation sets. Survival analysis showed the combined model performed similarly to molecular subtype in both tasks (p = 0.964 and p = 0.746).

The multiparametric MRI ML model effectively distinguished astrocytoma, CNS WHO grade 4 from GBM, IDH-wt (WHO 2021) and differentiated astrocytoma, IDH-mut from astrocytoma, IDH-wt, CNS WHO grade 4. Additionally, the model provided reliable survival stratification for glioma patients across different molecular subtypes.