Abstract Follow-up magnetic resonance imaging (MRI) of post-treatment glioblastoma (GBM) can be diagnostically challenging in differentiating progressive disease (PD) from coexisting treatment-related changes. The study aim was to train a machine learning model using multiple MRI timepoints from treated GBM patients with subsequent PD or at least six months of tumor-like, persistently stable disease (SD) to estimate PD risk. A retrospective, post-treatment GBM cohort (n=189) with 453 timepoints was identified with available MRI sequences (T1-weighted with and without contrast, T2-weighted, and fluid-attenuated inversion recovery). PD cases (n=154) showed new, enhancing PD followed by death within 3-6 months; timepoints included the MRI on the PD diagnosis date and the one directly prior. SD cases (n=35) exhibited stable, tumor-like enhancement over timepoints. Cases underwent voxel-wise annotation of PD versus SD. A multiclass, three-dimensional nnU-Net was trained to label voxels as PD, SD, or neither using timepoint sequences with five-fold cross-validation. Model performance was assessed using the ratio of predicted PD/SD voxels compared to each case’s actual PD or SD status. Classification accuracy of PD versus SD status, PD case-wise sensitivity and specificity, and a Receiver Operating Characteristic (ROC) analysis using the PD/SD ratio were presented. The five-fold model ensemble was evaluated on a holdout test set. Validation set performance showed 74.3% accuracy, 0.73 PD case-wise sensitivity, and 0.80 specificity. The holdout set exhibited 79.8% accuracy, 0.81 sensitivity, and 0.78 specificity for PD cases. The ROC analysis showed an area under the curve of 0.80 and 0.83 on the validation and holdout sets, respectively. The model showed high performance and classification accuracy in predicting which voxels were at risk of PD in post-treatment GBM cases. The model also differentiated between PD and SD regions. The model’s predicted PD/SD ratio may be clinically used to stratify patients’ PD risk.
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