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ObjectiveTo develop a machine learning-based nomogram for distinguishing between supratentorial extraventricular ependymoma (STEE) and supratentorial glioblastoma (GBM).MethodsWe conducted a retrospective analysis on MRI datasets obtained from 140 patients who were diagnosed with STEE (n=48) and GBM (n=92) from two institutions. Initially, we compared seven different machine learning algorithms to determine the most suitable signature (rad-score). Subsequently, univariate and multivariate logistic regression analyses were performed to identify significant clinical predictors that can differentiate between STEE and GBM. Finally, we developed a nomogram by visualizing the rad-score and clinical features for clinical evaluation.ResultsThe TreeBagger (TB) outperformed the other six algorithms, yielding the best diagnostic efficacy in differentiating STEE from GBM, with area under the curve (AUC) values of 0.735 (95% CI: 0.625-0.845) and 0.796 (95% CI: 0.644-0.949) in the training set and test set. Furthermore, the nomogram incorporating both the rad-score and clinical variables demonstrated a robust predictive performance with an accuracy of 0.787 in the training set and 0.832 in the test set.ConclusionThe nomogram could serve as a valuable tool for non-invasively discriminating between STEE and GBM.