Using Radiomics and Explainable Ensemble Learning to Predict Radiation Pneumonitis and Survival in NSCLC Patients...

Purpose: This study aimed to develop a precise predictive model to assess the risk of radiation pneumonitis (RP) and three-year survival in patients with non-small cell lung cancer (NSCLC) following volumetric modulated arc therapy (VMAT). Radiomics features, ensemble stacking, and explainable artificial intelligence (XAI) were integrated to enhance predictive performance and clinical interpretability. Materials and Methods: A retrospective cohort of 221 NSCLC patients treated with VMAT at Kaohsiung Veterans General Hospital between 2013 and 2023 was analyzed, including 168 patients for RP prediction (47 with ≥grade 2 RP) and 118 patients for survival prediction (34 deaths). Clinical variables, dose-volume histogram (DVH) parameters, and radiomic features (original, Laplacian of Gaussian [LoG], and wavelet filtered) were extracted. ANOVA was used for initial feature reduction, followed by LASSO and Boruta-SHAP for feature selection, which formed 10 feature subsets. The data were divided at an 8:2 ratio into training and testing sets, with SMOTE balancing and 10-fold cross-validation for parameter optimization. Six models-logistic regression (LR), random forest (RF), support vector machine (SVM), k-nearest neighbors (KNN), XGBoost, and Ensemble Stacking-were evaluated in terms of the AUC, accuracy (ACC), negative predictive value (NPV), precision, and F1 score. SHAP analysis was applied to interpret feature contributions. Results: For RP prediction, the LASSO-selected radiomic subset (FR) combined with Ensemble Stacking achieved optimal performance (AUC 0.91, ACC 0.89), with SHAP identifying V40 Firstorder_Min as the most influential feature. For survival prediction, the FR subset yielded an AUC of 0.97, an ACC of 0.92, and an NPV of 1.00, with V10 Wavelet Firstorder_Min as the top contributor. The multimodal subset (FC+R) also performed strongly, achieving an AUC of 0.91 for RP and 0.96 for survival. Conclusions: This study demonstrated the superior performance of radiomics combined with Ensemble Stacking and XAI for the prediction of RP and survival following VMAT in patients with NSCLC. SHAP-based interpretation enhances transparency and clinical trust, offering a robust foundation for personalized radiotherapy and precision medicine.