Dose-Guided Hybrid AI Model with Deep and Handcrafted Radiomics for Explainable Radiation Dermatitis Prediction in...

To improve the prediction accuracy of radiation dermatitis (RD) in breast cancer patients undergoing volumetric modulated arc therapy (VMAT), we developed a hybrid artificial intelligence (AI) model that integrates deep learning radiomics (DLR), handcrafted radiomics (HCR), clinical features, and dose-volume histogram (DVH) parameters, aiming to enhance the early identification of high-risk individuals and support personalized prevention strategies.

A retrospective cohort of 156 breast cancer patients treated with VMAT at Kaohsiung Veterans General Hospital (2018-2023) was analyzed; 148 patients were eligible after exclusions, with RD graded according to the RTOG criteria. Clinical variables and 12 DVH indices were collected, while HCR features were extracted via PyRadiomics. DLR features were derived from a pretrained VGG16 network across four input designs: original CT images (DLR_Original), a 5 mm subcutaneous region (DLR_Skin5mm), a planning target volume with a 100% prescription dose (DLR_PTV100%), and a subcutaneous region receiving ≥ 5 Gy (DLR_V5Gy). The features were preselected via ANOVA (p < 0.05), followed by Boruta-SHAP refinement across 11 feature sets. Predictive models were built via logistic regression, random forest, gradient boosting decision tree, and stacking ensemble (SE) methods. Explainability was assessed via SHapley Additive exPlanations (SHAPs) and gradient-weighted class activation mapping (Grad-CAM).

Among the 148 patients, 49 (33%) developed Grade ≥ 2 RD. The DLR models outperformed the HCR models (AUC = 0.72 vs. 0.66). The best performance was achieved with DLR_V5Gy + clinical + DVH features, yielding an AUC = 0.76, recall = 0.68, and F1 score = 0.60. SE consistently surpassed single classifiers. SHAP identified convolutional DLR features as the strongest predictors, whereas Grad-CAM focused attention on subcutaneous high-dose regions, which was consistent with the clinical RD distribution.

The proposed hybrid AI framework, which integrates DLR, clinical, and DVH features, provides accurate and explainable predictions of Grade ≥ 2 RD after VMAT in breast cancer patients. By combining ensemble learning with XAI methods, the model offers reliable high-risk stratification and potential clinical utility for personalized treatment planning.