Development and validation of an interpretable ultrasound radiomics model for benign and malignant classification of breast lesions: a multicenter large-sample study

OBJECTIVES: To develop and validate a combined ultrasound-based radiomics-clinical model for differentiating benign and malignant breast lesions. MATERIALS AND METHODS: A total of 3142 patients from eight hospitals between February 2012 and September 2024 were included in this multicenter retrospective development and validation study, with an additional single-center prospective test cohort. Lesions were manually segmented, and radiomics features were automatically extracted to construct five machine learning models. The best-performing radiomics model was combined with clinical features to build a combined model. Model performance and its impact on Breast Imaging Reporting and Data System (BI-RADS)-based biopsy decisions were evaluated. RESULTS: Logistic regression (LR) showed the best radiomics performance, with area under the curves (AUCs) of 0.83, 0.82, 0.81, and 0.82 across the training, internal test, external test, and prospective test sets. The clinical model achieved AUCs of 0.87, 0.85, 0.87, and 0.86, whereas the combined model achieved AUCs of 0.92, 0.90, 0.92, and 0.93, significantly outperforming both single-modality models (all p < 0.01). Decision curve analysis (DCA) showed that the combined model had a higher net benefit than the other models across a broad range of threshold probabilities (0.05-0.95) in this study. Performance remained stable across lesion size and age subgroups. In the reclassification analysis, the model suggested the potential to influence biopsy recommendations without a significant reduction in sensitivity and to increase the malignancy yield in BI-RADS 4a. Shapley additive explanations (SHAP) analysis provided clinically interpretable feature contributions. CONCLUSION: The interpretable ultrasound-based radiomics model enables reliable, noninvasive breast lesion diagnosis and may reduce unnecessary biopsies. CRITICAL RELEVANCE STATEMENT: This work developed an interpretable radiomics-clinical combined model in a multicenter retrospective development and validation study, with additional testing in a single-center prospective cohort, and may support breast lesion risk stratification and biopsy decision-making after further prospective clinical utility evaluation. KEY POINTS: Conventional ultrasound diagnosis of breast cancer shows limited specificity. A multicenter radiomics-clinical combined model showed improved diagnostic performance, with additional validation in a prospective test cohort.