An Ultrasound-based Machine Learning Model for Predicting Tumor-Infiltrating Lymphocytes in Breast Cancer

Introduction. Tumor-infiltrating lymphocytes (TILs) are key indicators of immune response and prognosis in breast cancer (BC). Accurate prediction of TIL levels is essential for guiding personalized treatment strategies. This study aimed to develop and evaluate machine learning models using ultrasound-derived radiomics and clinical features to predict TIL levels in BC. Methods. This retrospective study included 256 BC patients between January 2019 and August 2023, who were randomly divided into training (n = 179) and test (n = 77) cohorts. Radiomics features were extracted from the intratumor and peritumor regions in ultrasound images. Feature selection was performed using the "Boruta" package in R to iteratively remove non-significant features. Extra Trees Classifier was used to construct radiomics and clinical models. A combined radiomics-clinical (R-C) model was also developed. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, and decision curve analysis (DCA) to assess clinical utility. A nomogram was created based on the best-performing model. Results. A total of 1712 radiomics features were extracted from the intratumor and peritumor regions. The Boruta method selected five key features (four from the peritumor and one from the intratumor) for model construction. Clinical features, including immunohistochemistry, tumor size, shape, and echo characteristics, showed significant differences between high (>= 10%) and low (<10%) TIL groups. Both the R-C and radiomics models outperformed the clinical model in the test cohort (area under the curve values of 0.869/0.838 vs 0.627, P < .05). Calibration curves and Brier scores demonstrated superior accuracy and calibration for the R-C and radiomics models. DCA revealed the highest net benefit of the R-C model at intermediate threshold probabilities. Conclusion. Ultrasound-derived radiomics effectively predicts TIL levels in BC, providing valuable insights for personalized treatment and surveillance strategies.