Abstract
BACKGROUND: This study aims to develop and validate a multi-modal machine learning model for preoperative risk stratification in papillary thyroid carcinoma (PTC), addressing limitations of current systems that rely on postoperative pathological features. METHODS: We analyzed 974 PTC patients from three medical centers in China using a multi-modal approach integrating: (1) clinical indicators, (2) immunological indices, (3) ultrasound radiomics features, and (4) CT radiomics features. Our methodology employed gradient boosting machine for feature selection and random forest for classification, with model interpretability provided through SHapley Additive exPlanations (SHAP) analysis. The model was validated on internal (n = 225) and two external cohorts (n = 51, n = 174). RESULTS: The final 15-feature model achieved AUCs of 0.91, 0.84, and 0.77 across validation cohorts, improving to 0.96, 0.95, and 0.89 after cohort-specific refitting. SHAP analysis revealed CT texture features, ultrasound morphological features, and immune-inflammatory markers as key predictors, with consistent patterns across validation sites despite center-specific variations. Subgroup analysis showed superior performance in tumors > 1 cm and patients without extrathyroidal extension. CONCLUSION: Our multi-modal machine learning approach provides accurate preoperative risk stratification for PTC with robust cross-center applicability. This computational framework for integrating heterogeneous imaging and clinical data demonstrates the potential of multi-modal joint learning in healthcare imaging to transform clinical decision-making by enabling personalized treatment planning.