This study aims to develop a radiopathomics model based on preoperative ultrasoundand fine-needle aspiration cytology (FNAC) images to enable accurate, non-invasive preoperative risk stratification for patients with papillary thyroid carcinoma (PTC). The model seeks to enhance clinical decision-making by optimizing preoperative treatment strategies. A retrospective analysis was conducted on data from PTC patients who underwent thyroidectomy between October 2022 and May 2024 across six centers. Based on lymph node dissection outcomes, patients were categorized into high-risk and low-risk groups. Initially, a clinical predictive model was established based on the maximum diameter of the thyroid nodules. Radiomics features were extracted from preoperative two-dimensional ultrasound images, and pathomics features were extracted from 400x magnification H&E-stained tumor cell images from FNAC. The most predictive radiomics and pathomics features were identified through univariate analysis, Pearson correlation analysis and LASSO algorithm. The most valuable radiopathomics features were then selected by combining these predictive features. Finally, machine learningwith the XGBoost algorithm was employed to construct radiomics, pathomics, and radiopathomics models. The performance of the models was evaluated using the area under the curve (AUC), decision curve analysis, accuracy, specificity, sensitivity, positive predictive value, and negative predictive value. A total of 688 PTC patients were included, with 344 classified as intermediate/high-risk and 344 as low-risk. The multimodal radiopathomics model demonstrated excellent predictive performance, with AUCs of 0.886 (95% CI: 0.829-0.924) and 0.828 (95% CI: 0.751-0.879) in two external validation cohorts, significantly outperforming the clinical model (AUCs of 0.662 and 0.601), radiomics model (AUCs of 0.702 and 0.697), and pathomics model (AUCs of 0.741 and 0.712). The radiopathomics model exhibits significant advantages in accurately predicting preoperative risk stratification in PTC patients. Its application is expected to reduce unnecessary lymph node dissection surgeries, optimize treatment strategies, and improve therapeutic outcomes.
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