Interpretable machine learning models for predicting skip metastasis in cN0 papillary thyroid cancer based on clinicopathological and elastography radiomics features.

Background: Skip lymph node metastasis (SLNM) in papillary thyroid cancer (PTC) involves cancer cells bypassing central nodes to directly metastasize to lateral nodes, often undetected by standard preoperative ultrasonography. Although multiple models exist to identify SLNM, they are inadequate for clinically node-negative (cN0) patients, resulting in underestimated metastatic risks and compromised treatment effectiveness. Our study aims to develop and validate a machine learning (ML) model that combines elastography radiomics with clinicopathological data to predict pre-surgical SLNM risk in cN0 PTC patients with increased risk of lymph node metastasis (LNM), improving their treatment strategies. Methods: Our study conducted a retrospective analysis of 485 newly diagnosed primary PTC patients, divided into training and external validation cohorts. Patients were categorized into SLNM and non-SLNM groups based on follow-up outcomes and postoperative pathology. We collected preoperative clinicopathological data and extracted, standardized radiomics features from elastography imaging to develop various ML models. These models were internally validated using radiomics and clinicopathological data, with the optimal model's feature importance analyzed through the Shapley Additive Explanations (SHAP) approach and subsequently externally validated. Results: In our study of 485 patients, 67 (13.8%) exhibited SLNM. The extreme gradient boosting (XGBoost) model, integrating elastography radiomics with clinicopathological data, demonstrated superior performance in both internal and external validations. SHAP analysis identified five key determinants of SLNM: three radiomics features from elastography images, one clinical variable, and one pathological variable. Conclusion: Our evaluation highlights the XGBoost model, which integrates elastography radiomics and clinicopathological data, as the most effective ML approach for the prediction of SLNM in cN0 PTC patients with increased risk of LNM. This innovative model significantly enhances the accuracy of risk assessments for SLNM, enabling personalized treatments that could reduce postoperative metastases in these patients.