Abstract
OBJECTIVE: The neglect of occult lymph nodes metastasis (OLNM) is one of the pivotal causes of early non-small cell lung cancer (NSCLC) recurrence after local treatments such as stereotactic body radiotherapy (SBRT) or surgery. This study aimed to develop and validate a computed tomography (CT)-based radiomics and deep learning (DL) fusion model for predicting non-invasive OLNM. METHODS: Patients with radiologically node-negative lung adenocarcinoma from two centers were retrospectively analyzed. We developed clinical, radiomics, and radiomics-clinical models using logistic regression. A DL model was established using a three-dimensional squeeze-and-excitation residual network-34 (3D SE-ResNet34) and a fusion model was created by integrating seleted clinical, radiomics features and DL features. Model performance was assessed using the area under the curve (AUC) of the receiver operating characteristic (ROC) curve, calibration curves, and decision curve analysis (DCA). Five predictive models were compared; SHapley Additive exPlanations (SHAP) and Gradient-weighted Class Activation Mapping (Grad-CAM) were employed for visualization and interpretation. RESULTS: Overall, 358 patients were included: 186 in the training cohort, 48 in the internal validation cohort, and 124 in the external testing cohort. The DL fusion model incorporating 3D SE-Resnet34 achieved the highest AUC of 0.947 in the training dataset, with strong performance in internal and external cohorts (AUCs of 0.903 and 0.907, respectively), outperforming single-modal DL models, clinical models, radiomics models, and radiomics-clinical combined models (DeLong test: P<0.05). DCA confirmed its clinical utility, and calibration curves demonstrated excellent agreement between predicted and observed OLNM probabilities. Features interpretation highlighted the importance of textural characteristics and the surrounding tumor regions in stratifying OLNM risk. CONCLUSIONS: The DL fusion model reliably and accurately predicts OLNM in early-stage lung adenocarcinoma, offering a non-invasive tool to refine staging and guide personalized treatment decisions. These results may aid clinicians in optimizing surgical and radiotherapy strategies.