Consensus in the Parliament of AI: Harmonized Multi-Region CT-Radiomics and Foundation-Model Signatures for Multicentre NSCLC Risk Stratification

Purpose: This study evaluates the impact of harmonization and multi-region feature integration on survival prediction in non-small cell lung cancer (NSCLC) patients. We assess the prognostic utility of handcrafted radiomics and pretrained deep features from thoracic CT images, integrating them with clinical data using a multicentre dataset. Methods: Survival models were built using handcrafted radiomic and deep features from lung, tumor, mediastinal nodes, coronary arteries, and coronary artery calcium (CAC) scores from 876 patients across five centres. CT features were harmonized using ComBat, reconstruction kernel normalization (RKN), and RKN-ComBat. Models were constructed at the region of interest (ROI) level and through ensemble strategies. Regularized Cox models estimated overall survival, with performance assessed via the concordance index (C-index), 5-year time-dependent area under the curve (t-AUC), and hazard ratios. SHAP values interpreted feature contributions, while consensus analysis categorized predicted survival probabilities at fixed time points. Results: TNM staging showed prognostic value (C-index = 0.67; hazard ratio = 2.70; t-AUC = 0.85). The clinical and tumor texture radiomics model with ComBat yielded high performance (C-index = 0.76; t-AUC = 0.88). FM deep features from 50 voxel cubes also showed predictive value (C-index = 0.76; t-AUC = 0.89). An ensemble model combining tumor, lung, mediastinal node, CAC, and FM features achieved a C-index of 0.71 and t-AUC of 0.79. Consensus analysis identified a high-confidence patient subset, resulting in a model with a 5-year t-AUC of 0.92, sensitivity of 96.8%, and specificity of 70.0%. Conclusion: Harmonization and multi-region feature integration enhance survival prediction in NSCLC patients using CT imaging, supporting individualized risk stratification in multicentre settings.