Abstract
BACKGROUND: Radiomics holds great potential for the noninvasive evaluation of EGFR-TKIs and ICIs responses, but data privacy and model robustness challenges limit its current efficacy and safety. This study aims to develop and validate an encrypted multidimensional radiomics approach to enhance the stratification and analysis of therapeutic responses. MATERIALS AND METHODS: This multicenter study incorporated various data types from 506 NSCLC patients, which underwent preprocessing through anonymization methods and were securely encrypted using the AES-CBC algorithm. We developed one clinical model and three radiomics models based on clinical factors and radiomics scores (RadScore) of three distinct regions to evaluate treatment response. Additionally, an integrated radiomics-clinical model was created by combining clinical factors with RadScore. The study also explored the association between different EGFR mutations and PD-1/PD-L1 expression in radiomics biomarkers. FINDINGS: The radiomics-clinical model demonstrated high performance, with AUC values as follows: EGFR (0.884), 19Del (0.894), L858R (0.881), T790M (0.900), and PD-1/PD-L1 expression (0.893) in the test set. This model outperformed both clinical and single radiomics models. Decision curve analysis further supported its superior clinical utility. Additionally, our findings suggest that the efficacy of EGFR-TKIs and ICIs therapy may not depend on detecting a singular tumor feature or cell type. CONCLUSION: The proposed method effectively balances the level of evidence with privacy protection, enhancing the study's validity and security. Therefore, radiomics biomarkers are expected to complement molecular biology analyses and guide therapeutic strategies for EGFR-TKIs, ICIs, and their combinations.