Enhanced CT-based deep learning radiomics and biological correlations for predicting immunotherapy efficacy in advanced non-small cell lung cancer

Background: Identifying predictive markers for immunotherapy in non-small cell lung cancer (NSCLC) is critical for personalized treatment. This study aimed to construct a predictive model that integrates clinical features, enhanced computed tomography (CT)-radiomics, and deep learning (DL) features for the assessment of durable clinical benefit (DCB) from immunotherapy in patients with advanced NSCLC and to provide biological interpretability to predictions by integrating radiogenomic data. Methods: We conducted a retrospective analysis of 201 advanced NSCLC patients who underwent immunotherapy with CT images, with data supplemented from The Cancer Imaging Archive (TCIA). Radiomics features (RFs) were extracted from enhanced CT images, and DL features were derived using a pre-trained ResNet-34 model. DCB-related signatures were constructed using the least absolute shrinkage and selection operator (LASSO) algorithm, and fusion nomogram models were developed by integrating significant clinical variables, radiomics, and DL features. Shapley additive explanations were employed to quantify the impact of radiomics-DL features on model predictions. Gene set enrichment and biological correlation analyses based on transcriptomic TCIA data were performed to explore the biological significance of radiomics-DL score. Results: Statistically significant clinical predictors included initial efficacy, brain metastases, programmed death-ligand 1 (PD-L1) expression, and hemoglobin levels. The fusion nomogram model demonstrated the highest predictive accuracy for DCB, with area under the curve (AUC) values of 0.843 in the train cohort and 0.894 in the test cohort, surpassing individual feature sets. Biological exploration revealed associations between radiomics-DL score and biological characteristics, including immune responses and immunoregulation. Conclusions: This integrated approach shows the potential of combining clinical, radiomics and deep learning features (DLFs) as a noninvasive biomarker for predicting immunotherapy efficacy in NSCLC, assisting in patient selection and clinical decision-making. Radiotranscriptomic analysis may reveal key cellular and immune patterns associated with radiomics-DL signature.