Abstract
BACKGROUND: The non-invasive characterization of the tumor microenvironment (TME) is essential for stratifying non-small cell lung cancer (NSCLC) patients who may benefit from immunotherapy. This study investigates a novel approach by integrating dual-energy CT (DECT) parameters with radiomics to quantitatively assess stromal fibrosis (via α-SMA area) and CD8 + T-cell infiltration. METHODS: In this prospective study, 70 treatment-naive NSCLC patients were enrolled. Preoperative DECT scans were used to extract both DECT parameters and radiomics features. Corresponding surgical specimens were analyzed to determine the area percentage of α-SMA-positive stroma and the density of CD8 + T cells, with patients classified into high and low groups for each biomarker. After feature selection, models were constructed based on DECT parameters alone, radiomics features alone, and a combined feature set. Models were evaluated via 5-fold cross-validation. RESULTS: For predicting high α-SMA expression, the integrated model combining DECT parameters and radiomics features demonstrated superior performance (AUC: 0.766) compared to models using either modality alone (DECT AUC: 0.670; radiomics AUC: 0.703). In contrast, for predicting CD8 + T-cell density, the DECT-only model (AUC: 0.715) performed comparably to the radiomics model (AUC: 0.695), with no significant gain from integration. Key discriminating features, such as normalized iodine concentration for α-SMA and spectral slope of K40-70 for CD8+, showed significant intergroup differences and plausible biological correlations. CONCLUSION: The integration of DECT and radiomics presents a feasible, non-invasive strategy to assess specific TME components in NSCLC, underscoring the complementary value of different imaging data types towards developing biomarkers for personalized oncology.