Advancing presurgical non-invasive spread through air spaces prediction in clinical stage IA lung adenocarcinoma using artificial intelligence and CT signatures.

Background: To accurately identify spread through air spaces (STAS) in clinical stage IA lung adenocarcinoma, our study developed a non-invasive and interpretable biomarker combining clinical and radiomics features using preoperative CT.

Methods: The study included a cohort of 1,325 lung adenocarcinoma patients from three centers, which was divided into four groups: a training cohort ( = 930), a testing cohort ( = 238), an external validation 1 cohort ( = 93), and 2 cohort ( = 64). We collected clinical characteristics and semantic features, and extracted radiomics features. We utilized the LightGBM algorithm to construct prediction models using the selected features. Quantifying the contribution of radiomics features of CT to prediction model using Shapley additive explanations (SHAP) method. The models' performance was evaluated using metrics such as the area under the receiver operating characteristic curve (AUC), negative predictive value (NPV), positive predictive value (PPV), sensitivity, specificity, calibration curve, and decision curve analysis (DCA).

Results: In the training cohort, the clinical model achieved an AUC value of 0.775, the radiomics model achieved an AUC value of 0.836, and the combined model achieved an AUC value of 0.837. In the testing cohort, the AUC values of the models were 0.743, 0.755, and 0.768. In the external validation 1 cohort, the AUC values of the models were 0.717, 0.758, and 0.765, while in the external validation 2 cohort, 0.725, 0.726 and 0.746. The DeLong test results indicated that the combined model outperformed the clinical model ( < 0.05). DCA indicated that the models provided a net benefit in predicting STAS. The SHAP algorithm explains the contribution of each feature in the model, visually demonstrating the impact of each feature on the model's decisions.

Conclusion: The combined model has the potential to serve as a biomarker for predicting STAS using preoperative CT scans, determining the appropriate surgical strategy, and guiding the extent of resection.