A radiomics-based machine learning model and SHAP for predicting spread through air spaces and its prognostic implications in stage I lung adenocarcinoma: a multicenter cohort study.

Background: Despite early detection via low-dose computed tomography and complete surgical resection for early-stage lung adenocarcinoma, postoperative recurrence remains high, particularly in patients with tumor spread through air spaces. A reliable preoperative prediction model is urgently needed to adjust the treatment modality.

Methods: In this multicenter retrospective study, 609 patients with pathological stage I lung adenocarcinoma from 3 independent centers were enrolled. Regions of interest for the primary tumor and peritumoral areas (extended by three, six, and twelve voxel units) were manually delineated from preoperative CT imaging. Quantitative imaging features were extracted and filtered by correlation analysis and Random forest Ranking to yield 40 candidate features. Fifteen machine learning methods were evaluated, and a ten-fold cross-validated elastic net regression model was selected to construct the radiomics-based prediction model. A clinical model based on five key clinical variables and a combined model integrating imaging and clinical features were also developed.

Results: The radiomics model achieved accuracies of 0.801, 0.866, and 0.831 in the training set and two external test sets, with AUC of 0.791, 0.829, and 0.807. In one external test set, the clinical model had an AUC of 0.689, significantly lower than the radiomics model (0.807, p < 0.05). The combined model achieved the highest performance, with AUC of 0.834 in the training set and 0.894 in an external test set (p < 0.01 and p < 0.001, respectively). Interpretability analysis revealed that wavelet-transformed features dominated the model, with the highest contribution from a feature reflecting small high-intensity clusters within the tumor and the second highest from a feature representing low-intensity clusters in the six-voxel peritumoral region. Kaplan-Meier analysis demonstrated that patients with either pathologically confirmed or model-predicted spread had significantly shorter progression-free survival (p < 0.001).

Conclusion: Our novel machine learning model, integrating imaging features from both tumor and peritumoral regions, preoperatively predicts tumor spread through air spaces in stage I lung adenocarcinoma. It outperforms traditional clinical models, highlighting the potential of quantitative imaging analysis in personalizing treatment. Future prospective studies and further optimization are warranted.