Abstract
PURPOSE: Accurate classification of pulmonary pure ground-glass nodules (pGGNs) is essential for distinguishing invasive adenocarcinoma (IVA) from adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA), which significantly influences treatment decisions. This study aims to develop a high-precision integrated strategy by combining radiomics-based feature extraction, Quantum Machine Learning (QML) models, and SHapley Additive exPlanations (SHAP) analysis to improve diagnostic accuracy and interpretability in pGGN classification. METHODS: A total of 322 pGGNs from 275 patients were retrospectively analyzed. The CT images was randomly divided into training and testing cohorts (80:20), with radiomic features extracted from the training cohort. Three QML models-Quantum Support Vector Classifier (QSVC), Pegasos QSVC, and Quantum Neural Network (QNN)-were developed and compared with a classical Support Vector Machine (SVM). SHAP analysis was applied to interpret the contribution of radiomic features to the models' predictions. RESULTS: All three QML models outperformed the classical SVM, with the QNN model achieving the highest improvements ([Formula: see text]) in classification metrics, including accuracy (89.23%, 95% CI: 81.54% - 95.38%), sensitivity (96.55%, 95% CI: 89.66% - 100.00%), specificity (83.33%, 95% CI: 69.44% - 94.44%), and area under the curve (AUC) (0.937, 95% CI: 0.871 - 0.983), respectively. SHAP analysis identified Low Gray Level Run Emphasis (LGLRE), Gray Level Non-uniformity (GLN), and Size Zone Non-uniformity (SZN) as the most critical features influencing classification. CONCLUSION: This study demonstrates that the proposed integrated strategy, combining radiomics, QML models, and SHAP analysis, significantly enhances the accuracy and interpretability of pGGN classification, particularly in small-sample datasets. It offers a promising tool for early, non-invasive lung cancer diagnosis and helps clinicians make more informed treatment decisions. CLINICAL TRIAL NUMBER: Not applicable.