Intratumoral heterogeneity score enhances invasiveness prediction in pulmonary ground-glass nodules via stacking ensemble machine learning.

Abstract

Objectives: The preoperative differentiation of adenocarcinomas in situ, minimally invasive adenocarcinoma, and invasive adenocarcinoma using computed tomography (CT) is crucial for guiding clinical management decisions. However, accurately classifying ground-glass nodules poses a significant challenge. Incorporating quantitative intratumoral heterogeneity scores may improve the accuracy of this ternary classification.

Materials and methods: In this multicenter retrospective study, we developed ternary classification models by leveraging insights from both base and stacking ensemble machine learning models, incorporating intratumoral heterogeneity scores along with clinical-radiological features to distinguish adenocarcinomas in situ, minimally invasive adenocarcinoma, and invasive adenocarcinoma. The machine learning models were trained, and final model selection depended on maximizing the macro-average area under the curve (macro-AUC) in both the internal and external validation sets.

Results: Data from 802 patients from three centers were divided into a training set (n = 477) and an internal test set (n = 205), in a 7:3 ratio, with an additional external validation set comprising 120 patients. The stacking classifier exhibited superior performance relative to the other models, achieving macro-AUC values of 0.7850 and 0.7717 for the internal and external validation sets, respectively. Moreover, an interpretability analysis utilizing the Shapley Additive Explanation identified four key features of this ternary classification: intratumoral heterogeneity score, nodule size, nodule type, and age.

Conclusion: The stacking classifier, recognized as the optimal algorithm for integrating the intratumoral heterogeneity score and clinical-radiological features, effectively served as a ternary classification model for assessing the invasiveness of lung adenocarcinoma in chest CT images.

Critical relevance statement: Our stacking classifier integrated intratumoral heterogeneity scores and clinical-radiological features to improve the ternary classification of lung adenocarcinoma invasiveness (adenocarcinomas in situ/minimally invasive adenocarcinoma/invasive adenocarcinoma), aiding in precise diagnosis and clinical decision-making for ground-glass nodules.

Key points: The intratumoral heterogeneity score effectively assessed the invasiveness of lung adenocarcinoma. The stacking classifier outperformed other methods for this ternary classification task. Intratumoral heterogeneity score, nodule size, nodule type, and age predict invasiveness.