CT-derived Body Composition Associated with Pulmonary Nodule Malignancy and Growth

Background: Body composition may be a valuable biomarker for assessing pulmonary nodule malignancy. However, its relationship with nodule malignancy remains unexplored. Objective: This study investigated the association between body composition and pulmonary nodule malignancy and growth. Methods: A dataset of subjects with indeterminate pulmonary nodules (IPNs) was created from internal (n=216) and external (n=162) cohorts. Five different tissues were automatically segmented and quantified from baseline and follow-up chest low-dose computed tomography (LDCT) scans using artificial intelligence (AI) algorithms. Logistic regression, t-tests, and Person correlation analyses were performed to study the association between body tissues and malignancy, as well as nodule changes in density, size, and shape. Gender differences were investigated. The area under the receiver operating characteristic curve (ROC-AUC) assessed classifier performance. Feature importance was evaluated using several machine learning models. Causal relationships were analyzed and visualized using a novel graph method. Results: Univariate analysis revealed a significant association between Skeletal muscle density and nodule malignancy in both genders (p<0.001). The body composition model yielded AUCs of 0.77 (95% CI: 0.71-0.84) and 0.63 (95% CI: 0.54-0.72) on the internal and external datasets, respectively. The composite model combining body composition and nodule features yielded AUCs of 0.87 (95% CI: 0.82-0.91) and 0.62 (95% CI: 0.53-0.72) on the internal and external datasets, respectively. Skeletal muscle and intermuscular adipose tissue features were highly ranked among tissue features, with skeletal muscle density retaining its highest rank even after adjusting for clinical and nodule features. The causal graph identified two nodule features and skeletal muscle density as directly linked to malignancy. Skeletal muscle density and intramuscular adipose tissue density were identified as nodule growth indicators in both genders. Conclusions: Body composition could be a potential biomarker for assessing nodule malignancy and evaluating nodule growth in both genders.