Ternary-Classification Habitat Model for Invasiveness and Grade of Lung Adenocarcinoma Presenting as a Subsolid Nodule on Low-Dose Chest CT: A Multicenter Study.

Habitat imaging provides a novel approach to capture spatial heterogeneity within lesions. To develop a ternary-classification habitat model to characterize lung adenocarcinoma presenting as a subsolid nodule (SSN) on CT and to test the model's diagnostic performance compared with 2D and radiomic models. This retrospective study included 747 patients (median age, 56 years; 241 male, 506 female) with 834 resected lung adenocarcinomas that presented as SSNs on low-dose CT between July 2018 and May 2023. Adenocarcinomas from one center were divided into training (n=440) and internal test (n=189) sets; adenocarcinomas from three other centers formed an external test set (n=205). Adenocarcinomas were classified as noninvasive adenocarcinoma, grade 1 invasive adenocarcinoma (IAC), or grade 2 or 3 (hereafter, grade 2/3) IAC. Ternary-classification models were built in the training set using multivariable multinomial logistic regression analyses (2D model: diameter and consolidation-to-tumor ratio; habitat model: volume and volume ratio of attenuation-based subregions; radiomic model: extracted radiomic features; combined model: habitat and radiomic features). Performance was evaluated using macro-averaged and class-specific AUCs. The optimal number of habitats was four. The 2D, habitat, radiomic, and combined models had macro-averaged AUCs in the internal test set of 0.857, 0.909, 0.914, and 0.912, and in the external test of 0.871, 0.919, 0.924, and 0.926, respectively. Those four models had class-specific AUCs in the external test set for noninvasive adenocarcinoma of 0.945, 0.956, 0.961, and 0.955; grade 1 IAC of 0.792, 0.858, 0.857, and 0.862; and grade 2/3 IAC of 0.875, 0.940, 0.952, and 0.961, respectively. In the external test set, macro-averaged AUCs and class-specific AUCs for grades 1 and 2/3 IAC were significantly higher for habitat, radiomic, and combined models versus 2D model, but not for other model comparisons; class-specific AUCs for noninvasive adenocarcinoma were not significantly different for any model comparisons. The habitat model performed significantly better than the 2D model in ternary adenocarcinomas classification; its performance was not significantly different from radiomic and combined models. The habitat model's combination of interpretability and diagnostic performance support its utility for noninvasive risk stratification of SSNs encountered during lung cancer screening.