Whole-Lesion Computed Tomography-Based Entropy Parameters for the Differentiation of Minimally Invasive and Invasive Adenocarcinomas Appearing as Pulmonary Subsolid Nodules.

Objective: The aim of this study was to investigate the differentiation of computed tomography (CT)-based entropy parameters between minimally invasive adenocarcinoma (MIA) and invasive adenocarcinoma (IAC) lesions appearing as pulmonary subsolid nodules (SSNs).
Methods: This study was approved by the institutional review board in our hospital. From July 2015 to November 2018, 186 consecutive patients with solitary peripheral pulmonary SSNs that were pathologically confirmed as pulmonary adenocarcinomas (74 MIA and 112 IAC lesions) were included and subdivided into the training data set and the validation data set. Chest CT scans without contrast enhancement were performed in all patients preoperatively. The subjective CT features of the SSNs were reviewed and compared between the MIA and IAC groups. Each SSN was semisegmented with our in-house software, and entropy-related parameters were quantitatively extracted using another in-house software developed in the MATLAB platform. Logistic regression analysis and receiver operating characteristic analysis were performed to evaluate the diagnostic performances. Three diagnostic models including subjective model, entropy model, and combined model were built and analyzed using area under the curve (AUC) analysis.
Results: There were 119 nonsolid nodules and 67 part-solid nodules. Significant differences were found in the subjective CT features among nodule type, lesion size, lobulated shape, and irregular margin between the MIA and IAC groups. Multivariate analysis revealed that part-solid type and lobulated shape were significant independent factors for IAC (P < 0.0001 and P < 0.0001, respectively). Three entropy parameters including Entropy-0.8, Entropy-2.0-32, and Entropy-2.0-64 were identified as independent risk factors for the differentiation of MIA and IAC lesions. The median entropy model value of the MIA group was 0.266 (range, 0.174-0.590), which was significantly lower than the IAC group with value 0.815 (range, 0.623-0.901) (P < 0.0001). Multivariate analysis revealed that the combined model had an excellent diagnostic performance with sensitivity of 88.2%, specificity of 73.0%, and accuracy of 82.1%. The AUC value of the combined model was significantly higher (AUC, 0.869) than that of the subjective model (AUC, 0.809) or the entropy model alone (AUC, 0.836) (P < 0.0001).
Conclusions: The CT-based entropy parameters could help assess the aggressiveness of pulmonary adenocarcinoma via quantitative analysis of intratumoral heterogeneity. The MIA can be differentiated from IAC accurately by using entropy-related parameters in peripheral pulmonary SSNs.