Histogram-based models on non-thin section chest CT predict invasiveness of primary lung adenocarcinoma subsolid nodules

IQR 109 pathologically proven subsolid nodules (SSN) were segmented by 2 readers on non-thin section chest CT with a lung nodule analysis software followed by extraction of CT attenuation histogram and geometric features. Functional data analysis of histograms provided data driven features (FPC1,2,3) used in further model building. Nodules were classified as pre-invasive (P1, atypical adenomatous hyperplasia and adenocarcinoma in situ), minimally invasive (P2) and invasive adenocarcinomas (P3). P1 and P2 were grouped together (T1) versus P3 (T2). Various combinations of features were compared in predictive models for binary nodule classification (T1/T2), using multiple logistic regression and non-linear classifiers. Area under ROC curve (AUC) was used as diagnostic performance criteria. Inter-reader variability was assessed using Cohen's Kappa and intra-class coefficient (ICC). Three models predicting invasiveness of SSN were selected based on AUC. First model included 87.5 percentile of CT lesion attenuation (Q. 875), interquartile range (IQR), volume and maximum/minimum diameter ratio (AUC: 0.89, 95% CI:[0.75 1]). Second model included FPC1, volume and diameter ratio (AUC: 0.91, 95% CI:[0.77 1]). Third model included FPC1, FPC2 and volume (AUC: 0.89, 95% CI:[0.73 1]). Inter-reader variability was excellent (Kappa: 0.95, ICC: 0.98). Parsimonious models using histogram and geometric features differentiated invasive from minimally invasive/pre-invasive SSN with good predictive performance in non-thin section CT.