Prediction of lung cancer risk at follow-up screening with low-dose CT: a training and validation study of a deep learning method

Background Current lung cancer screening guidelines use either mean diameter, volume, or density of the largest lung nodule on the previous CT scan or appearance of a new nodule to ascertain the timing of the next CT scan. We aimed to develop an accurate screening protocol by estimating the 3-year lung cancer risk after two screening CT scans using deep learning of radiologists' CT readings and other universally available clinical information. Methods A deep learning algorithm (referred to as DeepLR) was developed using data from participants who had received at least two CT screening scans up to 2 years apart in the National Lung Screening Trial (NLST; training cohort). Double-blinded validation was done using data from participants in the Pan-Canadian Early Detection of Lung Cancer (PanCan) study (validation cohort). The primary analysis was to compare accuracy of DeepLR scores to predict lung cancer incidence at 1 year, 2 years, and 3 years with the Lung CT Screening Reporting & Data System (Lung-RADS) and volume doubling time, using time-dependent area under the receiver operating characteristic curve (AUC) analysis. Findings The training cohort consisted of 25 097 participants from NLST and the validation cohort comprised 2294 individuals from PanCan. In the validation cohort, DeepLR showed good discrimination, with 1-year, 2-year, and 3-year time-dependent AUC values for cancer diagnosis of 0.968 (SD 0.013), 0.946 (0.013), and 0.899 (0.017), respectively. Among individuals deemed high risk by DeepLR, 94%, 85%, and 71% of incident and interval lung cancers diagnosed within 1 year, 2 years, and 3 years, respectively, after the second screening CT scan were identified. Furthermore, individuals with high DeepLR scores had a significantly higher risk of mortality (hazard ratio 16.07, 95% CI 10.15-25.44; p<0.0001) among people with high scores on Lung-RADS. Interpretation DeepLR recognises patterns in both temporal and spatial changes and synergy among changes in nodule and non-nodule features. DeepLR scores could be used to accurately guide clinical management after the next scheduled repeat screening CT scan. Copyright (C) 2019 The Author(s). Published by Elsevier Ltd.