• Quantitative Sciences- Department of Bioinformatics & Biostatistics, H. Lee. Moffitt Cancer Center, Tampa, FL, USA. yogab@moffitt.org.
• Cancer Epidemiology, H. Lee. Moffitt Cancer Center, Tampa, FL, USA.
• Cancer Physiology, H. Lee. Moffitt Cancer Center, Tampa, FL, USA.
• Department of Radiology, H. Lee. Moffitt Cancer Center, Tampa, FL, USA.

Pulmonary nodules are frequently detected radiological abnormalities in lung cancer screening. Nodules of the highest- and lowest-risk for cancer are often easily diagnosed by a trained radiologist there is still a high rate of indeterminate pulmonary nodules (IPN) of unknown risk. Here, we test the hypothesis that computer extracted quantitative features ("radiomics") can provide improved risk-assessment in the diagnostic setting. Nodules were segmented in 3D and 219 quantitative features are extracted from these volumes. Using these features novel malignancy risk predictors are formed with various stratifications based on size, shape and texture feature categories. We used images and data from the National Lung Screening Trial (NLST), curated a subset of 479 participants (244 for training and 235 for testing) that included incident lung cancers and nodule-positive controls. After removing redundant and non-reproducible features, optimal linear classifiers with area under the receiver operator characteristics (AUROC) curves were used with an exhaustive search approach to find a discriminant set of image features, which were validated in an independent test dataset. We identified several strong predictive models, using size and shape features the highest AUROC was 0.80. Using non-size based features the highest AUROC was 0.85. Combining features from all the categories, the highest AUROC were 0.83.