The purpose of this study is to develop a computed tomography (CT) biomarker of emphysema that is robust across reconstruction settings, and evaluate its ability to predict mortality in patients at high risk for lung cancer. Data included baseline CT scans acquired between August 2002 and April 2004 from 1737 deceased subjects and 5740 surviving controls taken from the National Lung Screening Trial. Emphysema scores were computed in the original scans (origES) and after applying resampling, normalization and bullae analysis (normES). We compared the prognostic value of normES versus origES for lung cancer and all-cause mortality by computing the area under the receiver operator characteristic curve (AUC) and the net reclassification improvement (NRI) for follow-up times of 1-7 years. normES was a better predictor of mortality than origES. The 95% confidence intervals for the differences in AUC values indicated a significant difference for all-cause mortality for 2 through 6 years of follow-up, and for lung cancer mortality for 1 through 7 years of follow-up. 95% confidence intervals in NRI values showed a statistically significant improvement in classification for all-cause mortality for 2 through 7 years of follow-up, and for lung cancer mortality for 3 through 7 years of follow-up. Contrary to conventional emphysema score, our normalized emphysema score is a good predictor of all-cause and lung cancer mortality in settings where multiple CT scanners and protocols are used.
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