Normalized emphysema score progression: An improved CT biomarker for mortality

Purpose: Normalized emphysema score (normES) is a protocol-robust and validated CT biomarker for mortality. We aimed to improve mortality prediction by modelling its change over time. Method and materials: CT scans from all 1810 deceased participants from the National Lung Screening Trial were selected. Of these, 445 died from lung cancer. A random selection of 4190 surviving participants were sampled with replacement up to 24432 to approximate the full cohort. The normES was obtained by computing the emphysema scores after resampling, normalization, and bullae cluster analysis. The reference models contained solely the baseline (T0) normES. To investigate if progression of emphysema provides additional information, normES from the first (T1) and second annual screening rounds (T2) and normES progression (normESprog) were added to the base model. normESprog was calculated by subtracting the T0 log(normES) from the T1 or T2 log(normES) and dividing by the time in between. Proportional hazard models predicting all-cause and lung cancer mortality were compared by calculating the continuous net reclassification improvement (NRI) for each year of follow-up. Results: The analysis of T0 and T1 data was performed on 22695 samples; 3547 lacked T0 or T1 scans, or had corrupted data. NRI improvement for all-cause and lung cancer mortality prediction compared to the base models were 4.5% (95%CI: -7.3 to 8.4%) and 4.1% (-9.3 to 14.6%) 3 years after baseline, 6.1% (-5.3 to 9.4%) and 0.1% (-7.1 to 12.2%) after 5 years, and 6.1% (-6.2 to 8.7%) and -0.4% (-5.6 to 11.3%) after 7 years, respectively. When modelling the T0 to T2 interval, another 2603 samples were excluded. For all-cause mortality, the 3, 5, and 7 year time points showed respective NRI improvements of -0.5% (-6.7 to 8.0%), 10.8% (5.5% to 14.7%), and 12.2% (7.1% to 15.6%). Improvements in lung cancer mortality prediction were -6.1% (-24.0 to 12.6%), 19.6% (10.6 to 29.2%), and 24.1% (15.4% to 31.7%), respectively. All hazard models had a logrank test p<.001. Conclusion: Two normES measurements are better than one at predicting mortality over longer periods of time. The time between normES measurements should be sufficiently distant to account for the slow progression of emphysema.