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PLoS One. 2019 Feb 21;14(2):e0212756. doi: 10.1371/journal.pone.0212756. eCollection 2019.

Predicting all-cause and lung cancer mortality using emphysema score progression rate between baseline and follow-up chest CT images: A comparison of risk model performances.

Author information

Diagnostic Image Analysis Group, Department of Radiology and Nuclear Medicine, Radboudumc, Nijmegen, the Netherlands.
Thirona, Nijmegen, the Netherlands.
Department of Radiology, Meander Medisch Centrum, Amersfoort, the Netherlands.
Fraunhofer MEVIS, Bremen, Germany.



Normalized emphysema score is a protocol-robust CT biomarker of mortality. We aimed to improve mortality prediction by including the emphysema score progression rate-its change over time-into the models.


CT scans from 6000 National Lung Screening Trial CT arm participants were included. Of these, 1810 died (445 lung cancer-specific). The remaining 4190 survivors were sampled with replacement up to 24432 to approximate the full cohort. Three overlapping subcohorts were formed which required participants to have images from specific screening rounds. Emphysema scores were obtained after resampling, normalization, and bullae cluster analysis of the original images. Base models contained solely the latest emphysema score. Progression models included emphysema score progression rate. Models were adjusted by including baseline age, sex, BMI, smoking status, smoking intensity, smoking duration, and previous COPD diagnosis. Cox proportional hazard models predicting all-cause and lung cancer mortality were compared by calculating the area under the curve per year follow-up.


In the subcohort of participants with baseline and first annual follow-up scans, the analysis was performed on 4940 participants (23227 after resampling). Area under the curve for all-cause mortality predictions of the base and progression models 6 years after baseline were 0.564 (0.564 to 0.565) and 0.569 (0.568 to 0.569) when unadjusted, and 0.704 (0.703 to 0.704) to 0.705 (0.704 to 0.705) when adjusted. The respective performances predicting lung cancer mortality were 0.638 (0.637 to 0.639) and 0.643 (0.642 to 0.644) when unadjusted, and 0.724 (0.723 to 0.725) and 0.725 (0.725 to 0.726) when adjusted.


Including emphysema score progression rate into risk models shows no clinically relevant improvement in mortality risk prediction. This is because scan normalization does not adjust for an overall change in lung density. Adjusting for changes in smoking behavior is likely required to make this a clinically useful measure of emphysema progression.

Conflict of interest statement

This work was supported by: A. Schreuder: None. C. Jacobs: Grant Recipient; Research grant from MeVis Medical Solutions AG. L. Gallardo Estrella: None. M. Prokop: Grant Recipient; Research funding from Toshiba. Speaker; Speaker's bureau at Bracco, Bayer, Toshiba, and Siemens. Other; Department spin-off (no personal financial interest) at Thiroux. C.M. Schaefer-Prokop: None. B. Van Ginneken: Grant Recipient; Royalties from Mevis Medical Solutions and Delft Imaging Systems. Shareholder; Co-founder and shareholder of Thirona. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

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