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Principal Investigator
Caroline Chiles
Wake Forest Health Sciences Center
Position Title
Professor of Radiology
About this CDAS Project
NLST (Learn more about this study)
Project ID
Initial CDAS Request Approval
Jul 22, 2016
Association of CT-defined chronic obstructive pulmonary disease with lung cancer in the National Lung Screening Trial
I recently led a study team in the analysis of 817 CT scans from the ACRIN arm of the NLST. These included 200 cases with nodules between 6-19 mm in diameter, in whom lung cancer was diagnosed within 2 years, and 617 controls who also had nodules 6-19 mm in diameter but in whom lung cancer was not diagnosed. These cases were chosen exclusively from the ACRIN arm so that we would also have spirometry. Each of 8 readers downloaded approximately 120 cases from ACRIN, and performed a qualitative assessment of COPD. We have demonstrated that CT evidence of emphysema is associated with nodule malignancy risk. Our results have been presented at the annual meeting of the Radiological Society of North America. We now have the opportunity to obtain quantitative estimates of the percentage of emphysema within the lung. In collaboration with Imbio, LLC, we will use their Lung Density Software to provide estimates of centrilobular and paraseptal emphysema within each lung, and within the top/middle/lower 1/3 of each lung for each of the 817 cases previously analyzed. The analysis will be performed by Dr. Chuck Hatt at Imbio, and the results provided to Dr. Chrysanthopoulou and myself. We will use these emphysema percentages and distributions to calculate nodule malignancy risk and compare these quantitative results with the qualitative analysis previously performed by 8 readers.
At this time, ACRIN is anonymizing the NLST images with safe harbor anonymization criteria and has suggested that I obtain the same 817 cases from CDAS instead. Imbio has already analyzed 261 of the cases in our cohort for a separate project with Dr. Ella Kazerooni, and therefore I am requesting the baseline (T0) CT scans for each of the remaining 556 cases (see attached case list).

1. Determine the association of centrilobular emphysema and paraseptal emphysema, as defined by lung density analysis, with lung cancer in patients with indeterminate nodules 6 to 19 mm in diameter on low-dose CT obtained in a high-risk population
2. Compare the association of quantitative estimation of centrilobular and paraseptal emphysema with lung cancer, with the association of qualitative analysis of emphysema and lung cancer, as previously determined in a multi-reader study


All users with access to data:
Caroline Chiles MD, Department of Radiology, Wake Forest Health Sciences Center, Winston-Salem NC 27157,

Stavroula Chrysanthopoulou, Ph.D., the Center for Statistical Sciences and the Department of Biostatistics, Brown University School of Medicine, Providence, RI;

Margaret Uznanski, Sr. Director, Clinical Affairs and Strategy IMBIO LLC, mobile: (267)297-9175

Charles Hatt, Ph.D., Development Scientist, IMBIO LLC,, 734-915-7992