PROJECT SUMMARY/ABSTRACT Research: The National Lung Screening Trial (NLST) demonstrated a 20% reduction in mortality with the use of annual CT screening but with significant morbidity due to procedures performed for evaluation of the 94% of nodules that were not cancerous. The goal of this proposal is to improve the specificity for distinguishing which of these “indeterminate” nodules is lung cancer by using quantitative features associated with emphysema available from a single CT scan. Our preliminary data indicate that moderate centrilobular emphysema (MCE), and its associated vascular features, provide a niche for the growth of nascent lung. An innovative approach of this proposal is to use features of MCE in the sphere of lung around a nodule to improve specificity for detecting cancer. However, increasing specificity results in decreasing sensitivity. In the case of lung cancer screening more “missed” cancers may increase lung cancer deaths. To understand the effect of decreasing sensitivity on mortality we will use the novel UVM Lung Cancer Model, which accurately recapitulates lung cancer death and CT screening rates, to identify an optimal set of biomarkers for identifying cancer among the many screen detected nodules. Candidate: Dr. Kinsey’s clinical practice is in Interventional Pulmonary, a specialty that focuses on dealing with the problem of indeterminate nodules. He has applied his MPH epidemiology and biostatistical training, coupled with experience in quantitative CT imaging, to begin to address the problem of indeterminate nodules in the COPDGene data set and as the Principal Investigator of the UVM Molecular, Epigenetic, and Radiologic Biomarkers for Thoracic Cancers (MEROPTIC) study. However, he needs further training in the process of developing CT features as imaging biomarkers and in computer modeling, which will allow him to understand the effect of deployment of these biomarkers on lung cancer mortality. To address these critical gaps in knowledge his primary mentor, Dr. Jason Bates, has designed a program of didactic training and supervised research that will propel Dr. Kinsey to an independent investigator in the field of lung cancer diagnosis. Environment: Dr. Kinsey’s primary mentor, Dr. Bates, is internationally recognized for his work in pulmonary physiology and computer modeling and has a proven track record of training investigators and physician scientists. The co-mentor, Dr. George Washko, is an expert in quantitative imaging analysis and has an established mentoring relationship with Dr. Kinsey. A scientific advisory committee with established expertise in radiology, biostatistics, lung cancer, and biomarker development complements this outstanding mentoring team. Dr. Kinsey is ...