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Principal Investigator: Jennifer A Lewis
Organization: VETERANS HEALTH ADMINISTRATION
Fiscal Year: 2024
Funding agency: Veterans Affairs
Personalizing Veteran's Lung Cancer Screening and Diagnosis
Lung cancer is the leading cause of cancer-specific mortality in United States, including among Veterans. Annual
lung cancer screening with low-dose chest computed tomography (LDCT) in high-risk individuals has been
demonstrated to save lives in two large, randomized-controlled trials and is recommended by the US Preventive
Services Task Force (USPSTF) for individuals aged 50 to 80 with at least 20 pack years of smoking and who
currently smoke or quit in the past 15 years. Yet, individuals eligible under these criteria would only capture 45-
65% of all lung cancers. In this proposal, we seek to personalize lung cancer screening and diagnosis.
Veterans are at great risk for lung cancer given the higher prevalence of tobacco smoking and service-connected
exposures, including agent orange, asbestos, burn pits, and ionizing radiation. These hazardous materials and
exposures, frequently encountered in the military, are associated with lung cancer but are not part of current
recommended eligibility criteria. Furthermore, lung cancer screening results in an increase in the detection of
indeterminant pulmonary nodules. Our teams' data suggests that two candidate biomarkers could mitigate
sending Veterans with benign nodules for invasive procedures and shorten the time to lung cancer diagnosis.
First, an artificial intelligence model (Lung Cancer Predictor Convolutional Neural Network, LCP-CNN)
significantly improves discrimination between benign and malignant nodules on LDCTs. Our LCP-CNN algorithm
generates accurate reclassification of up to 30% of intermediate risk nodules (10-70% risk for cancer) to lower
or higher risk levels, thus, decreasing the number of invasive procedures and shortening the time to diagnosis.
The other biomarker is CYFRA 21-1, a serum protein cancer biomarker for which we developed a high sensitivity
assay. Based on these preliminary data, we propose to answer the following clinical question: Can we safely
offer lung cancer screening to Veterans who are at greater risk beyond their age and smoking history
but due to their personal and service-related exposures while improving the rate of early and non-
invasive detection of lung cancer?
Aim 1: In a prospective cohort of 800 Veterans at Nashville, Denver and Louisville between 50-80 years of age
who ever smoked cigarettes, we will evaluate if a new, personalized lung cancer screening eligibility criteria that
incorporates military exposures, COPD, personal history of tobacco-related cancer, and family history of lung
cancer results in at least the same number of lung cancers detected compared to the standard of care USPSTF
screening criteria in use by our Lung Precision Oncology Program lung cancer screening programs.
Aim 2: Among a cohort of Nashville Veterans with positive screenings (n=520), we will test the hypothesis that
the LCP-CNN in combination with hs-CYFRA 21-1 reduces the number of invasive procedures and shortens the
time to lung cancer diagnosis versus the Brock Model. We will manage positive screens from Aim 1 and test the
combined biomarker approach proposed in Aim 2 to rule in cancer early and rule out benign lung nodules.
Impact: We will safely personalize lung cancer screening in the Veteran community to improve the number of
cancers detected early, reduce the rate of invasive procedures, and avoid a missed chance for cure for early
detected lung cancers. This project will provide proof of principle for personalizing lung cancer screening criteria
among Veterans and test the clinical utility of a combined biomarker-based approach to manage screen-detected
indeterminate pulmonary nodules. The proposed research will provide actionable evidence for Veterans with
military exposures and would impact VHA policy. Our team is poised to conduct a rigorous and necessary
evaluation and the findings will inform the development of a larger, national randomized-controlled CSP trial to
test if LDCT screening among Veterans meeting expanded and personalized criteria results in improved survival.
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