The LEAP Study: A Multicenter Biospecimen and Imaging Resource for Lung Cancer Screening

Abstract Background: Blood-based biomarkers could improve the effectiveness of lung cancer screening (LCS) with low-dose computed tomography (LDCT) through more accurate LC risk stratification and nodule malignancy risk assessment. The LEAP study aims to establish a reference set to validate promising cancer biomarkers in the context of LCS. Methods: This prospective international cohort study (USA, France, Spain) enrolled individuals with elevated risk of developing LC based on National Comprehensive Cancer Network Guidelines into an LCS program. Participants underwent three annual rounds of LDCT-LCS with blood specimens collected at each timepoint. Questionnaires and medical chart reviews were utilized to determine participants’ cancers status. Results: Between 2014 and 2019, 2,841 participants were enrolled who underwent LDCT: 2,841 at baseline, 2,097 at year 1 (74%) and 1,779 at year 2 (63%). Rates at baseline, year 1, and year 2 were positive scans (13%, 7.5%, 7.5%), false positives (12%, 6.8%, 6.9%) and screen-detected LC (0.9%, 0.9%, 0.7%). After 5 years of follow-up, 74 LC were detected: 55% stage I, 11% stage II, 16% stage III and 12% stage IV. The LEAP biobank collected 6,586 blood specimens, including 126 (lung) and 201 (other) pre-diagnostic samples within 5 years of diagnosis. Conclusions: The LEAP cohort provides a resource with a longitudinal database of participant data, LDCT imaging, and matched blood specimens for biomarker validation, aiming to address unmet clinical needs in LCS. Impact: LEAP provides longitudinal biospecimens linked with clinical follow-up and LDCT imaging for biomarker validation in the context of imaging findings and LC diagnosis.