Abstract 1071: Circulation of rare events in the liquid biopsy for early detection of lung mass lesions

Abstract Lung cancer screening with low-dose CT scans (LDCT) has reduced mortality for patients with high-risk smoking histories. However, this method of screening remains imperfect. High rates of false positive scans expose patients to additional morbidity as they pursue subsequent diagnostic evaluation. Real-world application of screening LDCT remains low. Finally, current screening guidelines exclude those without smoking histories, a population which comprises up to a quarter of lung cancer patients. We sought to explore the utility of liquid biopsy (LBx) in lung cancer patients and its use in early cancer screening and diagnosis. Using the third generation High-Definition Single Cell Assay (HDSCA3.0) workflow, we analyzed 99 peripheral blood samples divided into three cohorts: Normal Donors (ND, n=50) who were healthy volunteers with no known pathology, Screening CT patients (CT, n=25) who underwent standard LDCT screening with resultant Lung-RADS 1-2, Biopsy patients (BX, n=24) who had abnormal CT scans requiring tissue biopsy. The ND group was used to characterize baseline epithelial, mesenchymal, endothelial, and immune cells, alongside acellular events (oncosomes). For the CT and BX patients, demographic information including age, gender, and average BMI was roughly equivalent, however average pack-years smoked differed owing to 10 (42%) patients in the BX group who had no prior smoking history. A total of 14 (58%) BX patients were diagnosed with primary lung cancer (BX+), of which 11(75%) were adenocarcinoma, 2 (19%) were squamous cell carcinoma and 1 (6%) was small cell. Across the cohorts we observed intra- and interpatient heterogeneity of rare events including multiple phenotypic rare cell populations and oncosomes. The comparison of the rare event enumerations between the ND, CT, BX+, and BX- cohorts revealed a greater incidence of total events, total rare cells and oncosomes, as well as specific cellular phenotypes in the CT and BX cohorts compared to the ND cohort. LBx analytes were detected at a significant elevation in the BX samples compared to the CT samples, but there was no significant difference between BX+ and BX- samples. The data supports the utility of the LBx in distinguishing patients with an alveolar mass lesion from those without, providing a mechanism for screening prior to LDCT to better inform clinical workup and avoid unnecessary radiation exposure and biopsy. Citation Format: Anya Shah, Karen Resnick, Jeremy Mason, Peter Kuhn, Jorge Nieva, Stephanie Shishido. Circulation of rare events in the liquid biopsy for early detection of lung mass lesions [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1071.