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

Background Lung cancer screening with low‐dose computed tomography (CT) scans (LDCT) has reduced mortality for patients with high‐risk smoking histories, but it has significant limitations: LDCT screening implementation remains low, high rates of false‐positive scans, and current guidelines exclude those without smoking histories. We sought to explore the utility of liquid biopsy (LBx) in early cancer screening and diagnosis of lung cancer. Methods Using the high‐definition single‐cell assay workflow, we analyzed 99 peripheral blood samples from three cohorts: normal donors (NDs) with no known pathology (n = 50), screening CT patients (n = 25) with Lung‐RADS score of 1–2, and biopsy (BX) patients (n = 24) with abnormal CT scans requiring tissue biopsy. Results For CT and BX patients, demographic information was roughly equivalent; however, average pack‐years smoked differed. A total of 14 (58%) BX patients were diagnosed with primary lung cancer (BX+). The comparison of the rare event enumerations among the cohorts revealed a greater incidence of total events, rare cells, and oncosomes, as well as specific cellular phenotypes in the CT and BX cohorts compared with the ND cohort. LBx analytes were also significantly elevated in the BX compared with the CT samples, but there was no difference between BX+ and BX− samples. Conclusions The data support the utility of the LBx in distinguishing patients with an alveolar lesion from those without, providing a potential avenue for prescreening before LDCT. Lung cancer screening with LDCT has reduced mortality for patients with high‐risk smoking histories, but it has significant limitations. We sought to explore the utility of LBx in early cancer screening and diagnosis of lung cancer. A comparison of the rare event enumerations among cohorts was able to stratify the ND cohort from the high‐risk and CT‐positive cohorts. The data support the utility of LBx in distinguishing patients with an alveolar lesion from those without, providing a potential avenue for prescreening before LDCT to better inform clinical workup.