Circulating Tumor Cells as a Potential Biomarker for Lung Cancer Screening: Results of the AIR Study

Abstract

Background: Lung cancer (LC) screening with low dose chest computed tomography (LDCT) reduces the mortality of eligible individuals. Biological blood signatures act as a screening tool per se and may refine the selection of patients at risk or may help to classify undetermined nodules detected on LDCT.We previously showed that circulating tumor cells (CTC) could be detected by the isolation by size of epithelial tumor cell technique (ISET) long before the cancer was diagnosed radiologically. So, we tested whether CTC could be used as biomarker for screening lung cancer. Methods: We conducted a prospective, multicenter, cohort study in 21 French university centers. Participants had to be eligible for LC screening and to have chronic obstructive pulmonary disease. They underwent 3 screening rounds at 1-year intervals including LDCT and a matched blood test for CTC detection. Participants and investigators were blinded to the results of CTC detection. Cytopathologists were blinded to clinical and radiological findings. Findings: We enrolled 614 participants, predominantly men (71%), aged 65.1 ± 6.5 years, heavy smokers with 52.7 ± 21.5 pack-years. Nodules were detected on 178 (29%) baseline LDCTs. Nineteen subjects (3.1%) were diagnosed with a prevalent LC and nineteen (2.8 %) with an incident LC. Extra-pulmonary cancers (EPC) were diagnosed in 26 (4.2 %) participants. At baseline, the sensitivity of CTC detection for LC detection was 26.3 %. The ISET test was unable to predict LC or EPC development. Interpretation: The CTC detection-based LC screening using ISET failed to confirm our initial promising results. Trial Registration: ClinicalTrials.gov identifier: NCT02500693. Funding Statement: Conseil Departemental 06, Fondation UNICE, Fondation AVENI, Fondation de France, and Ligue Contre le Cancer - Comite des Alpes-Maritimes and private donators. Declaration of Interests: The authors stated: None declared. Ethics Approval Statement: National ethic committee approval (CPP Sud Mediterranee V; registration # 15.072) and ANSM (Ministry of Health).