Circulating tumor cell clusters are a potential biomarker for detection of non-small cell lung cancer

• Published in: Lung cancer (Amsterdam, Netherlands) Vol. 134; pp. 147 - 150
• Main Authors: Manjunath, Yariswamy, Upparahalli, Sathisha V., Suvilesh, Kanve N., Avella, Diego M., Kimchi, Eric T., Staveley-O’Carroll, Kevin F., Li, Guangfu, Kaifi, Jussuf T.
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 01.08.2019
• Subjects: Circulating tumor cells; Liquid biomarkers; Lung cancer screening; Non-small cell lung cancer; Lung-RADS; CTC; NSCLC; Non-small cell lung cancer; LDCT; Circulating tumor cells; Lung cancer screening; Liquid biomarkers
• ISSN: 0169-5002; 1872-8332; 1872-8332
• DOI: 10.1016/j.lungcan.2019.06.016

•Circulating tumor cell clusters are candidates for NSCLC detection.•Circulating tumor cell clusters are found in NSCLC patients.•Circulating tumor cell clusters are undetectable in screening subjects.•Non-clustered circulating tumor cells can be detected in screening subjects. Circulating tumor cell (CTC) clusters (≥2 CTCs in aggregate) detected in the peripheral blood have predictive value in solid cancers, including non-small cell lung cancer (NSCLC). The goal of the study was to investigate the presence of CTC clusters in NSCLC patients and in high-risk screening subjects having no or benign nodules in a screening low-dose CT (LDCT). In a prospective pilot trial, 7.5 ml peripheral blood was collected from treatment-naïve NSCLC patients, LDCT screening subjects (55–80 years, ≥30 pack-year smoking history) with no (Lung-RADS 1) or benign lung nodules (Lung-RADS 2), and healthy never-smoking controls. CTCs were enriched by size, also allowing CTC cluster isolation. For CTC identification and enumeration, immunofluorescence staining was performed for cytokeratins (CK) 8/18 and/or 19, EpCAM, CD45, and nuclei were stained with DAPI. Clinicopathological data were collected, and LDCT interpreted by the American College of Radiology Lung-RADS criteria. CTC clusters were detected in 12/29 (41.4%) of all NSCLC patients, but not found in 31 high-risk screening subjects with Lung-RADS 1 or Lung-RADS 2 (P < 0.05). Since non-clustered, single CTCs were detectable in both groups of NSCLC patients (100%) and in 18/31 (58.1%) of high-risk screening subjects. No CTCs were detected in 20 healthy control subjects. This pilot study suggests that CTC clusters are a useful and specific liquid biomarker to further explore for screening by LDCT and risk stratification of NSCLC patients. Future prospective studies with higher subject numbers will need to be performed.