Yariswamy Manjunath1, Sathisha V Upparahalli2, Kanve N Suvilesh2, Diego M Avella1, Eric T Kimchi1, Kevin F Staveley-O'Carroll1, Guangfu Li1, Jussuf T Kaifi3. 1. Hugh E. Stephenson Jr., MD, Department of Surgery, Ellis Fischel Cancer Center, University of Missouri, USA; Harry S. Truman Memorial Veterans' Hospital, Columbia, MO, USA. 2. Hugh E. Stephenson Jr., MD, Department of Surgery, Ellis Fischel Cancer Center, University of Missouri, USA. 3. Hugh E. Stephenson Jr., MD, Department of Surgery, Ellis Fischel Cancer Center, University of Missouri, USA; Harry S. Truman Memorial Veterans' Hospital, Columbia, MO, USA. Electronic address: kaifij@health.missouri.edu.
Abstract
OBJECTIVES: 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). MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.
OBJECTIVES: 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 NSCLCpatients and in high-risk screening subjects having no or benign nodules in a screening low-dose CT (LDCT). MATERIALS AND METHODS: In a prospective pilot trial, 7.5 ml peripheral blood was collected from treatment-naïve NSCLCpatients, 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. RESULTS: CTC clusters were detected in 12/29 (41.4%) of all NSCLCpatients, 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 NSCLCpatients (100%) and in 18/31 (58.1%) of high-risk screening subjects. No CTCs were detected in 20 healthy control subjects. CONCLUSION: 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 NSCLCpatients. Future prospective studies with higher subject numbers will need to be performed.
Authors: Yariswamy Manjunath; Kanve Nagaraj Suvilesh; Jonathan B Mitchem; Diego M Avella Patino; Eric T Kimchi; Kevin F Staveley-O'Carroll; Klaus Pantel; Huang Yi; Guangfu Li; Peter K Harris; Aadel A Chaudhuri; Jussuf T Kaifi Journal: JCO Precis Oncol Date: 2022-03
Authors: Diego M Avella; Yariswamy Manjunath; Amolak Singh; Chelsea B Deroche; Eric T Kimchi; Kevin F Staveley-O'Carroll; Jonathan B Mitchem; Eric Kwon; Guangfu Li; Jussuf T Kaifi Journal: Transl Lung Cancer Res Date: 2020-06