Abstract 917: Circulating tumor cells accurately detect and characterize lung cancers in high-risk subjects undergoing low-dose CT screening
Authors: MANJUNATH YARISWAMY , Venkateshaiah Sathisha Upparahalli , Kimchi Eric T. , Staveley-O'Carroll Kevin F. , Coberly Jared , Avella Diego M. , Hoffman Timothy J. , Deroche Chelsea , Pantel Klaus , Li Guangfu , Kaifi Jussuf T. 
Published: August 2019

Abstract
Purpose: Lung cancer screening of high-risk subjects with low-dose CT (LDCT) significantly reduces mortality. Integrating liquid biomarkers circulating tumor cells (CTCs) screening could significantly improve the accuracy of findings on LDCT.
Experimental Design: In a prospective, observational clinical trial (NCT02838836; NCT03551951), high-risk screening subjects (≥30 pack-years smoking history, age 55-80) undergoing screening LDCT were enrolled. Peripheral blood (7.5ml) was collected, CTCs were enriched by microfilter isolation and immunofluorescence staining was performed for cytokeratin, EpCAM, CD14/45, PD-L1, vimentin, N-cadherin. Lung cancer tissues were similarly analyzed.
Results: In total, 136 subjects were enrolled prospectively. CTCs/7.5ml of blood were significantly higher in 14 subjects with proven lung cancer identified by screening LDCT (mean 23.57, SEM: ±3.73), in comparison to 37 high-risk subjects with benign-appearing lung nodules on LDCT (3.92 (±0.62)) (p&lt;0.0001). A threshold of ≥12 CTCs in screening subjects with a lung nodule had an accuracy of 96.1% to detect lung cancer. CTCs were absent in 15 healthy controls, and rare in 12 subjects with no lung nodules on LDCT (1.08 (±0.47)). Distinct, large, polymorphonuclear CD14/45+CTCs were at significantly increased ratios in stage III/IV lung cancer patients (p=0.005). PD-L1+, vimentin+, and N-cadherin+CTCs were present in all patients, and expression was found at higher rates in CTCs than in patient-matched lung cancer tissues.
Conclusions: This seminal study suggests that CTC detection can accurately identify lung cancers in high-risk subjects with a nodule on screening LDCT. CTC phenotyping in lung cancer patients allows real-time insights that are potentially highly relevant for personalized treatment strategies.
Table 1.Subjects’ characteristics and analysis for total CTCsCTCs presentCTC mean (±SEM); median (range)p valueSubjects included (total)136High-risk LDCT screening subjects6348 (76.2%)7.73 (±1.4); 3 (0-56)No lung nodules125 (41.7%)1.08 (±0.5); 0 (0-4)Benign lung nodules3729 (78.4%)3.92 (±0.6); 3 (0-14)n.s.*(vs. no lung nodule)Lung cancers (NSCLC)1414 (100%)23.57 (±3.7); 19 (13-56)&lt;0.0001*(vs. benign lung nodules)Lung cancer patients (NSCLC)7272 (100%)25.01 (±1.5); 22 (9-80)Not screened58 (81%)58 (100%)25.36 (±1.6); 23 (9-80)0.32† (vs. lung cancers diagnosed by screening)NSCLC stage (AJCC 8th ed.)•I•II•III•IV26 (36%)14 (20%)19 (26%)13 (18%)22 (±2.3); 18 (13-48)21.4 (±2.1); 20 (9-35)26.4 (±2.2); 27 (10-45)32.9 (±5.3); 24 (12-80)Healthy controls1500AJCC: American Joint Committee on Cancer; NSCLC: non-small cell lung cancer
Citation Format: YARISWAMY MANJUNATH, Sathisha Upparahalli Venkateshaiah, Eric T. Kimchi, Kevin F. Staveley-O'Carroll, Jared Coberly, Diego M. Avella, Timothy J. Hoffman, Chelsea Deroche, Klaus Pantel, Guangfu Li, Jussuf T. Kaifi. Circulating tumor cells accurately detect and characterize lung cancers in high-risk subjects undergoing low-dose CT screening [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 917.