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<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 CTCs

  CTCs present CTC mean (±SEM); median (range) p value 
Subjects included (total) 136    
High-risk LDCT screening subjects 63 48 (76.2%) 7.73 (±1.4); 3 (0-56)  
No lung nodules 12 5 (41.7%) 1.08 (±0.5); 0 (0-4)  
Benign lung nodules 37 29 (78.4%) 3.92 (±0.6); 3 (0-14) 

n.s.*

(vs. no lung nodule)

 
Lung cancers (NSCLC) 14 14 (100%) 23.57 (±3.7); 19 (13-56) 

<0.0001*

(vs. benign lung nodules)

 
Lung cancer patients (NSCLC) 72 72 (100%) 25.01 (±1.5); 22 (9-80)  
Not screened 58 (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

•

IV

 

26 (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 controls 15 0 0  
  CTCs present CTC mean (±SEM); median (range) p value 
Subjects included (total) 136    
High-risk LDCT screening subjects 63 48 (76.2%) 7.73 (±1.4); 3 (0-56)  
No lung nodules 12 5 (41.7%) 1.08 (±0.5); 0 (0-4)  
Benign lung nodules 37 29 (78.4%) 3.92 (±0.6); 3 (0-14) 

n.s.*

(vs. no lung nodule)

 
Lung cancers (NSCLC) 14 14 (100%) 23.57 (±3.7); 19 (13-56) 

<0.0001*

(vs. benign lung nodules)

 
Lung cancer patients (NSCLC) 72 72 (100%) 25.01 (±1.5); 22 (9-80)  
Not screened 58 (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

•

IV

 

26 (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 controls 15 0 0  

AJCC: American Joint Committee on Cancer; NSCLC: non-small cell lung cancer

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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.

©2019 American Association for Cancer Research.
2019
American Association for Cancer Research.