Tuberc Respir Dis.  2020 Jan;83(1):61-70. 10.4046/trd.2019.0048.

Circulating Tumor Cell Number Is Associated with Primary Tumor Volume in Patients with Lung Adenocarcinoma

• Kang BJ
• Ra SW
• Lee K
• Lim S
• Son SH
• Ahn JJ
• Kim BC

• KMID: 2466621
• DOI: http://doi.org/10.4046/trd.2019.0048

Abstract

BACKGROUND
Circulating tumor cells (CTCs) are frequently detected in patients with advanced-stage malignant tumors and could act as a predictor of poor prognosis. However, there is a paucity of data on the relationship between CTC number and primary tumor volume in patients with lung cancer. Therefore, our study aimed to evaluate the relationship between CTC number and primary tumor volume in patients with lung adenocarcinoma.
METHODS
We collected blood samples from 21 patients with treatment-naive lung adenocarcinoma and 73 healthy individuals. To count CTCs, we used a CTC enrichment method based on fluid-assisted separation technology. We compared CTC numbers between lung adenocarcinoma patients and healthy individuals using propensity score matching, and performed linear regression analysis to analyze the relationship between CTC number and primary tumor volume in lung adenocarcinoma patients.
RESULTS
CTC positivity was significantly more common in lung adenocarcinoma patients than in healthy individuals (p<0.001). The median primary tumor volume in CTC-negative and CTC-positive patients was 10.0 cm³ and 64.8 cm³, respectively. Multiple linear regression analysis showed that the number of CTCs correlated with primary tumor volume in lung adenocarcinoma patients (β=0.903, p=0.002). Further subgroup analysis showed a correlation between CTC number and primary tumor volume in patients with distant (p=0.024) and extra-thoracic (p=0.033) metastasis (not in patients with distant metastasis).
CONCLUSION
Our study showed that CTC numbers may be associated with primary tumor volume in lung adenocarcinomas patients, especially in those with distant metastasis.

Keyword

Neoplastic Cells, Circulating; Tumor Burden; Adenocarcinoma of Lung

MeSH Terms

Adenocarcinoma*
Humans
Linear Models
Lung Neoplasms
Lung*
Methods
Neoplasm Metastasis
Neoplastic Cells, Circulating*
Prognosis
Propensity Score
Tumor Burden*

Figure

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  Figure 1 Four cases of primary tumor volume measurement using a high-performance workstation. The transverse (left upper, F), coronal (left lower, A), and sagittal (right lower, L) area of the tumor was examined using computed tomography attenuation values. Then, the device automatically reconstructed 3D images of the tumor (right upper, A).

• 

  Figure 2 Workflow of circulating tumor cell (CTC) enrichment and enumeration (A), and CTC analysis (B) by the BioView Duet Workstation. WBC: white blood cell; PBMC: peripheral blood mononuclear cell.

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  Figure 3 Schematic flow chart of study population selection. CTC: circulating tumor cell; FAST: fluid-assisted separation technology.

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  Figure 4 Receiver operating characteristics curve for the diagnostic performance of circulating tumor cell positivity for lung adenocarcinoma, assessed using the propensity score-matched cohort. AUC: area under the curve.

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  Figure 5 Linear regression model analysis for the association of circulating tumor cell (CTC) number with primary tumor volume. (A) All lung adenocarcinoma patients (n=21) (R2=0.542, β=0.736, p<0.001, CTC=−0.050+0.272×primary tumor volume). (B) Lung adenocarcinoma patients without distant metastasis (n=11) (R2=0.030, β=−0.172, p=0.612, CTC=0.496−0.091×primary tumor volume). (C) Lung adenocarcinoma patients with distant metastasis (n=10) (R2=0.491, β=0.701, p=0.024, CTC=−0.230+0.286×primary tumor volume). (D) Lung adenocarcinoma patients with extra-thoracic metastasis (n=6) (R2=0.719, β=0.848, p=0.033, CTC=−1.558+0.277×primary tumor volume).

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