Circulating Tumor Cells As a Response Monitor in Stage IV Non-small Cell Lung Cancer

Overview

Journal J Transl Med

Publisher Biomed Central

Specialties Biomedical Engineering
General Medicine

Date 2019 Aug 30

PMID 31462312

Citations 29

Authors

Stephanie N Shishido

Anders Carlsson

Jorge Nieva

Kelly Bethel

James B Hicks

Lyudmila Bazhenova

Peter Kuhn

Affiliations

Soon will be listed here.

Abstract

Background: Monitoring circulating tumor cells (CTC) has been shown to be prognostic in most solid malignancies. There is no CTC assay in clinical use for lung cancer therapy monitoring due to inconclusive clinical utility data. Limited data has been published outside of the standard CTC enumerations, regarding clinical significance of phenotypic heterogeneity of CTCs in late stage NSCLC and its ability to correlate with treatment outcomes.

Methods: In 81 patients with stage IV NSCLC, multiple timepoints for CTC analysis were collected after initiation of treatment across 139 lines of therapy using single cell high definition diagnostic pathology imaging of all nucleated cells from 362 peripheral blood samples as a liquid biopsy.

Results: We analyzed the subset of 25 patients with complete time series data, totaling 117 blood samples, to determine the significance of HD-CTC kinetics during the initiation of treatment. These kinetics follow three distinct patterns: an increase in HD-CTCs with therapy (mean + 118.40 HD-CTCs/mL), unchanged HD-CTCs numbers (stable; mean 0.54 HD-CTCs/mL), and a decrease in HD-CTCs numbers (mean - 81.40 HD-CTCs/mL). Patients with an increasing CTC count during the first 3 months post initiation of new treatment had a better PFS and OS compared to the other groups. There was weak correlation between the absolute number of HD-CTCs at a single time point of therapy and patient outcomes (OS p value = 0.0754). In the whole cohort of 81 patients, HD-CTCs were detected in 51 (63%) patients at initiation of therapy with a median of 2.20 (range 0-509.20) and a mean of 26.21 HD-CTCs/mL (± 15.64).

Conclusions: CTCs are identifiable in most patients with stage IV NSCLC. While absolute HD-CTC counts do not correlate with prognosis, the changes in CTC counts were predictive of survival in patients with metastatic lung cancer receiving chemotherapy. The level and dynamics of CTCs indicate very different biological and pharmacological phenomena at different stages of disease and timepoints of treatment, highlighting the complex role of CTCs in cancer research and clinical management.

Citing Articles

Longitudinal tracking of circulating rare events in the liquid biopsy of stage III-IV non-small cell lung cancer patients.

Bai L, Courcoubetis G, Mason J, Hicks J, Nieva J, Kuhn P Discov Oncol. 2024; 15(1):142.

PMID: 38700626 PMC: 11068717. DOI: 10.1007/s12672-024-00984-4.

The application, safety, and future of immune cell therapies and prognosis in different malignancies.

Einloth K, Gayfield S, McMaster T, Didier A, Dworkin L, Creeden J Bioimpacts. 2023; 13(6):439-455.

PMID: 38022382 PMC: 10676524. DOI: 10.34172/bi.2023.27521.

Significance of circulating tumor cells in lung cancer: a narrative review.

Hamilton G, Rath B, Stickler S Transl Lung Cancer Res. 2023; 12(4):877-894.

PMID: 37197632 PMC: 10183408. DOI: 10.21037/tlcr-22-712.

Current and future applications of liquid biopsy in non-small-cell lung cancer-a narrative review.

Tomasik B, Skrzypski M, Bienkowski M, Dziadziuszko R, Jassem J Transl Lung Cancer Res. 2023; 12(3):594-614.

PMID: 37057121 PMC: 10087994. DOI: 10.21037/tlcr-22-742.

Isolation of TTF-1 Positive Circulating Tumor Cells for Single-Cell Sequencing by Using an Automatic Platform Based on Microfluidic Devices.

Jou H, Ho H, Huang K, Chen C, Chen S, Lo P Int J Mol Sci. 2022; 23(23).

PMID: 36499466 PMC: 9736518. DOI: 10.3390/ijms232315139.

References

Earhart C, Hughes C, Gaster R, Ooi C, Wilson R, Zhou L . Isolation and mutational analysis of circulating tumor cells from lung cancer patients with magnetic sifters and biochips. Lab Chip. 2013; 14(1):78-88. PMC: 4144998. DOI: 10.1039/c3lc50580d. View

Xu Y, Zhou J, Pan X . Detecting circulating tumor cells in patients with advanced non-small cell lung cancer. Genet Mol Res. 2015; 14(3):10352-8. DOI: 10.4238/2015.September.1.1. View

Hofman V, Ilie M, Long E, Selva E, Bonnetaud C, Molina T . Detection of circulating tumor cells as a prognostic factor in patients undergoing radical surgery for non-small-cell lung carcinoma: comparison of the efficacy of the CellSearch Assay™ and the isolation by size of epithelial tumor cell method. Int J Cancer. 2010; 129(7):1651-60. DOI: 10.1002/ijc.25819. View

Chen X, Wang X, He H, Liu Z, Hu J, Li W . Combination of circulating tumor cells with serum carcinoembryonic antigen enhances clinical prediction of non-small cell lung cancer. PLoS One. 2015; 10(5):e0126276. PMC: 4440620. DOI: 10.1371/journal.pone.0126276. View

Wu C, Hao H, Li L, Zhou X, Guo Z, Zhang L . Preliminary investigation of the clinical significance of detecting circulating tumor cells enriched from lung cancer patients. J Thorac Oncol. 2008; 4(1):30-6. DOI: 10.1097/JTO.0b013e3181914125. View

Dago A, Stepansky A, Carlsson A, Luttgen M, Kendall J, Baslan T . Rapid phenotypic and genomic change in response to therapeutic pressure in prostate cancer inferred by high content analysis of single circulating tumor cells. PLoS One. 2014; 9(8):e101777. PMC: 4118839. DOI: 10.1371/journal.pone.0101777. View

Krebs M, Hou J, Sloane R, Lancashire L, Priest L, Nonaka D . Analysis of circulating tumor cells in patients with non-small cell lung cancer using epithelial marker-dependent and -independent approaches. J Thorac Oncol. 2011; 7(2):306-15. DOI: 10.1097/JTO.0b013e31823c5c16. View

Went P, Lugli A, Meier S, Bundi M, Mirlacher M, Sauter G . Frequent EpCam protein expression in human carcinomas. Hum Pathol. 2004; 35(1):122-8. DOI: 10.1016/j.humpath.2003.08.026. View

Marrinucci D, Bethel K, Luttgen M, Bruce R, Nieva J, Kuhn P . Circulating tumor cells from well-differentiated lung adenocarcinoma retain cytomorphologic features of primary tumor type. Arch Pathol Lab Med. 2009; 133(9):1468-71. PMC: 4422331. DOI: 10.5858/133.9.1468. View

10.

Marrinucci D, Bethel K, Bruce R, Curry D, Hsieh B, Humphrey M . Case study of the morphologic variation of circulating tumor cells. Hum Pathol. 2006; 38(3):514-9. DOI: 10.1016/j.humpath.2006.08.027. View

11.

Cohen S, Punt C, Iannotti N, Saidman B, Sabbath K, Gabrail N . Relationship of circulating tumor cells to tumor response, progression-free survival, and overall survival in patients with metastatic colorectal cancer. J Clin Oncol. 2008; 26(19):3213-21. DOI: 10.1200/JCO.2007.15.8923. View

12.

Bayarri-Lara C, Ortega F, Cueto Ladron de Guevara A, Puche J, Ruiz Zafra J, de Miguel-Perez D . Circulating Tumor Cells Identify Early Recurrence in Patients with Non-Small Cell Lung Cancer Undergoing Radical Resection. PLoS One. 2016; 11(2):e0148659. PMC: 4767413. DOI: 10.1371/journal.pone.0148659. View

13.

Hou H, Warkiani M, Khoo B, Li Z, Soo R, Tan D . Isolation and retrieval of circulating tumor cells using centrifugal forces. Sci Rep. 2013; 3:1259. PMC: 3569917. DOI: 10.1038/srep01259. View

14.

Hartkopf A, Wagner P, Wallwiener D, Fehm T, Rothmund R . Changing levels of circulating tumor cells in monitoring chemotherapy response in patients with metastatic breast cancer. Anticancer Res. 2011; 31(3):979-84. View

15.

Fukuoka M, Wu Y, Thongprasert S, Sunpaweravong P, Leong S, Sriuranpong V . Biomarker analyses and final overall survival results from a phase III, randomized, open-label, first-line study of gefitinib versus carboplatin/paclitaxel in clinically selected patients with advanced non-small-cell lung cancer in Asia (IPASS). J Clin Oncol. 2011; 29(21):2866-74. DOI: 10.1200/JCO.2010.33.4235. View

16.

Hirose T, Murata Y, Oki Y, Sugiyama T, Kusumoto S, Ishida H . Relationship of circulating tumor cells to the effectiveness of cytotoxic chemotherapy in patients with metastatic non-small-cell lung cancer. Oncol Res. 2012; 20(2-3):131-7. DOI: 10.3727/096504012x13473664562583. View

17.

Bidard F, Mathiot C, Degeorges A, Etienne-Grimaldi M, Delva R, Pivot X . Clinical value of circulating endothelial cells and circulating tumor cells in metastatic breast cancer patients treated first line with bevacizumab and chemotherapy. Ann Oncol. 2010; 21(9):1765-1771. DOI: 10.1093/annonc/mdq052. View

18.

Pachmann K, Clement J, Schneider C, Willen B, Camara O, Pachmann U . Standardized quantification of circulating peripheral tumor cells from lung and breast cancer. Clin Chem Lab Med. 2005; 43(6):617-27. DOI: 10.1515/CCLM.2005.107. View

19.

Nel I, Jehn U, Gauler T, Hoffmann A . Individual profiling of circulating tumor cell composition in patients with non-small cell lung cancer receiving platinum based treatment. Transl Lung Cancer Res. 2015; 3(2):100-6. PMC: 4367657. DOI: 10.3978/j.issn.2218-6751.2014.03.05. View

20.

Sandler A, Gray R, Perry M, Brahmer J, Schiller J, Dowlati A . Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med. 2006; 355(24):2542-50. DOI: 10.1056/NEJMoa061884. View