Unbiased and Automated Identification of a Circulating Tumour Cell Definition That Associates with Overall Survival

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2011 Nov 17

PMID 22087312

Citations 26

Authors

Sjoerd T Ligthart

Frank A W Coumans

Gerhardt Attard

Amy Mulick Cassidy

Johann S de Bono

Leon W M M Terstappen

Affiliations

Soon will be listed here.

Abstract

Circulating tumour cells (CTC) in patients with metastatic carcinomas are associated with poor survival and can be used to guide therapy. Classification of CTC however remains subjective, as they are morphologically heterogeneous. We acquired digital images, using the CellSearch™ system, from blood of 185 castration resistant prostate cancer (CRPC) patients and 68 healthy subjects to define CTC by computer algorithms. Patient survival data was used as the training parameter for the computer to define CTC. The computer-generated CTC definition was validated on a separate CRPC dataset comprising 100 patients. The optimal definition of the computer defined CTC (aCTC) was stricter as compared to the manual CellSearch CTC (mCTC) definition and as a consequence aCTC were less frequent. The computer-generated CTC definition resulted in hazard ratios (HRs) of 2.8 for baseline and 3.9 for follow-up samples, which is comparable to the mCTC definition (baseline HR 2.9, follow-up HR 4.5). Validation resulted in HRs at baseline/follow-up of 3.9/5.4 for computer and 4.8/5.8 for manual definitions. In conclusion, we have defined and validated CTC by clinical outcome using a perfectly reproducing automated algorithm.

Citing Articles

Contemporary Molecular Markers for Predicting Systemic Treatment Response in Urothelial Bladder Cancer: A Narrative Review.

Dimitrov G, Mangaldzhiev R, Slavov C, Popov E Cancers (Basel). 2024; 16(17).

PMID: 39272913 PMC: 11394076. DOI: 10.3390/cancers16173056.

New Perspectives on the Role of Liquid Biopsy in Bladder Cancer: Applicability to Precision Medicine.

Alberca-Del Arco F, Prieto-Cuadra D, Santos-Perez de la Blanca R, Saez-Barranquero F, Matas-Rico E, Herrera-Imbroda B Cancers (Basel). 2024; 16(4).

PMID: 38398192 PMC: 10886494. DOI: 10.3390/cancers16040803.

Clinical and prognostic significance of detecting , , , and mRNA-positive cells in the peripheral blood, tumor-draining blood and bone marrow of non-small cell lung cancer patients.

Rehulkova A, Chudacek J, Prokopova A, Vidlarova M, Stranska J, Drabek J Transl Lung Cancer Res. 2023; 12(5):1034-1050.

PMID: 37323172 PMC: 10261864. DOI: 10.21037/tlcr-22-801.

Circulating Tumor Cell Identification Based on Deep Learning.

Guo Z, Lin X, Hui Y, Wang J, Zhang Q, Kong F Front Oncol. 2022; 12:843879.

PMID: 35252012 PMC: 8889528. DOI: 10.3389/fonc.2022.843879.

Applications of liquid biopsy in the Pharmacological Audit Trail for anticancer drug development.

Pal A, Shinde R, Miralles M, Workman P, de Bono J Nat Rev Clin Oncol. 2021; 18(7):454-467.

PMID: 33762744 DOI: 10.1038/s41571-021-00489-x.

References

Budd G, Cristofanilli M, Ellis M, Stopeck A, Borden E, Miller M . Circulating tumor cells versus imaging--predicting overall survival in metastatic breast cancer. Clin Cancer Res. 2006; 12(21):6403-9. DOI: 10.1158/1078-0432.CCR-05-1769. View

de Bono J, Ashworth A . Translating cancer research into targeted therapeutics. Nature. 2010; 467(7315):543-9. DOI: 10.1038/nature09339. View

Kraan J, Sleijfer S, Strijbos M, Ignatiadis M, Peeters D, Pierga J . External quality assurance of circulating tumor cell enumeration using the CellSearch(®) system: a feasibility study. Cytometry B Clin Cytom. 2011; 80(2):112-8. DOI: 10.1002/cyto.b.20573. View

Allard W, Matera J, Miller M, Repollet M, Connelly M, Rao C . Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with nonmalignant diseases. Clin Cancer Res. 2004; 10(20):6897-904. DOI: 10.1158/1078-0432.CCR-04-0378. View

Zack G, Rogers W, LATT S . Automatic measurement of sister chromatid exchange frequency. J Histochem Cytochem. 1977; 25(7):741-53. DOI: 10.1177/25.7.70454. View

Scher H, Jia X, de Bono J, Fleisher M, Pienta K, Raghavan D . Circulating tumour cells as prognostic markers in progressive, castration-resistant prostate cancer: a reanalysis of IMMC38 trial data. Lancet Oncol. 2009; 10(3):233-9. PMC: 2774131. DOI: 10.1016/S1470-2045(08)70340-1. View

Olmos D, Arkenau H, Ang J, Ledaki I, Attard G, Carden C . Circulating tumour cell (CTC) counts as intermediate end points in castration-resistant prostate cancer (CRPC): a single-centre experience. Ann Oncol. 2008; 20(1):27-33. DOI: 10.1093/annonc/mdn544. View

Hayes D, Cristofanilli M, Budd G, Ellis M, Stopeck A, Miller M . Circulating tumor cells at each follow-up time point during therapy of metastatic breast cancer patients predict progression-free and overall survival. Clin Cancer Res. 2006; 12(14 Pt 1):4218-24. DOI: 10.1158/1078-0432.CCR-05-2821. View

Attard G, Reid A, AHern R, Parker C, Oommen N, Folkerd E . Selective inhibition of CYP17 with abiraterone acetate is highly active in the treatment of castration-resistant prostate cancer. J Clin Oncol. 2009; 27(23):3742-8. PMC: 3535569. DOI: 10.1200/JCO.2008.20.0642. View

10.

Reid A, Attard G, Danila D, Oommen N, Olmos D, Fong P . Significant and sustained antitumor activity in post-docetaxel, castration-resistant prostate cancer with the CYP17 inhibitor abiraterone acetate. J Clin Oncol. 2010; 28(9):1489-95. PMC: 2849770. DOI: 10.1200/JCO.2009.24.6819. View

11.

Racila E, Euhus D, Weiss A, Rao C, McConnell J, Terstappen L . Detection and characterization of carcinoma cells in the blood. Proc Natl Acad Sci U S A. 1998; 95(8):4589-94. PMC: 22534. DOI: 10.1073/pnas.95.8.4589. View

12.

Attard G, de Bono J . Utilizing circulating tumor cells: challenges and pitfalls. Curr Opin Genet Dev. 2010; 21(1):50-8. DOI: 10.1016/j.gde.2010.10.010. View

13.

Cristofanilli M, Budd G, Ellis M, Stopeck A, Matera J, Miller M . Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med. 2004; 351(8):781-91. DOI: 10.1056/NEJMoa040766. View

14.

de Bono J, Scher H, Montgomery R, Parker C, Miller M, Tissing H . Circulating tumor cells predict survival benefit from treatment in metastatic castration-resistant prostate cancer. Clin Cancer Res. 2008; 14(19):6302-9. DOI: 10.1158/1078-0432.CCR-08-0872. View

15.

Tibbe A, Miller M, Terstappen L . Statistical considerations for enumeration of circulating tumor cells. Cytometry A. 2007; 71(3):154-62. DOI: 10.1002/cyto.a.20369. View

16.

Bubley G, Carducci M, Dahut W, Dawson N, Daliani D, Eisenberger M . Eligibility and response guidelines for phase II clinical trials in androgen-independent prostate cancer: recommendations from the Prostate-Specific Antigen Working Group. J Clin Oncol. 1999; 17(11):3461-7. DOI: 10.1200/JCO.1999.17.11.3461. View

17.

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

18.

Coumans F, Doggen C, Attard G, de Bono J, Terstappen L . All circulating EpCAM+CK+CD45- objects predict overall survival in castration-resistant prostate cancer. Ann Oncol. 2010; 21(9):1851-1857. DOI: 10.1093/annonc/mdq030. View

19.

Attard G, Reid A, Yap T, Raynaud F, Dowsett M, Settatree S . Phase I clinical trial of a selective inhibitor of CYP17, abiraterone acetate, confirms that castration-resistant prostate cancer commonly remains hormone driven. J Clin Oncol. 2008; 26(28):4563-71. DOI: 10.1200/JCO.2007.15.9749. View