This Article Full Text Full Text (PDF) Erratum (v27,p1923) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cohen, S. J. Articles by Meropol, N. J. Search for Related Content PubMed PubMed Citation Articles by Cohen, S. J. Articles by Meropol, N. J. Social Bookmarking                            What's this?

Relationship of Circulating Tumor Cells to Tumor Response, Progression-Free Survival, and Overall Survival in Patients With Metastatic Colorectal Cancer

Steven J. Cohen, Cornelis J.A. Punt, Nicholas Iannotti, Bruce H. Saidman, Kert D. Sabbath, Nashat Y. Gabrail, Joel Picus, Michael Morse, Edith Mitchell, M. Craig Miller, Gerald V. Doyle, Henk Tissing, Leon W.M.M. Terstappen, Neal J. Meropol

From the Fox Chase Cancer Center; Thomas Jefferson University, Philadelphia; Medical Oncology Associates, Kingston; Immunicon Corp, Huntingdon Valley, PA; the Dutch Colorectal Cancer Group; Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands; Hematology Oncology Associates, Port Saint Lucie, FL; Medical Oncology and Hematology PC, New Haven, CT; Union Hospital, Canton, OH; Washington University, St Louis, MO; and Duke University Medical Center, Durham, NC

Corresponding author: Steven J. Cohen, MD, Department of Medical Oncology, Fox Chase Cancer Center, 333 Cottman Ave, Philadelphia, PA 19111; e-mail: S_Cohen{at}fccc.edu

Purpose As treatment options expand for metastatic colorectal cancer (mCRC), a blood marker with a prognostic and predictive role could guide treatment. We tested the hypothesis that circulating tumor cells (CTCs) could predict clinical outcome in patients with mCRC.

Patients and Methods In a prospective multicenter study, CTCs were enumerated in the peripheral blood of 430 patients with mCRC at baseline and after starting first-, second-, or third-line therapy. CTCs were measured using an immunomagnetic separation technique.

Results Patients were stratified into unfavorable and favorable prognostic groups based on CTC levels of three or more or less than three CTCs/7.5 mL, respectively. Patients with unfavorable compared with favorable baseline CTCs had shorter median progression-free survival (PFS; 4.5 v 7.9 months; P = .0002) and overall survival (OS; 9.4 v 18.5 months; P < .0001). Differences persisted at 1 to 2, 3 to 5, 6 to 12, and 13 to 20 weeks after therapy. Conversion of baseline unfavorable CTCs to favorable at 3 to 5 weeks was associated with significantly longer PFS and OS compared with patients with unfavorable CTCs at both time points (PFS, 6.2 v 1.6 months; P = .02; OS, 11.0 v 3.7 months; P = .0002). Among nonprogressing patients, favorable compared with unfavorable CTCs within 1 month of imaging was associated with longer survival (18.8 v 7.1 months; P < .0001). Baseline and follow-up CTC levels remained strong predictors of PFS and OS after adjustment for clinically significant factors.

Conclusion The number of CTCs before and during treatment is an independent predictor of PFS and OS in patients with metastatic colorectal cancer. CTCs provide prognostic information in addition to that of imaging studies.

Supported by Immunicon Corporation.

Presented in part at the 43rd Annual Meeting of the American Society of Clinical Oncology, June 1-5, 2007, Chicago, IL.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Clinical Trials repository link available on www.JCO.org.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				J. Tol, M. Koopman, M. C. Miller, A. Tibbe, A. Cats, G. J. M. Creemers, A. H. Vos, I. D. Nagtegaal, L. W. M. M. Terstappen, and C. J. A. Punt Circulating tumour cells early predict progression-free and overall survival in advanced colorectal cancer patients treated with chemotherapy and targeted agents Ann. Onc., October 27, 2009; (2009) mdp463v1. [Abstract] [Full Text] [PDF]

				S. Ogino, K. Nosho, N. Irahara, K. Shima, Y. Baba, G. J. Kirkner, J. A. Meyerhardt, and C. S. Fuchs Prognostic Significance and Molecular Associations of 18q Loss of Heterozygosity: A Cohort Study of Microsatellite Stable Colorectal Cancers J. Clin. Oncol., September 20, 2009; 27(27): 4591 - 4598. [Abstract] [Full Text] [PDF]

				J.-M. Hou, A. Greystoke, L. Lancashire, J. Cummings, T. Ward, R. Board, E. Amir, S. Hughes, M. Krebs, A. Hughes, et al. Evaluation of Circulating Tumor Cells and Serological Cell Death Biomarkers in Small Cell Lung Cancer Patients Undergoing Chemotherapy Am. J. Pathol., August 1, 2009; 175(2): 808 - 816. [Abstract] [Full Text] [PDF]

				S. J. Cohen, C. J. A. Punt, N. Iannotti, B. H. Saidman, K. D. Sabbath, N. Y. Gabrail, J. Picus, M. A. Morse, E. Mitchell, M. C. Miller, et al. Prognostic significance of circulating tumor cells in patients with metastatic colorectal cancer Ann. Onc., July 1, 2009; 20(7): 1223 - 1229. [Abstract] [Full Text] [PDF]

				M. Connelly, Y. Wang, G. V. Doyle, L. Terstappen, and R. Mccormack Re: Anti-Epithelial Cell Adhesion Molecule Antibodies and the Detection of Circulating Normal-Like Breast Tumor Cells J Natl Cancer Inst, June 16, 2009; 101(12): 895 - 895. [Full Text] [PDF]

				Y. Okumura, F. Tanaka, K. Yoneda, M. Hashimoto, T. Takuwa, N. Kondo, and S. Hasegawa Circulating Tumor Cells in Pulmonary Venous Blood of Primary Lung Cancer Patients. Ann. Thorac. Surg., June 1, 2009; 87(6): 1669 - 1675. [Abstract] [Full Text] [PDF]

				N. Dhani, D. Tu, D. J. Sargent, L. Seymour, and M. J. Moore Alternate Endpoints for Screening Phase II Studies Clin. Cancer Res., March 15, 2009; 15(6): 1873 - 1882. [Abstract] [Full Text] [PDF]

				M. A. Leversha, J. Han, Z. Asgari, D. C. Danila, O. Lin, R. Gonzalez-Espinoza, A. Anand, H. Lilja, G. Heller, M. Fleisher, et al. Fluorescence In situ Hybridization Analysis of Circulating Tumor Cells in Metastatic Prostate Cancer Clin. Cancer Res., March 15, 2009; 15(6): 2091 - 2097. [Abstract] [Full Text] [PDF]

				A. H. Talasaz, A. A. Powell, D. E. Huber, J. G. Berbee, K.-H. Roh, W. Yu, W. Xiao, M. M. Davis, R. F. Pease, M. N. Mindrinos, et al. Isolating highly enriched populations of circulating epithelial cells and other rare cells from blood using a magnetic sweeper device PNAS, March 10, 2009; 106(10): 3970 - 3975. [Abstract] [Full Text] [PDF]

				D. Olmos, H.-T. Arkenau, J. E. Ang, I. Ledaki, G. Attard, C. P. Carden, A. H. M. Reid, R. A'Hern, P. C. Fong, N. B. Oomen, et al. Circulating tumour cell (CTC) counts as intermediate end points in castration-resistant prostate cancer (CRPC): a single-centre experience Ann. Onc., January 1, 2009; 20(1): 27 - 33. [Abstract] [Full Text] [PDF]