Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
BMC Cancer
Published in: BMC Cancer 1/2015

Open Access 01-12-2015 | Research article

Meta-analysis of the prognostic value of circulating tumor cells detected with the CellSearch System in colorectal cancer

Authors: Xuanzhang Huang, Peng Gao, Yongxi Song, Jingxu Sun, Xiaowan Chen, Junhua Zhao, Huimian Xu, Zhenning Wang

Published in: BMC Cancer | Issue 1/2015

Login to get access

Abstract

Background

The prognostic value of circulating tumor cells (CTCs) detected with the CellSearch System in patients with colorectal cancer (CRC) is controversial. The aim of our meta-analysis was to evaluate whether the detection of CTCs in the peripheral blood with the standardized CellSearch System has prognostic utility for patients with CRC.

Methods

The PubMed, Science Citation Index, Cochrane Database, Embase, and the references in relevant studies were systematically searched (up to December, 2014). No search restrictions were imposed. Our meta-analysis was performed in Stata software, version 12.0 (2011) (Stata Corp, College Station, TX, USA), with the odds ratio (OR), risk ratio (RR), hazard ratio (HR), and 95% confidence interval (95% CI) as the effect measures. Subgroup and sensitivity analyses were also conducted.

Results

Eleven studies containing 1847 patients with CRC were analyzed. There was a significantly higher incidence of CTCs in the metastasis-positive group than in the metastasis-negative group (OR = 4.06, 95% CI [1.74, 9.50], P < 0.01, I2 = 0%). For hepatic metastasis, a type of metastasis, a higher incidence of CTCs was observed in the hepatic-metastasis-positive group than in the -negative group (OR = 2.61, 95% CI [1.73, 3.96], P < 0.01, I2 = 0%). The presence of CTCs was significantly related to overall survival (HR = 2.00, 95% CI [1.49, 2.69], P < 0.01, I2 = 67.1%) and progression-free survival (HR = 1.80, 95% CI [1.52, 2.13], P < 0.01, I2 = 43.9%) of patients with CRC, regardless of the sampling time. The response rate for the CTC+ groups was significantly lower than that for the CTC− groups at baseline and during treatment (baseline: 33% versus 39%, RR = 0.79, 95% CI [0.63, 0.99], P = 0.04, I2 = 7.0%; during treatment: 17% versus 46%, RR = 0.41, 95% CI [0.22, 0.77], P = 0.01, I2 = 0.0%;).

Conclusions

Our meta-analysis indicates that the detection of CTCs in the peripheral blood with the CellSearch System has prognostic utility for patients with CRC.
Appendix
Available only for authorised users
Literature
1.
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61(2):69–90.CrossRefPubMed
2.
Seymour MT, Maughan TS, Ledermann JA, Topham C, James R, Gwyther SJ, et al. Different strategies of sequential and combination chemotherapy for patients with poor prognosis advanced colorectal cancer (MRC FOCUS): a randomised controlled trial. Lancet. 2007;370(9582):143–52.CrossRefPubMed
3.
Shah SA, Haddad R, Al-Sukhni W, Kim RD, Greig PD, Grant DR, et al. Surgical resection of hepatic and pulmonary metastases from colorectal carcinoma. J Am Coll Surg. 2006;202(3):468–75.CrossRefPubMed
4.
Fidler IJ. The pathogenesis of cancer metastasis: the ‘seed and soil’ hypothesis revisited. Nat Rev Cancer. 2003;3(6):453–8.CrossRefPubMed
5.
Chen WS, Chung MY, Liu JH, Liu JM, Lin JK. Impact of circulating free tumor cells in the peripheral blood of colorectal cancer patients during laparoscopic surgery. World J Surg. 2004;28(6):552–7.CrossRefPubMed
6.
Sadahiro S, Suzuki T, Maeda Y, Yurimoto S, Yasuda S, Makuuchi H, et al. Detection of carcinoembryonic antigen messenger RNA-expressing cells in peripheral blood 7 days after curative surgery is a novel prognostic factor in colorectal cancer. Ann Surg Oncol. 2007;14(3):1092–8.CrossRefPubMed
7.
de Albuquerque A, Kubisch I, Stolzel U, Ernst D, Boese-Landgraf J, Breier G, et al. Prognostic and predictive value of circulating tumor cell analysis in colorectal cancer patients. J Transl Med. 2012;10:222.CrossRefPubMedPubMedCentral
8.
Wong SC, Ng SS, Cheung MT, Luk LY, Chan CM, Cheung AH, et al. Clinical significance of CDX2-positive circulating tumour cells in colorectal cancer patients. Br J Cancer. 2011;104(6):1000–6.CrossRefPubMedPubMedCentral
9.
10.
Riethdorf S, Fritsche H, Muller V, Rau T, Schindlbeck C, Rack B, et al. Detection of circulating tumor cells in peripheral blood of patients with metastatic breast cancer: a validation study of the Cell Search system. Clin Cancer Res. 2007;13(3):920–8.CrossRefPubMed
11.
Groot Koerkamp B, Rahbari NN, Buchler MW, Koch M, Weitz J. Circulating tumor cells and prognosis of patients with resectable colorectal liver metastases or widespread metastatic colorectal cancer: a meta-analysis. Ann Surg Oncol. 2013;20(7):2156–65.CrossRefPubMed
12.
Cohen SJ, Punt CJ, Iannotti N, Saidman BH, Sabbath KD, Gabrail NY, et al. 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.CrossRefPubMed
13.
Deneve E, Riethdorf S, Ramos J, Nocca D, Coffy A, Daures JP, et al. Capture of viable circulating tumor cells in the liver of colorectal cancer patients. Clin Chem. 2013;59(9):1384–92.CrossRefPubMed
14.
Kuboki Y, Matsusaka S, Minowa S, Shibata H, Suenaga M, Shinozaki E, et al. Circulating tumor cell (CTC) count and epithelial growth factor receptor expression on CTCs as biomarkers for cetuximab efficacy in advanced colorectal cancer. Anticancer Res. 2013;33(9):3905–10.PubMed
15.
Hiraiwa K, Takeuchi H, Hasegawa H, Saikawa Y, Suda K, Ando T, et al. Clinical significance of circulating tumor cells in blood from patients with gastrointestinal cancers. Ann Surg Oncol. 2008;15(11):3092–100.CrossRefPubMed
16.
Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000;92(3):205–16.CrossRefPubMed
17.
Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol. 2010;25(9):603–5.CrossRefPubMed
18.
Panic N, Leoncini E, de Belvis G, Ricciardi W, Boccia S. Evaluation of the endorsement of the preferred reporting items for systematic reviews and meta-analysis (PRISMA) statement on the quality of published systematic review and meta-analyses. PLoS One. 2013;8(12):e83138.CrossRefPubMedPubMedCentral
19.
20.
Tierney JF, Stewart LA, Ghersi D, Burdett S, Sydes MR. Practical methods for incorporating summary time-to-event data into meta-analysis. Trials. 2007;8:16.CrossRefPubMedPubMedCentral
21.
22.
23.
Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics. 1994;50(4):1088–101.CrossRefPubMed
24.
Sotelo MJ, Sastre J, Maestro ML, Veganzones S, Vieitez JM, Alonso V, et al. Role of circulating tumor cells as prognostic marker in resected stage III colorectal cancer. Ann Oncol. 2015;26(3):535–41.CrossRefPubMed
25.
Seeberg LT, Waage A, Brunborg C, Hugenschmidt H, Renolen A, Stav I, et al. Circulating tumor cells in patients with colorectal liver metastasis predict impaired survival. Ann Surg. 2015;261(1):164–71.CrossRefPubMed
26.
Gazzaniga P, Raimondi C, Gradilone A, Biondi Zoccai G, Nicolazzo C, Gandini O, et al. Circulating tumor cells in metastatic colorectal cancer: do we need an alternative cutoff? J Cancer Res Clin Oncol. 2013;139(8):1411–6.CrossRefPubMed
27.
Aggarwal C, Meropol NJ, Punt CJ, Iannotti N, Saidman BH, Sabbath KD, et al. Relationship among circulating tumor cells, CEA and overall survival in patients with metastatic colorectal cancer. Annals Oncol. 2013;24(2):420–8.CrossRef
28.
Sastre J, Maestro ML, Gomez-Espana A, Rivera F, Valladares M, Massuti B, et al. Circulating tumor cell count is a prognostic factor in metastatic colorectal cancer patients receiving first-line chemotherapy plus bevacizumab: a Spanish Cooperative Group for the Treatment of Digestive Tumors study. Oncologist. 2012;17(7):947–55.CrossRefPubMedPubMedCentral
29.
Sato N, Hayashi N, Imamura Y, Tanaka Y, Kinoshita K, Kurashige J, et al. Usefulness of transcription-reverse transcription concerted reaction method for detecting circulating tumor cells in patients with colorectal cancer. Ann Surg Oncol. 2012;19(6):2060–5.CrossRefPubMed
30.
Papavasiliou P, Fisher T, Kuhn J, Nemunaitis J, Lamont J. Circulating tumor cells in patients undergoing surgery for hepatic metastases from colorectal cancer. Proc. 2010;23(1):11–4.
31.
Tol J, Koopman M, Miller MC, Tibbe A, Cats A, Creemers GJ, et al. Circulating tumour cells early predict progression-free and overall survival in advanced colorectal cancer patients treated with chemotherapy and targeted agents. Annals Oncol. 2010;21(5):1006–12.CrossRef
32.
Sastre J, Vidaurreta M, Gomez A, Rivera F, Massuti B, Lopez MR, et al. Prognostic value of the combination of circulating tumor cells plus kras in patients with metastatic colorectal cancer treated with chemotherapy plus bevacizumab. Clin Colorectal Cancer. 2013;12(4):280–6.CrossRefPubMed
33.
Sobrero AF, Maurel J, Fehrenbacher L, Scheithauer W, Abubakr YA, Lutz MP, et al. EPIC: phase III trial of cetuximab plus irinotecan after fluoropyrimidine and oxaliplatin failure in patients with metastatic colorectal cancer. J Clin Oncol. 2008;26(14):2311–9.CrossRefPubMed
34.
Zinser-Sierra JW, Rodriguez-Ramirez S, Villalobos-Valencia R, Ramirez-Marquez M. Use of bevacizumab in metastatic colorectal cancer: report from the Mexican opinion and analysis forum on colorectal cancer treatment with bevacizumab (September 2009). Drugs R D. 2011;11(2):101–11.CrossRefPubMed
35.
Center MM, Jemal A, Smith RA, Ward E. Worldwide variations in colorectal cancer. CA Cancer J Clin. 2009;59(6):366–78.CrossRefPubMed
36.
Rahbari NN, Aigner M, Thorlund K, Mollberg N, Motschall E, Jensen K, et al. Meta-analysis shows that detection of circulating tumor cells indicates poor prognosis in patients with colorectal cancer. Gastroenterology. 2010;138(5):1714–26.CrossRefPubMed
37.
Yalcin S, Kilickap S, Portakal O, Arslan C, Hascelik G, Kutluk T. Determination of circulating tumor cells for detection of colorectal cancer progression or recurrence. Hepatogastroenterology. 2010;57(104):1395–8.PubMed
38.
Hayes DF, Cristofanilli M, Budd GT, Ellis MJ, Stopeck A, Miller MC, et al. 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.CrossRefPubMed
39.
Iinuma H, Watanabe T, Mimori K, Adachi M, Hayashi N, Tamura J, et al. Clinical significance of circulating tumor cells, including cancer stem-like cells, in peripheral blood for recurrence and prognosis in patients with Dukes’ stage B and C colorectal cancer. J Clin Oncol. 2011;29(12):1547–55.CrossRefPubMed
40.
Weitz J, Kienle P, Lacroix J, Willeke F, Benner A, Lehnert T, et al. Dissemination of tumor cells in patients undergoing surgery for colorectal cancer. Clin Cancer Res. 1998;4(2):343–8.PubMed
41.
Molnar B, Sipos F, Galamb O, Tulassay Z. Molecular detection of circulating cancer cells. Role in diagnosis, prognosis and follow-up of colon cancer patients. Dig Dis. 2003;21(4):320–5.CrossRefPubMed
42.
Lim SH, Becker TM, Chua W, Caixeiro NJ, Ng WL, Kienzle N, et al. Circulating tumour cells and circulating free nucleic acid as prognostic and predictive biomarkers in colorectal cancer. Cancer Lett. 2014;346(1):24–33.CrossRefPubMed
43.
Katsuno H, Zacharakis E, Aziz O, Rao C, Deeba S, Paraskeva P, et al. Does the presence of circulating tumor cells in the venous drainage of curative colorectal cancer resections determine prognosis? A meta-analysis. Ann Surg Oncol. 2008;15(11):3083–91.CrossRefPubMed
44.
Colombano SP, Reese PA. The cascade theory of metastatic spread: are there generalizing sites? Cancer. 1980;46(10):2312–4.CrossRefPubMed
45.
Taniguchi T, Makino M, Suzuki K, Kaibara N. Prognostic significance of reverse transcriptase-polymerase chain reaction measurement of carcinoembryonic antigen mRNA levels in tumor drainage blood and peripheral blood of patients with colorectal carcinoma. Cancer. 2000;89(5):970–6.CrossRefPubMed
46.
Stoecklein NH, Hosch SB, Bezler M, Stern F, Hartmann CH, Vay C, et al. Direct genetic analysis of single disseminated cancer cells for prediction of outcome and therapy selection in esophageal cancer. Cancer Cell. 2008;13(5):441–53.CrossRefPubMed
47.
Dieter SM, Ball CR, Hoffmann CM, Nowrouzi A, Herbst F, Zavidij O, et al. Distinct types of tumor-initiating cells form human colon cancer tumors and metastases. Cell Stem Cell. 2011;9(4):357–65.CrossRefPubMed
48.
Heiss MM, Strohlein MA, Jager M, Kimmig R, Burges A, Schoberth A, et al. Immunotherapy of malignant ascites with trifunctional antibodies. Int J Cancer. 2005;117(3):435–43.CrossRefPubMed
49.
Burges A, Wimberger P, Kumper C, Gorbounova V, Sommer H, Schmalfeldt B, et al. Effective relief of malignant ascites in patients with advanced ovarian cancer by a trifunctional anti-EpCAM x anti-CD3 antibody: a phase I/II study. Clin Cancer Res. 2007;13(13):3899–905.CrossRefPubMed
50.
Gotzmann J, Mikula M, Eger A, Schulte-Hermann R, Foisner R, Beug H, et al. Molecular aspects of epithelial cell plasticity: implications for local tumor invasion and metastasis. Mutat Res. 2004;566(1):9–20.CrossRefPubMed
51.
Aznavoorian S, Murphy AN, Stetler-Stevenson WG, Liotta LA. Molecular aspects of tumor cell invasion and metastasis. Cancer. 1993;71(4):1368–83.CrossRefPubMed
52.
Raimondi C, Nicolazzo C, Gradilone A, Giannini G, De Falco E, Chimenti I, et al. Circulating tumor cells: Exploring intratumor heterogeneity of colorectal cancer. Cancer Biol Ther. 2014;15(5):496–503.CrossRefPubMedPubMedCentral
53.
Cristofanilli M, Budd GT, Ellis MJ, Stopeck A, Matera J, Miller MC, et al. Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med. 2004;351(8):781–91.CrossRefPubMed
54.
Lucci A, Hall CS, Lodhi AK, Bhattacharyya A, Anderson AE, Xiao L, et al. Circulating tumour cells in non-metastatic breast cancer: a prospective study. Lancet Oncol. 2012;13(7):688–95.CrossRefPubMed
55.
Thorsteinsson M, Jess P. The clinical significance of circulating tumor cells in non-metastatic colorectal cancer–a review. European J Surg Oncol. 2011;37(6):459–65.CrossRef
56.
Torino F, Bonmassar E, Bonmassar L, De Vecchis L, Barnabei A, Zuppi C, et al. Circulating tumor cells in colorectal cancer patients. Cancer Treat Rev. 2013;39(7):759–72.CrossRefPubMed
Metadata
Title
Meta-analysis of the prognostic value of circulating tumor cells detected with the CellSearch System in colorectal cancer
Authors
Xuanzhang Huang
Peng Gao
Yongxi Song
Jingxu Sun
Xiaowan Chen
Junhua Zhao
Huimian Xu
Zhenning Wang
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2015
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-015-1218-9

Other articles of this Issue 1/2015

BMC Cancer 1/2015 Go to the issue

Research article

DNA copy number analysis of metastatic urothelial carcinoma with comparison to primary tumors

Study protocol

NEOSCOPE: a randomised Phase II study of induction chemotherapy followed by either oxaliplatin/capecitabine or paclitaxel/carboplatin based chemoradiation as pre-operative regimen for resectable oesophageal adenocarcinoma

Research article

Psychometric properties of the Chinese version of the fatigue scale-adolescent

Research article

The novel histone deacetylase inhibitor, N-hydroxy-7-(2-naphthylthio) hepatonomide, exhibits potent antitumor activity due to cytochrome-c-release-mediated apoptosis in renal cell carcinoma cells

Research article

Mesothelioma patient derived tumor xenografts with defined BAP1 mutations that mimic the molecular characteristics of human malignant mesothelioma

Research article

Targeting glycolysis by 3-bromopyruvate improves tamoxifen cytotoxicity of breast cancer cell lines
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits