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Published in: Journal of Translational Medicine 1/2018

Open Access 01-12-2018 | Research

Circulating tumor cells criteria (CyCAR) versus standard RECIST criteria for treatment response assessment in metastatic colorectal cancer patients

Authors: Mayte Delgado-Ureña, Francisco G. Ortega, Diego de Miguel-Pérez, Alba Rodriguez-Martínez, Jose L. García-Puche, Hugh Ilyine, Jose A. Lorente, Jose Exposito-Hernandez, M. Carmen Garrido-Navas, Miguel Delgado-Ramirez, M. José Serrano

Published in: Journal of Translational Medicine | Issue 1/2018

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Abstract

Background

The use of circulating tumor cells (CTCs) as indicators of treatment response in metastatic colorectal cancer (mCRC) needs to be clarified. The objective of this study is to compare the Response Evaluation Criteria in Solid Tumors (RECIST) with the Cytologic Criteria Assessing Response (CyCAR), based on the presence and phenotypic characterization of CTCs, as indicators of FOLFOX–bevacizumab treatment response.

Methods

77 mCRC blood samples from FOLFOX–bevacizumab treated patients were analyzed to isolate CTCs before and after (12 and 24 weeks) treatment, using an immunomagnetic separation method. VEGFR expression was identified by double immunostaining.

Results

We observed a decrease of CTCs (42.8 vs. 18.2%) and VEGFR positivity (69.7% vs. 41.7%) after treatment. According to RECIST, 6.45% of the patients did not show any clinical benefit, whereas 93.55% patients showed a favorable response at 12 weeks. According to CyCAR, 29% had a non-favorable response and 71% patients did not. No significant differences were found between the response assessment by RECIST and CyCAR at 12 or 24 weeks. However, in the multivariate analysis, RECIST at 12 weeks and CyCAR at 24 weeks were independent prognostic factors for OS (HR: 0.1, 95% CI 0.02–0.58 and HR: 0.35, 95% CI 0.12–0.99 respectively).

Conclusions

CyCAR results were comparable to RECIST in evaluating the response in mCRC and can be used as an alternative when the limitation of RECIST requires additional response analysis techniques.
Literature
1.
go back to reference Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, et al. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11. Lyon: International Agency for Research on Cancer; 2014. http://globocan.iarc.fr. Accessed 19 June 2017. Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, et al. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11. Lyon: International Agency for Research on Cancer; 2014. http://​globocan.​iarc.​fr. Accessed 19 June 2017.
2.
go back to reference Edwards MS, Chadda SD, Zhao Z, Barber BL, Sykes DP. A systematic review of treatment guidelines for metastatic colorectal cancer. Colorectal Dis. 2012;14:e31–47.CrossRefPubMedPubMedCentral Edwards MS, Chadda SD, Zhao Z, Barber BL, Sykes DP. A systematic review of treatment guidelines for metastatic colorectal cancer. Colorectal Dis. 2012;14:e31–47.CrossRefPubMedPubMedCentral
4.
go back to reference Nadal R, Lorente JA, Rosell R, Serrano MJ. Relevance of molecular characterization of circulating tumor cells in breast cancer in the era of targeted therapies. Expert Rev Mol Diagn. 2013;13:295–307.CrossRefPubMed Nadal R, Lorente JA, Rosell R, Serrano MJ. Relevance of molecular characterization of circulating tumor cells in breast cancer in the era of targeted therapies. Expert Rev Mol Diagn. 2013;13:295–307.CrossRefPubMed
5.
go back to reference Lu CY, Tsai HL, Uen YH, Hu HM, Chen CW, Cheng TL, et al. Circulating tumor cells as a surrogate marker for determining clinical outcome to mFOLFOX chemotherapy in patients with stage III colon cancer. Br J Cancer. 2013;108:791–7.CrossRefPubMedPubMedCentral Lu CY, Tsai HL, Uen YH, Hu HM, Chen CW, Cheng TL, et al. Circulating tumor cells as a surrogate marker for determining clinical outcome to mFOLFOX chemotherapy in patients with stage III colon cancer. Br J Cancer. 2013;108:791–7.CrossRefPubMedPubMedCentral
6.
go back to reference Tanimoto K, Yoshiga K, Eguchi H, Kaneyasu H, Ukon K, Kumazaki T, et al. Hypoxia-inducible factor-1α polymorphisms associated with enhanced transactivation capacity, implying clinical significance. Carcinogenesis. 2003;24:1779–83.CrossRefPubMed Tanimoto K, Yoshiga K, Eguchi H, Kaneyasu H, Ukon K, Kumazaki T, et al. Hypoxia-inducible factor-1α polymorphisms associated with enhanced transactivation capacity, implying clinical significance. Carcinogenesis. 2003;24:1779–83.CrossRefPubMed
7.
go back to reference Mancuso MR, Davis R, Norberg SM, O’Brien S, Sennino B, Nakahara T, et al. Rapid vascular regrowth in tumors after reversal of VEGF inhibition. J Clin Invest. 2006;116:2610–21.CrossRefPubMedPubMedCentral Mancuso MR, Davis R, Norberg SM, O’Brien S, Sennino B, Nakahara T, et al. Rapid vascular regrowth in tumors after reversal of VEGF inhibition. J Clin Invest. 2006;116:2610–21.CrossRefPubMedPubMedCentral
8.
go back to reference Kowanetz M, Ferrara N. Vascular endotelial growth factor signaling pathways: therapeutic perspective. Clin Cancer Res. 2006;12:5018–22.CrossRefPubMed Kowanetz M, Ferrara N. Vascular endotelial growth factor signaling pathways: therapeutic perspective. Clin Cancer Res. 2006;12:5018–22.CrossRefPubMed
10.
go back to reference Hurwitz HI, Tebbutt NC, Kabbinavar F. Efficacy and safety of bevacizumab in metastatic colorectal cancer: pooled analysis from seven randomized controlled trials. Oncologist. 2013;18:1004–12.CrossRefPubMedPubMedCentral Hurwitz HI, Tebbutt NC, Kabbinavar F. Efficacy and safety of bevacizumab in metastatic colorectal cancer: pooled analysis from seven randomized controlled trials. Oncologist. 2013;18:1004–12.CrossRefPubMedPubMedCentral
11.
go back to reference Dy GK, Hobday TJ, Nelson G, Windschitl HE, O’Connell MJ, Alberts SR, et al. Long-term survivors of metastatic colorectal cancer treated with systemic chemotherapy alone: a North Central Cancer Treatment Group review of 3811 patients, n0144. Clin Colorectal Cancer. 2009;8:88–93.CrossRefPubMedCentralPubMed Dy GK, Hobday TJ, Nelson G, Windschitl HE, O’Connell MJ, Alberts SR, et al. Long-term survivors of metastatic colorectal cancer treated with systemic chemotherapy alone: a North Central Cancer Treatment Group review of 3811 patients, n0144. Clin Colorectal Cancer. 2009;8:88–93.CrossRefPubMedCentralPubMed
12.
go back to reference Maru D, Venook AP, Ellis LM. Predictive biomarkers for bevacizumab: are we there yet? Clin Cancer Res. 2013;19:2824–7.CrossRefPubMed Maru D, Venook AP, Ellis LM. Predictive biomarkers for bevacizumab: are we there yet? Clin Cancer Res. 2013;19:2824–7.CrossRefPubMed
13.
go back to reference Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45:228–47.CrossRefPubMed Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45:228–47.CrossRefPubMed
14.
go back to reference Serrano MJ, Ortega FG, Alvarez-Cubero MJ, Nadal R, Sanchez-Rovira P, Salido M, et al. EMT and EGFR in CTCs cytokeratin negative non-metastatic breast cancer. Oncotarget. 2014;5:7486–97.CrossRefPubMedPubMedCentral Serrano MJ, Ortega FG, Alvarez-Cubero MJ, Nadal R, Sanchez-Rovira P, Salido M, et al. EMT and EGFR in CTCs cytokeratin negative non-metastatic breast cancer. Oncotarget. 2014;5:7486–97.CrossRefPubMedPubMedCentral
15.
go back to reference Maldonado G, Greenland S. Simulation study of confounder-selection strategies. Am J Epidemiol. 1993;138:923–36.CrossRefPubMed Maldonado G, Greenland S. Simulation study of confounder-selection strategies. Am J Epidemiol. 1993;138:923–36.CrossRefPubMed
16.
go back to reference Yang D, Woodard G, Zhou C, Wang X, Liu Z, Ye Z, et al. Significance of different response evaluation criteria in predicting progression-free survival of lung cancer with certain imaging characteristics. Thorac Cancer. 2016;7:535–42.CrossRefPubMedPubMedCentral Yang D, Woodard G, Zhou C, Wang X, Liu Z, Ye Z, et al. Significance of different response evaluation criteria in predicting progression-free survival of lung cancer with certain imaging characteristics. Thorac Cancer. 2016;7:535–42.CrossRefPubMedPubMedCentral
17.
go back to reference Nishino M, Jagannathan JP, Krajewski KM, O’Regan K, Hatabu H, Shapiro G, et al. Personalized tumor response assessment in the era of molecular medicine: cancer-specific and therapy-specific response criteria to complement pitfalls of RECIST. AJR Am J Roentgenol. 2012;198:737–45.CrossRefPubMedPubMedCentral Nishino M, Jagannathan JP, Krajewski KM, O’Regan K, Hatabu H, Shapiro G, et al. Personalized tumor response assessment in the era of molecular medicine: cancer-specific and therapy-specific response criteria to complement pitfalls of RECIST. AJR Am J Roentgenol. 2012;198:737–45.CrossRefPubMedPubMedCentral
18.
go back to reference 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;351:781–91.CrossRefPubMed 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;351:781–91.CrossRefPubMed
19.
go back to reference Ashworth TR. A case of cancer in which cells similar to those in the tumors were seen in the blood after death. Aust Med J. 1869;14:146–9. Ashworth TR. A case of cancer in which cells similar to those in the tumors were seen in the blood after death. Aust Med J. 1869;14:146–9.
20.
go back to reference Nadal R, Fernandez A, Sanchez-Rovira P, Salido M, Rodríguez M, García-Puche JL, et al. Biomarkers characterization of circulating tumour cells in breast cancer patients. Breast Cancer Res. 2012;14:R71.CrossRefPubMedPubMedCentral Nadal R, Fernandez A, Sanchez-Rovira P, Salido M, Rodríguez M, García-Puche JL, et al. Biomarkers characterization of circulating tumour cells in breast cancer patients. Breast Cancer Res. 2012;14:R71.CrossRefPubMedPubMedCentral
22.
go back to reference Das A, Kunkel M, Joudeh J. Clinico-pathological correlation of serial measurement of circulating tumor cells in 24 metastatic colorectal cancer patients receiving chemotherapy reveals interpatient heterogeneity correlated with CEA levels but independent of KRAS and BRAF mutation. Cancer Biol Ther. 2015;16:709–13.CrossRefPubMedPubMedCentral Das A, Kunkel M, Joudeh J. Clinico-pathological correlation of serial measurement of circulating tumor cells in 24 metastatic colorectal cancer patients receiving chemotherapy reveals interpatient heterogeneity correlated with CEA levels but independent of KRAS and BRAF mutation. Cancer Biol Ther. 2015;16:709–13.CrossRefPubMedPubMedCentral
23.
go back to reference Buim ME, Fanelli MF, Souza VS, Romero J, Abdallah EA, Mello CA, et al. Detection of KRAS mutations in circulating tumor cells from patients with metastatic colorectal cancer. Cancer Biol Ther. 2015;16:1289–95.CrossRefPubMedPubMedCentral Buim ME, Fanelli MF, Souza VS, Romero J, Abdallah EA, Mello CA, et al. Detection of KRAS mutations in circulating tumor cells from patients with metastatic colorectal cancer. Cancer Biol Ther. 2015;16:1289–95.CrossRefPubMedPubMedCentral
24.
go back to reference Tsai WS, Chen JS, Shao HJ, Wu JC, Lai JM, Lu SH, et al. Circulating tumor cell count correlates with colorectal neoplasm progression and is a prognostic marker for distant metastasis in non-metastatic patients. Sci Rep. 2016;6:24517.CrossRefPubMedPubMedCentral Tsai WS, Chen JS, Shao HJ, Wu JC, Lai JM, Lu SH, et al. Circulating tumor cell count correlates with colorectal neoplasm progression and is a prognostic marker for distant metastasis in non-metastatic patients. Sci Rep. 2016;6:24517.CrossRefPubMedPubMedCentral
25.
go back to reference Xu H, Xia Z, Jia X, Chen K, Li D, Dai Y, et al. Primary tumor resection is associated with improved survival in stage IV colorectal cancer: an instrumental variable analysis. Sci Rep. 2015;5:16516.CrossRefPubMedPubMedCentral Xu H, Xia Z, Jia X, Chen K, Li D, Dai Y, et al. Primary tumor resection is associated with improved survival in stage IV colorectal cancer: an instrumental variable analysis. Sci Rep. 2015;5:16516.CrossRefPubMedPubMedCentral
26.
go back to reference Tseng JY, Yang CY, Liang SC, Liu RS, Jiang JK, Lin CH. Dynamic changes in numbers and properties of circulating tumor cells and their potential applications. Cancers (Basel). 2014;6:2369–86.CrossRef Tseng JY, Yang CY, Liang SC, Liu RS, Jiang JK, Lin CH. Dynamic changes in numbers and properties of circulating tumor cells and their potential applications. Cancers (Basel). 2014;6:2369–86.CrossRef
27.
go back to reference Simiantonaki N, Taxeidis M, Jayasinghe C, Kirkpatrick CJ. Epithelial expression of VEGF receptors in colorectal carcinomas and their relationship to metastatic status. Anticancer Res. 2007;27:3245–50.PubMed Simiantonaki N, Taxeidis M, Jayasinghe C, Kirkpatrick CJ. Epithelial expression of VEGF receptors in colorectal carcinomas and their relationship to metastatic status. Anticancer Res. 2007;27:3245–50.PubMed
28.
go back to reference Hanrahan V, Currie MJ, Gunningham SP, Morrin HR, Scott PA, Robinson BA, et al. The angiogenic switch for vascular endothelial growth factor (VEGF)-A, VEGF-B, VEGF-C, and VEGF-D in the adenoma-carcinoma sequence during colorectal cancer progression. J Pathol. 2003;200:183–94.CrossRefPubMed Hanrahan V, Currie MJ, Gunningham SP, Morrin HR, Scott PA, Robinson BA, et al. The angiogenic switch for vascular endothelial growth factor (VEGF)-A, VEGF-B, VEGF-C, and VEGF-D in the adenoma-carcinoma sequence during colorectal cancer progression. J Pathol. 2003;200:183–94.CrossRefPubMed
29.
go back to reference Lebok P, Huber J, Burandt EC, Lebeau A, Marx AH, Terracciano L, et al. Loss of membranous VEGFR1 expression is associated with an adverse phenotype and shortened survival in breast cancer. Mol Med Rep. 2016;14:1443–50.CrossRefPubMedPubMedCentral Lebok P, Huber J, Burandt EC, Lebeau A, Marx AH, Terracciano L, et al. Loss of membranous VEGFR1 expression is associated with an adverse phenotype and shortened survival in breast cancer. Mol Med Rep. 2016;14:1443–50.CrossRefPubMedPubMedCentral
30.
32.
go back to reference Zhang R, Xu J, Zhao J, Bai J. Expression of vascular endothelial growth factor in circulating tumor cells for prediction of colorectal cancer. Int J Clin Exp Pathol. 2017;10:5859–67. Zhang R, Xu J, Zhao J, Bai J. Expression of vascular endothelial growth factor in circulating tumor cells for prediction of colorectal cancer. Int J Clin Exp Pathol. 2017;10:5859–67.
Metadata
Title
Circulating tumor cells criteria (CyCAR) versus standard RECIST criteria for treatment response assessment in metastatic colorectal cancer patients
Authors
Mayte Delgado-Ureña
Francisco G. Ortega
Diego de Miguel-Pérez
Alba Rodriguez-Martínez
Jose L. García-Puche
Hugh Ilyine
Jose A. Lorente
Jose Exposito-Hernandez
M. Carmen Garrido-Navas
Miguel Delgado-Ramirez
M. José Serrano
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2018
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-018-1624-2

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