ES-RO-BMC-01719-MI

Delgado‑Ureña et al. J Transl Med (2018) 16:251 https://doi.org/10.1186/s12967‑ 018‑1624‑2 RESEARCH Circulating tumor cells criteria (CyCAR) versus standard RECIST criteria for treatment response assessment in metastatic colorectal cancer patients Mayte Delgado‑Ureña 1† , Francisco G. Ortega 2† , Diego de Miguel‑Pérez 2,3† , Alba Rodriguez‑Martínez 1,2,3,4,5 , Jose L. García‑Puche 1,2 , Hugh Ilyine 4 , Jose A. Lorente 2,3 , Jose Exposito‑Hernandez 1 , M. Carmen Garrido‑Navas 2 , Miguel Delgado‑Ramirez 5 and M. José Serrano 1,2* 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. How‑ ever, 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. Keywords: Metastatic colorectal cancer, Bevacizumab, Circulating tumor cells, RECIST, CyCAR, Prognosis © The Author(s) 2018. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/ ) , which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/ publicdomain/zero/1.0/ ) applies to the data made available in this article, unless otherwise stated. Background In colorectal cancer (CRC), metastasis is the main cause of death [ 1 ]. Distant metastasis is identified in approximately 25% of patients at initial diagnosis, and half of CRC patients will develop it [ 2 ]. During this pro- cess, circulating tumor cells (CTCs), detach from pri- mary sites, enter the bloodstream and extravasate in distant organs. CTCs are now being studied in order to have a deeper understanding of the metastatic processes [ 3 ]. The phenotypic and genetic characterization of CTCs is especially important; as different subpopulations of CTCs can be detected in the blood of these patients [ 4 ]. These CTCs subclones can depict in real time the het- erogeneity of a tumor, displaying its different abilities Open Access Journal of Translational Medicine *Correspondence: mjose.serrano@genyo.es † Mayte Delgado‑Ureña, Francisco G. Ortega and Diego de Miguel‑Pérez contributed equally to this work 2 Liquid Biopsy and Metastasis Research Group, GENYO, Centre for Genomics and Oncological Research, Pfizer/University of Granada/ Andalusian Regional Government PTS, Granada, Avenida de la Ilustración, 114, 18016 Granada, Spain Full list of author information is available at the end of the article

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