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      Circulating Tumor Cells (CTC) and Cell-Free DNA (cfDNA) Workshop 2016: Scientific Opportunities and Logistics for Cancer Clinical Trial Incorporation

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          Abstract

          Despite the identification of circulating tumor cells (CTCs) and cell-free DNA (cfDNA) as potential blood-based biomarkers capable of providing prognostic and predictive information in cancer, they have not been incorporated into routine clinical practice. This resistance is due in part to technological limitations hampering CTC and cfDNA analysis, as well as a limited understanding of precisely how to interpret emergent biomarkers across various disease stages and tumor types. In recognition of these challenges, a group of researchers and clinicians focused on blood-based biomarker development met at the Canadian Cancer Trials Group (CCTG) Spring Meeting in Toronto, Canada on 29 April 2016 for a workshop discussing novel CTC/cfDNA technologies, interpretation of data obtained from CTCs versus cfDNA, challenges regarding disease evolution and heterogeneity, and logistical considerations for incorporation of CTCs/cfDNA into clinical trials, and ultimately into routine clinical use. The objectives of this workshop included discussion of the current barriers to clinical implementation and recent progress made in the field, as well as fueling meaningful collaborations and partnerships between researchers and clinicians. We anticipate that the considerations highlighted at this workshop will lead to advances in both basic and translational research and will ultimately impact patient management strategies and patient outcomes.

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          Most cited references34

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          Circulating tumor cells predict survival benefit from treatment in metastatic castration-resistant prostate cancer.

          A method for enumerating circulating tumor cells (CTC) has received regulatory clearance. The primary objective of this prospective study was to establish the relationship between posttreatment CTC count and overall survival (OS) in castration-resistant prostate cancer (CRPC). Secondary objectives included determining the prognostic utility of CTC measurement before initiating therapy, and the relationship of CTC to prostate-specific antigen (PSA) changes and OS at these and other time points. Blood was drawn from CRPC patients with progressive disease starting a new line of chemotherapy before treatment and monthly thereafter. Patients were stratified into predetermined Favorable or Unfavorable groups ( or =5 CTC/7.5mL). Two hundred thirty-one of 276 enrolled patients (84%) were evaluable. Patients with Unfavorable pretreatment CTC (57%) had shorter OS (median OS, 11.5 versus 21.7 months; Cox hazard ratio, 3.3; P 26 to 9.3 months). CTC are the most accurate and independent predictor of OS in CRPC. These data led to Food and Drug Administration clearance of this assay for the evaluation of CRPC.
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            Biology, detection, and clinical implications of circulating tumor cells

            Cancer metastasis is the main cause of cancer-related death, and dissemination of tumor cells through the blood circulation is an important intermediate step that also exemplifies the switch from localized to systemic disease. Early detection and characterization of circulating tumor cells (CTCs) is therefore important as a general strategy to monitor and prevent the development of overt metastatic disease. Furthermore, sequential analysis of CTCs can provide clinically relevant information on the effectiveness and progression of systemic therapies (e.g., chemo-, hormonal, or targeted therapies with antibodies or small inhibitors). Although many advances have been made regarding the detection and molecular characterization of CTCs, several challenges still exist that limit the current use of this important diagnostic approach. In this review, we discuss the biology of tumor cell dissemination, technical advances, as well as the challenges and potential clinical implications of CTC detection and characterization.
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              EGFR mutation detection in ctDNA from NSCLC patient plasma: A cross-platform comparison of leading technologies to support the clinical development of AZD9291.

              To assess the ability of different technology platforms to detect epidermal growth factor receptor (EGFR) mutations, including T790M, from circulating tumor DNA (ctDNA) in advanced non-small cell lung cancer (NSCLC) patients.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                08 September 2016
                September 2016
                : 17
                : 9
                : 1505
                Affiliations
                [1 ]London Regional Cancer Program, London Health Sciences Centre, London, ON N6K 4L6, Canada; Lori.Lowes@ 123456lhsc.on.ca
                [2 ]Special Hematology/Flow Cytometry, London Health Sciences Centre, London, ON N6K 4L6, Canada
                [3 ]Departments of Radiation Oncology and Medical Biophysics, University of Toronto, Toronto, ON M5G 1L7, Canada; Scott.Bratman@ 123456rmp.uhn.ca
                [4 ]Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada
                [5 ]Epic Sciences Inc., San Diego, CA 92121, USA; ryan.dittamore@ 123456epicsciences.com
                [6 ]Campbell Family Institute for Breast Cancer Research and Laboratory Medicine Program, University Health Network, Toronto, ON M5G 2C4, Canada; Susan.Done@ 123456uhn.ca
                [7 ]Departments of Laboratory Medicine and Pathobiology, and Medical Biophysics, Faculty of Medicine, University of Toronto, Toronto, ON M5G 2C4, Canada
                [8 ]Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON M5S 3M2, Canada; shana.kelley@ 123456utoronto.ca
                [9 ]Department of Biochemistry, Faculty of Medicine, University of Toronto, Toronto, ON M5S 3M2, Canada
                [10 ]Department of Chemistry, Faculty of Arts and Science, University of Toronto, Toronto, ON M5S 3M2, Canada
                [11 ]Manitoba Institute of Cell Biology, Cancer Care Manitoba, University of Manitoba, Winnipeg, MB R3E 0V9, Canada; Sabine.Mai@ 123456umanitoba.ca
                [12 ]Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC V5A 1S6, Canada; rdmorin@ 123456sfu.ca
                [13 ]Vancouver Prostate Centre and Department of Urologic Sciences, University of British Columbia, Vancouver, BC V6H 3Z6, Canada; awyatt@ 123456prostatecentre.com
                [14 ]Departments of Anatomy & Cell Biology and Oncology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON N6K 4L6, Canada
                Author notes
                [* ]Correspondence: Alison.Allan@ 123456lhsc.on.ca ; Tel.: +1-519-685-8600 (ext. 55134)
                Article
                ijms-17-01505
                10.3390/ijms17091505
                5037782
                27618023
                ea66bd4e-327c-42d4-a709-2ec3e17a288e
                © 2016 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 15 July 2016
                : 31 August 2016
                Categories
                Conference Report

                Molecular biology
                oncology,circulating tumor cells (ctc),cell-free dna (cfdna),circulating tumor dna (ctdna),clinical trials,conference report

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