title: Genomic classifier ColoPrint predicts recurrence in stage II colorectal cancer patients more accurately than clinical factors.
abstract: BACKGROUND
  Approximately 20% of patients with stage II colorectal cancer will experience a relapse. Current clinical-pathologic stratification factors do not allow clear identification of these high-risk patients. ColoPrint (Agendia, Amsterdam, The Netherlands, http://www.agendia.com) is a gene expression classifier that distinguishes patients with low or high risk of disease relapse.
  
  
  METHODS
  ColoPrint was developed using whole-genome expression data and validated in several independent validation cohorts. Stage II patients from these studies were pooled (n = 416), and ColoPrint was compared with clinical risk factors described in the National Comprehensive Cancer Network (NCCN) 2013 Guidelines for Colon Cancer. Median follow-up was 81 months. Most patients (70%) did not receive adjuvant chemotherapy. Risk of relapse (ROR) was defined as survival until first event of recurrence or death from cancer.
  
  
  RESULTS
  In the pooled stage II data set, ColoPrint identified 63% of patients as low risk with a 5-year ROR of 10%, whereas high-risk patients (37%) had a 5-year ROR of 21%, with a hazard ratio (HR) of 2.16 (p = .004). This remained significant in a multivariate model that included number of lymph nodes retrieved and microsatellite instability. In the T3 microsatellite-stable subgroup (n = 301), ColoPrint classified 59% of patients as low risk with a 5-year ROR of 9.9%. High-risk patients (31%) had a 22.4% ROR (HR: 2.41; p = .005). In contrast, the NCCN clinical high-risk factors were unable to distinguish high- and low-risk patients (15% vs. 13% ROR; p = .55).
  
  
  CONCLUSIONS
  ColoPrint significantly improved prognostic accuracy independent of microsatellite status or clinical variables, facilitating the identification of patients at higher risk who might be considered for additional treatment.
authors.affiliation: Departments of Gastrointestinal Medical Oncology and Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA; Vall d'Hebron University Hospital and Institute of Oncology, Universitat Autònoma de Barcelona, Barcelona, Spain; Department of Surgery, Klinikum Rechts der Isar, Technische University, Munich, Germany; Institut Català d'Oncologia, IDIBELL L'Hospitalet de Llobregat, Barcelona, Spain; Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, Barcelona, Spain; Department of Surgery, Medical University of Vienna, Vienna, Austria; Department of Surgery, University of Ferrara, Ferrara, Italy; Agendia NV, Amsterdam, The Netherlands; Agendia Inc., Irvine, California, USA skopetz@mdanderson.org.
authors.forename: Scott
authors.initials: S
authors.lastname: Kopetz
authors.affiliation: Departments of Gastrointestinal Medical Oncology and Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA; Vall d'Hebron University Hospital and Institute of Oncology, Universitat Autònoma de Barcelona, Barcelona, Spain; Department of Surgery, Klinikum Rechts der Isar, Technische University, Munich, Germany; Institut Català d'Oncologia, IDIBELL L'Hospitalet de Llobregat, Barcelona, Spain; Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, Barcelona, Spain; Department of Surgery, Medical University of Vienna, Vienna, Austria; Department of Surgery, University of Ferrara, Ferrara, Italy; Agendia NV, Amsterdam, The Netherlands; Agendia Inc., Irvine, California, USA.
authors.forename: Josep
authors.initials: J
authors.lastname: Tabernero
authors.affiliation: Departments of Gastrointestinal Medical Oncology and Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA; Vall d'Hebron University Hospital and Institute of Oncology, Universitat Autònoma de Barcelona, Barcelona, Spain; Department of Surgery, Klinikum Rechts der Isar, Technische University, Munich, Germany; Institut Català d'Oncologia, IDIBELL L'Hospitalet de Llobregat, Barcelona, Spain; Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, Barcelona, Spain; Department of Surgery, Medical University of Vienna, Vienna, Austria; Department of Surgery, University of Ferrara, Ferrara, Italy; Agendia NV, Amsterdam, The Netherlands; Agendia Inc., Irvine, California, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Rosenberg
authors.affiliation: Departments of Gastrointestinal Medical Oncology and Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA; Vall d'Hebron University Hospital and Institute of Oncology, Universitat Autònoma de Barcelona, Barcelona, Spain; Department of Surgery, Klinikum Rechts der Isar, Technische University, Munich, Germany; Institut Català d'Oncologia, IDIBELL L'Hospitalet de Llobregat, Barcelona, Spain; Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, Barcelona, Spain; Department of Surgery, Medical University of Vienna, Vienna, Austria; Department of Surgery, University of Ferrara, Ferrara, Italy; Agendia NV, Amsterdam, The Netherlands; Agendia Inc., Irvine, California, USA.
authors.forename: Zhi-Qin
authors.initials: ZQ
authors.lastname: Jiang
authors.affiliation: Departments of Gastrointestinal Medical Oncology and Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA; Vall d'Hebron University Hospital and Institute of Oncology, Universitat Autònoma de Barcelona, Barcelona, Spain; Department of Surgery, Klinikum Rechts der Isar, Technische University, Munich, Germany; Institut Català d'Oncologia, IDIBELL L'Hospitalet de Llobregat, Barcelona, Spain; Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, Barcelona, Spain; Department of Surgery, Medical University of Vienna, Vienna, Austria; Department of Surgery, University of Ferrara, Ferrara, Italy; Agendia NV, Amsterdam, The Netherlands; Agendia Inc., Irvine, California, USA.
authors.forename: Víctor
authors.initials: V
authors.lastname: Moreno
authors.affiliation: Departments of Gastrointestinal Medical Oncology and Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA; Vall d'Hebron University Hospital and Institute of Oncology, Universitat Autònoma de Barcelona, Barcelona, Spain; Department of Surgery, Klinikum Rechts der Isar, Technische University, Munich, Germany; Institut Català d'Oncologia, IDIBELL L'Hospitalet de Llobregat, Barcelona, Spain; Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, Barcelona, Spain; Department of Surgery, Medical University of Vienna, Vienna, Austria; Department of Surgery, University of Ferrara, Ferrara, Italy; Agendia NV, Amsterdam, The Netherlands; Agendia Inc., Irvine, California, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Bachleitner-Hofmann
authors.affiliation: Departments of Gastrointestinal Medical Oncology and Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA; Vall d'Hebron University Hospital and Institute of Oncology, Universitat Autònoma de Barcelona, Barcelona, Spain; Department of Surgery, Klinikum Rechts der Isar, Technische University, Munich, Germany; Institut Català d'Oncologia, IDIBELL L'Hospitalet de Llobregat, Barcelona, Spain; Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, Barcelona, Spain; Department of Surgery, Medical University of Vienna, Vienna, Austria; Department of Surgery, University of Ferrara, Ferrara, Italy; Agendia NV, Amsterdam, The Netherlands; Agendia Inc., Irvine, California, USA.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Lanza
authors.affiliation: Departments of Gastrointestinal Medical Oncology and Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA; Vall d'Hebron University Hospital and Institute of Oncology, Universitat Autònoma de Barcelona, Barcelona, Spain; Department of Surgery, Klinikum Rechts der Isar, Technische University, Munich, Germany; Institut Català d'Oncologia, IDIBELL L'Hospitalet de Llobregat, Barcelona, Spain; Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, Barcelona, Spain; Department of Surgery, Medical University of Vienna, Vienna, Austria; Department of Surgery, University of Ferrara, Ferrara, Italy; Agendia NV, Amsterdam, The Netherlands; Agendia Inc., Irvine, California, USA.
authors.forename: Lisette
authors.initials: L
authors.lastname: Stork-Sloots
authors.affiliation: Departments of Gastrointestinal Medical Oncology and Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA; Vall d'Hebron University Hospital and Institute of Oncology, Universitat Autònoma de Barcelona, Barcelona, Spain; Department of Surgery, Klinikum Rechts der Isar, Technische University, Munich, Germany; Institut Català d'Oncologia, IDIBELL L'Hospitalet de Llobregat, Barcelona, Spain; Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, Barcelona, Spain; Department of Surgery, Medical University of Vienna, Vienna, Austria; Department of Surgery, University of Ferrara, Ferrara, Italy; Agendia NV, Amsterdam, The Netherlands; Agendia Inc., Irvine, California, USA.
authors.forename: Dipen
authors.initials: D
authors.lastname: Maru
authors.affiliation: Departments of Gastrointestinal Medical Oncology and Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA; Vall d'Hebron University Hospital and Institute of Oncology, Universitat Autònoma de Barcelona, Barcelona, Spain; Department of Surgery, Klinikum Rechts der Isar, Technische University, Munich, Germany; Institut Català d'Oncologia, IDIBELL L'Hospitalet de Llobregat, Barcelona, Spain; Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, Barcelona, Spain; Department of Surgery, Medical University of Vienna, Vienna, Austria; Department of Surgery, University of Ferrara, Ferrara, Italy; Agendia NV, Amsterdam, The Netherlands; Agendia Inc., Irvine, California, USA.
authors.forename: Iris
authors.initials: I
authors.lastname: Simon
authors.affiliation: Departments of Gastrointestinal Medical Oncology and Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA; Vall d'Hebron University Hospital and Institute of Oncology, Universitat Autònoma de Barcelona, Barcelona, Spain; Department of Surgery, Klinikum Rechts der Isar, Technische University, Munich, Germany; Institut Català d'Oncologia, IDIBELL L'Hospitalet de Llobregat, Barcelona, Spain; Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, Barcelona, Spain; Department of Surgery, Medical University of Vienna, Vienna, Austria; Department of Surgery, University of Ferrara, Ferrara, Italy; Agendia NV, Amsterdam, The Netherlands; Agendia Inc., Irvine, California, USA.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Capellà
authors.affiliation: Departments of Gastrointestinal Medical Oncology and Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA; Vall d'Hebron University Hospital and Institute of Oncology, Universitat Autònoma de Barcelona, Barcelona, Spain; Department of Surgery, Klinikum Rechts der Isar, Technische University, Munich, Germany; Institut Català d'Oncologia, IDIBELL L'Hospitalet de Llobregat, Barcelona, Spain; Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, Barcelona, Spain; Department of Surgery, Medical University of Vienna, Vienna, Austria; Department of Surgery, University of Ferrara, Ferrara, Italy; Agendia NV, Amsterdam, The Netherlands; Agendia Inc., Irvine, California, USA.
authors.forename: Ramon
authors.initials: R
authors.lastname: Salazar
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D023281:Genomics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D009367:Neoplasm Staging; D009426:Netherlands; D011379:Prognosis; D018570:Risk Assessment
keywords: Gene expression signature; Risk classification; Risk prediction; Stage II colon cancer