title: Association Between Results of a Gene Expression Signature Assay and Recurrence-Free Interval in Patients With Stage II Colon Cancer in Cancer and Leukemia Group B 9581 (Alliance).
abstract: Conventional staging methods are inadequate to identify patients with stage II colon cancer (CC) who are at high risk of recurrence after surgery with curative intent. ColDx is a gene expression, microarray-based assay shown to be independently prognostic for recurrence-free interval (RFI) and overall survival in CC. The objective of this study was to further validate ColDx using formalin-fixed, paraffin-embedded specimens collected as part of the Alliance phase III trial, C9581.
  
  
  
  C9581 evaluated edrecolomab versus observation in patients with stage II CC and reported no survival benefit. Under an initial case-cohort sampling design, a randomly selected subcohort (RS) comprised 514 patients from 901 eligible patients with available tissue. Forty-nine additional patients with recurrence events were included in the analysis. Final analysis comprised 393 patients: 360 RS (58 events) and 33 non-RS events. Risk status was determined for each patient by ColDx. The Self-Prentice method was used to test the association between the resulting ColDx risk score and RFI adjusting for standard prognostic variables.
  
  
  
  Fifty-five percent of patients (216 of 393) were classified as high risk. After adjustment for prognostic variables that included mismatch repair (MMR) deficiency, ColDx high-risk patients exhibited significantly worse RFI (multivariable hazard ratio, 2.13; 95% CI, 1.3 to 3.5; P < .01). Age and MMR status were marginally significant. RFI at 5 years for patients classified as high risk was 82% (95% CI, 79% to 85%), compared with 91% (95% CI, 89% to 93%) for patients classified as low risk.
  
  
  
  ColDx is associated with RFI in the C9581 subsample in the presence of other prognostic factors, including MMR deficiency. ColDx could be incorporated with the traditional clinical markers of risk to refine patient prognosis.
authors.affiliation: Donna Niedzwiecki and Xing Ye, Duke University, Durham; Federico Innocenti, University of North Carolina at Chapel Hill, Chapel Hill, NC; Wendy L. Frankel and Richard M. Goldberg, The Ohio State University, Columbus, OH; Alan P. Venook and Robert S. Warren, University of California-San Francisco, San Francisco, CA; Paula N. Friedman, The University of Chicago, Chicago, IL; Robert J. Mayer, Dana-Farber Cancer Institute; Monica M. Bertagnolli, Brigham and Women's Hospital, Boston, MA; Thomas Anthony Colacchio, Dartmouth-Hitchcock Medical Center, Lebanon, NH; Jude Marie Mulligan, Timothy S. Davison, Eamonn O'Brien, Peter Kerr, Richard D. Kennedy, and D. Paul Harkin, Almac Diagnostics, Craigavon; Patrick G. Johnston, Queen's University, Belfast, Northern Ireland; and Richard L. Schilsky, American Society of Clinical Oncology, Alexandria, VA. donna.niedzwiecki@duke.edu.
authors.forename: Donna
authors.initials: D
authors.lastname: Niedzwiecki
authors.affiliation: Donna Niedzwiecki and Xing Ye, Duke University, Durham; Federico Innocenti, University of North Carolina at Chapel Hill, Chapel Hill, NC; Wendy L. Frankel and Richard M. Goldberg, The Ohio State University, Columbus, OH; Alan P. Venook and Robert S. Warren, University of California-San Francisco, San Francisco, CA; Paula N. Friedman, The University of Chicago, Chicago, IL; Robert J. Mayer, Dana-Farber Cancer Institute; Monica M. Bertagnolli, Brigham and Women's Hospital, Boston, MA; Thomas Anthony Colacchio, Dartmouth-Hitchcock Medical Center, Lebanon, NH; Jude Marie Mulligan, Timothy S. Davison, Eamonn O'Brien, Peter Kerr, Richard D. Kennedy, and D. Paul Harkin, Almac Diagnostics, Craigavon; Patrick G. Johnston, Queen's University, Belfast, Northern Ireland; and Richard L. Schilsky, American Society of Clinical Oncology, Alexandria, VA.
authors.forename: Wendy L
authors.initials: WL
authors.lastname: Frankel
authors.affiliation: Donna Niedzwiecki and Xing Ye, Duke University, Durham; Federico Innocenti, University of North Carolina at Chapel Hill, Chapel Hill, NC; Wendy L. Frankel and Richard M. Goldberg, The Ohio State University, Columbus, OH; Alan P. Venook and Robert S. Warren, University of California-San Francisco, San Francisco, CA; Paula N. Friedman, The University of Chicago, Chicago, IL; Robert J. Mayer, Dana-Farber Cancer Institute; Monica M. Bertagnolli, Brigham and Women's Hospital, Boston, MA; Thomas Anthony Colacchio, Dartmouth-Hitchcock Medical Center, Lebanon, NH; Jude Marie Mulligan, Timothy S. Davison, Eamonn O'Brien, Peter Kerr, Richard D. Kennedy, and D. Paul Harkin, Almac Diagnostics, Craigavon; Patrick G. Johnston, Queen's University, Belfast, Northern Ireland; and Richard L. Schilsky, American Society of Clinical Oncology, Alexandria, VA.
authors.forename: Alan P
authors.initials: AP
authors.lastname: Venook
authors.affiliation: Donna Niedzwiecki and Xing Ye, Duke University, Durham; Federico Innocenti, University of North Carolina at Chapel Hill, Chapel Hill, NC; Wendy L. Frankel and Richard M. Goldberg, The Ohio State University, Columbus, OH; Alan P. Venook and Robert S. Warren, University of California-San Francisco, San Francisco, CA; Paula N. Friedman, The University of Chicago, Chicago, IL; Robert J. Mayer, Dana-Farber Cancer Institute; Monica M. Bertagnolli, Brigham and Women's Hospital, Boston, MA; Thomas Anthony Colacchio, Dartmouth-Hitchcock Medical Center, Lebanon, NH; Jude Marie Mulligan, Timothy S. Davison, Eamonn O'Brien, Peter Kerr, Richard D. Kennedy, and D. Paul Harkin, Almac Diagnostics, Craigavon; Patrick G. Johnston, Queen's University, Belfast, Northern Ireland; and Richard L. Schilsky, American Society of Clinical Oncology, Alexandria, VA.
authors.forename: Xing
authors.initials: X
authors.lastname: Ye
authors.affiliation: Donna Niedzwiecki and Xing Ye, Duke University, Durham; Federico Innocenti, University of North Carolina at Chapel Hill, Chapel Hill, NC; Wendy L. Frankel and Richard M. Goldberg, The Ohio State University, Columbus, OH; Alan P. Venook and Robert S. Warren, University of California-San Francisco, San Francisco, CA; Paula N. Friedman, The University of Chicago, Chicago, IL; Robert J. Mayer, Dana-Farber Cancer Institute; Monica M. Bertagnolli, Brigham and Women's Hospital, Boston, MA; Thomas Anthony Colacchio, Dartmouth-Hitchcock Medical Center, Lebanon, NH; Jude Marie Mulligan, Timothy S. Davison, Eamonn O'Brien, Peter Kerr, Richard D. Kennedy, and D. Paul Harkin, Almac Diagnostics, Craigavon; Patrick G. Johnston, Queen's University, Belfast, Northern Ireland; and Richard L. Schilsky, American Society of Clinical Oncology, Alexandria, VA.
authors.forename: Paula N
authors.initials: PN
authors.lastname: Friedman
authors.affiliation: Donna Niedzwiecki and Xing Ye, Duke University, Durham; Federico Innocenti, University of North Carolina at Chapel Hill, Chapel Hill, NC; Wendy L. Frankel and Richard M. Goldberg, The Ohio State University, Columbus, OH; Alan P. Venook and Robert S. Warren, University of California-San Francisco, San Francisco, CA; Paula N. Friedman, The University of Chicago, Chicago, IL; Robert J. Mayer, Dana-Farber Cancer Institute; Monica M. Bertagnolli, Brigham and Women's Hospital, Boston, MA; Thomas Anthony Colacchio, Dartmouth-Hitchcock Medical Center, Lebanon, NH; Jude Marie Mulligan, Timothy S. Davison, Eamonn O'Brien, Peter Kerr, Richard D. Kennedy, and D. Paul Harkin, Almac Diagnostics, Craigavon; Patrick G. Johnston, Queen's University, Belfast, Northern Ireland; and Richard L. Schilsky, American Society of Clinical Oncology, Alexandria, VA.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Goldberg
authors.affiliation: Donna Niedzwiecki and Xing Ye, Duke University, Durham; Federico Innocenti, University of North Carolina at Chapel Hill, Chapel Hill, NC; Wendy L. Frankel and Richard M. Goldberg, The Ohio State University, Columbus, OH; Alan P. Venook and Robert S. Warren, University of California-San Francisco, San Francisco, CA; Paula N. Friedman, The University of Chicago, Chicago, IL; Robert J. Mayer, Dana-Farber Cancer Institute; Monica M. Bertagnolli, Brigham and Women's Hospital, Boston, MA; Thomas Anthony Colacchio, Dartmouth-Hitchcock Medical Center, Lebanon, NH; Jude Marie Mulligan, Timothy S. Davison, Eamonn O'Brien, Peter Kerr, Richard D. Kennedy, and D. Paul Harkin, Almac Diagnostics, Craigavon; Patrick G. Johnston, Queen's University, Belfast, Northern Ireland; and Richard L. Schilsky, American Society of Clinical Oncology, Alexandria, VA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Mayer
authors.affiliation: Donna Niedzwiecki and Xing Ye, Duke University, Durham; Federico Innocenti, University of North Carolina at Chapel Hill, Chapel Hill, NC; Wendy L. Frankel and Richard M. Goldberg, The Ohio State University, Columbus, OH; Alan P. Venook and Robert S. Warren, University of California-San Francisco, San Francisco, CA; Paula N. Friedman, The University of Chicago, Chicago, IL; Robert J. Mayer, Dana-Farber Cancer Institute; Monica M. Bertagnolli, Brigham and Women's Hospital, Boston, MA; Thomas Anthony Colacchio, Dartmouth-Hitchcock Medical Center, Lebanon, NH; Jude Marie Mulligan, Timothy S. Davison, Eamonn O'Brien, Peter Kerr, Richard D. Kennedy, and D. Paul Harkin, Almac Diagnostics, Craigavon; Patrick G. Johnston, Queen's University, Belfast, Northern Ireland; and Richard L. Schilsky, American Society of Clinical Oncology, Alexandria, VA.
authors.forename: Thomas Anthony
authors.initials: TA
authors.lastname: Colacchio
authors.affiliation: Donna Niedzwiecki and Xing Ye, Duke University, Durham; Federico Innocenti, University of North Carolina at Chapel Hill, Chapel Hill, NC; Wendy L. Frankel and Richard M. Goldberg, The Ohio State University, Columbus, OH; Alan P. Venook and Robert S. Warren, University of California-San Francisco, San Francisco, CA; Paula N. Friedman, The University of Chicago, Chicago, IL; Robert J. Mayer, Dana-Farber Cancer Institute; Monica M. Bertagnolli, Brigham and Women's Hospital, Boston, MA; Thomas Anthony Colacchio, Dartmouth-Hitchcock Medical Center, Lebanon, NH; Jude Marie Mulligan, Timothy S. Davison, Eamonn O'Brien, Peter Kerr, Richard D. Kennedy, and D. Paul Harkin, Almac Diagnostics, Craigavon; Patrick G. Johnston, Queen's University, Belfast, Northern Ireland; and Richard L. Schilsky, American Society of Clinical Oncology, Alexandria, VA.
authors.forename: Jude Marie
authors.initials: JM
authors.lastname: Mulligan
authors.affiliation: Donna Niedzwiecki and Xing Ye, Duke University, Durham; Federico Innocenti, University of North Carolina at Chapel Hill, Chapel Hill, NC; Wendy L. Frankel and Richard M. Goldberg, The Ohio State University, Columbus, OH; Alan P. Venook and Robert S. Warren, University of California-San Francisco, San Francisco, CA; Paula N. Friedman, The University of Chicago, Chicago, IL; Robert J. Mayer, Dana-Farber Cancer Institute; Monica M. Bertagnolli, Brigham and Women's Hospital, Boston, MA; Thomas Anthony Colacchio, Dartmouth-Hitchcock Medical Center, Lebanon, NH; Jude Marie Mulligan, Timothy S. Davison, Eamonn O'Brien, Peter Kerr, Richard D. Kennedy, and D. Paul Harkin, Almac Diagnostics, Craigavon; Patrick G. Johnston, Queen's University, Belfast, Northern Ireland; and Richard L. Schilsky, American Society of Clinical Oncology, Alexandria, VA.
authors.forename: Timothy S
authors.initials: TS
authors.lastname: Davison
authors.affiliation: Donna Niedzwiecki and Xing Ye, Duke University, Durham; Federico Innocenti, University of North Carolina at Chapel Hill, Chapel Hill, NC; Wendy L. Frankel and Richard M. Goldberg, The Ohio State University, Columbus, OH; Alan P. Venook and Robert S. Warren, University of California-San Francisco, San Francisco, CA; Paula N. Friedman, The University of Chicago, Chicago, IL; Robert J. Mayer, Dana-Farber Cancer Institute; Monica M. Bertagnolli, Brigham and Women's Hospital, Boston, MA; Thomas Anthony Colacchio, Dartmouth-Hitchcock Medical Center, Lebanon, NH; Jude Marie Mulligan, Timothy S. Davison, Eamonn O'Brien, Peter Kerr, Richard D. Kennedy, and D. Paul Harkin, Almac Diagnostics, Craigavon; Patrick G. Johnston, Queen's University, Belfast, Northern Ireland; and Richard L. Schilsky, American Society of Clinical Oncology, Alexandria, VA.
authors.forename: Eamonn
authors.initials: E
authors.lastname: O'Brien
authors.affiliation: Donna Niedzwiecki and Xing Ye, Duke University, Durham; Federico Innocenti, University of North Carolina at Chapel Hill, Chapel Hill, NC; Wendy L. Frankel and Richard M. Goldberg, The Ohio State University, Columbus, OH; Alan P. Venook and Robert S. Warren, University of California-San Francisco, San Francisco, CA; Paula N. Friedman, The University of Chicago, Chicago, IL; Robert J. Mayer, Dana-Farber Cancer Institute; Monica M. Bertagnolli, Brigham and Women's Hospital, Boston, MA; Thomas Anthony Colacchio, Dartmouth-Hitchcock Medical Center, Lebanon, NH; Jude Marie Mulligan, Timothy S. Davison, Eamonn O'Brien, Peter Kerr, Richard D. Kennedy, and D. Paul Harkin, Almac Diagnostics, Craigavon; Patrick G. Johnston, Queen's University, Belfast, Northern Ireland; and Richard L. Schilsky, American Society of Clinical Oncology, Alexandria, VA.
authors.forename: Peter
authors.initials: P
authors.lastname: Kerr
authors.affiliation: Donna Niedzwiecki and Xing Ye, Duke University, Durham; Federico Innocenti, University of North Carolina at Chapel Hill, Chapel Hill, NC; Wendy L. Frankel and Richard M. Goldberg, The Ohio State University, Columbus, OH; Alan P. Venook and Robert S. Warren, University of California-San Francisco, San Francisco, CA; Paula N. Friedman, The University of Chicago, Chicago, IL; Robert J. Mayer, Dana-Farber Cancer Institute; Monica M. Bertagnolli, Brigham and Women's Hospital, Boston, MA; Thomas Anthony Colacchio, Dartmouth-Hitchcock Medical Center, Lebanon, NH; Jude Marie Mulligan, Timothy S. Davison, Eamonn O'Brien, Peter Kerr, Richard D. Kennedy, and D. Paul Harkin, Almac Diagnostics, Craigavon; Patrick G. Johnston, Queen's University, Belfast, Northern Ireland; and Richard L. Schilsky, American Society of Clinical Oncology, Alexandria, VA.
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Johnston
authors.affiliation: Donna Niedzwiecki and Xing Ye, Duke University, Durham; Federico Innocenti, University of North Carolina at Chapel Hill, Chapel Hill, NC; Wendy L. Frankel and Richard M. Goldberg, The Ohio State University, Columbus, OH; Alan P. Venook and Robert S. Warren, University of California-San Francisco, San Francisco, CA; Paula N. Friedman, The University of Chicago, Chicago, IL; Robert J. Mayer, Dana-Farber Cancer Institute; Monica M. Bertagnolli, Brigham and Women's Hospital, Boston, MA; Thomas Anthony Colacchio, Dartmouth-Hitchcock Medical Center, Lebanon, NH; Jude Marie Mulligan, Timothy S. Davison, Eamonn O'Brien, Peter Kerr, Richard D. Kennedy, and D. Paul Harkin, Almac Diagnostics, Craigavon; Patrick G. Johnston, Queen's University, Belfast, Northern Ireland; and Richard L. Schilsky, American Society of Clinical Oncology, Alexandria, VA.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Kennedy
authors.affiliation: Donna Niedzwiecki and Xing Ye, Duke University, Durham; Federico Innocenti, University of North Carolina at Chapel Hill, Chapel Hill, NC; Wendy L. Frankel and Richard M. Goldberg, The Ohio State University, Columbus, OH; Alan P. Venook and Robert S. Warren, University of California-San Francisco, San Francisco, CA; Paula N. Friedman, The University of Chicago, Chicago, IL; Robert J. Mayer, Dana-Farber Cancer Institute; Monica M. Bertagnolli, Brigham and Women's Hospital, Boston, MA; Thomas Anthony Colacchio, Dartmouth-Hitchcock Medical Center, Lebanon, NH; Jude Marie Mulligan, Timothy S. Davison, Eamonn O'Brien, Peter Kerr, Richard D. Kennedy, and D. Paul Harkin, Almac Diagnostics, Craigavon; Patrick G. Johnston, Queen's University, Belfast, Northern Ireland; and Richard L. Schilsky, American Society of Clinical Oncology, Alexandria, VA.
authors.forename: D Paul
authors.initials: DP
authors.lastname: Harkin
authors.affiliation: Donna Niedzwiecki and Xing Ye, Duke University, Durham; Federico Innocenti, University of North Carolina at Chapel Hill, Chapel Hill, NC; Wendy L. Frankel and Richard M. Goldberg, The Ohio State University, Columbus, OH; Alan P. Venook and Robert S. Warren, University of California-San Francisco, San Francisco, CA; Paula N. Friedman, The University of Chicago, Chicago, IL; Robert J. Mayer, Dana-Farber Cancer Institute; Monica M. Bertagnolli, Brigham and Women's Hospital, Boston, MA; Thomas Anthony Colacchio, Dartmouth-Hitchcock Medical Center, Lebanon, NH; Jude Marie Mulligan, Timothy S. Davison, Eamonn O'Brien, Peter Kerr, Richard D. Kennedy, and D. Paul Harkin, Almac Diagnostics, Craigavon; Patrick G. Johnston, Queen's University, Belfast, Northern Ireland; and Richard L. Schilsky, American Society of Clinical Oncology, Alexandria, VA.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Schilsky
authors.affiliation: Donna Niedzwiecki and Xing Ye, Duke University, Durham; Federico Innocenti, University of North Carolina at Chapel Hill, Chapel Hill, NC; Wendy L. Frankel and Richard M. Goldberg, The Ohio State University, Columbus, OH; Alan P. Venook and Robert S. Warren, University of California-San Francisco, San Francisco, CA; Paula N. Friedman, The University of Chicago, Chicago, IL; Robert J. Mayer, Dana-Farber Cancer Institute; Monica M. Bertagnolli, Brigham and Women's Hospital, Boston, MA; Thomas Anthony Colacchio, Dartmouth-Hitchcock Medical Center, Lebanon, NH; Jude Marie Mulligan, Timothy S. Davison, Eamonn O'Brien, Peter Kerr, Richard D. Kennedy, and D. Paul Harkin, Almac Diagnostics, Craigavon; Patrick G. Johnston, Queen's University, Belfast, Northern Ireland; and Richard L. Schilsky, American Society of Clinical Oncology, Alexandria, VA.
authors.forename: Monica M
authors.initials: MM
authors.lastname: Bertagnolli
authors.affiliation: Donna Niedzwiecki and Xing Ye, Duke University, Durham; Federico Innocenti, University of North Carolina at Chapel Hill, Chapel Hill, NC; Wendy L. Frankel and Richard M. Goldberg, The Ohio State University, Columbus, OH; Alan P. Venook and Robert S. Warren, University of California-San Francisco, San Francisco, CA; Paula N. Friedman, The University of Chicago, Chicago, IL; Robert J. Mayer, Dana-Farber Cancer Institute; Monica M. Bertagnolli, Brigham and Women's Hospital, Boston, MA; Thomas Anthony Colacchio, Dartmouth-Hitchcock Medical Center, Lebanon, NH; Jude Marie Mulligan, Timothy S. Davison, Eamonn O'Brien, Peter Kerr, Richard D. Kennedy, and D. Paul Harkin, Almac Diagnostics, Craigavon; Patrick G. Johnston, Queen's University, Belfast, Northern Ireland; and Richard L. Schilsky, American Society of Clinical Oncology, Alexandria, VA.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Warren
authors.affiliation: Donna Niedzwiecki and Xing Ye, Duke University, Durham; Federico Innocenti, University of North Carolina at Chapel Hill, Chapel Hill, NC; Wendy L. Frankel and Richard M. Goldberg, The Ohio State University, Columbus, OH; Alan P. Venook and Robert S. Warren, University of California-San Francisco, San Francisco, CA; Paula N. Friedman, The University of Chicago, Chicago, IL; Robert J. Mayer, Dana-Farber Cancer Institute; Monica M. Bertagnolli, Brigham and Women's Hospital, Boston, MA; Thomas Anthony Colacchio, Dartmouth-Hitchcock Medical Center, Lebanon, NH; Jude Marie Mulligan, Timothy S. Davison, Eamonn O'Brien, Peter Kerr, Richard D. Kennedy, and D. Paul Harkin, Almac Diagnostics, Craigavon; Patrick G. Johnston, Queen's University, Belfast, Northern Ireland; and Richard L. Schilsky, American Society of Clinical Oncology, Alexandria, VA.
authors.forename: Federico
authors.initials: F
authors.lastname: Innocenti
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived; D017326:Clinical Trials, Phase III as Topic; D015331:Cohort Studies; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D018572:Disease-Free Survival; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000473:pathology; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D016032:Randomized Controlled Trials as Topic
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; C400149:Edrecolomab