Validation of the 12-gene colon cancer recurrence score in NSABP C-07 as a predictor of recurrence in patients with stage II and III colon cancer treated with fluorouracil and leucovorin (FU/LV) and FU/LV plus oxaliplatin

Greg Yothers; Michael J O'Connell; Mark Lee; Margarita Lopatin; Kim M Clark-Langone; Carl Millward; Soonmyung Paik; Saima Sharif; Steven Shak; Norman Wolmark

doi:10.1200/JCO.2012.47.3116

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Validation of the 12-gene colon cancer recurrence score in NSABP C-07 as a predictor of recurrence in patients with stage II and III colon cancer treated with fluorouracil and leucovorin (FU/LV) and FU/LV plus oxaliplatin

Journal article

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Peer reviewed

Validation of the 12-gene colon cancer recurrence score in NSABP C-07 as a predictor of recurrence in patients with stage II and III colon cancer treated with fluorouracil and leucovorin (FU/LV) and FU/LV plus oxaliplatin

Greg Yothers, Michael J O'Connell, Mark Lee, Margarita Lopatin, Kim M Clark-Langone, Carl Millward, Soonmyung Paik, Saima Sharif, Steven Shak and Norman Wolmark

Journal of clinical oncology, Vol.31(36), pp.4512-4519

12/20/2013

DOI: 10.1200/JCO.2012.47.3116

PMCID: PMC3871512

PMID: 24220557

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Abstract

Accurate assessments of recurrence risk and absolute treatment benefit are needed to inform colon cancer adjuvant therapy. The 12-gene Recurrence Score assay has been validated in patients with stage II colon cancer from the Cancer and Leukemia Group B 9581 and Quick and Simple and Reliable (QUASAR) trials. We conducted an independent, prospectively designed clinical validation study of Recurrence Score, with prespecified end points and analysis plan, in archival specimens from patients with stage II and III colon cancer randomly assigned to fluorouracil (FU) or FU plus oxaliplatin in National Surgical Adjuvant Breast and Bowel Project C-07. Recurrence Score was assessed in 892 fixed, paraffin-embedded tumor specimens (randomly selected 50% of patients with tissue). Data were analyzed by Cox regression adjusting for stage and treatment. Continuous Recurrence Score predicted recurrence (hazard ratio for a 25-unit increase in score, 1.96; 95% CI, 1.50 to 2.55; P < .001), as well as disease-free and overall survival (both P < .001). Recurrence Score predicted recurrence risk (P = .001) after adjustment for stage, mismatch repair, nodes examined, grade, and treatment. Recurrence Score did not have significant interaction with stage (P = .90) or age (P = .76). Relative benefit of oxaliplatin was similar across the range of Recurrence Score (interaction P = .48); accordingly, absolute benefit of oxaliplatin increased with higher scores, most notably in patients with stage II and IIIA/B disease. The 12-gene Recurrence Score predicts recurrence risk in stage II and stage III colon cancer and provides additional information beyond conventional clinical and pathologic factors. Incorporating Recurrence Score into the clinical context may better inform adjuvant therapy decisions in stage III as well as stage II colon cancer.

Leucovorin - administration & dosage

Predictive Value of Tests

Colonic Neoplasms - genetics

Reproducibility of Results

Prospective Studies

Colonic Neoplasms - drug therapy

Humans

Middle Aged

Gene Expression Regulation, Neoplastic

Proportional Hazards Models

Male

DNA Mismatch Repair - genetics

Disease-Free Survival

Organoplatinum Compounds - administration & dosage

Fluorouracil - administration & dosage

Antineoplastic Combined Chemotherapy Protocols - therapeutic use

Colonic Neoplasms - pathology

Survival Analysis

Adult

Female

Neoplasm Recurrence, Local - genetics

Aged

Neoplasm Staging

Details

Title: Subtitle: Validation of the 12-gene colon cancer recurrence score in NSABP C-07 as a predictor of recurrence in patients with stage II and III colon cancer treated with fluorouracil and leucovorin (FU/LV) and FU/LV plus oxaliplatin
Creators: Greg Yothers - Greg Yothers, Michael J. O'Connell, Soonmyung Paik, Saima Sharif, and Norman Wolmark, National Surgical Adjuvant Breast and Bowel Project (NSABP) Operations and Biostatistical Centers; Greg Yothers, University of Pittsburgh Graduate School of Public Health; Saima Sharif and Norman Wolmark, Allegheny Cancer Center at Allegheny General Hospital, Pittsburgh, PA; Mark Lee, Margarita Lopatin, Kim M. Clark-Langone, and Steven Shak, Genomic Health, Redwood City, CA
Michael J O'Connell
Mark Lee
Margarita Lopatin
Kim M Clark-Langone
Carl Millward
Soonmyung Paik
Saima Sharif
Steven Shak
Norman Wolmark
Resource Type: Journal article
Publication Details: Journal of clinical oncology, Vol.31(36), pp.4512-4519
DOI: 10.1200/JCO.2012.47.3116
PMID: 24220557
PMCID: PMC3871512
NLM abbreviation: J Clin Oncol
ISSN: 0732-183X
eISSN: 1527-7755
Grant note: U10 CA012027 / NCI NIH HHS U10-CA-37377 / NCI NIH HHS U10-CA-69974 / NCI NIH HHS U10 CA069651 / NCI NIH HHS U10-CA-12027 / NCI NIH HHS U10-CA-69651 / NCI NIH HHS U10 CA069974 / NCI NIH HHS U10 CA037377 / NCI NIH HHS
Language: English
Date published: 12/20/2013
Academic Unit: Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
Record Identifier: 9984094549102771

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