Web of Science: 157 citations, Scopus: 163 citations, Google Scholar: citations,
Prediction of overall survival in stage II and III colon cancer beyond TNM system : a retrospective, pooled biomarker study
Dienstmann, Rodrigo. (Hospital Universitari Vall d'Hebron)
Mason, M. J. (Computational Oncology, Sage Bionetworks, Seattle, USA)
Sinicrope, F. A. (Mayo Clinic and Mayo Comprehensive Cancer Center, Rochester, USA)
Phipps, A. I. (Fred Hutchinson Cancer Research Center, Seattle, USA)
Tejpar, Sabine (University Hospitals Gasthuisberg (Leuven, Bélgica))
Nesbakken, A. (Oslo University Hospital (Oslo, Noruega))
Danielsen, S. A. (Oslo University Hospital (Oslo, Noruega))
Sveen, A. (Oslo University Hospital (Oslo, Noruega))
Buchanan, Daniel D (The University of Melbourne)
Clendenning, M. (The University of Melbourne)
Rosty, C. (The University of Melbourne)
Bot, Brian M (Computational Oncology, Sage Bionetworks, Seattle, USA)
Alberts, S. R. (Mayo Clinic and Mayo Comprehensive Cancer Center, Rochester, USA)
Milburn Jessup, J. (National Cancer Institute (Rockville, Estats Units d'Amèrica))
Lothe, R. A. (Oslo University Hospital (Oslo, Noruega))
Delorenzi, Mauro (SIB Swiss Institute Bioinformatics, Lausanne, Switzerland)
Newcomb, P. A. (Fred Hutchinson Cancer Research Center, Seattle, USA)
Sargent, D. (Mayo Clinic, Rochester, USA)
Guinney, J. (Computational Oncology, Sage Bionetworks, Seattle, USA)
Universitat Autònoma de Barcelona

Date: 2017
Abstract: TNM staging alone does not accurately predict outcome in colon cancer (CC) patients who may be eligible for adjuvant chemotherapy. It is unknown to what extent the molecular markers microsatellite instability (MSI) and mutations in BRAF or KRAS improve prognostic estimation in multivariable models that include detailed clinicopathological annotation. After imputation of missing at random data, a subset of patients accrued in phase 3 trials with adjuvant chemotherapy (n = 3016)-N0147 (NCT00079274) and PETACC3 (NCT00026273)-was aggregated to construct multivariable Cox models for 5-year overall survival that were subsequently validated internally in the remaining clinical trial samples (n = 1499), and also externally in different population cohorts of chemotherapy-treated (n = 949) or -untreated (n = 1080) CC patients, and an additional series without treatment annotation (n = 782). TNM staging, MSI and BRAF V600E mutation status remained independent prognostic factors in multivariable models across clinical trials cohorts and observational studies. Concordance indices increased from 0. 61-0. 68 in the TNM alone model to 0. 63-0. 71 in models with added molecular markers, 0. 65-0. 73 with clinicopathological features and 0. 66-0. 74 with all covariates. In validation cohorts with complete annotation, the integrated time-dependent AUC rose from 0. 64 for the TNM alone model to 0. 67 for models that included clinicopathological features, with or without molecular markers. In patient cohorts that received adjuvant chemotherapy, the relative proportion of variance explained (R 2) by TNM, clinicopathological features and molecular markers was on an average 65%, 25% and 10%, respectively. Incorporation of MSI, BRAF V600E and KRAS mutation status to overall survival models with TNM staging improves the ability to precisely prognosticate in stage II and III CC patients, but only modestly increases prediction accuracy in multivariable models that include clinicopathological features, particularly in chemotherapy-treated patients.
Note: Altres ajuts: This work was partially supported by grant UM1 CA167551 from the National Cancer Institute (NCI), National Institutes of Health (NIH), and through cooperative agreements with members of the Colon Cancer Family Registry (CCFR) and Principal Investigators. Centers contributing to this analysis include the Seattle Colorectal Cancer Family Registry (U01/U24CA074794), Australasian Colorectal Cancer Family Registry (U01 CA074778 and U01/U24 CA097735), Mayo Clinic Cooperative Family Registry for Colon Cancer Studies (U01/U24 CA074800), and Ontario Familial Colorectal Cancer Registry (U01/U24 CA074783). This work was also supported by NCI/NIH grant K07CA172298 and K05CA152715 (to AIP). The content of this article does not necessarily reflect the views or policies of the NIH or any of the collaborating centers in the CCFR, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. This study was partly supported by the "Norwegian Cancer Society" and the "Research Council of Norway" (no grants apply).
Rights: Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. Creative Commons
Language: Anglès
Document: Article ; recerca ; Versió publicada
Subject: Colon cancer ; BRAF mutation ; KRAS mutation ; Microsatellite instability ; Prognosis
Published in: Annals of oncology, Vol. 28 (february 2017) , p. 1023-1031, ISSN 1569-8041

DOI: 10.1093/annonc/mdx052
PMID: 28453697


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 Record created 2018-02-08, last modified 2023-02-07



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