Prediction of overall survival in stage II and III colon cancer beyond TNM system: a retrospective, pooled biomarker study.

Details

Ressource 1Download: mdx052.pdf (435.91 [Ko])
State: Public
Version: Final published version
Serval ID
serval:BIB_8E7F51316719
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Prediction of overall survival in stage II and III colon cancer beyond TNM system: a retrospective, pooled biomarker study.
Journal
Annals of oncology
Author(s)
Dienstmann R., Mason M.J., Sinicrope F.A., Phipps A.I., Tejpar S., Nesbakken A., Danielsen S.A., Sveen A., Buchanan D.D., Clendenning M., Rosty C., Bot B., Alberts S.R., Milburn Jessup J., Lothe R.A., Delorenzi M., Newcomb P.A., Sargent D., Guinney J.
ISSN
1569-8041 (Electronic)
ISSN-L
0923-7534
Publication state
Published
Issued date
01/05/2017
Peer-reviewed
Oui
Volume
28
Number
5
Pages
1023-1031
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
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 BRAFV600E 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 (R2) by TNM, clinicopathological features and molecular markers was on an average 65%, 25% and 10%, respectively.
Incorporation of MSI, BRAFV600E 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.

Keywords
Adult, Aged, Aged, 80 and over, Biomarkers, Tumor/metabolism, Colonic Neoplasms/metabolism, Colonic Neoplasms/mortality, Colonic Neoplasms/pathology, Female, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Neoplasm Staging, Proportional Hazards Models, Retrospective Studies, Treatment Outcome, Young Adult, BRAF mutation, KRAS mutation, colon cancer, microsatellite instability, prognosis
Pubmed
Web of science
Open Access
Yes
Create date
09/05/2017 17:38
Last modification date
20/08/2019 14:52
Usage data