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

Détails

Ressource 1Télécharger: mdx052.pdf (435.91 [Ko])
Etat: Serval
Version: Final published version
ID Serval
serval:BIB_8E7F51316719
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Prediction of overall survival in stage II and III colon cancer beyond TNM system: a retrospective, pooled biomarker study.
Périodique
Annals of oncology
Auteur(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
Statut éditorial
Publié
Date de publication
01/05/2017
Peer-reviewed
Oui
Volume
28
Numéro
5
Pages
1023-1031
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
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.

Mots-clé
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
Oui
Création de la notice
09/05/2017 18:38
Dernière modification de la notice
08/05/2019 21:52
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