Prognostic Value of Angiopoietin-2 for death risk stratification in Patients with Metastatic Colorectal Carcinoma.
Fiche publication
Date publication
janvier 2015
Auteurs
Membres identifiés du Cancéropôle Est :
Pr ADOTEVI Olivier, Pr BORG Christophe, Pr BOUCHE Olivier, Pr GHIRINGHELLI François, Dr GODET Yann, Mr MONNIEN Franck, Dr VERNEREY Dewi, Dr KIM Stephano
Tous les auteurs :
Jary M, Vernerey D, Lecomte T, Dobi E, Ghiringhelli F, Monnien F, Godet Y, Kim S, Bouche O, Fratte S, Goncalves A, Leger J, Queiroz L, Adotevi O, Bonnetain F, Borg C
Lien Pubmed
Résumé
Background: Baseline prognostic biomarkers stratifying treatment strategies in first-line metastatic colorectal cancer (mCRC) are lacking. Angiopoietin-2 (Ang-2) is proposed as a potential biomarker in several cancers. We therefore decided to establish the additional prognostic value of Ang-2 for overall survival (OS) in first-line mCRC patients. Methods: We enrolled 177 patients treated with a bevacizumab containing chemotherapy in two prospective phase II clinical trials. Patient plasma samples were collected at baseline. Enzyme-linked immunosorbent assays were used to measure Ang-2. Results: The multivariable Cox model identified increased LDH (HR=1.60, 95%CI: 1.04-2.45, p=0.03) and Ang-2 log-transformation level (HR=1.59, 95%CI: 1.14-2.21, p=0.0065) as two significant independent OS prognostic factors. It exhibited good calibration (p=0.8) and discrimination (C-index: 0.64; 95%CI: 0.58-0.68). Ang-2 parameter inclusion in the GERCOR reference model significantly and strongly improved its discriminative ability since the C-statistic increased significantly from 0.61 to 0.63 (bootstrap mean difference=0.07, 95%CI: 0.069-0.077). Interestingly, the addition of Ang-2 binary information with a 5 ng/mL cut-off value to the GERCOR model allowed the reclassification of intermediate-risk profile patients (41%) into two subsets of low and high-risks. Conclusions: Our study provides robust evidence in favor of baseline Ang-2 prognostic value for OS adding to the conventional factors. Its assessment appears to be useful for the improvement in risk stratification for patients with intermediate-risk profile. Impact: Ang-2 ability to predict OS at diagnosis could be of interest in the selection of patients eligible to intermittent or sequential therapeutic strategies dedicated to the optimization of patient's quality of life and chemotherapy cost-effectiveness.
Référence
Cancer Epidemiol Biomarkers Prev. 2015 Jan 12. pii: cebp.1059.2014.