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Cancer Epidemiol Biomarkers Prev. 2015 Mar;24(3):603-12. doi: 10.1158/1055-9965.EPI-14-1059. Epub 2015 Jan 12.

Prognostic value of angiopoietin-2 for death risk stratification in patients with metastatic colorectal carcinoma.

Author information

1
Department of Medical Oncology, University Hospital, Besançon, France. INSERM, Unit 1098, University of Franche-Comté, Besançon, France. marine.jary@univ-fcomte.fr.
2
Methodological and Quality of Life in Oncology Unit, University Hospital of Besançon, Besançon, France.
3
INSERM, Unit 7292, University François-Rabelais, CNRS, Tours, France. Department of Hepatogastroenterology and Digestive Oncology, University Hospital, Tours, France.
4
Department of Medical Oncology, University Hospital, Besançon, France.
5
Department of Medical Oncology, Leclerc Anticancer Center, Dijon, France.
6
INSERM, Unit 1098, University of Franche-Comté, Besançon, France.
7
Department of Medical Oncology, University Hospital, Besançon, France. Department of Oncology and Radiotherapy, Hospital of Belfort-Montbeliard, Montbeliard, France.
8
Department of Hepatogastroenterology and Digestive Oncology, University Hospital Robert Debré, Reims, France.
9
Department of Gastroenterology, Hospital of Belfort-Montbeliard, Montbeliard, France.
10
Department of Medical Oncology, Paoli-Calmettes Institute, Marseille, France.
11
INSERM, Clinical Investigational Center CIC 1415, Tours, France.
12
INSERM, Unit 1098, University of Franche-Comté, Besançon, France. Clinical Investigational Center, CIC-Biotherapy-506, University Hospital of Besançon, Besançon, France.
13
Department of Medical Oncology, University Hospital, Besançon, France. INSERM, Unit 1098, University of Franche-Comté, Besançon, France.

Abstract

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 patients with first-line mCRC.

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. ELISAs were used to measure Ang-2.

RESULTS:

The multivariable Cox model identified increased lactate dehydrogenase [HR, 1.60; 95% confidence interval (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 because 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 cutoff 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 for intermittent or sequential therapeutic strategies dedicated to the optimization of patients' quality of life and chemotherapy cost-effectiveness. Cancer Epidemiol Biomarkers Prev; 24(3); 603-12. ©2015 AACR.

PMID:
25583947
PMCID:
PMC4805754
DOI:
10.1158/1055-9965.EPI-14-1059
[Indexed for MEDLINE]
Free PMC Article

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