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Cancer Epidemiology, Biomarkers & Prevention
Cancer Epidemiology, Biomarkers & Prevention
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Prognostic Value of Angiopoietin-2 for Death Risk Stratification in Patients with Metastatic Colorectal Carcinoma

Marine Jary, Dewi Vernerey, Thierry Lecomte, Erion Dobi, François Ghiringhelli, Franck Monnien, Yann Godet, Stefano Kim, Olivier Bouché, Serge Fratte, Anthony Gonçalves, Julie Leger, Lise Queiroz, Olivier Adotevi, Franck Bonnetain and Christophe Borg
Marine Jary
1Department of Medical Oncology, University Hospital, Besançon, France.
2INSERM, Unit 1098, University of Franche-Comté, Besançon, France.
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  • For correspondence: marine.jary@univ-fcomte.fr
Dewi Vernerey
3Methodological and Quality of Life in Oncology Unit, University Hospital of Besançon, Besançon, France.
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Thierry Lecomte
4INSERM, Unit 7292, University François-Rabelais, CNRS, Tours, France.
5Department of Hepatogastroenterology and Digestive Oncology, University Hospital, Tours, France.
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Erion Dobi
1Department of Medical Oncology, University Hospital, Besançon, France.
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François Ghiringhelli
6Department of Medical Oncology, Leclerc Anticancer Center, Dijon, France.
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Franck Monnien
1Department of Medical Oncology, University Hospital, Besançon, France.
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Yann Godet
2INSERM, Unit 1098, University of Franche-Comté, Besançon, France.
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Stefano Kim
1Department of Medical Oncology, University Hospital, Besançon, France.
7Department of Oncology and Radiotherapy, Hospital of Belfort-Montbeliard, Montbeliard, France.
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Olivier Bouché
8Department of Hepatogastroenterology and Digestive Oncology, University Hospital Robert Debré, Reims, France.
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Serge Fratte
9Department of Gastroenterology, Hospital of Belfort-Montbeliard, Montbeliard, France.
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Anthony Gonçalves
10Department of Medical Oncology, Paoli-Calmettes Institute, Marseille, France.
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Julie Leger
11INSERM, Clinical Investigational Center CIC 1415, Tours, France.
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Lise Queiroz
2INSERM, Unit 1098, University of Franche-Comté, Besançon, France.
12Clinical Investigational Center, CIC-Biotherapy-506, University Hospital of Besançon, Besançon, France.
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Olivier Adotevi
1Department of Medical Oncology, University Hospital, Besançon, France.
2INSERM, Unit 1098, University of Franche-Comté, Besançon, France.
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Franck Bonnetain
3Methodological and Quality of Life in Oncology Unit, University Hospital of Besançon, Besançon, France.
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Christophe Borg
1Department of Medical Oncology, University Hospital, Besançon, France.
2INSERM, Unit 1098, University of Franche-Comté, Besançon, France.
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DOI: 10.1158/1055-9965.EPI-14-1059 Published March 2015
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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.

Footnotes

  • Note: Supplementary data for this article are available at Cancer Epidemiology, Biomarkers & Prevention Online (http://cebp.aacrjournals.org/).

  • Received September 22, 2014.
  • Revision received December 15, 2014.
  • Accepted December 23, 2014.
  • ©2015 American Association for Cancer Research.
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Cancer Epidemiology Biomarkers & Prevention: 24 (3)
March 2015
Volume 24, Issue 3
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Prognostic Value of Angiopoietin-2 for Death Risk Stratification in Patients with Metastatic Colorectal Carcinoma
Marine Jary, Dewi Vernerey, Thierry Lecomte, Erion Dobi, François Ghiringhelli, Franck Monnien, Yann Godet, Stefano Kim, Olivier Bouché, Serge Fratte, Anthony Gonçalves, Julie Leger, Lise Queiroz, Olivier Adotevi, Franck Bonnetain and Christophe Borg
Cancer Epidemiol Biomarkers Prev March 1 2015 (24) (3) 603-612; DOI: 10.1158/1055-9965.EPI-14-1059

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Prognostic Value of Angiopoietin-2 for Death Risk Stratification in Patients with Metastatic Colorectal Carcinoma
Marine Jary, Dewi Vernerey, Thierry Lecomte, Erion Dobi, François Ghiringhelli, Franck Monnien, Yann Godet, Stefano Kim, Olivier Bouché, Serge Fratte, Anthony Gonçalves, Julie Leger, Lise Queiroz, Olivier Adotevi, Franck Bonnetain and Christophe Borg
Cancer Epidemiol Biomarkers Prev March 1 2015 (24) (3) 603-612; DOI: 10.1158/1055-9965.EPI-14-1059
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