title: Prognostic value of angiopoietin-2 for death risk stratification in patients with metastatic colorectal carcinoma.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medical Oncology, University Hospital, Besançon, France. INSERM, Unit 1098, University of Franche-Comté, Besançon, France. marine.jary@univ-fcomte.fr.
authors.forename: Marine
authors.initials: M
authors.lastname: Jary
authors.affiliation: Methodological and Quality of Life in Oncology Unit, University Hospital of Besançon, Besançon, France.
authors.forename: Dewi
authors.initials: D
authors.lastname: Vernerey
authors.affiliation: INSERM, Unit 7292, University François-Rabelais, CNRS, Tours, France. Department of Hepatogastroenterology and Digestive Oncology, University Hospital, Tours, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Lecomte
authors.affiliation: Department of Medical Oncology, University Hospital, Besançon, France.
authors.forename: Erion
authors.initials: E
authors.lastname: Dobi
authors.affiliation: Department of Medical Oncology, Leclerc Anticancer Center, Dijon, France.
authors.forename: François
authors.initials: F
authors.lastname: Ghiringhelli
authors.affiliation: Department of Medical Oncology, University Hospital, Besançon, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Monnien
authors.affiliation: INSERM, Unit 1098, University of Franche-Comté, Besançon, France.
authors.forename: Yann
authors.initials: Y
authors.lastname: Godet
authors.affiliation: Department of Medical Oncology, University Hospital, Besançon, France. Department of Oncology and Radiotherapy, Hospital of Belfort-Montbeliard, Montbeliard, France.
authors.forename: Stefano
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Hepatogastroenterology and Digestive Oncology, University Hospital Robert Debré, Reims, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Bouché
authors.affiliation: Department of Gastroenterology, Hospital of Belfort-Montbeliard, Montbeliard, France.
authors.forename: Serge
authors.initials: S
authors.lastname: Fratte
authors.affiliation: Department of Medical Oncology, Paoli-Calmettes Institute, Marseille, France.
authors.forename: Anthony
authors.initials: A
authors.lastname: Gonçalves
authors.affiliation: INSERM, Clinical Investigational Center CIC 1415, Tours, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Leger
authors.affiliation: INSERM, Unit 1098, University of Franche-Comté, Besançon, France. Clinical Investigational Center, CIC-Biotherapy-506, University Hospital of Besançon, Besançon, France.
authors.forename: Lise
authors.initials: L
authors.lastname: Queiroz
authors.affiliation: Department of Medical Oncology, University Hospital, Besançon, France. INSERM, Unit 1098, University of Franche-Comté, Besançon, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Adotevi
authors.affiliation: Methodological and Quality of Life in Oncology Unit, University Hospital of Besançon, Besançon, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Bonnetain
authors.affiliation: Department of Medical Oncology, University Hospital, Besançon, France. INSERM, Unit 1098, University of Franche-Comté, Besançon, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Borg
mesh_terms: D000368:Aged; D042702:Angiopoietin-2 / Q000097:blood*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000068258:Bevacizumab / Q000008:administration & dosage; D014408:Biomarkers, Tumor / Q000097:blood*; D017322:Clinical Trials, Phase II as Topic; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D009362:Neoplasm Metastasis; D011379:Prognosis; D011446:Prospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D042702:Angiopoietin-2; D014408:Biomarkers, Tumor; D000068258:Bevacizumab