title: The Prognostic Value of Plasma YKL-40 in Patients With Chemotherapy-Resistant Ovarian Cancer Treated With Bevacizumab.
abstract: YKL-40 is a proangiogenic glycoprotein that is secreted by cancer cells and inflammatory cells. The expression of YKL-40 is induced by vascular endothelial growth factor inhibition. We tested the hypothesis that low baseline plasma YKL-40 is associated with improved outcomes in patients with ovarian cancer treated with bevacizumab.
  
  
  
  One hundred forty patients with chemotherapy-refractory epithelian ovarian cancer were treated with single-agent bevacizumab 10 mg/kg every 3 weeks in a prospective trial. Plasma YKL-40 was determined by enzyme-linked immunosorbent assay before and during treatment. Both raw YKL-40 concentrations and age-corrected percentiles of normal YKL-40 level were used. Associations between plasma YKL-40 level and progression-free survival (PFS) and overall survival were tested using univariate and multivariate Cox proportional hazards models.
  
  
  
  Baseline plasma YKL-40 levels were higher in patients with poor performance status, less differentiated tumors, residual disease after primary surgery, higher than the median serum CA-125 level, and higher than the median serum vascular endothelial growth factor level. Age-corrected percentile of normal plasma YKL-40 greater than the lowest quartile (Q1, 85th percentile) was associated with shorter PFS in univariate (hazard ratio, 1.83; 95% confidence interval, 1.15-2.89; P = 0.010) and multivariate analyses and shorter overall survival in univariate analysis (hazard ratio, 1.96; 95% confidence interval, 1.27-3.03; P = 0.003). Increase in plasma YKL-40 during bevacizumab treatment, with correction for baseline plasma YKL-40, was a predictor of shorter PFS. Using normal versus elevated plasma YKL-40 as a cutoff did not provide the same discriminative value.
  
  
  
  Low plasma YKL-40 at baseline and during treatment is associated with improved outcomes in patients with chemotherapy-refractory advanced ovarian cancer treated with single-agent bevacizumab.
authors.affiliation: *Department of Oncology, University of Copenhagen Herlev Hospital, Herlev; †Department of Oncology, Vejle Hospital, Vejle; ‡Danish Cancer Society, Danish Cancer Society Research Center, Copenhagen; §Department of Medicine, University of Copenhagen Herlev Hospital, Herlev; and ∥Faculty of Health and Medical Sciences, Institute of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Mogens K
authors.initials: MK
authors.lastname: Boisen
authors.forename: Christine V
authors.initials: CV
authors.lastname: Madsen
authors.forename: Christian
authors.initials: C
authors.lastname: Dehlendorff
authors.forename: Anders
authors.initials: A
authors.lastname: Jakobsen
authors.forename: Julia S
authors.initials: JS
authors.lastname: Johansen
authors.forename: Karina D
authors.initials: KD
authors.lastname: Steffensen
mesh_terms: D000368:Aged; D000074322:Antineoplastic Agents, Immunological / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood; D000077216:Carcinoma, Ovarian Epithelial; D000071451:Chitinase-3-Like Protein 1 / Q000097:blood*; D015331:Cohort Studies; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D009375:Neoplasms, Glandular and Epithelial / Q000097:blood* / Q000188:drug therapy*; D010051:Ovarian Neoplasms / Q000097:blood* / Q000188:drug therapy*; D011237:Predictive Value of Tests; D011379:Prognosis; D016896:Treatment Outcome
chemical_list: D000074322:Antineoplastic Agents, Immunological; D014408:Biomarkers, Tumor; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D000068258:Bevacizumab