title: Prognostic importance of cell-free DNA in chemotherapy resistant ovarian cancer treated with bevacizumab.
abstract: OBJECTIVE
  Treatment of multiresistant epithelial ovarian cancer (EOC) is palliative and patients who have become resistant after multiple lines of chemotherapy often have an unmet need for further and less toxic treatment. Anti-angiogenic therapy has attracted considerable attention in the treatment of EOC in combination with chemotherapy. However, only a minor subgroup will benefit from the treatment and there is an obvious need for new markers to select such patients. The purpose of this study was to investigate the effect of single-agent bevacizumab in multiresistant EOC and the importance of circulating cell-free DNA (cfDNA) in predicting treatment response.
  
  
  METHODS
  One hundred and forty-four patients with multi-resistant EOC were treated with single-agent bevacizumab 10mg/kg every three weeks. Baseline plasma samples were analysed for levels of cfDNA by real-time polymerase chain reaction (PCR).
  
  
  RESULTS
  Eighteen percent responded to treatment according to CA125 and 5.6% had partial response by Response Evaluation Criteria in Solid Tumours (RECIST). Stable disease was seen in 53.5% and 48.6% of the patients by CA125 and RECIST, respectively. Median progression free survival (PFS) and overall survival (OS) were 4.2 and 6.7 months, respectively. Cell-free DNA was highly correlated to PFS (p=0.0004) and OS (p=0.005) in both univariate and multivariate analyses (PFS, hazard ratio (HR)=1.98, p=0.002; OS, HR=1.66, p=0.02), as patients with high cfDNA had a poor outcome.
  
  
  CONCLUSIONS
  Single-agent bevacizumab treatment in multiresistant EOC appears to be a valuable treatment option with acceptable side-effects. Cell-free DNA showed independent prognostic importance in patients treated with bevacizumab and could be applied as an adjunct for treatment selection.
authors.affiliation: Department of Oncology, Vejle Hospital, Kabbeltoft 25, DK-7100 Vejle, Denmark; Institute of Regional Health Research, University of Southern Denmark, Winsløwparken 19,3, DK-5000 Odense C, Denmark. Electronic address: Karina.Dahl.Steffensen@rsyd.dk.
authors.forename: Karina Dahl
authors.initials: KD
authors.lastname: Steffensen
authors.affiliation: Department of Oncology, Vejle Hospital, Kabbeltoft 25, DK-7100 Vejle, Denmark; Institute of Regional Health Research, University of Southern Denmark, Winsløwparken 19,3, DK-5000 Odense C, Denmark. Electronic address: Christine.Vestergaard.Madsen@rsyd.dk.
authors.forename: Christine Vestergaard
authors.initials: CV
authors.lastname: Madsen
authors.affiliation: Department of Clinical Biochemistry, Vejle Hospital, Kabbeltoft 25, DK-7100 Vejle, Denmark. Electronic address: Rikke.Fredslund.Andersen@rsyd.dk.
authors.forename: Rikke Fredslund
authors.initials: RF
authors.lastname: Andersen
authors.affiliation: Department of Pathology, Vejle Hospital, Kabbeltoft 25, DK-7100 Vejle, Denmark. Electronic address: Marianne.Waldstroem@rsyd.dk.
authors.forename: Marianne
authors.initials: M
authors.lastname: Waldstrøm
authors.affiliation: Department of Oncology, Vejle Hospital, Kabbeltoft 25, DK-7100 Vejle, Denmark. Electronic address: Parvin.Adimi@rsyd.dk.
authors.forename: Parvin
authors.initials: P
authors.lastname: Adimi
authors.affiliation: Department of Oncology, Vejle Hospital, Kabbeltoft 25, DK-7100 Vejle, Denmark; Institute of Regional Health Research, University of Southern Denmark, Winsløwparken 19,3, DK-5000 Odense C, Denmark. Electronic address: Anders.Jakobsen@rsyd.dk.
authors.forename: Anders
authors.initials: A
authors.lastname: Jakobsen
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D004273:DNA, Neoplasm / Q000097:blood* / Q000235:genetics; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D006973:Hypertension / Q000139:chemically induced; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D015999:Multivariate Analysis; D009375:Neoplasms, Glandular and Epithelial / Q000097:blood / Q000188:drug therapy*; D010051:Ovarian Neoplasms / Q000097:blood / Q000188:drug therapy*; D011379:Prognosis; D011507:Proteinuria / Q000139:chemically induced; D060888:Real-Time Polymerase Chain Reaction; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D004273:DNA, Neoplasm; D000068258:Bevacizumab
keywords: Bevacizumab; Multiresistant; Ovarian cancer; Prognosis; cfDNA