title: Measurements of adiposity as clinical biomarkers for first-line bevacizumab-based chemotherapy in epithelial ovarian cancer.
abstract: OBJECTIVE
  There is a lack of reliable indicators to predict who will benefit most from anti-angiogenic therapy, such as bevacizumab. Recognizing obesity is associated with increased levels of VEGF, the main target of bevacizumab, we sought to assess if adiposity, measured in terms of BMI, subcutaneous fat area (SFA), and visceral fat area (VFA) was prognostic.
  
  
  METHODS
  Reviewed 46 patients with advanced EOC who received primary treatment with bevacizumab-based chemotherapy (N=21) or chemotherapy alone (N=25) for whom complete records, CT prior to the first cycle of chemo, and serum were available. CT was used to measure SFA and VFA by radiologists blinded to outcomes. ELISA was used to measure serum levels of VEGF and angiopoietin-2 in the bevacizumab group.
  
  
  RESULTS
  BMI, SFA, and VFA were dichotomized using the median and categorized as "high" or "low". In the bevacizumab group median PFS was shorter for patients with high BMI (9.8 vs. 24.7months, p=0.03), while in the chemotherapy group median PFS was similar between high and low BMI (17.6 vs. 11.9months, p=0.19). In the bevacizumab group patients with a high BMI had higher median levels of VEGF and angiopoietin-2, 371.9 vs. 191.4pg/ml (p=0.05) and 45.9 vs. 16.6pg/ml (p=0.09) respectively. On multivariate analysis neither BMI, SFA, nor VFA were associated with PFS (p=0.13, p=0.86, p=0.16 respectively) or OS (p=0.14, p=0.93, p=0.28 respectively) in the chemotherapy group. However, in the bevacizumab group BMI was significantly associated with PFS (p=0.02); accounting for confounders adjusted HR for high vs. low BMI was 5.16 (95% CI 1.31-20.24). Additionally in the bevacizumab group SFA was significantly associated with OS (p=0.03); accounting for confounders adjusted HR for high vs. low SFA was 3.58 (95% CI 1.12-11.43).
  
  
  CONCLUSIONS
  Results provide the first evidence in EOC that patients with high levels of adiposity may not derive benefit from bevacizumab and that measurements of adiposity are likely to be a useful biomarker.
authors.affiliation: University of Oklahoma Health Sciences Center, USA. Electronic address: Katrina-slaughter@ouhsc.edu.
authors.forename: Katrina N
authors.initials: KN
authors.lastname: Slaughter
authors.affiliation: University of Oklahoma Health Sciences Center, USA.
authors.forename: Theresa
authors.initials: T
authors.lastname: Thai
authors.affiliation: University of Oklahoma Health Sciences Center, USA.
authors.forename: Shayla
authors.initials: S
authors.lastname: Penaroza
authors.affiliation: University of Oklahoma Health Sciences Center, USA.
authors.forename: Doris M
authors.initials: DM
authors.lastname: Benbrook
authors.affiliation: University of Oklahoma Health Sciences Center, USA.
authors.forename: Elangovan
authors.initials: E
authors.lastname: Thavathiru
authors.affiliation: University of Oklahoma Health Sciences Center, USA.
authors.forename: Kai
authors.initials: K
authors.lastname: Ding
authors.affiliation: University of Oklahoma Health Sciences Center, USA.
authors.forename: Tina
authors.initials: T
authors.lastname: Nelson
authors.affiliation: University of Oklahoma Health Sciences Center, USA.
authors.forename: D Scott
authors.initials: DS
authors.lastname: McMeekin
authors.affiliation: University of Oklahoma Health Sciences Center, USA.
authors.forename: Kathleen N
authors.initials: KN
authors.lastname: Moore
mesh_terms: D050154:Adiposity; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D015992:Body Mass Index; D016190:Carboplatin / Q000008:administration & dosage; D000077216:Carcinoma, Ovarian Epithelial; D005260:Female; D006801:Humans; D050152:Intra-Abdominal Fat / Q000000981:diagnostic imaging*; D008875:Middle Aged; D015999:Multivariate Analysis; D009375:Neoplasms, Glandular and Epithelial / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D009765:Obesity / Q000097:blood / Q000150:complications*; D010051:Ovarian Neoplasms / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D050177:Overweight / Q000097:blood / Q000150:complications; D017239:Paclitaxel / Q000008:administration & dosage; D010865:Pilot Projects; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D050151:Subcutaneous Fat / Q000000981:diagnostic imaging*; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D016190:Carboplatin; D017239:Paclitaxel
keywords: Angiogenesis; Clinical biomarker; Subcutaneous fat; Visceral fat