title: Increased visceral to subcutaneous fat ratio is associated with decreased overall survival in patients with metastatic melanoma receiving anti-angiogenic therapy.
abstract: BACKGROUND
  Body fat distribution is an emerging prognostic indicator in patients treated with anti-angiogenic (AA) therapy. We sought to evaluate the association of visceral and subcutaneous fat with progression free survival (PFS) and overall survival (OS) in patients with metastatic melanoma treated with AA therapy.
  
  
  METHODS
  Stage IV melanoma patients received bevacizumab ± interferon-alpha. Total abdominal fat, visceral fat area (VFA) and subcutaneous fat area (SFA) were measured at L3-L4 on CT images (cm(2)). PFS and OS were estimated by the Kaplan-Meier method. Cox proportional hazards model was used to assess the association of fat and clinical variables with PFS and OS. Prediction accuracy was evaluated using receiver operating characteristic curve with area under the curve (AUC).
  
  
  RESULTS
  Forty-two patients were evaluated. Median VFA/SFA and body mass index (BMI) were used to group patients into high and low cohorts. PFS and OS were significantly decreased in patients with high VFA/SFA versus low (PFS, p=0.009; OS, p = 0.007), but not for BMI (PFS, p=0.774; OS, p=0.881). VFA/SFA, LDH and liver metastasis (LM) were predictors of PFS and OS on multivariate analysis. A prognostic score combining VFA/SFA, LDH, and presence or absence of LM had a higher accuracy for predicting PFS at 3 months (AUC 0.759) and OS at 24 months (AUC 0.846) than LDH and LM alone (PFS, AUC 0.705; OS, AUC 0.786).
  
  
  CONCLUSIONS
  Increased VFA/SFA is associated with decreased PFS and OS in patients with metastatic melanoma treated with AA therapy, indicating body fat distribution is an important prognostic factor.
authors.affiliation: Division of Surgical Oncology, The Ohio State University, Columbus, OH, USA.
authors.forename: Valerie P
authors.initials: VP
authors.lastname: Grignol
authors.affiliation: Department of Radiology, University of Mississippi, Jackson, MS, USA.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Smith
authors.affiliation: Department of Radiology, University of Mississippi, Jackson, MS, USA.
authors.forename: Darya
authors.initials: D
authors.lastname: Shlapak
authors.affiliation: Center of Biostatistics and Bioinformatics, University of Mississippi, Jackson, MS, USA.
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Division of Surgical Oncology, The Ohio State University, Columbus, OH, USA.
authors.forename: Sara Martin
authors.initials: SM
authors.lastname: Del Campo
authors.affiliation: Division of Surgical Oncology, The Ohio State University, Columbus, OH, USA. Electronic address: william.carson@osumc.edu.
authors.forename: William E
authors.initials: WE
authors.lastname: Carson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000627:therapeutic use; D000068258:Bevacizumab / Q000627:therapeutic use*; D015992:Body Mass Index; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D050152:Intra-Abdominal Fat / Q000473:pathology*; D008297:Male; D008545:Melanoma / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D012189:Retrospective Studies; D050151:Subcutaneous Fat / Q000473:pathology*; D015996:Survival Rate; D014057:Tomography, X-Ray Computed
chemical_list: D020533:Angiogenesis Inhibitors; D000998:Antiviral Agents; D016898:Interferon-alpha; D000068258:Bevacizumab
keywords: Abdominal fat; Anti-angiogenic therapy; Melanoma; Visceral fat