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).

Conclusion: 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.

Keywords: Abdominal fat; Anti-angiogenic therapy; Melanoma; Visceral fat.

Figure 1.

CT imaging of patient with SFA 208 cm2 and VFA 199 cm 2 (VFA/SFA = 1.0). a) A single slice at the L3-L4 level was used to make all measurements. b) Total abdominal fat (TAF) included all fat measured in the slice. c) Subcutaneous abdominal fat (SAF) segmentation included fat external to the abdominal wall and paravertebral muscles. d) Visceral abdominal fat (VAF) segmentation included fat deep to the abdominal wall and paravertebral muscles.

Figure 2.

Kaplan-Meier estimated PFS and OS in patients with (a,c) high VFA/SFA versus low and (b,d) high BMI vs low. Significantly worse PFS and OS were observed for those with VFA/SFA above the median. No difference was seen for BMI.

Figure 3.

Receiver operating characteristics analysis shows accuracy (AUC) of various models for predicting (a) PFS at 3 months and (b) OS at 24 months.