title: Soluble Vascular Endothelial Growth Factor (sVEGF) and the Risk of Venous Thromboembolism in Patients with Cancer: Results from the Vienna Cancer and Thrombosis Study (CATS).
abstract: OBJECTIVE
  Cancer patients are at an increased risk of venous thromboembolism (VTE). VEGF promotes the growth of highly thrombogenic tumor vessels. Here, we explored the utility of soluble plasma VEGF-A (sVEGF) as a biomarker for the prediction of VTE in patients with cancer.
  
  
  METHODS
  Eight hundred four patients with newly diagnosed cancer or progression after remission were prospectively followed for 2 years until the occurrence of VTE or death [tumor sites: brain (n = 87), breast (n = 137), lung (n = 120), gastrointestinal (n = 143), pancreas (n = 53), prostate (n = 95), kidney (n = 22), myeloma and lymphoma (n = 99), and others (n = 48)]. Primary endpoint was symptomatic or fatal VTE. sVEGF was measured by immunoassay in baseline plasma.
  
  
  RESULTS
  Fifty-five patients developed VTE (6.8%) and 364 patients (45.3%) died. Five-hundred and forty-two (68.3%) participants had sVEGF levels above the detection limit of 0.5 pg/mL. The median sVEGF level (25th-75th percentile) was 8.1 pg/mL (0-17.7). The cumulative 2-year incidence of VTE was 10.2% [95% confidence interval (CI), 6.4-14.9] in patients with sVEGF greater than the 75th percentile of the sVEGF distribution (Q3, cutoff: 17.7 pg/mL), and 5.9% (95% CI, 4.2-7.9) in patients with lower levels (P = 0.03). The corresponding 2-year risk of death was 52.8% (95% CI, 46.0-60.0) and 43.9% (95% CI, 40.0-48.0), respectively (P = 0.02). In univariable time-to-VTE regression, elevated sVEGF was associated with VTE [subhazard ratio (SHR) per 10 pg/mL increase, 1.04; 95% CI,1.00-1.09; P = 0.04)]. The association between sVEGF and risk of VTE prevailed after multivariable adjustment for high-risk tumor sites, age, gender, factor VIII, thrombin generation potential, and soluble P-Selectin (adjusted SHR, 1.04; 95% CI, 1.00-1.09, P = 0.05).
  
  
  CONCLUSIONS
  Elevated sVEGF is associated with an increased risk of VTE in patients with cancer.
authors: Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria.
authors: Florian
authors: F
authors: Posch
authors: Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria.
authors: Johannes
authors: J
authors: Thaler
authors: Institute of Immunology, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
authors: Gerhard-Johann
authors: GJ
authors: Zlabinger
authors: Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria.
authors: Oliver
authors: O
authors: Königsbrügge
authors: Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria.
authors: Silvia
authors: S
authors: Koder
authors: Clinical Division of Oncology, Department of Medicine I, Medical University of Vienna, Vienna, Austria.
authors: Christoph
authors: C
authors: Zielinski
authors: Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria.
authors: Ingrid
authors: I
authors: Pabinger
authors: Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria. cihan.ay@meduniwien.ac.at.
authors: Cihan
authors: C
authors: Ay
mesh_terms: D000368:Aged; D015415:Biomarkers; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009026:Mortality; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D009369:Neoplasms / Q000097:blood* / Q000150:complications* / Q000175:diagnosis; D011379:Prognosis; D012306:Risk; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*; D054556:Venous Thromboembolism / Q000175:diagnosis / Q000453:epidemiology* / Q000209:etiology*
chemical_list: D015415:Biomarkers; D042461:Vascular Endothelial Growth Factor A