title: Vascular endothelial growth factor C complements the ability of positron emission tomography to predict nodal disease in lung cancer.
abstract: OBJECTIVE
  Vascular endothelial growth factors (VEGFs) C and D are biologically rational markers of nodal disease that could improve the accuracy of lung cancer staging. We hypothesized that these biomarkers would improve the ability of positron emission tomography (PET) to predict nodal disease among patients with suspected or confirmed non-small cell lung cancer (NSCLC).
  
  
  METHODS
  A cross-sectional study (2010-2013) was performed of patients prospectively enrolled in a lung nodule biorepository, staged by computed tomography (CT) and PET, and who underwent pathologic nodal evaluation. Enzyme-linked immunosorbent assay was used to measure biomarker levels in plasma from blood drawn before anesthesia. Likelihood ratio testing was used to compare the following logistic regression prediction models: ModelPET, ModelPET/VEGF-C, ModelPET/VEGF-D, and ModelPET/VEGF-C/VEGF-D. To account for 5 planned pairwise comparisons, P values <.01 were considered significant.
  
  
  RESULTS
  Among 62 patients (median age, 67 years; 48% men; 87% white; and 84% NSCLC), 58% had fluorodeoxyglucose uptake in hilar and/or mediastinal lymph nodes. The prevalence of pathologically confirmed lymph node metastases was 40%. Comparisons of prediction models revealed the following: ModelPET/VEGF-C versus ModelPET (P = .0069), ModelPET/VEGF-D versus ModelPET (P = .1886), ModelPET/VEGF-C/VEGF-D versus ModelPET (P = .0146), ModelPET/VEGF-C/VEGF-D versus ModelPET/VEGF-C (P = .2818), and ModelPET/VEGF-C/VEGF-D versus ModelPET/VEGF-D (P = .0095). In ModelPET/VEGF-C, higher VEGF-C levels were associated with an increased risk of nodal disease (odds ratio, 2.96; 95% confidence interval, 1.26-6.90).
  
  
  CONCLUSIONS
  Plasma levels of VEGF-C complemented the ability of PET to predict nodal disease among patients with suspected or confirmed NSCLC. VEGF-D did not improve prediction.
authors: Division of Cardiothoracic Surgery, Department of Surgery, University of Washington, Seattle, Wash; Surgical Outcomes Research Center, University of Washington, Seattle, Wash. Electronic address: ffarjah@uw.edu.
authors: Farhood
authors: F
authors: Farjah
authors: Division of Pulmonary and Critical Care Medicine, University of Washington, Seattle, Wash; Division of Pulmonary and Critical Care Medicine, Fred Hutchinson Cancer Research Center, Seattle, Wash.
authors: David K
authors: DK
authors: Madtes
authors: Division of Cardiothoracic Surgery, Department of Surgery, University of Washington, Seattle, Wash.
authors: Douglas E
authors: DE
authors: Wood
authors: Surgical Outcomes Research Center, University of Washington, Seattle, Wash.
authors: David R
authors: DR
authors: Flum
authors: Surgical Outcomes Research Center, University of Washington, Seattle, Wash.
authors: Megan E
authors: ME
authors: Zadworny
authors: Center for Lung Biology, University of Washington, Seattle, Wash.
authors: Rachel
authors: R
authors: Waworuntu
authors: Center for Lung Biology, University of Washington, Seattle, Wash.
authors: Billanna
authors: B
authors: Hwang
authors: Division of Cardiothoracic Surgery, Department of Surgery, University of Washington, Seattle, Wash; Center for Lung Biology, University of Washington, Seattle, Wash.
authors: Michael S
authors: MS
authors: Mulligan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood* / Q000000981:diagnostic imaging* / Q000556:secondary; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood* / Q000000981:diagnostic imaging* / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D042582:Vascular Endothelial Growth Factor C / Q000097:blood*; D042643:Vascular Endothelial Growth Factor D / Q000097:blood*
chemical_list: D014408:Biomarkers, Tumor; C579459:VEGFD protein, human; D042582:Vascular Endothelial Growth Factor C; D042643:Vascular Endothelial Growth Factor D
keywords: biomarkers; diagnostic test; lung cancer; prediction models; risk prediction