Vascular endothelial growth factor C complements the ability of positron emission tomography to predict nodal disease in lung cancer

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: Model(PET), Model(PET/VEGF-C), Model(PET/VEGF-D), and Model(PET/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: Model(PET/VEGF-C) versus Model(PET) (P = .0069), Model(PET/VEGF-D) versus Model(PET) (P = .1886), Model(PET/VEGF-C/VEGF-D) versus Model(PET) (P = .0146), Model(PET/VEGF-C/VEGF-D) versus Model(PET/VEGF-C) (P = .2818), and Model(PET/VEGF-C/VEGF-D) versus Model(PET/VEGF-D) (P = .0095). In Model(PET/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.