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.

Prediction Model for Nodal Disease Among Patients With Non–Small Cell Lung Cancer

“…Epidemiologic studies demonstrated an association between nodal disease and VEGF-C expression[16]–[20]. Previously, our team demonstrated that the use of VEGF-C levels and PET results better predicts nodal disease than PET findings alone[22]. Inexplicably, this study found no evidence of an association between plasma VEGF-C and nodal disease.…”

“…We collected blood using a previously-reported standardized protocol[22] and measured plasma VEGF-C levels using a commercially-available enzyme-linked immunosorbent assay (R&D Systems, Minneapolis, MN).…”

“…We did not consider variables with >10% missing data for inclusion in the model. We constructed another model including radiographic factors from the “final” model and log-transformed values of VEGF-C[22]. …”

Challenges in Predicting Recurrence After Resection of Node-Negative Non-Small Cell Lung Cancer

“…VEGF-C is a growth factor that stimulates lymphangiogenesis [22] and has been associated with lung cancer recurrence among patients with nodal disease [23]. A prior study showed variability in VEGF-C expression, suggesting it may be a predictor of recurrence [24]. …”

An infrared spectroscopic blood test for non-small cell lung carcinoma and subtyping into pulmonary squamous cell carcinoma or adenocarcinoma

“…Diagnostic approaches targeting potential blood borne biomarkers have been described [7,12,24,29]. Thus, it is meaningful to expect a biochemical difference between blood samples of lung carcinoma and control patients.…”