Pre-Therapeutic VEGF Level in Plasma Is a Prognostic Bio-Marker in Head and Neck Squamous Cell Carcinoma (HNSCC).

ABSTRACT: Vascular endothelial growth factor (VEGF) is centrally involved in cancer angiogenesis. We hypothesized that pre-therapeutic VEGF levels in serum and plasma differ in their potential as biomarkers for outcomes in head and neck squamous cell carcinoma (HNSCC) patients. As prospectively defined in the study protocols of TRANSCAN-DietINT and NICEI-CIH, we measured VEGF in pretreatment serum and plasma of 75 HNSCC test cohort (TC) patients. We analyzed the prognostic value of VEGF concentrations in serum (VEGF_Serum) and plasma (VEGF_Plasma) for event-free survival (EFS) utilizing receiver-operating characteristics (ROC). Mean VEGF concentrations in plasma (34.6, 95% CI 26.0-43.3 ng/L) were significantly lower (p = 3.35 × 10^-18) than in serum (214.8, 95% CI 179.6-250.0 ng/L) but, based on ROC (area under the curve, AUC_Plasma = 0.707, 95% CI 0.573-0.840; p = 0.006 versus AUC_Serum = 0.665, 95% CI 0.528-0.801; p = 0.030), superiorly correlated with event-free survival (EFS) of TC patients. Youden indices revealed optimum binary classification with VEGF_Plasma 26 ng/L and VEGF_Serum 264 ng/L. Kaplan-Meier plots demonstrated superiority of VEGF_Plasma in discriminating patients regarding outcome. Patients with VEGF_Plasma < 26 ng/L had superior nodal (NC), local (LC) and loco-regional control (LRC) leading to significant prolonged progression-free survival (PFS) and EFS. We successfully validated VEGF_Plasma according the cut-off <26 ng/L as predictive for superior outcome in an independent validation cohort (iVC) of 104 HNSCC patients from the studies DeLOS-II and LIFE and found better outcomes including prolonged tumor-specific (TSS) and overall survival (OS). Outcomes in TC and iVC combined again was related to VEGF_Plasma, and multivariate Cox regression revealed that VEGF_Plasma was an independent outcome predictor. In HNSCC, pre-therapeutic VEGF_Plasma is prognostic for outcomes.

SUBMITTER: Siemert J 

PROVIDER: S-EPMC8345208 | biostudies-literature |

REPOSITORIES: biostudies-literature