Prognostic impact of VEGF and FLT-1 receptor expression in patients with locally advanced squamous cell carcinoma of the head and neck

Abstract

This study investigated the prognostic value of tumor cell expression of vascular endothelial growth factor (VEGF) and its receptor fms-related tyrosine kinase1 (FLT-1) in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN) who had been treated with adjuvant radiotherapy or radiochemotherapy. The impact of tumor cell VEGF and FLT-1 expression plus 11additional factors on loco-regional control (LRC), metastases-free survival (MFS) and overall survival (OS) was retrospectively evaluated in 157patients. The additional factors were age, gender, performance status, pre-radiotherapy (pre-RT) hemoglobin levels, tumor site, histologic grade, T-category, N-category, human papillomavirus (HPV) status, extent of resection and chemotherapy. On multivariate analysis, improved LRC was significantly associated with an absence of VEGF expression (risk ratio, RR:5.02; p = 0.009), lower T-category (RR:2.00; p < 0.001), lower N-category (RR:3.75; p < 0.001) and pre-RT hemoglobin levels ≥ 12g/dl (RR:2.20; p = 0.029). Improved MFS was significantly associated with an absence of VEGF expression (RR:7.46; p = 0.002), lower T-category (RR:1.97; p = 0.002), lower N-category (RR:3.29; p = 0.005) and a favorable tumor location (RR:1.34; p = 0.033); HPV positivity showed a trend towards improved MFS (RR:1.43; p = 0.09). Improved OS was significantly associated with an absence of VEFG expression (RR:3.22; p = 0.041), pre-RT hemoglobin levels ≥ 12g/dl (RR:2.47; p = 0.009), lower T-category (RR:1.92; p < 0.001) and lower N-category (RR:3.39; p < 0.001). FLT-1 expression was significantly associated with LRC and OS in the univariate but not in the multivariate analysis. VEGF expression proved to be an independent negative predictor for LRC, MFS and OS in patients treated for locally advanced SCCHN with adjuvant radiotherapy or radiochemotherapy. FLT-1 expression was not significant in multivariate analyses.