title: Prognostic impact of VEGF and FLT-1 receptor expression in patients with locally advanced squamous cell carcinoma of the head and neck.
abstract: OBJECTIVE
  This study investigated the prognostic value of tumor cell expression of vascular endothelial growth factor (VEGF) and its receptor fms-related tyrosine kinase 1 (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.
  
  
  METHODS
  The impact of tumor cell VEGF and FLT-1 expression plus 11 additional factors on loco-regional control (LRC), metastases-free survival (MFS) and overall survival (OS) was retrospectively evaluated in 157 patients. 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.
  
  
  RESULTS
  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 ≥ 12 g/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 ≥ 12 g/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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Radiation Oncology, University of Lubeck, Ratzeburger Allee 160, 23538, Lubeck, Germany.
authors.forename: N D
authors.initials: ND
authors.lastname: Seibold
authors.forename: S E
authors.initials: SE
authors.lastname: Schild
authors.forename: K L
authors.initials: KL
authors.lastname: Bruchhage
authors.forename: M P
authors.initials: MP
authors.lastname: Gebhard
authors.forename: F
authors.initials: F
authors.lastname: Noack
authors.forename: D
authors.initials: D
authors.lastname: Rades
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000401:mortality / Q000628:therapy*; D059248:Chemoradiotherapy / Q000401:mortality*; D005260:Female; D005858:Germany / Q000453:epidemiology; D006258:Head and Neck Neoplasms / Q000378:metabolism / Q000401:mortality / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D011379:Prognosis; D020266:Radiotherapy, Conformal / Q000401:mortality*; D015203:Reproducibility of Results; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D016019:Survival Analysis; D015996:Survival Rate; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1