title: Tumor angiogenesis as a predictive marker for organ preservation in patients with advanced laryngeal carcinoma.
abstract: BACKGROUND
  The purpose of this study was to retrospectively investigate tumor angiogenesis as a predictive marker for response to neoadjuvant chemotherapy, organ preservation, and survival in patients with advanced laryngeal carcinoma.
  
  
  METHODS
  A total of 332 patients with stage III (188 patients) or stage IV (144 patients) squamous cell carcinoma of the larynx were entered in the prospective trial conducted by the Department of Veteran Affairs Laryngeal Cancer Study Group. Of this patient population, 20 pretreatment biopsy specimens were available from the chemotherapy arm for immunohistochemical analysis of Factor VIII expression. Two blinded investigators determined microvessel density in each patient by manual inspection of 10 high-power (400 x) fields (HPF).
  
  
  RESULTS
  The patients who had a partial response (>50% decrease in tumor volume) or complete response to chemotherapy had a mean value of 20.90 (+/- 8.09 standard deviation [SD]) blood vessels per HPF. Those who did not respond to chemotherapy and thus required a total laryngectomy had a mean value of 32.99 (+/- 10.10 SD) vessels per HPF. The difference of the means was statistically significant using a two-tailed t test (P < .0085). Kaplan-Meier survival curve analysis also revealed that patients with vessel counts above the mean tended to have poorer survival than those below the mean regardless of treatment selection. The most-vascular tumors, those greater than 1 SD above the mean, had a statistically significant difference in survival and laryngeal preservation (P = .0345).
  
  
  CONCLUSIONS
  These results indicate that tumor angiogenesis, as measured by number of vessels per HPF, was associated with decreased responsiveness to chemotherapy and radiation for larynx preservation. The most-vascular tumors also were associated with poorer survival than those with lesser degrees of angiogenesis.
authors.affiliation: University of Michigan Health System, Department of Otolaryngology-Head and Neck Surgery, Ann Arbor 48109-0312, USA. teknos@umich.edu
authors.forename: Theodoros N
authors.initials: TN
authors.lastname: Teknos
authors.forename: Claudell
authors.initials: C
authors.lastname: Cox
authors.forename: Martin A
authors.initials: MA
authors.lastname: Barrios
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Chepeha
authors.forename: Carol R
authors.initials: CR
authors.lastname: Bradford
authors.forename: Susan G
authors.initials: SG
authors.lastname: Fisher
authors.forename: Gregory T
authors.initials: GT
authors.lastname: Wolf
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001706:Biopsy; D002294:Carcinoma, Squamous Cell / Q000098:blood supply* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D005169:Factor VIII / Q000032:analysis; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007822:Laryngeal Neoplasms / Q000098:blood supply* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D007825:Laryngectomy; D007830:Larynx / Q000473:pathology; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000473:pathology; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D011379:Prognosis; D018714:Radiotherapy, Adjuvant; D016879:Salvage Therapy; D015996:Survival Rate
chemical_list: D005169:Factor VIII; D002945:Cisplatin; D005472:Fluorouracil