title: Heterogeneous distribution of tumor blood supply affects the response to chemotherapy in patients with head and neck cancer.
abstract: OBJECTIVE
  To evaluate if the heterogeneous distribution of tumor blood supply affects the response to chemotherapy in patients with head and neck cancer.
  
  
  METHODS
  We treated 25 stage III/IV patients with an intraarterial cisplatinum-bleomycin regimen. Prior to treatment, a blue dye was injected directly to tumors through the catheter. Well-stained areas were considered as profusely perfused areas whereas poorly stained areas were considered as poorly perfused areas. Biopsies of both areas of each tumor were taken prior to and after the treatment and the histopathological response was evaluated with the following grading: I, tumor disappearance; II, destruction of some tumor nests; III, no changes.
  
  
  RESULTS
  Grade I responses were attained in 13/25 (52%) of profusely perfused areas against 1/25 (4%) of poorly perfused areas (p < 0.001). Moreover, there were significant differences (p < 0.001) in the overall responses: 21/25 (84%) in the profusely perfused areas versus 7/25 (28%) in the poorly perfused areas; and in grade III responses (4/25, 16% vs. 18/25, 72%). To determine a possible correlation between the histopathological responses obtained in profusely perfused and in poorly perfused areas of each tumor, we then calculated the Kendall's tau-b statistics, obtaining a tau value of 0.279 (p = 0.145). This data indicated that histopathological responses to chemotherapy of profusely perfused and poorly perfused areas were independent in each tumor.
  
  
  CONCLUSIONS
  Heterogeneity in the distribution of tumor blood supply affects the response to chemotherapy by influencing the intratumoral delivery of therapeutic agents. After the administration of effective doses of anticancer drugs to a tumor, cells in profusely perfused areas receive enough to destroy them while cells in the poorly perfused areas are exposed to lower drug concentrations and, therefore, survive. This phenomenon could explain in part the difficulty in the treatment of human solid tumors.
authors.affiliation: Hospital Municipal de Oncología María Curie, Buenos Aires, Argentina. felipe.galmarini@mail.roche.com.ar
authors.forename: F C
authors.initials: FC
authors.lastname: Galmarini
authors.forename: C M
authors.initials: CM
authors.lastname: Galmarini
authors.forename: M I
authors.initials: MI
authors.lastname: Sarchi
authors.forename: J
authors.initials: J
authors.lastname: Abulafia
authors.forename: D
authors.initials: D
authors.lastname: Galmarini
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001706:Biopsy; D001761:Bleomycin / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000098:blood supply / Q000188:drug therapy / Q000473:pathology; D002945:Cisplatin / Q000627:therapeutic use; D006258:Head and Neck Neoplasms / Q000098:blood supply* / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007269:Injections, Intra-Arterial; D012394:Rosaniline Dyes
chemical_list: D012394:Rosaniline Dyes; D001761:Bleomycin; C008769:sulfan blue; D002945:Cisplatin