Heterogeneous distribution of tumor blood supply affects the response to chemotherapy in patients with head and neck cancer

被引:48
作者
Galmarini, FC
Galmarini, CM
Sarchi, MI
Abulafia, J
Galmarini, D
机构
[1] Hosp Municipal Oncol Maria Curie, Buenos Aires, DF, Argentina
[2] Fac Farm & Bioquim, Dept Fisicomatemat, Buenos Aires, DF, Argentina
关键词
drug delivery; drug resistance; tumor vascularization;
D O I
10.1038/sj.mn.7300126
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 heated 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 turner blood supply affects the response to chemotherapy by influencing the intratumoral delivery of therapeutic tic 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 pel fused 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.
引用
收藏
页码:405 / 410
页数:6
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