Galmarini F C, Galmarini C M, Sarchi M I, Abulafia J, Galmarini D
Hospital Municipal de Oncología María Curie, Buenos Aires, Argentina.
Microcirculation. 2000 Dec;7(6 Pt 1):405-10.
To evaluate if the heterogeneous distribution of tumor blood supply affects the response to chemotherapy in patients with head and neck cancer.
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.
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.
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.
评估肿瘤血供的异质性分布是否会影响头颈癌患者对化疗的反应。
我们采用动脉内顺铂-博来霉素方案治疗了25例III/IV期患者。治疗前，通过导管将蓝色染料直接注入肿瘤。染色良好的区域被视为灌注丰富区域，而染色不佳的区域被视为灌注不良区域。在每个肿瘤的这两个区域进行治疗前后的活检，并采用以下分级评估组织病理学反应：I级，肿瘤消失；II级，部分肿瘤巢破坏；III级，无变化。
在灌注丰富区域，13/25（52%）达到I级反应，而在灌注不良区域为1/25（4%）（p<0.001）。此外，总体反应存在显著差异（p<0.001）：灌注丰富区域为21/25（84%），而灌注不良区域为7/25（28%）；III级反应也有差异（4/25，16%对18/25，72%）。为了确定每个肿瘤的灌注丰富区域和灌注不良区域获得的组织病理学反应之间可能的相关性，我们随后计算了肯德尔tau-b统计量，得到tau值为0.279（p = 0.145）。该数据表明，每个肿瘤中灌注丰富区域和灌注不良区域对化疗的组织病理学反应是独立的。
肿瘤血供分布的异质性通过影响治疗药物在肿瘤内的递送而影响对化疗的反应。向肿瘤给予有效剂量的抗癌药物后，灌注丰富区域的细胞获得足够药物被破坏，而灌注不良区域的细胞暴露于较低的药物浓度，因此存活下来。这种现象可以部分解释人类实体瘤治疗的困难。
