Development of the practical methods to detect the hypoxic cell fraction of the tumor for prediction of results of radiotherapy

背景：低剂量率（LDR）近距离放射治疗是治疗口腔癌的有效方法，尤其是在早期。然而，人们对这种以持续低dr照射为特征的治疗的生物学机制知之甚少，也不知道这种治疗如何在临床上取得良好的效果。据报道，高微血管密度（MVD）和高Ki-67指数与外照射治疗患者的良好预后有关。低MVD与肿瘤的缺氧部分有关。较低的MVD表明肿瘤有更多的缺氧细胞和更强的放射抗性。方法：对60例接受LDR近距离放射治疗的舌癌患者，除临床病理因素外，评价Ki-67指数测定的生长分数和微血管密度（MVD）对预后的价值。采用放射治疗前舌癌标本进行免疫组化染色，检测抗Ki-67抗体和抗cd34抗体。结果：在单因素和多因素分析中，T期与局部对照之间存在显著相关。T1、T2和T3肿瘤患者5年精算局部无复发率分别为100%、76.4%和26.9%。Ki-67免疫反应性从8%到75%不等（中位数：34%）。在单因素分析中，ki -67标记指数低与较好的局部控制呈弱相关（P=0.0805）。MVD范围为5至45个微血管/田（50.391 mm^2）（中位数：23个血管/田）。高MVD组与低MVD组在局部控制方面无差异。结论：这些结果与外照射的报道完全不同，提示LDR照射可以克服静止肿瘤细胞和低氧细胞引起的放射耐药。因此，LDR近距离治疗可能具有不同于外照射的生物学特性，这是有利的。

Background : Low dose rate (LDR) brachytherapy is an effective treatment for oral tongue cancer, especially in the early stage. However, little is known about the biological mechanism underlying this therapy, characterized by delivery of continuous exposures of LDR irradiation, or how the good results are achieved in clinics. It is reported that a high microvessel density (MVD) and high Ki-67 index is related to the good prognosis of patients treated with external irradiation. A low MVD is related to the hypoxic fraction of the tumor . The lower MVD indicates that the tumor has the more hypoxic cells and is more radioresistent.METHODS : The prognostic value of the growth fraction determined by Ki-67 index and the microvessel density (MVD) was assessed in 60 tongue cancers treated with LDR brachytherapy, in addition to clinicopathological factors. The specimens were taken from the tongue cancers before radiation therapy and immunohistochemically stained with anti Ki-67 antibody and anti CD 34 antibody.RESULTS : There were significant correlations between T stage and local control in univariate and multivariate analyses. The actuarial local recurrence-free rate at 5 years was 100%, 76.4%, and 26.9% in the patients with T1, T2, and T3 tumors, respectively.The Ki-67 immunoreactivity ranged from 8 to 75% (median : 34%). In univariate analysis, a low Ki-67-labeling index was weakly correlated with better local control (P=0.0805).MVD ranged from 5 to 45 microvessels per field (50.391 mm^2)(median : 23 vessels/field ). There were no differences in local control between tumors with high MVD and those with low MVD.CONCLUSIONS : These results are totally different from reports obtained with external irradiation, suggesting that LDR irradiation could overcome the radoioresistance caused by quiescent tumor cells and hypoic cells. In this way, LDR brachytherapy may have different biological characteristics from external irradiation, which are advantageous.