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

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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.