Thames H D, Suit H D
Int J Radiat Oncol Biol Phys. 1986 Apr;12(4):687-91. doi: 10.1016/0360-3016(86)90081-7.
Since the introduction of mammalian cell survival curves, the parameters D0 and N have been used as quantitative measures of inherent radiation sensitivity, as was the shoulder width Dq. These parameters are more generally applicable at high doses. We propose to introduce a measure of tumor radioresponsitivity that is more applicable to the clinical treatment schedules that employ small fractional doses (1-2 Gy), the ratio alpha/E, derived from the linear quadratic model for cell inactivation as the intercept on the reciprocal-dose plot. For tumor-control experiments this ratio is the reciprocal of the TCD50 when radiation is given in very small fractions or at low dose rates (assuming negligible clonogen proliferation). The rationales for this choice are: alpha is a measure of the steepness of the initial linear segment of the dose-survival curve. Accordingly, at doses per fraction of 1-2 Gy the observed effect increases with alpha. E is by definition a positive measure of the clonogen kill required for a specified tumor response, e.g., E = -log (surviving fraction of clonogens at the 50% control level). Therefore it is also a measure of the number of clonogens present at the time of inception of treatment, which for a given dose is a prime determinant of the probability of tumor control. This measure of radioresponsitivity is to be distinguished from the ratio alpha/beta, which is a measure of fractionation sensitivity. A survey of the literature indicates that these do not correlate, except in highly hypoxic tumors (e.g., clamped); such tumors are characterized by low radioresponsitivity as well as low fractionation sensitivity (high alpha/beta ratio). There are at present only limited data for determination of this ratio, however, since reciprocal-dose analysis requires tumor control doses for several different sizes of dose per fraction.
自从引入哺乳动物细胞存活曲线以来，参数D0和N一直被用作固有辐射敏感性的定量指标，肩宽Dq也是如此。这些参数在高剂量时更普遍适用。我们建议引入一种更适用于采用小分次剂量（1 - 2 Gy）的临床治疗方案的肿瘤放射反应性指标，即α/E比值，它源自细胞失活的线性二次模型，是倒数剂量图上的截距。对于肿瘤控制实验，当以非常小的分次剂量或低剂量率给予辐射时（假设克隆源性细胞增殖可忽略不计），这个比值是TCD50的倒数。做出这种选择的理由如下：α是剂量 - 存活曲线初始线性段斜率的一种度量。因此，在每次分次剂量为1 - 2 Gy时，观察到的效应随α增大而增加。根据定义，E是特定肿瘤反应所需克隆源性细胞杀伤的正向度量，例如，E = -log（在50%对照水平时克隆源性细胞的存活分数）。所以它也是治疗开始时存在的克隆源性细胞数量的一种度量，对于给定剂量而言，这是肿瘤控制概率的一个主要决定因素。这种放射反应性指标应与α/β比值区分开来，α/β比值是分次敏感性的一种度量。对文献的调查表明，除了在高度缺氧的肿瘤（如钳夹的肿瘤）中，它们并不相关；这类肿瘤的特点是放射反应性低以及分次敏感性低（高α/β比值）。然而，目前用于确定这个比值的数据有限，因为倒数剂量分析需要针对几种不同大小的分次剂量的肿瘤控制剂量。
