Dikomey Ekkehard, Borgmann Kerstin, Peacock John, Jung Horst
Institute of Biophysics and Radiobiology, University Hospital Hamburg-Eppendorf, Hamburg, Germany. dikomey@uke..uni-hamburg.de
Int J Radiat Oncol Biol Phys. 2003 Jul 15;56(4):1194-200. doi: 10.1016/s0360-3016(03)00188-3.
New insights into the kinetics of late complications occurring after radiation therapy indicated that all patients have a constant risk of developing late tissue complications. These observations might have a great impact on studies relating normal tissue complications to individual radiosensitivity.
Data previously published by Peacock et al. were used for analysis. In this study, 39 breast cancer patients with severe reactions (responders) were compared with 65 matched patients showing no reactions (nonresponders). Cellular radiosensitivity as measured in vitro in terms of D(0.01) did not show significant differences between the two groups, both for high-dose-rate (5.84 +/- 0.06 vs. 5.85 +/- 0.07 Gy) and low-dose-rate (7.44 +/- 0.10 vs. 7.56 +/- 0.09 Gy) irradiation.
A theoretical distribution was calculated for the individual radiosensitivity of patients with Grade <or= 1, Grade 2, or Grade 3 reactions under the following assumptions: (1). The variation of the individual radiosensitivity is described by a normal distribution. (2). All patients and not only a subgroup have a risk of developing late complications. Based on the normal distribution of low-dose-rate data (mean value [MV] = 7.56 Gy, standard deviation [SD] = 0.5 Gy), a total of 200 hypothetical patients were divided into three groups: a resistant group with a sensitivity >or=(MV + SD), a normal group with a sensitivity between MV - SD and MV + SD, and a sensitive group <or=(MV - SD), the relative fractions being 16%, 68%, and 16%, respectively. It was assumed that these groups differed in the risk of developing late complication; for Grade 3 the annual incidence rate was set at 1%, 2%, and 4% and for Grade 2 at 5%, 10%, and 20% per year, respectively. It was shown that the mean cellular sensitivity calculated for Grade 3 (7.39 +/- 0.10 Gy) or Grade 2 patients (7.46 +/- 0.06 Gy) was slightly but not significantly lower than that of Grade <or= 1 patients (7.65 +/- 0.04 Gy). This result demonstrated that even if the risk was assumed to depend clearly on the individual radiosensitivity, significant differences in the mean cellular sensitivity between responders and nonresponders were not expected, just as found by Peacock et al. It was shown that a significant correlation between these two parameters could be detected only when the risk was analyzed separately for each group of patients.
Most data published so far aiming at establishing a relationship between cellular radiosensitivity and the risk of late complications might need to be reevaluated, because the questions asked up to now were inadequate to arrive at a meaningful answer.
对放射治疗后迟发并发症动力学的新见解表明，所有患者发生晚期组织并发症的风险是恒定的。这些观察结果可能对将正常组织并发症与个体放射敏感性相关的研究产生重大影响。
使用Peacock等人先前发表的数据进行分析。在本研究中，将39例有严重反应的乳腺癌患者（反应者）与65例匹配的无反应患者（无反应者）进行比较。就D(0.01)而言，体外测量的细胞放射敏感性在高剂量率（5.84±0.06 vs. 5.85±0.07 Gy）和低剂量率（7.44±0.10 vs. 7.56±0.09 Gy）照射下两组之间均未显示出显著差异。
在以下假设下计算了1级及以下、2级或3级反应患者个体放射敏感性的理论分布：(1). 个体放射敏感性的变化用正态分布描述。(2). 所有患者而非仅一个亚组有发生迟发并发症的风险。基于低剂量率数据的正态分布（平均值[MV]=7.56 Gy，标准差[SD]=0.5 Gy），总共200名假设患者被分为三组：敏感性≥(MV + SD)的抗性组、敏感性在MV - SD和MV + SD之间的正常组以及敏感性≤(MV - SD)的敏感组，相对比例分别为16%、68%和16%。假设这些组在发生迟发并发症的风险方面存在差异；对于3级，年发病率分别设定为1%、2%和4%，对于2级分别设定为5%、10%和20%。结果显示，3级（7.39±0.10 Gy）或2级患者（7.46±0.06 Gy）计算出的平均细胞敏感性略低于1级及以下患者（7.65±0.04 Gy），但差异不显著。该结果表明，即使假设风险明显取决于个体放射敏感性，反应者和无反应者之间平均细胞敏感性的显著差异也未出现，正如Peacock等人所发现的那样。结果表明，只有当对每组患者分别分析风险时，才能检测到这两个参数之间的显著相关性。
迄今为止发表的大多数旨在建立细胞放射敏感性与迟发并发症风险之间关系的数据可能需要重新评估，因为到目前为止提出的问题不足以得出有意义的答案。
