Deterministic rather than stochastic factors explain most of the variation in the expression of skin telangiectasia after radiotherapy
Deterministic rather than stochastic factors explain most of the variation in the expression of skin telangiectasia after radiotherapy
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DOI：
10.1016/s0360-3016(01)02690-6
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发表时间：
2002-01-01
影响因子：
7
通讯作者：
Hendry, JH
中科院分区：
文献类型：
--
作者：
Safwat, A;Bentzen, SM;Hendry, JH
背景：在标准疗程的放射治疗后，正常组织损伤的等级在患者与患者之间的差异很大，这在临床上得到了充分的证实。更好地理解这种个体差异可能为辐射损伤的发病机制和预测结果的前景提供有价值的见解。目的：评估随机和患者相关的变异性成分在辐射诱导的正常组织损伤表达中的相对重要性。方法和材料：研究数据来自哥德堡的Turesson的剂量分割研究。包括接受双侧内乳房野治疗的患者，他们完成了至少10年的随访。材料包括22个不同的分馏时间表(每边11个)。使用照射野的临床照片对毛细血管扩张症进行任意6分的分级。对于每个视野，在每个患者中，绘制了一条曲线，显示毛细血管扩张程度随时间的变化。放射反应性的测量是通过个体患者特定野的曲线下面积(AUC)减去接受相同剂量分割计划的野的平均AUC之间的差值来获得的。作为验证性步骤，用加权曲线下面积(WAUC)方法重复相同的分析，计算每个患者的每个视野在5个非零等级或以上所花费的时间。这些时间被用作生物当量剂量的线性回归分析中的解释变量，以统计地建立每个等级的权重，从而提供剂量与效果之间的最佳关系。结果：AUC与2-Gy分次等效剂量(ID2)显著相关。方差分量分析。用极大似然法，表明右侧视野放射反应性的90%(95%可信区间为65%和100%)可以用左侧视野的放射反应性来解释。通过AUC和1132之间的线性回归分析，估计反应距离总体平均值为1SD的患者将需要大约23GY的剂量修正(从组平均值56GY)，以使他们的反应水平与组平均水平相似。同样，WAUC与ID2显著相关，81%(95%可信区间为49%和100%)右侧视野的放射反应性变异可用左侧视野的放射反应性来解释。如果患者的反应与总体平均水平相差不大，则需要对剂量进行调整，使其达到与群体平均水平相似的水平。结论：对于给定的分割计划，患者相关因素解释了放射治疗后毛细血管扩张水平的81%-90%的患者间差异。剩下的10%-19%用随机效应来解释。这一观察结果鼓励了对正常组织放射反应的遗传或表型分析的进一步研究。(C)2002年爱思唯尔科学公司。
Background: The large patient-to-patient variability in the grade of normal tissue injury after a standard course of radiotherapy is well established clinically. A better understanding of this individual variation may provide valuable insights into the pathogenesis of radiation damage and the prospects of predicting the outcome.Purpose: To estimate the relative importance of the stochastic vs. patient-related components of variability in the expression of radiation-induced normal tissue damage.Methods and Materials: The study data were selected from the dose fractionation studies of Turesson in Gothenburg. Patients treated with bilateral internal mammary fields, who completed at least 10 years of follow-up, were included. The material included 22 different fractionation schedules (11 on each side). Telangiectasia was graded on an arbitrary 6-point scale using clinical photographs of the irradiated fields. For each field, in each patient, a curve showing the grade of telangiectasia as a function of time was constructed. A measure of radioresponsiveness was obtained from the difference between the area under the curve (AUC) for a specific field in an individual patient minus the mean AUC of fields receiving the same dose fractionation schedule. As a confirmatory procedure, the same analysis was repeated with a weighted area under the curve (WAUC) approach, in which the time spent at or above each of the 5 nonzero grades was calculated for each field in each patient. These times were used as explanatory variables in a linear regression analysis of biological equivalent dose to establish statistically the weight of each grade providing the optimal relationship between dose and effect. Using these regression coefficients, the weighted area under the grade-time curve (WAUC) was estimated.Results: The AUC was significantly correlated with the isoeffective dose in 2-Gy fractions (ID2). An analysis of variance components. using the maximum likelihood method, showed that 90% (with 95% confidence limits 65% and 100%) of the variance in radioresponsiveness in the right-sided field was explained by the radioresponsiveness on the left-sided field. Through the linear regression analysis between the AUC and the 1132, it was estimated that patients with a reaction that is 1 SD from the population mean would require a dose modification of approximately 23 Gy (from the group mean of 56 Gy) to give them a level of reaction similar to the group average. Similarly, the WAUC was significantly correlated with the ID2, and 81% (with 95% confidence limits 49% and 100%) of the variance in radioresponsiveness in the right-sided field was explained by the radioresponsiveness on the left-sided field. Patients with a reaction that is I SD from the population mean would require a dose modification of approximately 21 Gy (from the group mean of 56 Gy) to give them a level of reaction similar to the group average.Conclusion: For a given fractionation schedule, patient-related factors explain 81-90% of the patient-to-patient variation in telangiectasia level seen after radiotherapy. The remaining 10-19% are explained by stochastic effects. This observation encourages further research into genetic or phenotypic assays of normal tissue radioresponsiveness. (C) 2002 Elsevier Science Inc.