Gray Laboratory, CRUK/MRC Oxford Institute for Radiation Oncology , Oxford.
Int J Radiat Biol. 2014 Sep;90(9):731-41. doi: 10.3109/09553002.2014.925151. Epub 2014 Jul 7.
To review the available experimental animal and patient data on response of the spinal cord to re-irradiation in order to identify appropriate data sets to investigate the clinical potential of models that would allow evaluation of the increase in the retreatment dose with elapsed time from the initial exposure.
MATERIALS/METHODS: Analysis of published data on irradiated rat and primate spinal cord identified results for the rat cervical spinal cord that could be compared, where the development of myelopathy was caused by selective white matter necrosis. This data, although limited, provide some important insights. Two models, derived from simple differential equations, provide a time- and dose-dependency for recovery and could be fitted to these data. These models predict the remaining tolerance, in a phase space above the line that connects the 100% biological effectiveness (BEDTOL) tolerance dose of the first and second treatment courses when these are plotted together. A third, much simpler, linear model, assumed that recovery was time but not initial dose dependent.
The experimental results showed a non-linear time dependency for the change in biological effectiveness (BED) of the re-irradiation dose. Comparison of the three different models paid particular attention to changes in the re-irradiation dose, when the initial radiation dose was either low or high. For each model, cautious data interpretations were also introduced to reduce the effects of the near completeness of recovery with time derived from the important experiments with primates, which include few data points. Model 1 predicts the least recovery following low initial doses, but with greater recovery following larger initial doses. Model 2 allowed no further irradiation after an initial full tolerance dose, but also greater than expected recovery following the use of smaller priming doses. Model 3 gives unrealistically high doses when used after an initial full tolerance irradiation dose.
These results show that it is possible to model these time-dependent relationships for the spinal cord and that Model 1 is probably the most realistic, especially when it is used conservatively. To give greater confidence as to which of the three presented methods is best, further experiments and/or more analysis of human data are necessary. In the meantime clinicians will need to exert caution and judgement as to the choice of the re-irradiation BED, bearing in mind the other clinical factors that influence radio-tolerance. Further research is necessary to provide the safest recommendations and best clinical outcomes. Some suggestions as to what needs to be done are given.
回顾有关脊髓对再照射反应的现有实验动物和患者数据，以确定合适的数据集，用于研究允许评估从初始暴露开始经过时间后增加再治疗剂量的模型的临床潜力。
材料/方法：对已发表的辐射大鼠和灵长类动物脊髓数据进行分析，确定了可比较的大鼠颈脊髓结果，其中脊髓病的发展是由选择性白质坏死引起的。尽管这些数据有限，但提供了一些重要的见解。两个模型，源自简单的微分方程，提供了恢复的时间和剂量依赖性，并且可以拟合这些数据。这些模型预测在第一次和第二次治疗过程的 100%生物有效剂量（BEDTOL）耐受剂量一起绘制时，相空间中超过连接线的剩余耐受度。第三个，简单得多的线性模型，假设恢复是时间而不是初始剂量的函数。
实验结果表明，再照射剂量的生物有效（BED）变化呈非线性时间依赖性。比较三个不同的模型特别注意初始辐射剂量低或高时再照射剂量的变化。对于每个模型，还引入了谨慎的数据解释，以减少从包括少数数据点的灵长类动物重要实验中得出的随时间恢复接近完全的影响。模型 1 预测初始低剂量后恢复最小，但初始大剂量后恢复更大。模型 2 不允许在初始全耐受剂量后进行进一步照射，但在使用较小的起始剂量后也会有超过预期的恢复。模型 3 在初始全耐受照射剂量后使用时给出不切实际的高剂量。
这些结果表明，可以对脊髓的这些时间依赖性关系进行建模，并且模型 1 可能是最现实的，尤其是在保守使用时。为了更有信心地确定所提出的三种方法中哪一种最好，需要进行进一步的实验和/或对人类数据进行更多的分析。在此期间，临床医生需要谨慎判断并选择再照射 BED，同时考虑影响放射耐受性的其他临床因素。需要进一步的研究来提供最安全的建议和最佳的临床结果。给出了一些需要做的建议。
