Fowler Jack F, Welsh James S, Howard Steven P
Department of Human Oncology, Medical School, University of Wisconsin, Madison, WI 53792, USA.
Int J Radiat Oncol Biol Phys. 2004 May 1;59(1):242-9. doi: 10.1016/j.ijrobp.2004.01.004.
The decrease of biologic effect if delivery of dose fractions takes more than a few minutes has been occasionally recognized in the literature but has been insufficiently studied. It has been recognized as a problem in the long exposures necessary for stereotactic radiotherapy and is also a potential problem in some applications of IMRT. Modeling repair rates is a complex function of dose per fraction, dose rate, half-times of repair, and nature of the tissue of interest (the alpha/beta ratio of intrinsic radiosensitivity to repair capacity). In this article, we model repair rates for a range of doses per fraction and draw conclusions.
We review the data on half-times of repair in tissues in situ in animals and human patients and conclude that a single first-order (exponential) repair rate is no longer an appropriate assumption for most tissues. At least 2 half-times of repair, and perhaps a distribution of half-times, are required. The faster components have a median half-time of 0.3 h (range, 0.08-1.2 h), and the longer components have a median of 4 h (range, 2.4->6 h). Modeling repair rates by a two-component model is the simplest approach. We have used two models of repair to represent these ranges, one with equal proportions of 0.2 h + 4.0 h half-times, the other with 0.4 h + 4.0 h half-times of repair. Data are also reviewed on the few experiments that have been reported with cell culture that investigate this problem.
Computations indicate that any fraction delivery that lasts more than half an hour might experience a clinically significant loss of cell-sterilizing effect. We suggest that a loss of more than 10% in biologically effective dose should be compensated for and show modeled doses and fraction durations for which this situation seems to be likely. It will be dose, tissue, and system dependent and will require more investigation at the clinical level.
It is suggested that any radiotherapy schedule that requires more than half an hour for the delivery of 1 fraction should have careful records made and reported, to look for a possible decrease of biologic effect with fraction duration.
如果分次剂量的给予时间超过几分钟，生物效应会降低，这一点在文献中偶尔有所提及，但研究并不充分。在立体定向放射治疗所需的长时间照射中，这已被视为一个问题，在调强放射治疗的某些应用中也是一个潜在问题。修复率建模是一个复杂的函数，它取决于每次分割剂量、剂量率、修复半衰期以及所关注组织的性质（固有放射敏感性与修复能力的α/β比值）。在本文中，我们对一系列每次分割剂量的修复率进行建模并得出结论。
我们回顾了动物和人类患者原位组织修复半衰期的数据，得出结论：对于大多数组织而言，单一的一级（指数）修复率不再是一个合适的假设。至少需要2个修复半衰期，甚至可能是半衰期的分布。较快的成分中位半衰期为0.3小时（范围为0.08 - 1.2小时），较长的成分中位半衰期为4小时（范围为2.4 -> 6小时）。用双成分模型对修复率进行建模是最简单的方法。我们使用了两种修复模型来代表这些范围，一种是0.2小时 + 4.0小时半衰期各占相等比例，另一种是0.4小时 + 4.0小时半衰期。我们还回顾了少数已报道的研究此问题的细胞培养实验数据。
计算表明，任何持续超过半小时的分次剂量给予可能会导致临床上显著的细胞杀灭效应损失。我们建议，生物有效剂量损失超过10%时应予以补偿，并展示出似乎可能出现这种情况的建模剂量和分次持续时间。这将取决于剂量、组织和系统，并且在临床层面需要更多研究。
建议对于任何单次分割剂量给予需要超过半小时的放射治疗方案，都应仔细记录并报告，以查找生物效应随分次持续时间可能出现的降低情况。
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