Kim J J, Hao Y, Jang D, Wong C S
Department of Radiation Oncology, University of Toronto, Ontario, Canada.
Radiother Oncol. 1997 May;43(2):211-7. doi: 10.1016/s0167-8140(97)01928-2.
The rat spinal cord model was used to determine whether repair kinetics changed during a course of fractionated radiotherapy if twice daily doses were given either at the initial or final period of a concomitant boost irradiation schedule.
The rat cervical spinal cord was irradiated from C2-T2 in 870 animals with top-up doses of three daily fractions of 9 Gy representing 75% of the biologic dose at the ED50 level for white matter necrosis. To simulate concomitant boost protocols, these top-up doses were given either preceding (initial top-up) or following (final top-up) a b.i.d. schedule of 1 Gy/F delivered at 0, 1, 2, 4, 8 or 24 h interfraction intervals. The end point was forelimb paralysis secondary to white matter necrosis.
For interfraction intervals of 0, 1, 2, 4, 8 and 24 h, the initial top-up schedules yielded ED50 values of 18.2, 19.2, 23.7, 21.3, 27.2 and 29.7 Gy, respectively; the corresponding ED50s from the final top-up schedules were 17.5, 19.0, 20.7, 21.2, 26.9 and 30.3 Gy, respectively. A 10% reduction in the ED50 value from pooled data was observed when the interfraction interval was reduced from 24 (ED50 = 30.3 Gy) to 8 h (ED50 = 27.1 Gy). Fitting the incomplete repair (IR) version of the LQ model with mono-exponential repair kinetics gave alpha/beta values of 1.4 and 1.5 Gy, and similar repair half-times of 4.3 and 5.0 h for the initial and final top-up experiments, respectively. The IR model with bi-exponential repair kinetics did not provide a better fit to the data.
We conclude that the sequence of top-up doses has no apparent influence on radiation sensitivity or repair kinetics in the rat spinal cord. The clinical implication is that the interfraction interval but not the timing of the boost is a critical determinant of spinal cord tolerance in concomitant boost protocols.
采用大鼠脊髓模型来确定在分次放疗过程中，如果在同步加量照射方案的初始阶段或最后阶段给予每日两次剂量，修复动力学是否会发生变化。
对870只动物的大鼠颈段脊髓从C2至T2进行照射，给予每日三次的追加剂量，每次9 Gy，相当于白质坏死的ED50水平时生物剂量的75%。为模拟同步加量方案，这些追加剂量在1 Gy/F、分两次每日照射（照射间隔时间分别为0、1、2、4、8或24小时）之前（初始追加）或之后（最终追加）给予。终点指标是白质坏死继发的前肢麻痹。
对于照射间隔时间为0、1、2、4、8和24小时的情况，初始追加方案的ED50值分别为18.2、19.2、23.7、21.3、27.2和29.7 Gy；最终追加方案相应的ED50值分别为17.5、19.0、20.7、21.2、26.9和30.3 Gy。当照射间隔时间从24小时（ED50 = 30.3 Gy）缩短至8小时（ED50 = 27.1 Gy）时，合并数据显示ED50值降低了10%。采用单指数修复动力学对LQ模型的不完全修复（IR）版本进行拟合，初始追加和最终追加实验的α/β值分别为1.4和1.5 Gy，修复半衰期相似，分别为4.3和5.0小时。具有双指数修复动力学的IR模型对数据的拟合效果并未更好。
我们得出结论，追加剂量的顺序对大鼠脊髓的放射敏感性或修复动力学没有明显影响。临床意义在于，在同步加量方案中，照射间隔时间而非加量的时机是脊髓耐受性的关键决定因素。
