Fowler J F
Department of Human Oncology, University of Wisconsin Medical School, Madison, WI 53792, USA.
Clin Oncol (R Coll Radiol). 2008 Mar;20(2):113-26. doi: 10.1016/j.clon.2007.11.003. Epub 2007 Dec 26.
A previous paper in this journal (part I) concluded that there was no pronounced optimum overall time, at least up to 70 fractions of 1.15 Gy at two fractions/day in 50 days. The maximum tolerable tumour doses increased only 2% from the best short schedules of 21 or 23 days to those of 50 days. Only this range was modelled in part I because it covered the fewest and the most fractions, and the longest overall times that will probably be used in practice. Most UK schedules, typically using five fractions a week, yield tumour effective doses about 10% less than the best schedules in other developed countries. The present paper covers a much wider range of fraction numbers from one to 115, and from 1 to 80 days. Some numerical errors in the Tables in part I are also corrected in the present appendix. These made no difference to the main conclusions just described.
Standard linear quadratic modelling was used, assuming at first alpha/beta=10 Gy, alpha=0.35 ln/Gy, Tk=21 days, Tp=3 days for tumours, but with Tk=7 days, Tp=2.5 Gy for acute mucosal reactions, as before. A late complications constraint of 70 Gy was accepted, and an acute constraint of 51 Gy (both at 2 Gy fractions). Alternative values of more rapid or slower repopulation were also explored (Tp=2 days or Tp=5 days, respectively).
Optimal values were shown at 22-32 days for one fraction/day five times a week, and at 42-49 days for two fractions/day at 10 fractions/week. Repopulation caused a rapid fall in tumour dose after 30 days with one fraction/day, but not until after 50 days with two fractions/day, and so was not seen in part I with its too-practical end time.
Biological modelling can extrapolate calculations outside the borders of published treatment schedules to clarify borderline situations. Optimum schedules in radiotherapy can reliably give more tumour control if two fractions/day are used. The potential gains are equivalent to about two fractions of 2 Gy as given by this modelling. However, the late complications will be less with some nearly tumour equivalent shorter schedules if optimally designed.
本刊之前的一篇论文（第一部分）得出结论，至少在50天内每天两次分割、每次1.15 Gy、共70次分割的情况下，不存在明显的最佳总治疗时间。从21天或23天的最佳短疗程到50天的疗程，最大耐受肿瘤剂量仅增加了2%。第一部分仅对这个范围进行了建模，因为它涵盖了最少和最多的分割次数，以及实际中可能使用的最长总治疗时间。英国的大多数治疗方案通常每周进行五次分割，其产生的肿瘤有效剂量比其他发达国家的最佳方案低约10%。本文涵盖了从1到115次分割以及从1到80天的更广泛分割次数范围。本附录还纠正了第一部分表格中的一些数值错误。这些错误对上述主要结论没有影响。
采用标准的线性二次模型，最初假设α/β = 10 Gy，α = 0.35 ln/Gy，肿瘤的Tk = 21天, Tp = 3天，但如前所述，急性黏膜反应的Tk = 7天, Tp = 2.5 Gy。接受70 Gy的晚期并发症限制和51 Gy的急性限制（均为2 Gy分割）。还探讨了更快或更慢再增殖的替代值（分别为Tp = 2天或Tp = 5天）。
每周五次、每天一次分割时，最佳值出现在22 - 32天；每周10次、每天两次分割时，最佳值出现在42 - 49天。每天一次分割时，再增殖在30天后导致肿瘤剂量迅速下降，但每天两次分割时直到50天后才出现这种情况，因此在第一部分因其过于实际的结束时间未观察到。
生物学建模可以将计算外推到已发表治疗方案范围之外，以阐明临界情况。如果采用每天两次分割，放射治疗中的最佳方案可以可靠地实现更好的肿瘤控制。根据该模型，潜在获益相当于约两次2 Gy的分割剂量。然而，如果设计优化，一些接近肿瘤等效剂量的较短疗程的晚期并发症会更少。
