Sminia P, Schneider C J, Koedooder K, van Tienhoven G, Blank L E, González D G
Academic Medical Center, University of Amsterdam, Department of Radiotherapy, The Netherlands.
Int J Radiat Oncol Biol Phys. 1998 Apr 1;41(1):139-50. doi: 10.1016/s0360-3016(98)00023-6.
Investigation of normal tissue sparing in pulsed brachytherapy (PB) relative to continuous low-dose rate irradiation (CLDR) by adjusting pulse frequency based on tissue repair characteristics.
Using the linear quadratic model, the relative effectiveness (RE) of a 20 Gy boost was calculated for tissue with an alpha/beta ratio ranging from 2 to 10 Gy and a half-time of sublethal damage repair between 0.1 and 3 h. The boost dose was considered to be delivered either in a number of pulses varying from 2 to 25, or continuously at a dose rate of 0.50, 0.80, or 1.20 Gy/h.
The RE of 20 Gy was found to be identical for PB in 25 pulses of 0.80 Gy each h and CLDR delivered at 0.80 Gy/h for any alpha/beta value and for a repair half-time > 0.75 h. When normal tissue repair half-times are assumed to be longer than tumor repair half-times, normal tissue sparing can be obtained, within the restriction of a fixed overall treatment time, with higher dose per pulse and longer period time (time elapsed between start of pulse n and start of pulse n + 1). An optimum relative normal tissue sparing larger than 10% was found with 4 pulses of 5 Gy every 8 h. Hence, a therapeutic gain might be obtained when changing from CLDR to PB by adjusting the physical dose in such a way that the biological dose on the tumor is maintained. The normal tissue-sparing phenomenon can be explained by an increase in RE with longer period time for tissue with high alpha/beta ratio and fast or intermediate repair half-time, and the RE for tissue with low alpha/beta ratio and long repair half-time remains almost constant.
Within the benchmark of the LQ model, advantage in normal tissue-sparing is expected when matching the pulse frequency to the repair kinetics of the normal tissue exposed. A period time longer than 1 h may lead to a reduction of late normal tissue complications. This theoretical advantage emphasizes the need for better knowledge of human tissue-repair kinetics.
根据组织修复特性调整脉冲频率,研究脉冲近距离放射治疗(PB)相对于连续低剂量率照射(CLDR)对正常组织的保护作用。
使用线性二次模型,计算α/β比值在2至10 Gy之间且亚致死损伤修复半衰期在0.1至3 h之间的组织接受20 Gy增敏剂量时的相对有效性(RE)。增敏剂量被认为是以2至25个脉冲的形式给予,或者以0.50、0.80或1.20 Gy/h的剂量率连续给予。
对于任何α/β值以及修复半衰期> 0.75 h的情况,发现每小时25个0.80 Gy脉冲的PB与0.80 Gy/h的CLDR的20 Gy的RE相同。当假设正常组织修复半衰期长于肿瘤修复半衰期时,在固定的总治疗时间限制内,通过更高的每脉冲剂量和更长的间隔时间(脉冲n开始与脉冲n + 1开始之间经过的时间),可以实现对正常组织的保护。每8小时4个5 Gy脉冲可获得大于10%的最佳相对正常组织保护。因此,通过调整物理剂量使肿瘤上的生物剂量保持不变,从CLDR改为PB时可能会获得治疗增益。正常组织保护现象可以通过高α/β比值且修复半衰期快或中等的组织的RE随间隔时间延长而增加来解释,而低α/β比值且修复半衰期长的组织的RE几乎保持不变。
在LQ模型的基准范围内,当脉冲频率与暴露的正常组织的修复动力学相匹配时,预计在正常组织保护方面具有优势。间隔时间超过1 h可能会减少晚期正常组织并发症。这一理论优势强调了更好地了解人体组织修复动力学的必要性。