Fowler J F, Van Limbergen E F
Department of Oncology, University Hospital Gasthuisberg, Leuven, Belgium.
Int J Radiat Oncol Biol Phys. 1997 Mar 1;37(4):877-83. doi: 10.1016/s0360-3016(96)00565-2.
To explore the possible increase of radiation effect in tissues irradiated by pulsed brachytherapy (PDR) for local tissue dose rates between those "averaged over the whole pulse" and the instantaneous high dose rates close to the dwell positions. Increased effect is more likely for tissues with short half-times of repair of the order of a few minutes, similar to pulse durations.
Calculations were done assuming the linear quadratic formula for radiation damage, in which only the dose-squared term is subject to exponential repair. The situation with two components of T1,2 is addressed. A constant overall time of 140 h and a constant total dose of 70 Gy were assumed throughout, the continuous low dose rate of 0.5 Gy/h (CLDR) providing the unitary standard effects for each PDR condition. Effects of dose rates ranging from 4 Gy/h to 120 Gy/h (HDR at 2 Gy/min) were studied, covering the gap in an earlier publication. Four schedules were examined: doses per pulse of 0.5, 1, 1.5, and 2 Gy given at repetiton frequencies of 1, 2, 3, and 4 h, respectively, each with a range of assumed half-times of repair of 4 min to 1.5 h. Results are presented for late-responding tissues, the differences from CLDR being two or three times greater than for early-responding tissues and most tumors.
Curves are presented relating the ratio of increased biological effect (proportional to log cell kill) calculated for PDR relative to CLDR. Ratios as high as 1.5 can be found for large doses per pulse (2 Gy) if the half-time of repair in tissues is as short as a few minutes. The major influences on effect are dose per pulse, half-time of repair in tissue, and--when T1/2 is short--the instantaneous dose rate. Maximum ratios of PDR/CLDR occur when the dose rate is such that pulse duration is approximately equal to T1/2. As dose rate in the pulse is increased, a plateau of effect is reached, for most T1/2s, above 10 to 20 Gy/h, which is therefore radiobiologically equivalent to the highest HDR. A stepping source of 1 curie carries a sphere of "HDR" of radius 20 mm with it in its track through tissue. High ratios of PDR/LDR effect can be avoided by keeping dose per pulse below 1 Gy.
Therefore, about 75% of the total dose is delivered at HDR in a PDR implant of moderate volume, reducing to 40% as the source decays from 1 to 0.3 curies. Even so, restricting the dose per pulse to 0.5 or 0.6 Gy should avoid ratios of increased effect larger than about 10%. It appears likely that PDR delivered by stepping source might behave more like HDR than LDR, especially for tissues with a substantial component of repair of very short T1/2.
探讨在脉冲近距离放射治疗（PDR）中，对于局部组织剂量率处于“整个脉冲平均剂量率”与靠近驻留位置的瞬时高剂量率之间的情况，组织辐射效应可能的增加。对于修复半衰期为几分钟量级（与脉冲持续时间相似）的组织，更有可能出现效应增加。
计算基于辐射损伤的线性二次公式，其中只有剂量平方项进行指数修复。研究了具有两个T1,2成分的情况。始终假设总时间为140小时且总剂量为70 Gy不变，连续低剂量率0.5 Gy/h（CLDR）为每种PDR条件提供单一标准效应。研究了4 Gy/h至120 Gy/h（2 Gy/min的高剂量率）范围内的剂量率效应，填补了早期出版物中的空白。检查了四个方案：每个脉冲剂量分别为0.5、1、1.5和2 Gy，重复频率分别为1、2、3和4小时，每种方案假设修复半衰期范围为4分钟至1.5小时。给出了晚期反应组织的结果，与CLDR的差异比早期反应组织和大多数肿瘤大两到三倍。
给出了与PDR相对于CLDR计算的生物效应增加率（与对数细胞杀伤成正比）相关的曲线。如果组织中的修复半衰期短至几分钟，对于每个脉冲大剂量（2 Gy），可发现高达1.5的比率。对效应的主要影响因素是每个脉冲的剂量、组织中的修复半衰期，以及（当T1/2短时）瞬时剂量率。当剂量率使得脉冲持续时间近似等于T1/2时，PDR/CLDR的比率最大。随着脉冲中的剂量率增加，对于大多数T1/2，在10至20 Gy/h以上达到效应平台期，因此在放射生物学上等同于最高的高剂量率。一个1居里的步进源在穿过组织的轨迹中携带一个半径为20 mm的“高剂量率”球体。通过将每个脉冲的剂量保持在1 Gy以下，可以避免PDR/低剂量率效应的高比率。
因此，在中等体积的PDR植入物中，约75%的总剂量以高剂量率输送，当源从1居里衰减到0.3居里时，该比例降至40%。即便如此，将每个脉冲的剂量限制在0.5或0.6 Gy应可避免效应增加比率大于约10%。由步进源输送的PDR似乎可能比低剂量率更像高剂量率，特别是对于具有非常短T1/2的大量修复成分的组织。
