Pop L A, Millar W T, Visser A G, van der Kogel A J
Institute of Radiotherapy, University of Nijmegen, Nijmegen, The Netherlands.
Int J Radiat Oncol Biol Phys. 2001 Sep 1;51(1):215-26. doi: 10.1016/s0360-3016(01)01543-7.
To evaluate the clinical implications of the repair parameters determined experimentally in rat spinal cord and to test the feasibility of large doses per fraction or pulses in daytime high-dose-rate (HDR) or pulsed-dose-rate (PDR) brachytherapy treatment schedules as an alternative to continuous low-dose-rate (CLDR) brachytherapy.
BED calculations with the incomplete repair LQ-model were performed for a primary CLDR-brachytherapy treatment of 70 Gy in 140 h or a typical boost protocol of 25 Gy in 50 h after 46-Gy conventional external beam irradiation (ERT) at 2 Gy per fraction each day. Assuming biphasic repair kinetics and a variable dose rate for the iridium-192- (192Ir) stepping source, the LQ-model parameters for rat spinal cord as derived in three different experimental studies were used: (a) two repair processes with an alpha/beta ratio = 2.47 Gy and repair half-times of 0.2 h (12 min) and 2.2 h (Pop et. al.); (b) two repair processes with an alpha/beta ratio = 2.0 Gy and repair half-times of 0.7 h (42 min) and 3.8 h (Ang et al.); and (c) two repair processes with an alpha/beta ratio = 2.0 Gy and repair half-times of 0.25 h (15 min) and 6.4 h (Landuyt et al.). For tumor tissue, an alpha/beta ratio of 10 Gy and a monoexponential repair half time of 0.5 h was assumed. The calculated BED values were compared with the biologic effect of a clinical reference dose of conventional ERT with 2 Gy/day and complete repair between the fractions. Subsequently, assuming a two-catheter implant similar to that used in our experimental study and with the repair parameters derived in our rat model, BED calculations were performed for alternative PDR- and HDR-brachytherapy treatment schedules, in which the irradiation was delivered only during daytime.
If the repair parameters of the study of Pop et al., Ang et al., or Landuyt et al. are used, for a CLDR-treatment of 70 Gy in 140 h, the calculated BED values were 117, 193, or 216 Gy(sc) (Gy(sc) was used to express the BED value for the spinal cord), respectively. These BED values correspond with total doses of conventional ERT of 65, 96, or 104 Gy. The latter two are unrealistic high values and illustrate the danger of a straightforward comparison of BED values if repair parameters are used in situations quite different from those in which they were derived. For a brachytherapy boost protocol, the impact of the different repair parameters is less, due to the fact that the percentage increase in total BED value by the brachytherapy boost is less than 50%. If a primary treatment with CLDR brachytherapy delivering 70 Gy in 140 h has to be replaced, high doses per fraction or pulses (> 1 Gy) during daytime can only be used if the overall treatment time is prolonged with 3-4 days. The dose rate during the fraction or pulse should not exceed 6 Gy/h. For a typical brachytherapy boost protocol after 46 Gy ERT, it seems to be safe to replace CLDR delivering a total dose of 25 Gy in 50 h by a total dose of 24 Gy in 4 days with HDR or PDR brachytherapy during daytime only. Total dose per day should be limited to 6 Gy, and the largest time interval as possible between each fraction or pulse should be used.
Extrapolations based on longer repair half-times in a CLDR reference scheme may lead to the calculation of unrealistically high BED values and dangerously high doses for alternative HDR and PDR treatment schedules. Based on theoretical calculations with the IR model and using the repair parameters derived in our rat spinal cord model, it is estimated that with certain restrictions, large doses per fraction or pulses can be used during daytime schedules of HDR or PDR brachytherapy as an alternative to CLDR brachytherapy, especially for those treatment conditions in which brachytherapy is used after ERT for only less than 50% of the total dose.
评估在大鼠脊髓中实验确定的修复参数的临床意义，并测试在日间高剂量率（HDR）或脉冲剂量率（PDR）近距离放射治疗方案中采用大分割剂量或脉冲作为连续低剂量率（CLDR）近距离放射治疗替代方案的可行性。
使用不完全修复LQ模型进行生物等效剂量（BED）计算，用于在140小时内进行70 Gy的原发性CLDR近距离放射治疗，或在每天2 Gy的常规外照射（ERT）46 Gy后，在50小时内进行25 Gy的典型增敏方案。假设铱-192（192Ir）步进源的双相修复动力学和可变剂量率，使用在三项不同实验研究中得出的大鼠脊髓的LQ模型参数：（a）两个修复过程，α/β比值 = 2.47 Gy，修复半衰期分别为0.2小时（12分钟）和2.2小时（Pop等人）；（b）两个修复过程，α/β比值 = 2.0 Gy，修复半衰期分别为0.7小时（42分钟）和3.8小时（Ang等人）；（c）两个修复过程，α/β比值 = 2.0 Gy，修复半衰期分别为0.25小时（15分钟）和6.4小时（Landuyt等人）。对于肿瘤组织，假设α/β比值为10 Gy，单指数修复半衰期为0.5小时。将计算出的BED值与每天2 Gy的常规ERT临床参考剂量的生物学效应以及分次之间的完全修复进行比较。随后，假设与我们实验研究中使用的类似的双导管植入，并采用我们大鼠模型中得出的修复参数，对替代的PDR和HDR近距离放射治疗方案进行BED计算，其中照射仅在白天进行。
如果使用Pop等人、Ang等人或Landuyt等人研究中的修复参数，对于在140小时内进行70 Gy的CLDR治疗，计算出的BED值分别为117、193或216 Gy（sc）（Gy（sc）用于表示脊髓的BED值）。这些BED值分别对应于常规ERT的总剂量65、96或104 Gy。后两个值是不切实际的高值，说明了在与参数推导情况截然不同的情况下使用修复参数时直接比较BED值的危险性。对于近距离放射治疗增敏方案，不同修复参数的影响较小，因为近距离放射治疗增敏导致的总BED值增加百分比小于50%。如果必须替代在140小时内给予70 Gy的CLDR近距离放射治疗的初始治疗，只有在总治疗时间延长3 - 4天时，才能在白天使用大分割剂量或脉冲（> 1 Gy）。分割或脉冲期间的剂量率不应超过6 Gy/h。对于46 Gy ERT后的典型近距离放射治疗增敏方案，似乎可以安全地用仅在白天进行的HDR或PDR近距离放射治疗，将在50小时内给予25 Gy总剂量的CLDR替换为在4天内给予24 Gy总剂量。每天的总剂量应限制在6 Gy，并应尽可能使用各分割或脉冲之间的最大时间间隔。
基于CLDR参考方案中较长修复半衰期的推断可能导致计算出不切实际的高BED值以及替代HDR和PDR治疗方案的危险性高剂量。基于IR模型的理论计算并使用我们大鼠脊髓模型中得出的修复参数，估计在某些限制条件下，HDR或PDR近距离放射治疗的白天方案中可以使用大分割剂量或脉冲作为CLDR近距离放射治疗的替代方案，特别是对于那些在ERT后仅将近距离放射治疗用于总剂量不到50%的治疗情况。
