Balderson Michael J, Kirkby Charles
Department of Medical Physics, Jack Ady Cancer Centre , Lethbridge, Alberta.
Int J Radiat Biol. 2015 Jan;91(1):54-61. doi: 10.3109/09553002.2014.942014.
In light of in vitro evidence suggesting that radiation-induced bystander effects may enhance non-local cell killing, there is potential for impact on radiotherapy treatment planning paradigms such as the goal of delivering a uniform dose throughout the clinical target volume (CTV). This work applies a bystander effect model to calculate equivalent uniform dose (EUD) and tumor control probability (TCP) for external beam prostate treatment and compares the results with a more common model where local response is dictated exclusively by local absorbed dose. The broad assumptions applied in the bystander effect model are intended to place an upper limit on the extent of the results in a clinical context.
EUD and TCP of a prostate cancer target volume under conditions of increasing dose heterogeneity were calculated using two models: One incorporating bystander effects derived from previously published in vitro bystander data ( McMahon et al. 2012 , 2013a); and one using a common linear-quadratic (LQ) response that relies exclusively on local absorbed dose. Dose through the CTV was modelled as a normal distribution, where the degree of heterogeneity was then dictated by changing the standard deviation (SD). Also, a representative clinical dose distribution was examined as cold (low dose) sub-volumes were systematically introduced.
The bystander model suggests a moderate degree of dose heterogeneity throughout a target volume will yield as good or better outcome compared to a uniform dose in terms of EUD and TCP. For a typical intermediate risk prostate prescription of 78 Gy over 39 fractions maxima in EUD and TCP as a function of increasing SD occurred at SD ∼ 5 Gy. The plots only dropped below the uniform dose values for SD ∼ 10 Gy, almost 13% of the prescribed dose. Small, but potentially significant differences in the outcome metrics between the models were identified in the clinically-derived dose distribution as cold sub-volumes were introduced.
In terms of EUD and TCP, the bystander model demonstrates the potential to deviate from the common local LQ model predictions as dose heterogeneity through a prostate CTV varies. The results suggest, at least in a limiting sense, the potential for allowing some degree of dose heterogeneity within a CTV, although further investigation of the assumptions of the bystander model are warranted.
鉴于体外证据表明辐射诱导的旁观者效应可能增强非局部细胞杀伤，这有可能影响放射治疗计划范式，例如在整个临床靶区（CTV）给予均匀剂量的目标。本研究应用旁观者效应模型计算外照射前列腺治疗的等效均匀剂量（EUD）和肿瘤控制概率（TCP），并将结果与一种更常见的模型进行比较，在该模型中局部反应仅由局部吸收剂量决定。旁观者效应模型中应用的广泛假设旨在在临床背景下对结果范围设定一个上限。
使用两种模型计算前列腺癌靶区在剂量不均匀性增加情况下的EUD和TCP：一种纳入了源自先前发表的体外旁观者数据的旁观者效应（McMahon等人，2012年，2013a）；另一种使用仅依赖局部吸收剂量的常见线性二次（LQ）反应。通过CTV的剂量被建模为正态分布，然后通过改变标准差（SD）来决定不均匀程度。此外，当系统引入冷（低剂量）子体积时，检查了代表性的临床剂量分布。
旁观者模型表明，在整个靶区内中等程度的剂量不均匀性在EUD和TCP方面将产生与均匀剂量一样好或更好的结果。对于典型的中等风险前列腺处方，在39次分割中给予78 Gy剂量，EUD和TCP的最大值作为SD增加的函数出现在SD约为5 Gy时。这些图仅在SD约为10 Gy时降至均匀剂量值以下，几乎是规定剂量的13%。当引入冷子体积时，在临床衍生的剂量分布中，模型之间的结果指标存在小但可能显著的差异。
就EUD和TCP而言，旁观者模型表明，随着通过前列腺CTV的剂量不均匀性变化，有可能偏离常见的局部LQ模型预测。结果表明，至少在有限的意义上，在CTV内允许一定程度剂量不均匀性的可能性，尽管旁观者模型的假设值得进一步研究。
