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Abstract：
OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
摘要：
目的：根据体外证据表明，辐射诱导的旁观者效应可能会增强非局部细胞杀伤，可能会影响放射治疗计划范例,例如在整个临床靶体积(CTV)内提供均匀剂量的目标.这项工作应用了旁观者效应模型来计算外束前列腺治疗的等效均匀剂量（EUD）和肿瘤控制概率（TCP），并将结果与更常见的模型进行比较，其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对临床背景下结果的范围设置上限。
方法：使用两种模型计算了在剂量异质性增加的条件下前列腺癌靶体积的EUD和TCP：一种结合了来自先前发表的体外旁观者数据的旁观者效应（McMahon等人。2012,2013a）；以及一种使用仅依赖于局部吸收剂量的常见线性二次（LQ）响应的响应。通过CTV的剂量被建模为正态分布，然后通过改变标准偏差(SD)来确定异质性的程度。此外，在系统地引入冷(低剂量)子体积时,检查了代表性的临床剂量分布.
结果：旁观者模型表明，与EUD和TCP的均匀剂量相比，整个目标体积中中等程度的剂量异质性将产生良好或更好的结果。对于一个典型的中等风险前列腺处方78Gy超过39个分数最大值在EUD和TCP作为增加SD的函数发生在SD~5Gy。这些图仅低于SD~10Gy的均匀剂量值，几乎是处方剂量的13%。小,但由于引入了冷子体积,在临床推导的剂量分布中发现了模型之间结局指标的潜在显著差异.
结论：就EUD和TCP而言，旁观者模型显示,随着前列腺CTV剂量异质性的变化,可能偏离普通局部LQ模型的预测.结果表明,至少在有限的意义上，在CTV内允许一定程度的剂量异质性的可能性，尽管需要进一步研究旁观者模型的假设。
方法：使用两种模型计算了在剂量异质性增加的条件下前列腺癌靶体积的EUD和TCP：一种结合了来自先前发表的体外旁观者数据的旁观者效应（McMahon等人。2012,2013a）；以及一种使用仅依赖于局部吸收剂量的常见线性二次（LQ）响应的响应。通过CTV的剂量被建模为正态分布，然后通过改变标准偏差(SD)来确定异质性的程度。此外，在系统地引入冷(低剂量)子体积时,检查了代表性的临床剂量分布.
结果：旁观者模型表明，与EUD和TCP的均匀剂量相比，整个目标体积中中等程度的剂量异质性将产生良好或更好的结果。对于一个典型的中等风险前列腺处方78Gy超过39个分数最大值在EUD和TCP作为增加SD的函数发生在SD~5Gy。这些图仅低于SD~10Gy的均匀剂量值，几乎是处方剂量的13%。小,但由于引入了冷子体积,在临床推导的剂量分布中发现了模型之间结局指标的潜在显著差异.
结论：就EUD和TCP而言，旁观者模型显示,随着前列腺CTV剂量异质性的变化,可能偏离普通局部LQ模型的预测.结果表明,至少在有限的意义上，在CTV内允许一定程度的剂量异质性的可能性，尽管需要进一步研究旁观者模型的假设。
