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.
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。