Carleton Laboratory for Radiotherapy Physics, Department of Physics, Carleton University, Ottawa, ON, K1S 5B6, Canada.
Centre de recherche sur le cancer, Université Laval, Québec, QC, G1R 3S3, Canada.
Med Phys. 2017 Aug;44(8):4329-4340. doi: 10.1002/mp.12306. Epub 2017 Jul 12.
To investigate the coupling of radiobiological models with patient-specific Monte Carlo (MC) dose calculations for permanent implant prostate brachytherapy (PIPB). To compare radiobiological indices evaluated with different radiobiological models using MC and simulated AAPM TG-43 dose calculations.
Three-dimensional dose distributions previously computed using MC techniques with two types of patient models, TG43sim (AAPM TG-43 water-based conditions) and MCDmm (realistic tissues and interseed effects), for 613 PIPB patients are coupled with biological dose and tumour control probability (TCP) models. Two approaches and their extensions are considered to evaluate biological doses, biologically effective dose (BED) and isoeffective dose (IED), as well as two methods to evaluate TCP. Three novel extensions of equivalent uniform biologically effective dose (EUBED) are suggested which consider the spatial distribution of doses within the target volume. Adopted radiobiological model parameter values (α, β, etc) are those suggested by AAPM TG-137, and sensitivity to parameter choice is discussed.
MCDmm dose calculations can reveal low doses in the prostate target volume, due to tissue heterogeneities or inter-seed effects; considering these low doses in EUBED calculations can lower TCP estimates by up to 70%, with largest differences in patients with calcifications. There are large variations in biological doses and TCPs evaluated over the 613 patient cohort for each radiobiological model considered, reflecting the spectrum of physical doses calculated for these patients with either MCDmm or TG43sim. Depending on the model details, BED, IED and EUBED are, on average, 6.0-9.8%, 7.4-9.2% and 1.8-15% higher, respectively, with TG43sim than MCDmm. TCP estimates computed using MCDmm dose distributions are much lower than expected based on past treatment outcome studies, suggesting a need to re-assess model parameters when evaluating radiobiological indices coupled with heterogeneous tissue model-based dose calculations.
Cohort average differences in biological dose and TCP estimates between radiobiological models are generally larger than differences for any one radiobiological model evaluated with TG43sim or MCDmm dose calculations. However, heterogeneous tissue dose calculations, like MCDmm, can identify clinically-relevant low dose volumes, e.g., in patients with calcifications, which would otherwise be missed with TG-43. In addition to affecting physical dose distributions, these low dose volumes can largely impact radiobiological dose and TCP estimates, which further motivates the clinical implementation of model-based dose calculations for PIPB.
研究放射生物学模型与患者特定的蒙特卡罗(MC)剂量计算在永久性植入前列腺近距离治疗(PIPB)中的结合。比较使用 MC 和模拟 AAPM TG-43 剂量计算评估不同放射生物学模型的放射生物学指标。
将以前使用 MC 技术针对 613 例 PIPB 患者的两种类型的患者模型 TG43sim(基于 AAPM TG-43 的水基条件)和 MCDmm(真实组织和间隔物效应)计算的三维剂量分布与生物剂量和肿瘤控制概率(TCP)模型相结合。考虑了两种方法及其扩展,以评估生物剂量,生物有效剂量(BED)和等效应剂量(IED),以及评估 TCP 的两种方法。提出了三种新的等效均匀生物有效剂量(EUBED)扩展,这些扩展考虑了靶区内部剂量的空间分布。采用的放射生物学模型参数值(α,β等)是 AAPM TG-137 建议的值,并讨论了对参数选择的敏感性。
MCDmm 剂量计算可以揭示由于组织异质性或间隔物效应导致前列腺靶区中的低剂量;在 EUBED 计算中考虑这些低剂量会使 TCP 估计值降低多达 70%,在有钙化的患者中差异最大。对于每个考虑的放射生物学模型,在 613 例患者队列中,生物剂量和 TCP 的评估差异很大,反映了对这些患者用 MCDmm 或 TG43sim 计算的物理剂量的范围。根据模型细节,BED,IED 和 EUBED 分别比 MCDmm 高 6.0-9.8%,7.4-9.2%和 1.8-15%。使用 MCDmm 剂量分布计算的 TCP 估计值远低于过去治疗结果研究的预期,这表明在评估与异质组织模型剂量计算相结合的放射生物学指标时,需要重新评估模型参数。
放射生物学模型之间的生物剂量和 TCP 估计的队列平均差异通常大于任何一个放射生物学模型用 TG43sim 或 MCDmm 剂量计算评估的差异。然而,像 MCDmm 这样的异质组织剂量计算可以识别临床相关的低剂量体积,例如在有钙化的患者中,否则会错过 TG-43。除了影响物理剂量分布外,这些低剂量体积还会极大地影响放射生物学剂量和 TCP 估计值,这进一步促使为 PIPB 实施基于模型的剂量计算。