School of Physics, Mathematics and Computing, University of Western Australia, Perth, Australia.
Institute of Medical Physics, University of Sydney, Sydney, Australia.
Radiat Oncol. 2020 Jul 13;15(1):172. doi: 10.1186/s13014-020-01568-6.
This study aimed to develop a framework for optimising prostate intensity-modulated radiotherapy (IMRT) based on patient-specific tumour biology, derived from multiparametric MRI (mpMRI). The framework included a probabilistic treatment planning technique in the effort to yield dose distributions with an improved expected treatment outcome compared with uniform-dose planning approaches.
IMRT plans were generated for five prostate cancer patients using two inverse planning methods: uniform-dose to the planning target volume and probabilistic biological optimisation for clinical target volume tumour control probability (TCP) maximisation. Patient-specific tumour location and clonogen density information were derived from mpMRI and geometric uncertainties were incorporated in the TCP calculation. Potential reduction in dose to sensitive structures was assessed by comparing dose metrics of uniform-dose plans with biologically-optimised plans of an equivalent level of expected tumour control.
The planning study demonstrated biological optimisation has the potential to reduce expected normal tissue toxicity without sacrificing local control by shaping the dose distribution to the spatial distribution of tumour characteristics. On average, biologically-optimised plans achieved 38.6% (p-value: < 0.01) and 51.2% (p-value: < 0.01) reduction in expected rectum and bladder equivalent uniform dose, respectively, when compared with uniform-dose planning.
It was concluded that varying the dose distribution within the prostate to take account for each patient's clonogen distribution was feasible. Lower doses to normal structures compared to uniform-dose plans was possible whilst providing robust plans against geometric uncertainties. Further validation in a larger cohort is warranted along with considerations for adaptive therapy and limiting urethral dose.
本研究旨在开发一种基于多参数 MRI（mpMRI）得出的患者特定肿瘤生物学的前列腺调强放疗（IMRT）优化框架。该框架包括一种概率治疗计划技术，旨在与均匀剂量计划方法相比，产生改善预期治疗效果的剂量分布。
使用两种逆规划方法为五名前列腺癌患者生成 IMRT 计划：均匀剂量到计划靶区和概率生物优化以最大化临床靶区肿瘤控制概率（TCP）。从 mpMRI 中得出患者特定的肿瘤位置和克隆源密度信息，并在 TCP 计算中纳入几何不确定性。通过比较均匀剂量计划的剂量指标与具有等效预期肿瘤控制水平的生物优化计划来评估对敏感结构剂量的潜在减少。
该计划研究表明，生物优化有可能通过将剂量分布塑造成肿瘤特征的空间分布来降低预期的正常组织毒性，而不会牺牲局部控制。平均而言，与均匀剂量计划相比，生物优化计划可使预期直肠和膀胱等效均匀剂量分别降低 38.6%（p 值：<0.01）和 51.2%（p 值：<0.01）。
可以得出结论，在前列腺内改变剂量分布以考虑每个患者的克隆源分布是可行的。与均匀剂量计划相比，正常结构的剂量可能更低，同时可以提供针对几何不确定性的稳健计划。需要在更大的队列中进行进一步验证，并考虑适应性治疗和限制尿道剂量。
