Shan Jie, Yang Yunze, Schild Steven E, Daniels Thomas B, Wong William W, Fatyga Mirek, Bues Martin, Sio Terence T, Liu Wei
Department of Radiation Oncology, Mayo Clinic, Phoenix, AZ, 85054, USA.
Med Phys. 2020 Nov;47(11):5428-5440. doi: 10.1002/mp.14491. Epub 2020 Oct 13.
Intensity-modulated proton therapy (IMPT) is sensitive to uncertainties from patient setup and proton beam range, as well as interplay effect. In addition, respiratory motion may vary from cycle to cycle, and also from day to day. These uncertainties can severely degrade the original plan quality and potentially affect patient's outcome. In this work, we developed a new tool to comprehensively consider the impact of all these uncertainties and provide plan robustness evaluation under them.
We developed a comprehensive plan robustness evaluation tool that considered both uncertainties from patient setup and proton beam range, as well as respiratory motion simultaneously. To mimic patients' respiratory motion, the time spent in each phase was randomly sampled based on patient-specific breathing pattern parameters as acquired during the four-dimensional (4D)-computed tomography (CT) simulation. Spots were then assigned to one specific phase according to the temporal relationship between spot delivery sequence and patients' respiratory motion. Dose in each phase was calculated by summing contributions from all the spots delivered in that phase. The final 4D dynamic dose was obtained by deforming all doses in each phase to the maximum exhalation phase. Three hundred (300) scenarios (10 different breathing patterns with 30 different setup and range uncertainty scenario combinations) were calculated for each plan. The dose-volume histograms (DVHs) band method was used to assess plan robustness. Benchmarking the tool as an application's example, we compared plan robustness under both three-dimensional (3D) and 4D robustly optimized IMPT plans for 10 nonrandomly selected patients with non-small cell lung cancer.
The developed comprehensive plan robustness tool had been successfully applied to compare the plan robustness between 3D and 4D robustly optimized IMPT plans for 10 lung cancer patients. In the presence of interplay effect with uncertainties considered simultaneously, 4D robustly optimized plans provided significantly better CTV coverage (D , P = 0.002), CTV homogeneity (D -D , P = 0.002) with less target hot spots (D , P = 0.002), and target coverage robustness (CTV D bandwidth, P = 0.004) compared to 3D robustly optimized plans. Superior dose sparing of normal lung (lung D , P = 0.020) favoring 4D plans and comparable normal tissue sparing including esophagus, heart, and spinal cord for both 3D and 4D plans were observed. The calculation time for all patients included in this study was 11.4 ± 2.6 min.
A comprehensive plan robustness evaluation tool was successfully developed and benchmarked for plan robustness evaluation in the presence of interplay effect, setup and range uncertainties. The very high efficiency of this tool marks its clinical adaptation, highly practical and versatile nature, including possible real-time intra-fractional interplay effect evaluation as a potential application for future use.
调强质子治疗（IMPT）对患者摆位、质子束射程的不确定性以及相互作用效应敏感。此外，呼吸运动在不同周期甚至不同日期可能会有所变化。这些不确定性会严重降低原始计划质量，并可能影响患者的治疗结果。在本研究中，我们开发了一种新工具，以全面考虑所有这些不确定性的影响，并在这些不确定性条件下提供计划稳健性评估。
我们开发了一种全面的计划稳健性评估工具，该工具同时考虑了患者摆位和质子束射程的不确定性以及呼吸运动。为了模拟患者的呼吸运动，根据在四维（4D）计算机断层扫描（CT）模拟中获取的患者特定呼吸模式参数，对每个阶段所花费的时间进行随机采样。然后根据束斑投放序列与患者呼吸运动之间的时间关系，将束斑分配到一个特定阶段。通过对该阶段投放的所有束斑的贡献求和来计算每个阶段的剂量。通过将每个阶段的所有剂量变形到最大呼气阶段，获得最终的4D动态剂量。为每个计划计算了300种情况（10种不同的呼吸模式与30种不同的摆位和射程不确定性情况组合）。使用剂量体积直方图（DVH）带法评估计划稳健性。作为应用示例对该工具进行基准测试，我们比较了10例非小细胞肺癌患者在三维（3D）和4D稳健优化IMPT计划下的计划稳健性。
所开发的全面计划稳健性工具已成功应用于比较10例肺癌患者在3D和4D稳健优化IMPT计划之间的计划稳健性。在同时考虑不确定性的相互作用效应的情况下，与3D稳健优化计划相比，4D稳健优化计划提供了显著更好的临床靶区（CTV）覆盖（D ，P = 0.002）、CTV均匀性（D-D ，P = 0.002），靶区热点更少（D ，P = 0.002）以及靶区覆盖稳健性（CTV D带宽，P = 0.004）。观察到4D计划在正常肺组织剂量 sparing方面更优（肺D ，P = 0.020），并且3D和4D计划在包括食管、心脏和脊髓在内的正常组织 sparing方面相当。本研究中纳入的所有患者的计算时间为11.4±2.6分钟。
成功开发了一种全面的计划稳健性评估工具，并在存在相互作用效应、摆位和射程不确定性的情况下对计划稳健性评估进行了基准测试。该工具的极高效率标志着其临床适用性、高度实用性和通用性，包括作为未来潜在应用的可能的实时分次内相互作用效应评估。
