Department of Oncology, Aarhus University Hospital, Aarhus, Denmark.
Danish Center for Particle Therapy, Aarhus University Hospital, Aarhus, Denmark.
Phys Med Biol. 2021 Oct 12;66(20). doi: 10.1088/1361-6560/ac2880.
Compared to x-ray-based stereotactic body radiotherapy (SBRT) of liver cancer, proton SBRT may reduce the normal liver tissue dose. For an optimal trade-off between target and liver dose, a non-uniform dose prescription is often applied in x-ray SBRT, but lacks investigation for proton SBRT. Also, proton SBRT is prone to breathing-induced motion-uncertainties causing target mishit or dose alterations by interplay with the proton delivery. This study investigated non-uniform and uniform dose prescription in proton-based liver SBRT, including effects of rigid target motion observed during planning-4DCT and treatment. The study was based on 42 x-ray SBRT fractions delivered to 14 patients under electromagnetic motion-monitoring. For each patient, a non-uniform and uniform proton plan were made. The uniform plan was renormalized to be iso-toxic with the non-uniform plan using a NTCP model for radiation-induced liver disease. The motion data were used in treatment simulations to estimate the delivered target dose with rigid motion. Treatment simulations were performed with and without a repainting scheme designed to mitigate interplay effects. Including rigid motion, the achieved CTV mean dose after three fractions delivered without repainting was on average (±SD) 24.8 ± 8.4% higher and the Dwas 16.2 ± 11.3% higher for non-uniform plans than for uniform plans. The interplay-induced increase in Drelative to the static plans was reduced from 3.2 ± 4.1% without repainting to -0.5 ± 1.7% with repainting for non-uniform plans and from 1.5 ± 2.0% to 0.1 ± 1.3% for uniform plans. Considerable differences were observed between estimated CTV doses based on 4DCT motion and intra-treatment motion. In conclusion, non-uniform dose prescription in proton SBRT may provide considerably higher tumor doses than uniform prescription for the same complication risk. Due to motion variability, target doses estimated from 4DCT motion may not accurately reflect the delivered dose. Future studies including modelling of deformations and associated range uncertainties are warranted to confirm the findings.
与肝癌基于 X 射线的立体定向体放射治疗（SBRT）相比，质子 SBRT 可能会降低正常肝脏组织的剂量。为了在靶区和肝脏剂量之间达到最佳平衡，X 射线 SBRT 中通常采用不均匀剂量处方，但质子 SBRT 缺乏相关研究。此外，质子 SBRT 容易受到呼吸运动不确定性的影响，导致靶区失准或因与质子输送的相互作用而改变剂量。本研究调查了质子肝脏 SBRT 中的不均匀和均匀剂量处方，包括在计划 4DCT 和治疗期间观察到的刚性靶区运动的影响。该研究基于 14 名患者在电磁运动监测下接受的 42 次 X 射线 SBRT 分次治疗。对于每个患者，均制定了不均匀和均匀的质子计划。使用用于放射性肝损伤的 NTCP 模型，将均匀计划重新归一化为与不均匀计划等毒性。使用运动数据在治疗模拟中估计具有刚性运动的靶区实际剂量。在没有设计用于减轻相互作用效应的重绘方案的情况下进行了治疗模拟。包括刚性运动，在没有重绘的情况下，不连续分次治疗 3 次后的 CTV 平均剂量平均（±SD）比均匀计划高 24.8±8.4%，Dwas 高 16.2±11.3%。对于不均匀计划，与静态计划相比，无重绘时相互作用引起的 D 增加从 3.2±4.1%减少到 0.5±1.7%，而对于均匀计划，从 1.5±2.0%减少到 0.1±1.3%。基于 4DCT 运动和治疗期间运动的估计 CTV 剂量之间观察到相当大的差异。总之，对于相同的并发症风险，质子 SBRT 中的不均匀剂量处方可能会提供明显更高的肿瘤剂量。由于运动变异性，基于 4DCT 运动的靶区剂量估计可能无法准确反映实际剂量。需要进行包括变形和相关射程不确定性建模的未来研究，以证实这一发现。
