Fracchiolla Francesco, Engwall Erik, Mikhalev Victor, Cianchetti Marco, Giacomelli Irene, Siniscalchi Benedetta, Sundström Johan, Marthin Otte, Wase Viktor, Bertolini Mattia, Righetto Roberto, Trianni Annalisa, Lohr Frank, Lorentini Stefano
UO Fisica Sanitaria, Trento Hospital APSS, Proton Therapy Center, Trento, Italy.
RaySearch Laboratories AB, Stockholm, Sweden.
Med Phys. 2025 May;52(5):3191-3203. doi: 10.1002/mp.17669. Epub 2025 Feb 12.
Proton Arc Treatment (PAT) has shown potential over Multi-Field Optimization (MFO) for out-of-target dose reduction in particular for head and neck (H&N) patients. A feasibility test, including delivery in a clinical environment is still missing in the literature and a necessary requirement before clinical application of PAT.
To perform a comprehensive comparison between clinically delivered MFO plans and static PAT plans for H&N treatments, followed by end-to-end commissioning of the system to prepare for clinical treatments.
Anonymized datasets of 10 patients treated for H&N cancer (median prescription dose 70 GyRBE) were selected for this study. Both MFO and PAT plans were created in RayStation and robustly optimized for setup and range uncertainties as in our clinical routine. PAT plans were created with 30 angle directions. 1. Comparisons were performed regarding: 2. nominal dose distributions in terms of target coverage, dose to primary and secondary OARs 3. robustness evaluation (D of the target and D of primary OARs) 4. Normal tissue complication probability (NTCP) values for xerostomia, swallowing dysfunction, tube feeding, and sticky saliva 5. D·LET distributions 6. the probability of replanning at least once due to anatomical changes 7. delivery time: MFO and PAT plans, for one patient, were delivered in a clinical gantry room. For PAT, two plans with 30 and with 20 discrete beam directions were optimized and delivered.
In PAT plans, a significant reduction was observed in the near maximum dose to the brainstem, while no statistically significant differences were found for other primary OARs or target coverage metrics (D and D) in both nominal plans and robustness evaluation scenarios. For secondary OARs, PAT plans achieved an impressive reduction in mean dose. Max D·LETd distributions in brainstem, brain, and temporal lobes showed no statistical differences between MFO and PAT plans while mean D·LETd values were lower with PAT. Median NTCP was significantly reduced for xerostomia as endpoint (ΔNTCP = 8.5%), while reductions in other endpoints were not statistically significant. The number of patients that would need at least one replanning during the treatment for PAT was similar to MFO, showing that the established clinical workflow for monitoring of anatomy changes will remain the same for both delivery methods. Comparison in terms of delivery time from the start of the first beam until the end of the last (comprising all the technically motivated delays due to operation of OIS/Therapy Control System operation, gantry rotations, couch rotations, beam line preparation etc.) resulted in delivery times that were similar for both techniques.
Static PAT plans demonstrate the capability to increase plan quality with respect to state-of-the-art MFO planning, since dose reduction outside of the target is significant with no reduction of the quality of the target dose distribution. NTCP evaluations, as well as linear energy transfer (LET) distributions, do not indicate risks for unexpected toxicity. Delivery time tests with different beam direction configurations have shown that PAT plans can already be delivered within similar time slots as highly conformal MFO plans. The successful end-to-end commissioning led to the world's first patient treatments using PAT, with eight patients treated to date.
质子弧形治疗(PAT)在减少靶外剂量方面显示出优于多野优化(MFO)的潜力,特别是对于头颈部(H&N)患者。文献中仍缺少包括在临床环境中进行治疗的可行性测试,而这是PAT临床应用之前的必要条件。
对头颈部治疗中临床实施的MFO计划和静态PAT计划进行全面比较,随后对系统进行端到端调试,为临床治疗做准备。
本研究选择了10例接受头颈部癌症治疗患者的匿名数据集(中位处方剂量70 GyRBE)。MFO和PAT计划均在RayStation中创建,并像我们的临床常规那样针对摆位和射程不确定性进行稳健优化。PAT计划以30个角度方向创建。1. 进行了以下比较:2. 名义剂量分布,包括靶区覆盖情况、对主要和次要危及器官的剂量;3. 稳健性评估(靶区的D和主要危及器官的D);4. 口干、吞咽功能障碍、鼻饲和唾液黏稠的正常组织并发症概率(NTCP)值;5. D·LET分布;6. 因解剖结构变化至少重新计划一次的概率;7. 治疗时间:一名患者的MFO和PAT计划在临床机架室进行治疗。对于PAT,优化并实施了具有30个和20个离散射束方向的两个计划。
在PAT计划中,观察到脑干的近最大剂量显著降低,而在名义计划和稳健性评估方案中,其他主要危及器官或靶区覆盖指标(D和D)均未发现统计学显著差异。对于次要危及器官,PAT计划实现了平均剂量的显著降低。脑干、脑和颞叶的最大D·LETd分布在MFO和PAT计划之间无统计学差异,而PAT的平均D·LETd值较低。以口干为终点的中位NTCP显著降低(ΔNTCP = 8.5%),而其他终点的降低无统计学显著意义。PAT治疗期间至少需要重新计划一次的患者数量与MFO相似,表明既定的监测解剖结构变化的临床工作流程对于两种治疗方式将保持不变。从第一束射线开始到最后一束射线结束(包括由于影像引导系统/治疗控制系统操作、机架旋转、治疗床旋转、束流线路准备等技术原因导致的所有延迟)的治疗时间比较结果显示,两种技术的治疗时间相似。
静态PAT计划表明相对于先进的MFO计划有提高计划质量的能力,因为靶外剂量降低显著,而靶区剂量分布质量未降低。NTCP评估以及线能量传递(LET)分布未表明存在意外毒性风险。不同射束方向配置的治疗时间测试表明,PAT计划已经可以在与高度适形的MFO计划相似的时间段内实施。成功的端到端调试促成了世界上首例使用PAT的患者治疗,迄今已治疗了8例患者。