Department of General and Translational Oncology and Hematology, Karl Landsteiner University of Health Sciences, Krems an der Donau, Austria.
MedAustron Ion Therapy Center, Wiener Neustadt, Austria.
Med Phys. 2024 Jun;51(6):3950-3960. doi: 10.1002/mp.17102. Epub 2024 May 2.
Carbon ion beams are well accepted as densely ionizing radiation with a high linear energy transfer (LET). However, the current clinical practice does not fully exploit the highest possible dose-averaged LET (LET) and, consequently, the biological potential in the target. This aspect becomes worse in larger tumors for which inferior clinical outcomes and corresponding lower LET was reported.
The vicinity to critical organs in general and the inferior overall survival reported for larger sacral chordomas treated with carbon ion radiotherapy (CIRT), makes the treatment of such tumors challenging. In this work it was aimed to increase the LET in large volume tumors while maintaining the relative biological effectiveness (RBE)-weighted dose, utilizing the LET optimization functions of a commercial treatment planning system (TPS).
Ten reference sequential boost carbon ion treatment plans, designed to mimic clinical plans for large sacral chordoma tumors, were generated. High dose clinical target volumes (CTV-HD) larger than were considered as large targets. The total RBE-weighted median dose prescription with the local effect model (LEM) was in 16 fractions (nine to low dose and seven to high dose planning target volume). No LET optimization was performed in the reference plans, while LET optimized plans used the minimum LET (L) optimization function in RayStation 2023B. Three different L values were investigated and specified for the seven boost fractions: , and . To compare the LET optimized against reference plans, LET and RBE-weighted dose based goals similar to and less strict than clinical ones were specified for the target. The goals for the organs at risk (OAR) remained unchanged. Robustness evaluation was studied for eight scenarios ( range uncertainty and setup uncertainty along the main three axes).
The optimization method with resulted in an optimal LET distribution with an average increase of (and ) in the CTV-HD by ( ) (and ( )), without significant difference in the RBE-weighted dose. By allowing over- and under-dosage in the target, the (and ) can be increased by ( ) (and ( )), using the optimization parameters . The pass rate for the OAR goals in the LET optimized plans was in the same level as the reference plans. LET optimization lead to less robust plans compared to reference plans.
Compared to conventionally optimized treatment plans, the LET in the target was increased while maintaining the RBE-weighted dose using TPS LET optimization functionalities. Regularly assessing RBE-weighted dose robustness and acquiring more in-room images remain crucial and inevitable aspects during treatment.
碳离子束被广泛认为是具有高线性能量转移(LET)的密集电离辐射。然而,目前的临床实践并未充分利用可能的最高平均剂量 LET(LET),从而未能充分发挥目标的生物学潜力。对于较大的肿瘤,这一情况更为严重,因为据报道,这些肿瘤的临床结果较差,相应的 LET 也较低。
在一般情况下,由于危及器官临近,以及对于接受碳离子放射治疗(CIRT)的较大骶骨脊索瘤报告的整体生存情况较差,因此此类肿瘤的治疗极具挑战性。在这项工作中,旨在利用商业治疗计划系统(TPS)的 LET 优化功能,在保持相对生物效应(RBE)加权剂量的同时,增加大体积肿瘤中的 LET。
设计了十个参考顺序增强碳离子治疗计划,旨在模拟大型骶骨脊索瘤肿瘤的临床计划。被认为是大目标的高剂量临床靶区(CTV-HD)大于 。使用局部效应模型(LEM)的总 RBE 加权中位数剂量处方为 16 个分数(9 个用于低剂量,7 个用于高剂量计划靶区)。参考计划中未进行 LET 优化,而 LET 优化计划则使用 RayStation 2023B 中的最小 LET(L)优化功能。研究了三种不同的 L 值,并指定用于七个增强分数: 、 、 。为了将 LET 优化与参考计划进行比较,针对靶区指定了与临床相似但更为严格的基于 LET 和 RBE 加权剂量的目标。危及器官(OAR)的目标保持不变。研究了八个场景( 范围不确定性和沿三个主要轴的 设定不确定性)的稳健性评估。
采用 的优化方法,可在 CTV-HD 中获得最佳 LET 分布,平均增加 (和 ),而 RBE 加权剂量无显著差异。通过允许靶区的超剂量和欠剂量,可将 (和 )增加 (和 ),使用优化参数 。在 LET 优化计划中,OAR 目标的通过率与参考计划相同。与参考计划相比,LET 优化导致计划的稳健性降低。
与常规优化的治疗计划相比,通过使用 TPS LET 优化功能,在保持 RBE 加权剂量的同时,增加了靶区中的 LET。在治疗过程中,定期评估 RBE 加权剂量的稳健性并获取更多的实时图像仍然是至关重要且不可避免的方面。