在调强质子治疗优化中引入质子射程末端目标以降低关键结构中的线性能量传递和相对生物效应。

Introducing Proton Track-End Objectives in Intensity Modulated Proton Therapy Optimization to Reduce Linear Energy Transfer and Relative Biological Effectiveness in Critical Structures.

机构信息

RaySearch Laboratories AB, Stockholm, Sweden.

RaySearch Laboratories AB, Stockholm, Sweden; Department of Physics, Medical Radiation Physics, Stockholm University, Stockholm, Sweden.

出版信息

Int J Radiat Oncol Biol Phys. 2019 Mar 1;103(3):747-757. doi: 10.1016/j.ijrobp.2018.10.031. Epub 2018 Nov 2.

DOI:10.1016/j.ijrobp.2018.10.031

PMID:30395906

Abstract

PURPOSE

We propose the use of proton track-end objectives in intensity modulated proton therapy (IMPT) optimization to reduce the linear energy transfer (LET) and the relative biological effectiveness (RBE) in critical structures.

METHODS AND MATERIALS

IMPT plans were generated for 3 intracranial patient cases (1.8 Gy (RBE) in 30 fractions) and 3 head-and-neck patient cases (2 Gy (RBE) in 35 fractions), assuming a constant RBE of 1.1. Two plans were generated for each patient: (1) physical dose objectives only (DOSEopt) and (2) same dose objectives as the DOSEopt plan, with additional proton track-end objectives (TEopt). The track-end objectives penalized protons stopping in the risk volume of choice. Dose evaluations were made using a RBE of 1.1 and the LET-dependent Wedenberg RBE model, together with estimates of normal tissue complication probabilities (NTCPs). In addition, the distributions of proton track-ends and dose-average LET (LET) were analyzed.

RESULTS

The TEopt plans reduced the mean LET in the critical structures studied by an average of 37% and increased the mean LET in the primary clinical target volume (CTV) by an average of 23%. This was achieved through a redistribution of the proton track-ends, concurrently keeping the physical dose distribution virtually unchanged compared to the DOSEopt plans. This resulted in substantial RBE-weighted dose (D) reductions, allowing the TEopt plans to meet all clinical goals for both RBE models and reduce the NTCPs by 0 to 19 percentage points compared to the DOSEopt plans, assuming the Wedenberg RBE model. The DOSEopt plans met all clinical goals assuming a RBE of 1.1 but failed 10 of 19 normal tissue goals assuming the Wedenberg RBE model.

CONCLUSIONS

Proton track-end objectives allow for LET reductions in critical structures without compromising the physical target dose. This approach permits the lowering of D and NTCP in critical structures, independent of the variable RBE model used, and it could be introduced in clinical practice without changing current protocols based on the constant RBE of 1.1.

摘要

目的

我们建议在强度调制质子治疗（IMPT）优化中使用质子射程末端目标，以降低关键结构中的线性能量转移（LET）和相对生物效应（RBE）。

方法与材料

针对 3 例颅内患者病例（30 次分割，每次 1.8 Gy（RBE））和 3 例头颈部患者病例（35 次分割，每次 2 Gy（RBE））生成了 IMPT 计划，假设 RBE 为 1.1 不变。为每位患者生成了两种计划：（1）仅物理剂量目标（DOSEopt）和（2）与 DOSEopt 计划相同的剂量目标，外加质子射程末端目标（TEopt）。射程末端目标惩罚质子在所选风险体积中停止。使用 RBE 为 1.1 的威登伯格 RBE 模型以及正常组织并发症概率（NTCP）的估计值进行剂量评估。此外，还分析了质子射程末端的分布和剂量平均 LET（LET）。

结果

与 DOSEopt 计划相比，TEopt 计划将研究中关键结构的平均 LET 降低了平均 37%，同时将主要临床靶体积（CTV）的平均 LET 增加了平均 23%。这是通过重新分配质子射程末端来实现的，同时与 DOSEopt 计划相比，物理剂量分布几乎保持不变。这导致 RBE 加权剂量（D）的大幅减少，使 TEopt 计划能够满足两种 RBE 模型的所有临床目标，并与 DOSEopt 计划相比，NTCP 降低了 0 至 19 个百分点，假设威登伯格 RBE 模型。假设 RBE 为 1.1，DOSEopt 计划满足了所有临床目标，但假设威登伯格 RBE 模型，10 个正常组织目标中有 10 个失败。