IMNC-UMR 8165, CNRS, Paris 7 and Paris 11 Universities, 15 rue Georges Clemenceau, 91406, Orsay Cedex, France.
Med Phys. 2018 Jun;45(6):2620-2627. doi: 10.1002/mp.12902. Epub 2018 Apr 19.
The alliance of charged particle therapy and the spatial fractionation of the dose, as in minibeam or Grid therapy, is an innovative strategy to improve the therapeutic index in the treatment of radioresistant tumors. The aim of this work was to assess the optimum irradiation configuration in heavy ion spatially fractionated radiotherapy (SFRT) in terms of ion species, beam width, center-to-center distances, and linear energy transfer (LET), information that could be used to guide the design of the future biological experiments. The nuclear fragmentation leading to peak and valley regions composed of different secondary particles, creates the need for a more complete dosimetric description that the classical one in SFRT.
Monte Carlo simulations (GATE 6.2) were performed to evaluate the dose distributions for different ions, beam widths, and spacings. We have also assessed the 3D-maps of dose-averaged LET and proposed a new parameter, the peak-to-valley-LET ratio, to offer a more thorough physical evaluation of the technique.
Our results show that beam widths larger than 400 μm are needed in order to keep a ratio between the dose in the entrance and the dose in the target of the same order as in conventional irradiations. A large ctc distance (3500 μm) would favor tissue sparing since it provides higher PVDR, it leads to a reduced contribution of the heavier nuclear fragments and a LET value in the valleys a factor 2 lower than the LET in the ctc leading to homogeneous distributions in the target.
Heavy ions MBRT provide advantageous dose distributions. Thanks to the reduced lateral scattering, the use of submillimetric beams still allows to keep a ratio between the dose in the entrance and the dose in the target of the same order as in conventional irradiations. Large ctc distances (3500 μm) should be preferred since they lead to valley doses composed of lighter nuclear fragments resulting in a much reduced dose-averaged LET values in normal tissue, favoring its preservation. Among the different ions species evaluated, Ne stands out as the one leading to the best balance between high PVDR and PVLR in normal tissues and high LET values (close to 100 keV/μm) and a favorable oxygen enhancement ratio in the target region.
带电粒子治疗与剂量空间分割(如微束或栅格治疗)的联合是一种创新策略,可以提高放射性抵抗肿瘤治疗的治疗指数。本工作的目的是评估重离子空间分割放射治疗(SFRT)中最优的照射配置,包括离子种类、束宽、中心到中心距离和线性能量传递(LET),这些信息可用于指导未来生物学实验的设计。核碎裂导致峰区和谷区由不同的次级粒子组成,这就需要更完整的剂量描述,而不仅仅是 SFRT 中的经典描述。
使用 Monte Carlo 模拟(GATE 6.2)来评估不同离子、束宽和间距的剂量分布。我们还评估了剂量平均 LET 的 3D 图谱,并提出了一个新的参数,即峰谷 LET 比,以提供对该技术更全面的物理评估。
我们的结果表明,为了保持与常规照射相同数量级的入口剂量与靶区剂量的比值,需要大于 400μm 的束宽。较大的 ctc 距离(3500μm)有利于组织保护,因为它提供了更高的 PVDR,减少了较重核碎片的贡献,并且在谷区的 LET 值比 ctc 低 2 倍,导致靶区中的剂量分布均匀。
重离子 MBRT 提供了有利的剂量分布。由于侧向散射减少,使用亚毫米束仍然可以保持与常规照射相同数量级的入口剂量与靶区剂量的比值。较大的 ctc 距离(3500μm)应该被优先考虑,因为它们导致谷区剂量由较轻的核碎片组成,从而导致正常组织中的剂量平均 LET 值大大降低,有利于其保护。在所评估的不同离子种类中,Ne 表现出在正常组织中高 PVDR 和低 PVLR 之间的最佳平衡,以及靶区中高 LET 值(接近 100keV/μm)和有利的氧增强比。