Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.
Department of Accelerator and Medical Physics, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan.
Int J Radiat Oncol Biol Phys. 2019 Sep 1;105(1):222-229. doi: 10.1016/j.ijrobp.2019.05.004. Epub 2019 May 11.
The biological effectiveness of proton beams may decrease with irradiation time because of sublethal damage repair (SLDR). The purpose of this study is to systematically evaluate this effect in hypofractionated proton therapy for various target sizes, depths, and prescribed doses per fraction.
Plans with a single spread-out Bragg peak beam were created using a constant relative biological effectiveness (RBE) of 1.1 to cover targets of 6 different sizes located at 3 different depths in water. Biological doses of 2, 3, 5, 10, and 20 Gy (RBE) were prescribed to the targets. First, to investigate the depth variation of the biological effectiveness, the biological dose in instantaneous irradiation was recalculated based on the microdosimetric kinetic model. SLDR was then taken into account in the microdosimetric kinetic model during treatments to obtain the irradiation time-dependent biological effectiveness for irradiation time T of 5 to 60 minutes and beam interruption time τ of 0 to 60 minutes. The tumor control probabilities were calculated for single-fraction proton therapy fields of different Ts and τs, and the curative doses were evaluated at a tumor control probability of 90%.
The biological effectiveness decreased with longer T and τ and higher prescribed dose. The maximum decrease in the biological effectiveness was 21% with a 20 Gy (RBE) prescribed dose. In single-fraction proton therapy, the curative dose increased linearly by approximately 33% to 35% with the increase of T from 0 to 60 minutes.
The biological effectiveness varies largely with T and τ because of SLDR during treatments. This effect was pronounced for high prescribed doses per fraction. Thus, the effect of SLDR needs to be considered in hypofractionated and single-fraction proton therapies in relation to size and depth of the target.
由于亚致死损伤修复（SLDR），质子束的生物学效应可能会随照射时间的延长而降低。本研究的目的是系统地评估在各种靶大小、深度和分次剂量下，这种效应在质子少分次治疗中的作用。
使用恒定的相对生物学效应（RBE）为 1.1 来创建具有单个扩展布拉格峰的计划，以覆盖位于水中 3 个不同深度的 6 个不同大小的靶标。将 2、3、5、10 和 20 Gy（RBE）的生物学剂量规定给靶标。首先，为了研究生物学效应的深度变化，根据微剂量动力学模型重新计算瞬时照射的生物学剂量。然后，在微剂量动力学模型中考虑 SLDR，以获得 T 为 5 至 60 分钟和中断时间τ为 0 至 60 分钟的照射时间相关的生物学效应。计算了不同 Ts 和τs 的单分次质子治疗场的肿瘤控制概率，并在肿瘤控制概率为 90%的情况下评估了治愈剂量。
生物学效应随 T 和τ的延长以及规定剂量的增加而降低。在规定剂量为 20 Gy（RBE）时，生物学效应的最大降低幅度为 21%。在单次质子治疗中，随着 T 从 0 分钟增加到 60 分钟，治愈剂量线性增加约 33%至 35%。
由于治疗过程中的 SLDR，生物学效应随 T 和τ而变化很大。这种效应在高剂量分次时更为明显。因此，在与靶标大小和深度相关的少分次和单次质子治疗中，需要考虑 SLDR 的影响。
