Medical Physics Research Program, Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba, Japan.
Radiat Res. 2013 Jul;180(1):44-59. doi: 10.1667/RR3178.1. Epub 2013 Jun 14.
Treatment plans of carbon-ion radiotherapy have been made on the assumption that the beams are delivered instantaneously irrespective to the dose delivery time as well as the interruption time. The advanced therapeutic techniques such as a hypofractionation and a respiratory gating usually require more time to deliver a fractioned dose than conventional techniques. The purpose of this study was to investigate the effects of dose-delivery time structure on biological effectiveness in carbon-ion radiotherapy. The rate equations defined in the microdosimetric kinetic model (MKM) for primary lesions caused in the DNA were reanalyzed and applied to continuous or interrupted irradiation with therapeutic carbon-ion beams. The rate constants characterizing the time of the primary nonlethal lesions to repair or to convert to lethal lesion were experimentally determined for human salivary gland (HSG) tumor cells. Treatment plans were made for a patient case on the assumption that the beam is delivered instantaneously. The RBE weighted absorbed doses of 2.65, 3.45 and 6.86 Gy (RBE) was prescribed to the target. These plans were recalculated by varying the dose delivery time and the interruption time ranging from 1-60 min based on the MKM with the determined parameters. The sum of rate constants for nonlethal lesion to repair a and to convert to lethal lesion c, (a + c), is 2.19 ± 0.40 h⁻¹. The biological effectiveness in the target decreases with the dose delivery time T in continuous irradiation compared to the planned one due to the repair of nonlethal lesions during the irradiation. The biological effectiveness in terms of equivalent acute dose decreases to 99.7% and 96.4% for T = 3 and 60 min in 2.65 Gy (RBE), 99.5% and 94.3% in 4.35 Gy (RBE), and 99.4% and 91.7% in 6.86 Gy (RBE), respectively. For all the cases, the decrease of biological effectiveness is larger at the proximal side with low-LET than the distal side with high-LET. Similar reductions of biological effectiveness with comparable amounts are observed in the interrupted irradiations with prolonged interruption time τ. For the fraction time, i.e., T and/or τ, shorter than 3 min, the decrease of the biological effectiveness with respect to the planned one is less than 1.0%. However, if the fraction time prolongs to 30 min or longer, the biological effectiveness is significantly influenced in carbon-ion radiotherapy, especially with high-prescribed doses. These effects, if confirmed by clinical studies, should be considered in designing the carbon-ion treatment planning.
碳离子放疗的治疗计划是假设射线是瞬间传输的，而不考虑剂量传输时间和中断时间。像分次剂量和呼吸门控这样的先进治疗技术通常需要比传统技术更长的时间来传输分次剂量。本研究的目的是研究剂量传输时间结构对碳离子放疗中生物效应的影响。对在 DNA 中引起的原发性损伤的微剂量动力学模型（MKM）中定义的速率方程进行了重新分析，并将其应用于连续或中断的治疗碳离子束照射。为了确定人唾液腺（HSG）肿瘤细胞中表征原发性非致死性损伤修复或转化为致死性损伤的时间的速率常数，进行了实验测定。基于 MKM 和确定的参数，针对假设射线瞬间传输的患者病例制定了治疗计划。将 2.65、3.45 和 6.86 Gy（RBE）的 RBE 加权吸收剂量规定给靶区。根据 MKM，基于所确定的参数，将这些计划基于剂量传输时间和中断时间从 1 到 60 分钟进行了重新计算。非致死性损伤修复的速率常数 a 和转化为致死性损伤的速率常数 c（a + c）之和为 2.19 ± 0.40 h⁻¹。与计划剂量相比，在连续照射下，由于照射过程中非致死性损伤的修复，靶区的生物效应随剂量传输时间 T 而降低。对于 2.65 Gy（RBE），T = 3 和 60 分钟时，等效急性剂量的生物效应降低到 99.7%和 96.4%；4.35 Gy（RBE）时，T = 3 和 60 分钟时，生物效应降低到 99.5%和 94.3%；6.86 Gy（RBE）时，T = 3 和 60 分钟时，生物效应降低到 99.4%和 91.7%。对于所有情况，低 LET 的近侧与高 LET 的远侧相比，生物效应的降低更大。在延长中断时间τ的中断照射中，观察到类似的具有可比性的生物效应的减少。对于分数时间（即 T 和/或τ）短于 3 分钟的情况，相对于计划的生物效应降低小于 1.0%。然而，如果分数时间延长至 30 分钟或更长，则碳离子放疗中的生物效应会受到显著影响，尤其是在高规定剂量的情况下。如果临床研究证实了这些影响，在设计碳离子治疗计划时应考虑这些影响。
