PDF(Pubmed)
Abstract：
Ultra-high dose-rate \'FLASH\' radiotherapy may be a pivotal step forward for cancer treatment, widening the therapeutic window between radiation tumour killing and damage to neighbouring normal tissues. The extent of normal tissue sparing reported in pre-clinical FLASH studies typically corresponds to an increase in isotoxic dose-levels of 5-20%, though gains are larger at higher doses. Conditions currently thought necessary for FLASH normal tissue sparing are a dose-rate ≥40 Gy s-1, dose-per-fraction ≥5-10 Gy and irradiation duration ≤0.2-0.5 s. Cyclotron proton accelerators are the first clinical systems to be adapted to irradiate deep-seated tumours at FLASH dose-rates, but even using these machines it is challenging to meet the FLASH conditions. In this review we describe the challenges for delivering FLASH proton beam therapy, the compromises that ensue if these challenges are not addressed, and resulting dosimetric losses. Some of these losses are on the same scale as the gains from FLASH found pre-clinically. We therefore conclude that for FLASH to succeed clinically the challenges must be systematically overcome rather than accommodated, and we survey physical and pre-clinical routes for achieving this.
摘要：
超高剂量率“FLASH”放疗可能是癌症治疗的关键一步，扩大辐射肿瘤杀伤和邻近正常组织损伤之间的治疗窗口。临床前FLASH研究中报告的正常组织保留的程度通常对应于5-20%的等氧剂量水平的增加，虽然在较高剂量下增益更大。目前认为FLASH正常组织保留所必需的条件是剂量率≥40Gys-1，剂量/分数≥5-10Gy，照射持续时间≤0.2-0.5s。回旋加速器质子加速器是第一个适合以FLASH剂量率照射深层肿瘤的临床系统，但即使使用这些机器，满足FLASH条件也是具有挑战性的。在这篇综述中，我们描述了提供FLASH质子束治疗的挑战，如果这些挑战得不到解决，随之而来的妥协，并导致剂量学损失。这些损失中的一些与临床前发现的FLASH的收益相同。因此，我们得出结论，要使FLASH在临床上取得成功，必须系统地克服而不是适应挑战，我们调查了实现这一目标的物理和临床前途径。
