Facilitation ultRahigh dOse-rate aNd spaTIally-fractionatEd Radiotherapy (FRONTIER)

每年约有8万加拿大人死于癌症，这是我国死亡的主要原因，占死亡人数的30%。放射治疗，与手术和化疗一起，是三种最常见的治疗选择之一，但不幸的是，其疗效受到辐射副作用的限制。两种新的放射治疗技术——超高剂量率（FLASH）和空间分割放射治疗（SFRT）最近在实验室环境中显示出改善放射治疗结果的巨大希望。快闪放射治疗包括以亚秒间隔提供治疗剂量，比典型的一分钟治疗时间短得多。另一方面，SFRT是通过一组小光束而不是传统放射治疗中使用的均匀光束来传递的。通过在专门设备上进行的FLASH和SFRT小动物研究，已证明两种治疗方式都能减少放射治疗的副作用。例如，用FLASH照射的小鼠大脑与常规照射的小鼠大脑相比，几乎没有认知功能的退化。在多形性胶质母细胞瘤（一种侵袭性脑癌）大鼠模型上进行SFRT，结果使常规放疗后的平均生存时间从34天显著增加到170天。这两种新的放疗技术，尤其是FLASH，无疑是当前所有放疗研究的前沿，它们的临床应用是诱人的。不幸的是，在这两种放疗方式转化为癌症患者的临床益处之前，必须克服许多障碍。该计划的总体目标是通过以下方式加速FLASH和SFRT的临床转化：1)建立三个FLASH和/或SFRT系统，以便对这两种治疗方式进行广泛的临床前测试；2)为FLASH和SFRT治疗结果的客观机构间比较提供准确的剂量计算方法；3)开发用于实时FLASH和SFRT剂量测定的设备。在成功完成拟议的研究后，我们将为放射肿瘤学社区提供一些必要的工具，用于广泛的临床前测试和FLASH和SFRT的临床翻译。

Each year about 80,000 Canadians succumb to cancer, the leading cause of death in our country corresponding to 30% of deaths. Radiation therapy, along with surgery and chemotherapy, is one of the three most common treatment options, but unfortunately its efficacy is limited by radiation side effects. Two novel RT techniques - ultrahigh dose-rate (FLASH) and spatially-fractionated radiotherapy (SFRT) have recently shown great promise in improving outcomes of radiotherapy in a laboratory setting. FLASH radiotherapy consists of treatment dose delivery in sub-second intervals that are much shorter than the typical minute-long treatments. SFRT, on the other hand, is delivered with a set of small beams rather than with a uniform beam used in conventional radiotherapy. By means of FLASH and SFRT small animal studies performed on specialized equipment, reductions in radiotherapy side effects have been demonstrated for both treatment modalities. For example, mouse brains irradiated with FLASH experienced almost no cognitive function deterioration unlike mouse brains irradiated conventionally. SFRT performed on a rat model of glioblastoma multiforme, an aggressive form of brain cancer, resulted in a significantly increased mean survival from 34 days after conventional radiotherapy to 170 days. These two novel radiotherapy techniques, especially FLASH, are undoubtedly on the forefront of all current radiotherapy research and their translation to clinical use is tantalizing. Unfortunately, many obstacles must be overcome before these two radiotherapy modalities can be translated to the clinic for cancer patients' benefit. The overarching goal of this proposal is to accelerate the clinical translation of FLASH and SFRT by means of 1) building three FLASH and/or SFRT systems to enable widespread preclinical testing of these two treatment modalities, 2) providing accurate dose calculation methods for an objective interinstitutional comparison of FLASH and SFRT treatment outcomes and 3) developing equipment for real-time FLASH and SFRT dosimetry. Upon a successful completion of the proposed research, we will have provided the radiation oncology community with a number of necessary tools for widespread preclinical testing and clinical translation of FLASH and SFRT.