Institute of Anatomy, University of Bern, Switzerland.
Department of Obstetrics and Gynaecology, University of Melbourne, Royal Women's Hospital, Melbourne, Australia.
Int J Radiat Oncol Biol Phys. 2021 Dec 1;111(5):1276-1288. doi: 10.1016/j.ijrobp.2021.07.1717. Epub 2021 Aug 6.
In the past 3 decades, synchrotron microbeam radiation therapy (S-MRT) has been shown to achieve both good tumor control and normal tissue sparing in a range of preclinical animal models. However, the use of S-MRT for the treatment of lung tumors has not yet been investigated. This study is the first to evaluate the therapeutic efficacy of S-MRT for the treatment of lung carcinoma, using a new syngeneic and orthotopic mouse model.
Lewis Lung carcinoma-bearing mice were irradiated with 2 cross-fired arrays of S-MRT or synchrotron broad-beam (S-BB) radiation therapy. S-MRT consisted of 17 microbeams with a width of 50 µm and center-to-center spacing of 400 µm. Each microbeam delivered a peak entrance dose of 400 Gy whereas S-BB delivered a homogeneous entrance dose of 5.16 Gy (corresponding to the S-MRT valley dose).
Both treatments prolonged the survival of mice relative to the untreated controls. However, mice in the S-MRT group developed severe pulmonary edema around the irradiated carcinomas and did not have improved survival relative to the S-BB group. Subsequent postmortem examination of tumor size revealed that the mice in the S-MRT group had notably smaller tumor volume compared with the S-BB group, despite the presence of edema. Mice that were sham-implanted did not display any decline in health after S-MRT, experiencing only mild and transient edema between 4 days and 3 months postirradiation which disappeared after 4 months. Finally, a parallel study investigating the lungs of healthy mice showed the complete absence of radiation-induced pulmonary fibrosis 6 months after S-MRT.
S-MRT is a promising tool for the treatment of lung carcinoma, reducing tumor size compared with mice treated with S-BB and sparing healthy lungs from pulmonary fibrosis. Future experiments should focus on optimizing S-MRT parameters to minimize pulmonary edema and maximize the therapeutic ratio.
在过去的 30 年中，同步辐射微束放射治疗（S-MRT）已在一系列临床前动物模型中显示出良好的肿瘤控制和正常组织保护作用。然而，S-MRT 尚未用于治疗肺癌。本研究首次使用新的同源性和原位小鼠模型评估 S-MRT 治疗肺癌的疗效。
Lewis 肺癌荷瘤小鼠接受 2 个交叉照射的 S-MRT 或同步辐射宽束（S-BB）放射治疗。S-MRT 由 17 个宽度为 50μm、中心间距为 400μm 的微束组成。每个微束的峰值入口剂量为 400Gy，而 S-BB 则提供均匀的入口剂量 5.16Gy（相当于 S-MRT 谷剂量）。
两种治疗方法均延长了小鼠的生存期，与未治疗对照组相比。然而，S-MRT 组的小鼠在照射的癌周围发生严重的肺水肿，与 S-BB 组相比，其生存并未得到改善。随后对肿瘤大小的尸检检查显示，S-MRT 组的小鼠肿瘤体积明显小于 S-BB 组，尽管存在水肿。假植入的小鼠在接受 S-MRT 后健康状况没有下降，仅在照射后 4 天至 3 个月之间出现轻度和短暂的水肿，4 个月后消失。最后，一项平行研究调查了健康小鼠的肺部，显示 S-MRT 后 6 个月完全没有辐射引起的肺纤维化。
S-MRT 是治疗肺癌的一种很有前途的工具，与接受 S-BB 治疗的小鼠相比，可缩小肿瘤体积，使健康肺部免受肺纤维化的影响。未来的实验应侧重于优化 S-MRT 参数，以尽量减少肺水肿并最大限度地提高治疗比率。
