Centre for Medical Radiation Physics, University of Wollongong, New South Wales, 2522, Australia.
Illawarra Health and Medical Research Institute, University of Wollongong, New South Wales, 2522, Australia.
Sci Rep. 2020 Jun 1;10(1):8833. doi: 10.1038/s41598-020-65729-z.
Synchrotron facilities produce ultra-high dose rate X-rays that can be used for selective cancer treatment when combined with micron-sized beams. Synchrotron microbeam radiation therapy (MRT) has been shown to inhibit cancer growth in small animals, whilst preserving healthy tissue function. However, the underlying mechanisms that produce successful MRT outcomes are not well understood, either in vitro or in vivo. This study provides new insights into the relationships between dosimetry, radiation transport simulations, in vitro cell response, and pre-clinical brain cancer survival using intracerebral gliosarcoma (9LGS) bearing rats. As part of this ground-breaking research, a new image-guided MRT technique was implemented for accurate tumor targeting combined with a pioneering assessment of tumor dose-coverage; an essential parameter for clinical radiotherapy. Based on the results of our study, we can now (for the first time) present clear and reproducible relationships between the in vitro cell response, tumor dose-volume coverage and survival post MRT irradiation of an aggressive and radioresistant brain cancer in a rodent model. Our innovative and interdisciplinary approach is illustrated by the results of the first long-term MRT pre-clinical trial in Australia. Implementing personalized synchrotron MRT for brain cancer treatment will advance this international research effort towards clinical trials.
同步加速器设施产生超高剂量率的 X 射线，当与微米大小的射束结合使用时，可以用于选择性癌症治疗。同步加速器微束辐射治疗（MRT）已被证明可以抑制小动物体内的癌症生长，同时保持健康组织的功能。然而，无论是在体外还是体内，产生成功的 MRT 结果的潜在机制都还没有得到很好的理解。本研究使用颅内成胶质肉瘤（9LGS）荷瘤大鼠，为了解剂量学、辐射传输模拟、体外细胞反应与临床前脑癌存活率之间的关系提供了新的见解。作为这项开创性研究的一部分，实施了一种新的图像引导 MRT 技术，以实现精确的肿瘤靶向，并开创性地评估了肿瘤剂量覆盖；这是临床放射治疗的一个重要参数。基于我们研究的结果，我们现在（第一次）可以在啮齿动物模型中呈现出侵袭性和耐辐射脑癌的体外细胞反应、肿瘤剂量-体积覆盖和 MRT 照射后存活之间的清晰和可重复的关系。我们的创新和跨学科方法通过澳大利亚首例长期 MRT 临床前试验的结果得到了说明。为脑癌治疗实施个性化的同步加速器 MRT 将推动这一国际研究努力走向临床试验。
