Hypofractionated FLASH-RT as an Effective Treatment against Glioblastoma that Reduces Neurocognitive Side Effects in Mice.
Hypofractionated FLASH-RT as an Effective Treatment against Glioblastoma that Reduces Neurocognitive Side Effects in Mice.
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DOI：
10.1158/1078-0432.ccr-20-0894
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发表时间：
2021-02-01
期刊：
影响因子：
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通讯作者：
Vozenin MC
中科院分区：
文献类型：
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作者：
Montay-Gruel P;Acharya MM;Gonçalves Jorge P;Petit B;Petridis IG;Fuchs P;Leavitt R;Petersson K;Gondré M;Ollivier J;Moeckli R;Bochud F;Bailat C;Bourhis J;Germond JF;Limoli CL;Vozenin MC
最近的数据表明，使用闪光放射治疗 (RT) 在不到十分之一秒的时间内对整个大脑进行单次照射，不会引起小鼠的神经认知缺陷。这一观察结果对于侵袭性和难治性脑肿瘤的治疗具有重要的临床意义，这些肿瘤涉及相对较大的照射量和高细胞毒性剂量。因此，我们的目的是使用充分表征的小鼠原位胶质母细胞瘤模型，同时研究 FLASH-RT 暴露 1 个月后的抗肿瘤功效和神经保护益处。由于分段放射治疗方案是胶质母细胞瘤治疗的标准治疗方法，因此我们采用分段剂量来同时验证 FLASH-RT 的神经保护作用和优化肿瘤治疗。 FLASH-RT 能够最大限度地减少辐射引起的脑毒性的能力归因于活性氧的减少，这引起了一些担忧，即这可能会导致抗肿瘤功效的丧失。我们的研究表明，对于所有测试的治疗方案来说，FLASH 和 CONV-RT 在延缓 GBM 生长方面均有效。此外，在接受大剂量神经毒性单剂量或大分割治疗方案后，发现只有 FLASH-RT 能够显着避免荷瘤动物的辐射引起的学习和记忆认知缺陷。目前的结果表明，采用大分割治疗方案进行的 FLASH-RT 能够使正常大脑免受辐射引起的毒性，而不会影响肿瘤的治愈。这一令人兴奋的功能为 FLASH-RT 的未来临床应用提供了初步框架。
Recent data has shown that single fraction irradiation delivered to the whole brain in less than tenths of a second using FLASH radiation therapy (RT), does not elicit neurocognitive deficits in mice. This observation has important clinical implications for the management of invasive and treatment-resistant brain tumors that involves relatively large irradiation volumes with high cytotoxic doses. Therefore, we aimed at simultaneously investigating the anti-tumor efficacy and neuroprotective benefits of FLASH-RT 1-month after exposure, using a well-characterized murine orthotopic glioblastoma model. As fractionated regimens of radiotherapy are the standard of care for glioblastoma treatment, we incorporated dose fractionation to simultaneously validate the neuroprotective effects and optimized tumor treatments with FLASH-RT. The capability of FLASH-RT to minimize the induction of radiation-induced brain toxicities has been attributed to the reduction of reactive oxygen species, casting some concern that this might translate to a possible loss of anti-tumor efficacy. Our study shows that FLASH and CONV-RT are iso-efficient in delaying GBM growth for all tested regimens. Furthermore, only FLASH-RT was found to significantly spare radiation-induced cognitive deficits in learning and memory in tumor bearing animals after the delivery of large neurotoxic single dose or hypo-fractionated regimens. The present results show that FLASH-RT delivered with hypo-fractionated regimens is able to spare the normal brain from radiation-induced toxicities without compromising tumor cure. This exciting capability provides an initial framework for future clinical applications of FLASH-RT.