对生物终点变异性的系统分析以及FLASH节约效应的定量建模的影响
Isabella Colizzi1,2, Mathilde Toschini1,2, Antony J Lomax1,2
1Center for Proton Therapy, Paul Scherrer Institut, 5232 Villigen, PSI, Switzerland.
超高剂量率 (UHDR) 放射疗法,或FLASH,显示出有希望的结果,但临床前数据的差异很大. 对终点的标准化对于开发预测模型和推进FLASH放射治疗应用至关重要.
科学领域:
- 辐射瘤学 辐射瘤学
- 临床前研究 临床前研究
- 量化建模 量化建模
背景情况:
- 超高剂量率 (UHDR) 放射治疗,称为FLASH,提供了改善正常组织节约和瘤控制的潜力.
- 在临床前FLASH实验中存在显著的异质性,阻碍了交叉研究比较和预测模型开发.
研究的目的:
- 在临床前FLASH放射治疗研究中识别终点和方法的变异性.
- 澄清未来定量建模所必需的不一致性和知识差距.
- 引导FLASH研究中的生物终点和实验方法的标准化.
主要方法:
- 从1966年到2024年进行的in-vivo质子和电子FLASH小鼠实验的系统审查.
- 对常见报告的终点进行定性和定量分析,包括密室细胞比率,存活率,脱皮率和认知测试.
- 后勤回归分析,以评估影响FLASH效应的参数在可比终点子集上的参数.
主要成果:
- 审查了50篇论文,揭示了终点选择,时间和方法的实质性异质性.
- 由于方法上的差异,有限数量的终点 (四个) 适合进行交叉研究分析.
- 逻辑回归分析受到参数对线性限制,表明实验异质性和缺乏协调性.
结论:
- 在临床前FLASH研究中迫切需要标准化生物终点和方法.
- 在FLASH数据中量化变异性和识别可比终点对于未来的建模至关重要.
- 这项工作为将生物证据与FLASH放射治疗治疗规划的定量方法相结合提供了指导.
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