Title: Quality assurance and reporting for FLASH clinical trials:the experience of the FEATHER trial Show Chinese title

Title: FLASH临床试验的质量保证和报告：FEATHER试验的经验

Abstract: Research on ultra-high dose rate (UHDR) radiation therapy has indicated its potential to spare normal tissue while maintaining equivalent tumor control compared to conventional treatments. First clinical trials are underway. The randomized phase II/III FEATHER clinical trial at the Paul Scherrer Institute in collaboration with the University of Zurich Animal Hospital is one of the first curative domestic animal trials to be attempted, and it is designed to provide a good example for human trials. However, the lack of standardized quality assurance (QA) guidelines for FLASH clinical trials presents a significant challenge in trial design. This work aims to demonstrate the development and testing of QA and reporting procedures implemented in the FEATHER clinical trial. We have expanded the clinical QA program to include UHDR-specific QA and additional patient-specific QA. Furthermore, we have modified the monitor readout to enable time-resolved measurements, allowing delivery log files to be used for dose and dose rate recalculations. Finally, we developed a reporting strategy encompassing relevant parameters for retrospective studies. We evaluated our QA and reporting procedures with simulated treatments. This testing confirmed that our QA procedures effectively ensure the correct and safe delivery of the planned dose. Additionally, we demonstrated that we could reconstruct the delivered dose and dose rate using the delivery log files. We developed and used in practice a comprehensive QA and reporting protocol for a FLASH clinical trial at the Paul Scherrer Institute. This work aims to establish guidelines and standardize reporting practices for future advancements in the FLASH-RT field. Show Chinese abstract

Abstract: 超高剂量率（UHDR）放射治疗的研究表明，与传统治疗相比，它在保持同等肿瘤控制的同时，具有保护正常组织的潜力。 首次临床试验正在进行中。 由保罗谢勒研究所与苏黎世大学动物医院合作进行的随机II/III期FEATHER临床试验是首批尝试的治愈性宠物动物试验之一，旨在为人类试验提供良好的范例。 然而，FLASH临床试验缺乏标准化的质量保证（QA）指南，这在试验设计中构成了重大挑战。 本研究旨在展示在FEATHER临床试验中实施的QA和报告程序的开发和测试。 我们扩大了临床QA计划，以包括UHDR特定的QA和额外的患者特定QA。 此外，我们修改了监测读数，以实现时间分辨测量，使交付日志文件可用于剂量和剂量率的重新计算。 最后，我们制定了一种涵盖回顾性研究相关参数的报告策略。 我们通过模拟治疗评估了我们的QA和报告程序。 这种测试证实了我们的QA程序能够有效确保计划剂量的正确和安全输送。 此外，我们展示了可以使用交付日志文件重建输送的剂量和剂量率。 我们在保罗谢勒研究所开发并实际应用了一个全面的FLASH临床试验QA和报告协议。 本研究旨在为FLASH-RT领域未来的进展建立指南并标准化报告实践。