Simultaneous dose and dose rate optimization for clinical FLASH proton radiotherapy

临床FLASH质子放疗的同步剂量和剂量率优化

• 批准号: 10443225
• 负责人: Hao Gao
• 金额: $ 50.38万
• 依托单位: UNIVERSITY OF KANSAS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-01 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10443225
• 关键词: Address; Animals; Award; Biology; Cancer Patient; Characteristics; Clinical; Clinical Research; Clinical Trials; Dose; Dose-Rate; Effectiveness; Future; Gold; Intensity modulated proton therapy; Joints; Location; Lung; Methods; Modality; Modeling; Nature; Normal tissue morphology; Outcome; Paper; Patients; Physics; Positioning Attribute; Protons; Quality of life; Radiation; Radiation Dose Unit; Radiation therapy; Radiobiology; Structure; System; Technology; Testing; Time; Toxic effect; Translations; Uncertainty; Validation; Work; cancer cell; cancer radiation therapy; clinical translation; dosimetry; high risk; improved; industry partner; innovation; irradiation; lung volume; novel; pre-clinical; predictive modeling; preservation; prospective; proton beam; radiation risk; response; transmission process; treatment planning; treatment site; tumor; verification and validation

Project Summary The irradiation at ultra-high dose rates, namely FLASH-RT, can substantially reduce normal-tissue toxicities while maintaining tumor response (so-called the FLASH effect), compared with the irradiation at conventional dose rates (CONV-RT). Although many preclinical and some clinical studies demonstrated the potential benefit of FLASH-RT, the effectiveness of FLASH-RT for general cancer patients is to be further validated through clinical trials. By far the only commercially available system that can deliver ultra-high dose rates needed for general- purpose clinical FLASH-RT is the proton modality, such as our IBA system. However, the state-of-the-art treatment planning method, i.e., intensity modulated proton therapy (IMPT), only optimizes the dose and does not directly optimize the dose rate or the FLASH effect. A missing prerequisite for proton FLASH-RT clinical trials is a compatible treatment planning method with FLASH optimization capability. The key innovation and enabling technology in this project for clinical FLASH-RT is the first-of-its-kind FLASH optimization engine via SDDRO, which was recently recognized by PTCOG 59 as the Michael Goitein Best Abstract Award in Physics for its innovation and impact for FLASH-RT (Gao et al 2021). To the best of our knowledge, SDDRO is the only method that can optimize the FLASH dose rate as well as the dose. Our preliminary work (Gao et al 2020) for lung patients has demonstrated that, compared with IMPT, SDDRO substantially improved the FLASH-dose-rate coverage (in order to have the FLASH effect for reducing normal- tissue toxicities) while preserving the dose coverage, e.g., increasing of the target-surrounding volume receiving ≥40Gy/s from ~40% to at least 98%, and the lung volume receiving ≥40Gy/s from ~30% to ~80%, which occurred at high-dose and high-uncertainty locations with high-risk radiation-induced toxicities. Such improved FLASH coverage is especially critical for reducing normal tissue toxicities given the hypofractionation nature of FLASH-RT. Given our innovative SDDRO, IBA proton machine with ultra-high-dose-rate capability, academic-industrial partnership with IBA, FLASH radiobiology and dosimetry expertise, we are uniquely positioned to develop novel SDDRO methods with FLASH optimization capability that is currently unavailable and urgently needed for clinical FLASH-RT, including (1) general SDDRO methods with realistic FLASH models, machine characteristics, and delivery mechanisms (transmission beams, conformal energy filters, or joint); (2) translation of SDDRO methods into our IBA system, with end-to-end validation and verified FLASH dosimetry. The completion of this project will render novel SDDRO methods with FLASH optimization capability that is currently unavailable and urgently needed for clinical FLASH-RT, and set the stage for FLASH animal studies and clinical trials.

项目摘要 超高剂量率的辐射，即闪存-RT，可以大大降低正常组织的毒性 在保持肿瘤反应（所谓的闪光效应）的同时，与常规的照射相比 剂量率（Cons-RT）。尽管许多临床前和一些临床研究表明了潜在的好处 在闪存中，应通过 临床试验。 到目前为止，唯一可以提供一般剂量率的市售系统 目的临床闪存-RT是质子模式，例如我们的IBA系统。但是，最新的 治疗计划方法，即强度调节质子治疗（IMPT），仅优化剂量并做 不直接优化剂量率或闪光效应。缺少质子闪存RT临床的先决条件 试验是具有闪光优化能力的兼容治疗计划方法。 该项目的临床闪存RT项目的关键创新和促成技术是首先 SDRO通过SDDRO的闪存优化引擎，该引擎最近被PTCOG 59识别为Michael Goitein 物理学的最佳摘要奖因其对Flash-RT的创新和影响（Gao等，2021）。尽我们所能 知识，SDDRO是唯一可以优化闪光剂量速率和剂量的方法。我们的 肺患者的初步工作（Gao等，2020年）已经证明，与Impt相比 大大改善了闪光剂量覆盖范围（为了降低正常的闪光效应 组织毒性）在保留剂量覆盖范围时，例如增加目标量的体积 从〜40％到至少98％的收到≥40GY/s，肺体积≥40GY/s从〜30％到〜80％， 这发生在高剂量和高度确定性位置，具有高风险辐射引起的毒性。 改善闪光覆盖范围对于降低正常组织毒性尤其重要 Flash-rt的性质。 鉴于我们具有超高剂量评估能力的创新性SDDRO，IBA质子机器，学术工业 与IBA，Flash放射性生物学和剂量学专业知识的合作伙伴关系，我们有独特的位置 具有闪光优化功能的新型SDDRO方法目前不可用，急需 对于临床闪存-RT，包括（1）具有现实闪光模型的一般SDDRO方法，机器 特性和递送机制（传输梁，保形能量过滤器或关节）； （2） 将SDDRO方法转换为我们的IBA系统，并具有端到端验证和经过验证的Flash剂量计。 该项目的完成将渲染具有闪光优化能力的新颖SDDRO方法 目前无法获得临床闪存RT，并迫切需要，并为闪光动物研究奠定了基础 和临床试验。