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: 10632126
• 负责人: Hao Gao
• 金额: $ 48.11万
• 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/10632126
• 关键词: Address; Animals; Award; Biology; Cancer Patient; Characteristics; Clinical; Clinical Research; Clinical Trials; Dose; Dose Rate; Effectiveness; Future; 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; Therapy Clinical Trials; Time; Toxic effect; Translations; Uncertainty; Validation; Work; cancer cell; cancer radiation therapy; clinical translation; conventional dosing; 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.

项目概要 超高剂量率照射，即FLASH-RT，可大幅降低正常组织毒性 与传统的照射相比，在保持肿瘤反应（所谓的闪光效应）的同时 尽管许多临床前和一些临床研究证明了潜在的益处。 FLASH-RT的应用，FLASH-RT对于一般癌症患者的有效性有待进一步验证 临床试验。 迄今为止，唯一可以提供一般所需超高剂量率的商用系统 目的临床 FLASH-RT 是质子模式，例如我们最先进的 IBA 系统。 治疗计划方法，即调强质子治疗（IMPT），仅优化剂量并且不 不能直接优化剂量率或 FLASH 效果，这是质子 FLASH-RT 临床缺失的先决条件。 试验是一种具有 FLASH 优化功能的兼容治疗计划方法。 该临床FLASH-RT项目的关键创新和使能技术是同类首创 通过 SDDRO 的 FLASH 优化引擎，最近被 PTCOG 59 认可为 Michael Goitein 因其对 FLASH-RT 的创新和影响而获得物理学最佳抽象奖（Gao 等人，2021 年）。 据了解，SDDRO 是唯一可以优化 FLASH 剂量率以及我们的剂量的方法。 针对肺部患者的初步工作（Gao et al 2020）表明，与 IMPT 相比，SDDRO 显着提高了 FLASH 剂量率覆盖范围（以便具有 FLASH 效果以减少正常剂量率） 组织毒性），同时保持剂量覆盖范围，例如增加目标周围体积 接受≥40Gy/s从~40%到至少98%，并且接受≥40Gy/s的肺体积从~30%到~80%， 发生在高剂量和高不确定性的地点，具有高风险辐射引起的毒性。 鉴于大分割，改善 FLASH 覆盖对于减少正常组织毒性尤其重要 FLASH-RT 的本质。 鉴于我们创新的 SDDRO、IBA 质子机具有超高剂量率能力，学术工业 与 IBA、FLASH 放射生物学和剂量学专业知识合作，我们拥有独特的优势来开发 目前尚不可用且急需的具有FLASH优化能力的新型SDDRO方法 用于临床 FLASH-RT，包括 (1) 具有真实 FLASH 模型的通用 SDDRO 方法、机器 特性和传输机制（传输光束、保形能量滤波器或接头）； 将 SDDRO 方法转换到我们的 IBA 系统中，并进行端到端验证和经过验证的 FLASH 剂量测定。 该项目的完成将提供具有FLASH优化能力的新颖SDDRO方法，即 目前临床 FLASH-RT 尚不可用且迫切需要，并为 FLASH 动物研究奠定了基础 和临床试验。