Conformal Total Body and Marrow Irradiation for Leukemia

白血病的适形全身和骨髓照射

• 批准号: 9283278
• 负责人: Susanta K Hui
• 金额: $ 21万
• 依托单位: BECKMAN RESEARCH INSTITUTE/CITY OF HOPE
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-06-01 至 2017-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9283278
• 关键词: Conformal; Total; Body; Marrow; Irradiation

DESCRIPTION (provided by applicant): Advances in conventional total body irradiation (TBI) used for bone marrow transplant regimens have been stalled for five decades due to the inherent conflict between the efficacy of high dose irradiation (i.e., reduced relapse) and radiation induced toxicity. More specifically, studies show that higher doses of radiation reduce relapse, but increase toxicity to organs at risk (OAR) including the lungs, heart, eyes, liver, and kidneys. We propose to study the feasibility of a novel technique called "adaptive total body and marrow irradiation" (adaptive TBMI). This new approach has three clear advantages: 1) Incorporation of image guided tomotherapy that allows "focused radiation" to be delivered to the target (bone marrow and other disease sites), thereby differentially delivering doses of radiation to various organs; 2) Monitoring of radiation dose delivered to the patients and adjustment of subsequent treatments (as needed) to achieve the prescribed dose, also known as the adaptive process; and, 3) Allowance for higher radiation doses (dose escalation) without increasing toxicity by using an enhanced therapeutic ratio of dose to disease sites versus dose to OARs and soft tissues. These advantages will make it possible to conduct clinical trials to determine a safe and efficacious maximum tolerated dose (MTD) of TBMI in the setting bone marrow transplant. We will conduct a feasibility trial, using adaptive TBMI techniques to: (i) provide an understanding of body motion and the accuracy of dose delivery; (ii) individualize treatment through the adaptive processes; and, (iii) improving radiobiological precision of dose escalation. The dose escalation available through the enhanced therapeutic ratio of adaptive TBMI is expected to increase efficacy (i.e. leukemia kill) without increased toxicity to healthy organs. The central hypothesis of this work is that the dose escalation of adaptive TBMI is safe and efficacious, and provides a treatment option to patients with high risk hematological malignancies. We will test this hypothesis through two aims: 1) To Determine the maximum radiation dose of TBMI by performing a phase I dose escalation study and to estimate the efficacy of this approach in a phase II study, and 2) To optimize TBMI delivery by measuring the accuracy of 3D whole body localization within the scanner, measuring the accuracy of the TBMI dose delivery, and establishing an adaptive TBMI therapy process. Subjects (0-45 years of age) with advanced, chemotherapy refractory leukemia (those who fail to achieve complete remission) will be eligible. These patients have very poor survival, with most dying from their disease within weeks to months. If successful, TBMI may offer significant benefits over TBI through better leukemia control and thus, is expected to have a significant impact on patients with advanced leukemia and other hematologic diseases. Adaptive TBMI has the potential for better disease control, reduced disease recurrence and increased patient survival, consistent with the well-established NIH scientific mission.

描述（由申请人提供）：用于骨髓移植方案的常规总体辐照（TBI）的进展已停滞了五十年，这是由于高剂量辐照的疗效（即减少复发）和辐射诱导的毒性之间的固有冲突。更具体地说，研究表明，较高剂量的辐射减少了复发，但会增加对处于风险的器官（包括肺，心脏，眼睛，肝脏和肾脏）的毒性。我们建议研究一种称为“自适应总体和骨髓照射”（自适应TBMI）的新技术的可行性。这种新方法具有三个明显的优势：1）纳入图像指导性的体疗法，该疗法允许将“聚焦辐射”传递到目标（骨髓和其他疾病部位），从而将辐射剂量差异为各种器官； 2）监测给患者输送的辐射剂量并调整后续治疗（根据需要），以达到规定的剂量，也称为适应过程； 3）允许较高的辐射剂量（剂量升级），而不会通过使用剂量与疾病部位的治疗比增强的毒性与剂量与桨和软组织的毒性增加。这些优点将使进行临床试验以确定TBMI在设置骨髓移植中的安全有效的最大耐受剂量（MTD）。我们将使用自适应TBMI技术进行可行性试验：（i）提供对身体运动和剂量递送准确性的理解； （ii）通过自适应过程个性化治疗； （iii）提高剂量升级的放射生物学精度。通过自适应TBMI的治疗比率提高可获得的剂量升级预计将提高疗效（即白血病杀死），而不会增加对健康器官的毒性。这项工作的核心假设是自适应TBMI的剂量升级是安全有效的，并为高风险血液学恶性肿瘤的患者提供了治疗选择。我们将通过两个目的测试这一假设：1）通过执行I期剂量升级研究的最大辐射剂量来确定TBMI的最大辐​​射剂量，并在II期研究中估计该方法的功效，以及2）2）通过测量Scanner中3D全体定位的准确性，以测量TBMI疗法的准确性，并在TBMI剂量的过程中测量3D全体定位的准确性，并建立了TBMI剂量的精度。患有晚期，化学疗法难治性白血病（未能完全缓解的人）的受试者（0-45岁）符合条件。这些患者的生存率很差，大多数患者在数周内到几个月内死于疾病。如果成功，TBMI可能会通过更好的白血病控制对TBI提供显着的好处，因此，预计将对患有晚期白血病和其他血液学疾病的患者产生重大影响。自适应TBMI具有更好的疾病控制，疾病复发减少和患者生存的潜力，与已建立的NIH科学任务一致。