Conformal Total Body and Marrow Irradiation for Leukemia

白血病的适形全身和骨髓照射

• 批准号: 8707216
• 负责人: Susanta K Hui
• 金额: $ 30.39万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-13 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8707216
• 关键词: Acute leukemia; Age-Years; Anatomy; Body measure procedure; Bone Marrow; Bone Marrow Transplantation; Cause of Death; Cells; Clinical; Collaborations; Complex; Conduct Clinical Trials; Conflict (Psychology); Disease; Disease remission; Disorder by Site; Dose; Engraftment; Eye; Feasibility Studies; Goals; Heart; Hematologic Neoplasms; Hematological Disease; Hematopoietic; Image; Kidney; Lead; Liver; Low Dose Radiation; Lung; Marrow; Maximum Tolerated Dose; Measures; Methods; Mission; Monitor; Morbidity - disease rate; Motion; National Institute of Child Health and Human Development; Organ; Patients; Phase; Physicians; Principal Investigator; Process; Publishing; Radiation; Radiation Monitoring; Radiation Toxicity; Recurrence; Recurrent disease; Refractory; Regimen; Relapse; Research; Research Personnel; Risk; SECTM1 gene; Staging; Structure; Techniques; Testing; Therapeutic; Toxic effect; Translating; United States National Institutes of Health; Variant; Whole-Body Irradiation; Work; chemotherapy; disorder control; hematopoietic cell transplantation; high risk; improved; irradiation; killings; leukemia; mortality; multidisciplinary; novel; novel strategies; phase 2 study; prevent; skeletal; soft tissue

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）：由于高剂量照射的功效（即减少复发）和辐射引起的毒性之间的内在冲突，用于骨髓移植方案的传统全身照射（TBI）的进展已停滞了五十年。更具体地说，研究表明，较高剂量的辐射可以减少复发，但会增加对肺、心脏、眼睛、肝脏和肾脏等危险器官 (OAR) 的毒性。我们建议研究一种称为“适应性全身和骨髓照射”（适应性TBMI）的新技术的可行性。这种新方法具有三个明显的优势：1）结合图像引导断层放射治疗，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化地传递到各个器官； 2）监测给予患者的辐射剂量并调整后续治疗（根据需要）以达到规定剂量，也称为适应性过程； 3) 通过使用提高的疾病部位剂量与 OAR 和软组织剂量的治疗比率，允许更高的辐射剂量（剂量递增）而不增加毒性。这些优势将使临床试验确定在骨髓移植中安全有效的 TBMI 最大耐受剂量 (MTD) 成为可能。我们将使用自适应 TBMI 技术进行可行性试验，以：(i) 提供对身体运动和剂量输送准确性的了解； (ii) 通过适应性过程进行个体化治疗； (iii) 提高剂量递增的放射生物学精度。通过增强适应性 TBMI 的治疗比例而实现的剂量递增预计将提高疗效（即杀死白血病），而不会增加对健康器官的毒性。这项工作的中心假设是适应性TBMI的剂量递增是安全有效的，并为高危血液恶性肿瘤患者提供了治疗选择。我们将通过两个目标来检验这一假设：1) 通过进行 I 期剂量递增研究来确定 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) 通过测量来优化 TBMI 递送扫描仪内 3D 全身定位的准确性，测量 TBMI 剂量输送的准确性，并建立适应性 TBMI 治疗流程。患有晚期化疗难治性白血病（未能达到完全缓解的患者）的受试者（0-45 岁）将符合资格。这些患者的生存率非常低，大多数患者在数周至数月内死于疾病。如果成功，TBMI 可能通过更好的白血病控制提供比 TBI 显着的益处，因此预计将对晚期白血病和其他血液疾病患者产生重大影响。适应性 TBMI 具有更好的疾病控制、减少疾病复发和提高患者生存率的潜力，这与 NIH 既定的科学使命一致。