Personalized Whole Body Staging for Children with Cancer: A Solution to the Conundrum of Long-Term Side Effects from CT and PET/CT Scans

癌症儿童的个性化全身分期：解决 CT 和 PET/CT 扫描长期副作用难题的解决方案

• 批准号: 8847952
• 负责人: Heike Elizabeth Daldrup-Link
• 金额: $ 50.37万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-04-01 至 2020-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8847952
• 关键词: Adult; Adverse effects; Blood Vessels; Bone Marrow; Bone Tissue; Child; Childhood; Clinical Trials; Contrast Media; Data; Detection; Development; Diagnosis; Diagnostic; Diagnostic Neoplasm Staging; Diffusion; Diffusion Magnetic Resonance Imaging; Dose; Evaluation; FDA approved; Goals; Histopathology; Image; Imaging Techniques; Incidence; Intravenous; Iron Compounds; Label; Life; Liver; Lymphoma; Magnetic Resonance; Magnetic Resonance Imaging; Malignant - descriptor; Malignant Childhood Neoplasm; Malignant Neoplasms; Malignant neoplasm of brain; Measurable; Organ; Organic Iron Compounds; PET/CT scan; Patient Care; Patients; Pediatric Hospitals; Pediatric Neoplasm; Phagocytes; Population; Positron-Emission Tomography; Problem Solving; Procedures; Protocols documentation; Protons; Radiation; Reference Standards; Reporting; Reticuloendothelial System; Risk; Scanning; Second Primary Cancers; Sensitivity and Specificity; Signal Transduction; Solutions; Spleen; Staging; Technology; Testing; Time; Tumor Tissue; Tumor stage; Weight; X-Ray Computed Tomography; alpha-Thalassemia; base; chemotherapy; cost effective; diagnostic accuracy; diffusion weighted; ferumoxytol; fluorodeoxyglucose positron emission tomography; health care economics; improved; innovation; intravenous injection; iron deficiency; iron oxide; iron supplement; lymph nodes; nanoparticle; older patient; patient population; pediatric patients; public health relevance; radiation effect; radiotracer; response; sarcoma; soft tissue; tool; tumor; uptake

 DESCRIPTION (provided by applicant): More than 175,000 children worldwide are diagnosed with malignant tumors every year. CT and radiotracer- based imaging tests are essential for tumor staging in these patients. However, it has been recognized that clinically needed radiographic staging procedures may cause radiation-induced secondary cancers later in life. Thus, there is an urgent need for the development of alternative radiation-free staging tests. In order to solve this problem, the overall goal of this proposal is to develop a new, radiation free MR imaging approach for whole body staging of children with cancer and to compare the diagnostic efficacy and accuracy of this new staging test with 18F-FDG-PET/CT based imaging tests. Our MR staging exam relies on whole body diffusion-weighted magnetic resonance (WB-DW MR) imaging and off-label use of the iron supplement ferumoxytol as a contrast agent for MR imaging. Our group has shown that ferumoxytol, which is composed of iron oxide nanoparticles, can be used as an MR contrast agent, as these nanoparticles provide measurable T1- and T2-signal changes on MRI. We hypothesize that ferumoxytol-enhanced WB-DW MR imaging will provide equal or improved sensitivities and specificities for cancer staging and re-staging compared to 18F-FDG-PET based imaging tests. We recently received FDA IND approval to initiate clinical trials for evaluation of ferumoxytol-enhanced MR imaging procedures in pediatric patients. To the best of our knowledge, this is the first study in pediatri patients that integrates an MR imaging technique for tumor detection (whole body diffusion) with an MR imaging technique for anatomical orientation (ferumoxytol- enhanced T1-weighted images), in accordance with the concept of integrated 18F-FDG PET/CT scans. In our pursuit of an improved and immediately clinically applicable imaging approach for comprehensive one-stop cancer staging in children, we will first optimize our imaging protocol for ferumoxytol-enhanced WB-DW MR scans, then compare the diagnostic value of this new staging test with 18F-FDG-PET/CT and 18F-FDG-PET/MR procedures and finally, determine if ferumoxytol-enhanced WB-DW MRI can provide equal or additional information for tumor therapy response assessment compared to 18F-FDG-PET based imaging tests. Thus, we propose a highly innovative diagnostic tool that should enable us to solve the conundrum of mandatory diagnostic staging procedures and concurrent risk of secondary cancer later in life. By developing this new imaging test and exploiting an FDA-approved iron supplement as a contrast agent for children via an off-label use, we anticipate to establish customized cancer staging protocols towards the specific needs of our pediatric patients, saving a large patient population from radiation exposure from diagnostic staging evaluations, and ultimately, eliminating associated risks of potential long-term secondary cancer development later in life.

 描述（由申请人提供）：全世界每年有超过 175,000 名儿童被诊断患有恶性肿瘤。基于 CT 和放射性示踪剂的成像测试对于这些患者的肿瘤分期至关重要。然而，人们已经认识到，临床所需的放射照相分期程序可能会在以后的生活中导致辐射诱发的继发性癌症。因此，迫切需要开发替代的无辐射分期测试。为了解决这个问题，本提案的总体目标是开发一种新的无辐射 MR 成像方法，用于癌症儿童的全身分期，并将这种新分期测试与基于 18F-FDG-PET/CT 的成像测试的诊断功效和准确性进行比较。我们的 MR 分期检查依赖于全身弥散加权磁共振 (WB-DW MR) 成像以及标签外使用铁补充剂 ferumoxytol 作为 MR 成像造影剂。我们的团队已经证明，由氧化铁纳米粒子组成的费鲁莫托可以用作 MR 造影剂，因为这些纳米粒子在 MRI 上提供可测量的 T1 和 T2 信号变化。我们假设，与基于 18F-FDG-PET 的成像测试相比，ferumoxytol 增强的 WB-DW MR 成像将为癌症分期和重新分期提供相同或更高的敏感性和特异性。我们最近获得了 FDA IND 批准，可以启动临床试验，以评估儿科患者的 ferumoxytol 增强 MR 成像程序。据我们所知，这是第一项针对儿科患者的研究，根据集成 18F-FDG PET/CT 扫描的概念，将用于肿瘤检测（全身扩散）的 MR 成像技术与用于解剖定位的 MR 成像技术（ferumoxytol 增强 T1 加权图像）相结合。为了寻求一种改进的、立即临床适用的儿童综合一站式癌症分期成像方法，我们将首先优化我们的 Ferumoxytol 增强 WB-DW MR 扫描成像方案，然后将这种新分期测试的诊断价值与 18F-FDG-PET/CT 和 18F-FDG-PET/MR 程序进行比较，最后确定 ferumoxytol 增强 WB-DW MRI 是否可以提供同等的诊断价值。 或与基于 18F-FDG-PET 的成像测试相比的肿瘤治疗反应评估的其他信息。因此，我们提出了一种高度创新的诊断工具，它应该使我们能够解决强制性诊断分期程序和晚年继发性癌症并发风险的难题。通过开发这种新的成像测试，并通过标签外使用，利用 FDA 批准的铁补充剂作为儿童造影剂，我们期望针对儿科患者的特定需求制定定制的癌症分期方案，使大量患者群体免受诊断分期评估中的辐射暴露，并最终消除晚年潜在的长期继发性癌症发展的相关风险。