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（由适用提供）：全世界有175,000多名儿童每年被诊断出患有恶性肿瘤。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。但是，人们已经认识到，临床需要的射线照相分期程序可能会导致辐射引起的次要癌症以后的生命。这是迫切需要开发替代无辐射的分期测试。为了解决这个问题，该提案的总体目标是为癌症儿童的全身分期开发一种新的，无辐射的MR成像方法，并将该新的分期测试的诊断效率和准确性与基于18F-FDG-PET/CT的基于基于基于的成像测试的诊断效率和准确性。我们的MR分期考试依赖于全身扩散加权磁共振（WB-DW MR）成像和标签不使用铁补充铁氧基二醇作为MR成像的对比剂。我们的小组表明，由氧化铁纳米颗粒组成的铁氧基二醇可用作MR造影剂，因为这些纳米颗粒在MRI上提供了可测量的T1-和T2信号变化。我们假设，与基于18F-FDG-PET的成像测试相比，我们可以提供相等或改善癌症分期和重新分期的敏感性和特异性的富含铁氧基增强的WB-DW MR成像。最近，我们获得了FDA IND批准，以启动临床试验，以评估小儿患者的铁氧基增强MR成像程序。据我们所知，这是对Pediatri患者进行的首次研究，该研究将MR成像技术集成了用于肿瘤检测的技术（全身扩散）与MR成像技术的解剖学取向​​（Ferumoxytol增强T1加权图像），该技术是根据集成的18F-F-FDG PET/CT/CT cts cans的概念。 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与基于18F-FDG-PET的成像测试相比，肿瘤治疗反应评估的其他信息。这就是我们提出了一种高度创新的诊断工具，该工具应该使我们能够解决强制性诊断分期程序的难题和后来生活中继发性癌症的同时风险。通过开发这种新的成像测试并利用FDA批准的铁补充剂作为对儿童的对比剂，我们预计将建立定制的癌症分期协议，以针对我们小儿患者的特定需求，从而使大量患者群体免于从诊断诊断的评估中免于诊断的诊断风险，并最终消除了潜在的长期癌症的生命。