FDG-PET/CT in the evaluation of persistent febrile neutropenia in cancer patients

描述(申请人提供)：尽管在评估和治疗导致癌症患者中性粒细胞减少症的感染方面取得了许多进展，但它仍然是癌症治疗的常见并发症，并占与化疗相关的死亡的大部分。我们由肿瘤学家、传染病专家、成像师和生物统计学家组成的跨学科小组的最终目标是进行一项大型、前瞻性、多中心试验，以确定PET/CT使用广泛可用的葡萄糖类似物[18F]氟-2-脱氧-D-葡萄糖(FDG)在确定患有持续性中性粒细胞减少症而没有明显可识别来源的癌症患者的感染部位方面的实用性和成本效益，从而改进靶向治疗。这项Quick-Trials探索性拨款申请的直接目标是在这些患者中的一小部分中进行试点项目，以提供关键信息，支持更大规模的多中心临床试验的概念，并帮助设计。这项探索性研究的主要目的是对大约130名持续发热的中性粒细胞减少的癌症患者进行FDG-PET/CT检查，这些患者的明显感染源尚未确定。只要有可能，每一个可疑的地方都将用病理基本事实进行确认。将对这些数据进行评估，以解决以下问题，这些问题是这项建议的子目标：1.FDG-PET/CT在识别无明显原因的持续性发热中性粒细胞减少症的癌症患者中的感染部位的有效性如何？2.FDG-PET/CT在多大程度上改善了仅通过CT对感染部位的检测？3.哪些FDG-PET/CT成像变量最能预测特定部位是否存在感染(例如，标准化摄取值[SUV]，CT上伴随的异常)？4.SUV在感染部位测量的FDG摄取的大小是否可以预测感染源(细菌、真菌和病毒)的身份？5.感染部位摄取的大小是否与中性粒细胞的绝对计数相关？6.能否开发一个临床评分系统来确定FDG-PET/CT在确定感染部位可能最有效的患者群体？FDG-PET/CT可能能够显著改变患有持续性中性粒细胞减少症的癌症患者的治疗方法，从而改善临床护理；降低某些有毒抗生素毒性的发病率；通过改进抗生素治疗的靶向性，潜在地降低医疗护理成本；并减少这些患者的住院天数。所有这些潜在的好处都可能带来显著的成本节约。FDG-PET/CT可能能够显著改变持续发热性中性粒细胞减少的癌症患者的治疗。FDG-PET/CT可能是定位隐匿性和潜在危及生命的感染来源的最合适的方法，从而直接影响治疗，从而降低发病率和死亡率，从而显著影响重症癌症患者的生活质量。

DESCRIPTION (provided by applicant): Although there have been many advances in the assessment and treatment of infections responsible for febrile neutropenia in cancer patients, it still remains a common complication of cancer therapy and accounts for the majority of chemotherapy-associated deaths. The ultimate goal of our interdisciplinary group of oncologists, infectious diseases experts, imagers, and biostatisticians is to conduct a large, prospective, multi-center trial to establish the utility and cost-effectiveness of PET/CT using the widely available glucose analogue [18F]fluoro-2-deoxy- D-glucose (FDG) in identifying sites of infection in cancer patients with persistent febrile neutropenia without an obvious identifiable source thus improving targeted therapy. The immediate goal of this Quick-Trials Exploratory Grant application is to conduct a pilot project in a smaller group of these patients to provide critical information that will support the concept, and aid in the design, of a larger multi-center clinical trial. The primary aim of this exploratory study is to perform FDG-PET/CT in approximately 130 cancer patients with persistent febrile neutropenia in whom an obvious source of infection has not been identified. Each suspicious site will be confirmed with pathologic ground truth whenever possible. The data will be evaluated to address the following questions, which are the sub-aims of this proposal: 1. How effective is FDG-PET/CT in identifying sites of infection in cancer patients with persistent febrile neutropenia without an obvious cause? 2. To what degree does FDG-PET/CT improve detection of sites of infection over CT alone? 3. What FDG-PET/CT imaging variables best predict the presence of infection at a specific site (e.g. standardized uptake value [SUV], concomitant abnormality on CT)? 4. Can the magnitude of FDG uptake as measured by an SUV at sites of infection predict the identity of the infective agent (bacterial vs. fungal vs. viral)? 5. Does the magnitude of uptake at sites of infection correlate with absolute neutrophil count? 6. Can a clinical scoring system be developed to identify a population of patients in whom FDG-PET/CT is likely to be most efficacious in identifying sites of infection? It is possible that FDG-PET/CT may be able to significantly change the management of the cancer patient with persistent febrile neutropenia resulting in improved clinical care; decrease the morbidity due to toxicities from certain toxic antibiotics; potentially decrease the cost of medical care by improved targeting of antibiotic therapy; and decrease days of hospitalization for these patients. All of these potential benefits may result in significant cost savings. FDG-PET/CT may be able to significantly change the management of cancer patients with persistent febrile neutropenia. FDG-PET/CT may be the most appropriate way to localize sources of occult and potentially life-threatening infections thus directly impacting therapy which may significantly impact the quality of life of very ill cancer patients by reducing morbidity and mortality.