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

描述（由申请人提供）：尽管在评估和治疗引起癌症患者发热性中性粒细胞减少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，并且占化疗相关死亡的大部分。我们由肿瘤学家、传染病专家、成像专家和生物统计学家组成的跨学科小组的最终目标是开展一项大型、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）在识别无明显可识别来源的持续性发热性中性粒细胞减少癌患者感染部位方面的效用和成本效益，从而改善靶向治疗。这项快速试验探索性拨款申请的直接目标是在较小的患者群体中开展试点项目，以提供支持概念的关键信息，并帮助设计更大的多中心临床试验。本探索性研究的主要目的是对大约130例持续性发热性中性粒细胞减少症的癌症患者进行FDG-PET/CT检查，这些患者的感染源尚未明确。每一个可疑部位都尽可能用病理基础真相进行确认。将对数据进行评估，以解决以下问题，这些问题是本提案的次级目标：FDG-PET/CT在无明显病因的持续性发热性中性粒细胞减少癌患者中识别感染部位的效果如何？2. 与单独CT相比，FDG-PET/CT在多大程度上提高了感染部位的检测？3. 哪些FDG-PET/CT成像变量最能预测特定部位感染的存在（例如，标准化摄取值[SUV]， CT伴随异常）？4. 由SUV在感染部位测量的FDG摄取量能否预测感染因子的身份（细菌、真菌、病毒）？5. 感染部位摄取的大小是否与绝对中性粒细胞计数相关？6. 能否开发一种临床评分系统，以确定FDG-PET/CT在确定感染部位方面可能最有效的患者群体？FDG-PET/CT可能会显著改变对持续性发热性中性粒细胞减少的癌症患者的管理，从而改善临床护理；减少因某些有毒抗生素中毒引起的发病率；通过改进抗生素治疗的靶向性，可能降低医疗保健的成本；并减少这些患者的住院天数。所有这些潜在的好处可能导致显著的成本节约。FDG-PET/CT可能会显著改变对持续性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，通过降低发病率和死亡率，可能显著影响重病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.