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

描述（由申请人提供）：尽管在评估和治疗癌症患者中引起发热性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，并导致大多数化疗相关死亡。我们的跨学科小组的肿瘤学家，传染病专家，成像师和生物统计学家的最终目标是进行一个大的，前瞻性的，一项多中心试验，使用广泛使用的葡萄糖类似物[18 F]氟-2-脱氧-D-葡萄糖（FDG）确定PET/CT的效用和成本效益在没有明显可识别来源的持续发热性中性粒细胞减少症癌症患者中识别感染部位，从而改善靶向治疗。这项快速试验探索性资助申请的近期目标是在这些患者中的一个较小的群体中进行试点项目，以提供关键信息，支持更大的多中心临床试验的概念和设计。本探索性研究的主要目的是在约130例患有持续性发热性中性粒细胞减少症且尚未确定明显感染源的癌症患者中进行FDG-PET/CT。在可能的情况下，将使用病理基础事实确认每个可疑部位。将对数据进行评估，以解决以下问题，这些问题是本提案的子目标：1. FDG-PET/CT在确定无明显原因的持续发热性中性粒细胞减少症癌症患者感染部位方面的有效性如何？2. FDG-PET/CT在多大程度上改善了对感染部位的检测？3.哪些FDG-PET/CT成像变量最能预测特定部位感染的存在（例如，标准化摄取值[SUV]、CT上的伴随异常）？4.通过SUV在感染部位测量的FDG摄取量的大小能否预测感染因子的身份（细菌vs.真菌vs.病毒）？5.感染部位的摄取量是否与中性粒细胞绝对计数相关？6.是否可以开发一个临床评分系统来识别FDG-PET/CT在识别感染部位方面可能最有效的患者人群？FDG-PET/CT可能能够显著改变持续性发热性中性粒细胞减少症癌症患者的管理，从而改善临床护理;降低某些毒性抗生素毒性导致的发病率;通过改善抗生素治疗的靶向，可能降低医疗护理成本;并减少这些患者的住院天数。所有这些潜在的好处都可能导致显著的成本节约。FDG-PET/CT可能能够显著改变持续性发热性中性粒细胞减少的癌症患者的管理。FDG-PET/CT可能是定位隐匿性和潜在危及生命的感染源的最合适方法，从而直接影响治疗，这可能通过降低发病率和死亡率来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.