FDG-PET/CT In the Evaluation of Persistent Febrile Neutropenia in Cancer Patients
Patients must be currently treated at the Huntsman Cancer Institute or Intermountain Primary Children's Medical Center to be eligible for this study.
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. This National Cancer Institute (NCI) funded proposal using the R-21 Quick-Trials Exploratory Grant mechanism is to conduct an exploratory/pilot project in a group of patients with persistent febrile neutropenia to provide critical information that will support the concept, and aid in the design, of a larger multi-center clinical trial. The ultimate goal of our interdisciplinary team of oncologists, infectious diseases experts, imagers, and biostatisticians is to conduct a 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.
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
|Official Title:||FDG-PET/CT In the Evaluation of Persistent Febrile Neutropenia in Cancer Patients|
- The primary goal of this study is to perform FDG-PET/CT scans in approximately 100 cancer patients (both adults and children) with persistent febrile neutropenia where the source of infection has not been identified. [ Time Frame: December 2011 ] [ Designated as safety issue: No ]
|Study Start Date:||August 2007|
|Estimated Study Completion Date:||July 2015|
|Estimated Primary Completion Date:||July 2015 (Final data collection date for primary outcome measure)|
Procedure: Imaging study (FDG-PET/CT scan)
FDG-PET/CT scan-The scans that will be done with a radioactive sugar ([18F]fluoro-2-deoxy-D-glucose) and positron emission tomography (FDG-PET/CT). These scans will help to identify areas of possible infection.
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What is the significance of this project? The significance is two fold: (1) the serious nature of the clinical condition that it addresses, and (2) in the potential ease and safety by which this approach could be translated to clinical practice. Although there have been many advances in treatment modalities related to febrile neutropenia, it still remains a common complication of cancer therapy and accounts for the majority of chemotherapy-associated deaths (Sipsas 2005). The broad-spectrum therapeutic management of febrile neutropenia is often "shotgun" in its approach, without a clear source to allow target-specific therapy. The subpopulation of patients with febrile neutropenia that present the greatest problem is that with persistent febrile neutropenia > 5 days despite broad spectrum antibiotics, and without an identifiable source of infection. As noted previously, however, the definition of persistence is changing in medical practice. Currently medical professionals are ordering diagnostic imaging studies such as CT scans earlier due to the need to localize a site of infection and use the most appropriate antibiotic therapy. Without a target, multi-drug antibiotic therapy in these patients can continue for many weeks. The drugs are often toxic, with substantial side effects. Hospitalization is extended. The cost of broad spectrum hospital course of antibacterial and antifungal drugs is in the range of multiples of $10,000, and the cost of extended hospitalization to treat an unknown infection in a patient with persistent febrile neutropenia may be multiples of $100,000. Chemotherapy may be suspended or discontinued, with risk of development of chemo-resistant tumor cells. Conventional imaging methods are limited in evaluation of febrile neutropenia due to lack of anatomic changes. The lack of sufficient white cells to mount an inflammatory reaction compromises detection of sites of infection by radiography or CT.
Because white cell number is severely reduced, the use of labeled white cell scans is often precluded. If FDG-PET/CT can provide a likely anatomic site for targeted antibiotic therapy in this specific high risk population, it is possible that morbidity/mortality from infection and antibiotic side effects may be minimized, hospitalization days may be reduced, and effective anti-cancer therapy may be continued without interruption. Although FDG-PET/CT is not cheap, the ultimate result may be highly cost-effective.
Our oncologist and infectious diseases co-investigators predict that a tissue diagnosis can be obtained in at least 80% of all FDG-PET/CT or CT findings that are suspicious for infection in children and 50% in adults. This confirmatory tissue diagnosis will serve as the "gold standard" to assess the effectiveness of FDG-PET/CT in finding a source of infection.
Additional confirmatory factors will include clinical response to targeted therapy and resolution of associated radiographic or CT findings. The data will be evaluated to address the following questions, which are the sub-aims of the funded proposal:
- How effective is FDG-PET/CT in identifying sites of infection in patients with febrile neutropenia without an obvious cause?
- To what degree does FDG-PET/CT improve detection of sites of infection over CT alone?
- 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)?
- Can the magnitude of uptake of FDG measured by an SUV at sites of infection predict the identity of the infective agent (bacterial vs. fungal vs. viral)?
- Does magnitude of uptake at sites of infection correlate with absolute neutrophil count (ANC)?
- 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?
This pilot data will be used to determine whether there is sufficient support for, and to aid in the design of, a large, prospective, multi-center clinical trial to establish the cost-effectiveness and efficacy of FDG-PET/CT in evaluation of febrile neutropenia, compared to patients who are managed by conventional methods.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00707213
|United States, Utah|
|Huntsman Cancer Institute|
|Salt Lake City, Utah, United States, 84112|
|Principal Investigator:||John M Hoffman, MD||Huntsman Cancer Institute|