A Pilot Study of the Utility of 18F-FLT-PET and Diffusion-Weighted MRI for Surgical Planning, Radiotherapy Target Delineation, and Treatment Response Evaluation in Ewing Sarcoma Patients
I. Establish correlation between 18F-FLT positron emission tomography (PET) activity,
apparent diffusion coefficients (ADC) values from diffusion-weighted magnetic resonance
imaging (DW-MRI), fludeoxyglucose F 18 (18F-FDG) PET activity, magnetic resonance imaging
(MRI) contrast enhancement, and pathologic response for Ewing sarcoma.
II. Assess the efficacy of detecting therapy induced changes in 18F-FLT PET uptake and ADC
from DW-MRI for more accurately predicting local control, event-free survival, and overall
survival as compared to standard prognostic factors (e.g. change in tumor size).
III. Compare radiotherapy target volume delineation with pre- and post-chemotherapy 18F-FLT
PET and DW-MRI information to delineation with pre-chemotherapy conventional MRI to
determine role of advanced imaging in radiotherapy treatment planning for Ewing sarcoma.
I. Establish correlation between 18F-FLT PET activity, ADC values from DW-MRI, 18F-FDG PET
activity, MRI contrast enhancement, and biomolecular assays for Ewing sarcoma.
II. Determine imaging thresholds to discriminate between viable and necrotic tumor, as
established through pathologic correlations.
III. Assess efficacy of advanced imaging for more accurately guiding biopsy targeting by
comparing planned targeting with standard (MRI contrast enhancement) vs. advanced imaging
(18F -FLT PET and DW-MRI).
IV. Compare post-treatment response assessment with 18F-FLT PET and DW-MRI vs. 18F-FDG PET
to determine whether 18F-FLT PET and ADC information is more accurate than 18F-FDG PET for
distinguishing between necrosis and non-specific inflammation immediately following
V. Estimate potential reduction in acute and late side effects based on modified radiation
therapy (RT) treatment volumes with pre- and post-chemotherapy 18F-FLT PET and DW-MRI
information as compared to volumes delineated with pre-chemotherapy conventional MRI.
VI. Evaluate automatic image segmentation techniques for 18F-FLT PET and DW-MRI, comparing
against biopsy determined imaging thresholds and expert Nuclear Medicine and MR Radiologist
Patients undergo 18F-FLT PET, 18F-FDG PET, and DW-MRI the week prior to induction therapy,
within one week after the completion of induction therapy, the week prior to RT (for
patients that received surgery), and within 1 week of completion of RT.
After completion of study intervention, patients are followed up every 3 months for 1 year
and then every 6 months for up to 4 years.
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic
18F-FLT PET activity
The primary measure of the samples will be % of viable malignant cells remaining. To examine the correlation of 18F-FLT PET, 18F-FDG PET, and ADC signals in areas of concordance and discordance with standard MR imaging as it impacts differentiation of viable and necrotic tumor extent, sensitivity/specificity and positive/negative predictive values will be estimated. Findings will be summarized using point-estimates and corresponding 95% confidence intervals as appropriate. Differences in sensitivity and specificity will be evaluated using McNemar's test.
At the time of surgical resection
Nadia N. Laack, M.D.
United States: Food and Drug Administration
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