FLT-PET/CT for Therapy Monitoring of DLBCL

Project: Research project

Description

DESCRIPTION (provided by applicant): Currently for lymphoma patients, 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/ computed tomography (CT) is used for interim restaging or therapy monitoring after 1-4 cycles of chemo-/chemoimmunotherapy. An excellent negative predictive value (NPV) of >80% with only a moderate positive predictive value (PPV) of between 25%- 70% has been reported. It has been shown that a substantial portion of the false-positive FDG-PET findings in this setting were caused by early post-therapy inflammatory changes. This hampers the accuracy and reliability of this test and, hence, its acceptance as an early prognostic tool in the clinical practice setting. An important recent advance in the area of molecular imaging of lymphoma is the development of the PET tracer18F-fluorothymidine (FLT) as an in vivo marker of cell proliferation. FLT uptake in lymphomas has been shown to be proportional to the Ki-67 index, a recognized histopathological marker of cell proliferation and since less affected by postherapy inflammatory changes caused by macrophages/monocyte infiltration, it is also a more tumor-specific tracer when compared to FDG. This higher tumor- specificity may be advantageous in early response assessment following chemo-/chemoimmunotherapy, radiation therapy (RT) or combined modality therapy. In this application, we propose to compare the predictive values of interim FLT- PET/CT and FGD-PET/CT in diffuse large B-cell lymphoma (DLBCL) patients after 2 cycles of R-CHOP chemotherapy. Our hypothesis is that FLT-PET/CT will have a substantially higher PPV when compared to FDG-PET/CT (i.e., e 91% vs. d 68%) while providing a similar or only slightly lower NPV and, therefore, prove superior to FDG-PET in this setting. We propose to prospectively study 137 DLBCL patients at 5 institutions. Study patients will be scanned by FLT-PET/CT and FDG-PET/CT 18-24 days after the second cycle of R-CHOP. After completion of six cycles of chemotherapy, conventional staging methods (CSM) will be performed in all patients to assess response and determine appropriate patient management. Patients will be followed for event-free survival (EFS) and overall survival (OS) for at least 24 months post- therapy or until definite determination of persistent disease (by biopsy) or disease progression (both considered an event). Specifically, we intend to: 1. Investigate whether the PPV of FLT-PET/CT is significantly higher (i.e., e 91% vs. d 68%) than that of FDG-PET/CT by following-up patients for at least 24 months posttherapy or until evidence of or disease progression. 2. Investigate whether the EFS of patients with FDG-PET/CT-positive and FLT-PET/CT negative scans is not significantly lower than that of patients with concordantly negative FDG-PET/CT and FLT-PET/CT scans (i.e.,
StatusFinished
Effective start/end date6/1/113/31/16

Funding

  • National Institutes of Health: $672,975.00
  • National Institutes of Health: $32,229.00
  • National Institutes of Health: $631,836.00
  • National Institutes of Health: $337,570.00

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Lymphoma, Large B-Cell, Diffuse
Therapeutics
Positron-Emission Tomography
Lymphoma
Positron Emission Tomography Computed Tomography
Disease-Free Survival
Disease Progression
Cell Proliferation
Combined Modality Therapy
Molecular Imaging
Fluorodeoxyglucose F18
Biopsy
Secondary Prevention

ASJC

  • Medicine(all)