Evaluation of FLT PET and MRI as Imaging Biomarkers of Early Treatment Response in Patients With Glioblastoma

Study Overview
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Brief Summary
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Glioblastoma is the most common primary malignant neoplasm of the adult brain. Even after multimodal therapy, outcomes remain poor, with a median survival of one year. Although advanced imaging methods have been suggested as molecular markers of prognosis and therapeutic response, these methods have not been validated for clinical use. In this exploratory, imaging-based, trial, thirty patients with a pathological diagnosis of glioblastoma will be followed prospectively for two years. The study examines how PET and MR imaging signals change following administration of a standard radio-chemotherapy treatment regimen to determine whether these imaging modalities can provide early indicators of response to therapeutic intervention. The investigators hypothesize that decreases in uptake of an investigational 18F-FLT PET tracer following treatment with radiation and chemotherapy will be a reliable predictor of glioblastoma response. In a more exploratory fashion, the investigators also will identify changes in diffusion and hypoxia MR imaging that may also correlate well with treatment response.

Detailed Description
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Patients with glioblastoma will be imaged with FLT PET/CT followed by MRI. The FLT uptake will be correlated with advanced MRI markers of tumor progression to determine the ability of using FLT PET and MRI for predicting response to treatment.

Official Title
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An Exploratory Study of Quantitative [18F]FLT-PET and Advanced MRI as Early Indicators of Treatment Response and Molecular Markers for Cell Proliferation in Patients With Glioblastoma Following Subtotal Resection

Conditions
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Glioblastoma

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients (> 18 yo) with a pathological diagnosis of malignant glioma (WHO grades III and IV, including all histological subtypes) Surgical intervention includes subtotal resection or biopsy with MRI evidence of residual disease after resection Patients with plan to undergo standard chemotherapy and radiation protocols including a combination of fractionated radiation and temozolomide Preoperative Karnofsky performance score (KPS) of > 60 Willingness of patient and his/her partner to use contraceptive measures for duration of trial that will include PET studies. Exclusion Criteria: Patient refuses adjunctive therapy Pregnancy Karnofsky scale < 60 Inability to undergo MR imaging studies Estimated GFR ≤ 60 ml/min (using GFR = 0.85*[140 - age(y)]*[bodyweight(kg)]/[72*Cr(mg/dl)] for women and GFR = [140 - age(y)]*[bodyweight(kg)]/[72*Cr(mg/dl)] for men). Inability or unwillingness to follow instructions for both PET and MR imaging sessions.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Treatment<br>All patients included in this study were treated with temozolomide and radiotherapy after subtotal resection of a WHO grade III or IV glioma. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in FLT uptake, measured by SUV tumor/SUV normal contralateral white matter | Determines the change in FLT uptake as a result of chemotherapy/radiation therapy | Before and after chemotherapy/radiation therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival | Number of months from date of diagnosis to date of death. | 2 years | 
| Ki-67 | Ki-67 proliferation index on tumor specimens obtained at biopsy or from surgical resection specimen | At diagnosis | 
| Radiographic progression defined by MacDonald criteria | MacDonald criteria to be used to determine whether tumor progress or not during the course of this study | 2 years | 
| O(6)-methylguanine DNA-methyltransferase (MGMT) activity | MGMT activity from tumor specimens | prior to treatment | 
| Time to progression | Months after completing radiation treatment to first instance of radiographic progression | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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positron emission tomography, magnetic resonance imaging, diffusion magnetic resonance imaging, radionuclide imaging, disease management, radiation therapy