Randomized Metabolic Response Monitoring Trial in Patients With Suspected Recurrence of Glioblastoma F-DOPA PET/CT
Malignant gliomas are aggressive primary brain tumors that almost always lead to rapid
patient deterioration and death. Timely diagnosis of recurrent disease as well as accurate
monitoring of therapeutic responses is critically important in glioblastoma patients.
Despite introduction of new treatment approaches patient prognosis is poor with less than
half of the patients being progression-free during the first 6 months after diagnosis of
disease recurrence (6-month-progression-free survival rates of 46%).
The current diagnostic standard of care for diagnosing and monitoring brain tumors is
contrast-enhanced, multi-planar magnetic resonance imaging (MRI). However, the ability of
MRI for early detection of disease recurrence or progression is limited. Moreover,
determination of treatment responses is difficult since benign tissue changes after
radiation and/or chemotherapy can have the appearance of tumor recurrence or progression on
MRI. Positron emission tomography (PET) is an established imaging technique that utilizes
small amounts of radioactivity attached to very minimal amounts of substances (tracers) that
are injected via a hand or arm vein. These substances can track certain features of cancers
that can be visualized by using the PET/CT scanner. For instance, a number of different
PET-tracers have been used to study brain tumor metabolism and to detect primary or
recurrent tumors. These include tracers of glucose (18F-FDG) and amino acid metabolism (e.g.
18F-DOPA). Metabolic imaging of brain tumors with amino acid analogues has advantages over
18F-FDG. Since FDG assess glucose metabolism and the normal brain consumes a lot of glucose
it can be difficult to detect tumors against high glucose use of normal brain tissue.
18FDOPA has been successfully used clinically for many years. The advantage of 18F-DOPA is
that normal brain tissue consumes very little 18F-DOPA. Thus, tumors can be seen easily
against a low background activity.
18F-DOPA PET imaging detects brain tumors with a very high accuracy and 18F-DOPA imaging
affects the management of 40% of patients. However, its impact on patient outcome defined as
survival, costs, and/or quality of life has not been demonstrated.
Randomized trials are needed to evaluate the impact of PET on patient management and
outcome. We will determine this by randomizing patients with suspected recurrence of
glioblastoma into those who are managed using conventional diagnostic imaging versus those
who will receive conventional imaging plus 18F-DOPA PET. Randomization is like flipping a
coin. Patients will have a 50% chance to undergo standard imaging or standard imaging
combined with 18F-DOPA PET.
Approximately 25-40% of the patients with suspected tumor recurrence will have
pseudo-progression on MRI (i.e. the images suggest that there is tumor recurrence when there
is in fact no recurrence). These patients will have correctly negative 18F-DOPA PET scans.
In these patient initiation of treatment can be postponed. In contrast, patients with
positive 18F-DOPA PET scans will undergo some kind of treatment at the discretion of the
treating physician (radiation therapy, chemotherapy or surgery). We will find out whether
the management and treatment change that is based on 18FDOPA PET affects the survival of
patients and affects the costs of caring for the patients.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Diagnostic
Diagnostic accuracy compared to standard diagnostics without PET
Imaging findings will be validated by histopathology, clinical follow-up and/or repetitive imaging. If no histopathology within 3 months is available, clinical follow-up and imaging findings will be used for validation. If within 6 months of randomization no clinical progression nor progression on other imaging modalities is found, the patient will be rated as "no disease present at time of imaging".
United States: Food and Drug Administration
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