Response Monitoring Trial in Patients With Suspected Recurrence of Glioblastoma

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.

Inclusion Criteria:

- Suspected first recurrence of a glioblastoma tumor by clinical measures and/or MRI

- Age 18-99 years

Exclusion Criteria:

- Breast feeding/ Pregnancy

- Severe psychiatric illness

- Primary diagnosis of a glioblastoma