Observation or Radiation Therapy in Treating Patients With Grade I, Grade II, or Grade III Meningioma

OBJECTIVES:

Primary

- To estimate the rates of progression-free survival at 3 years in patients with low-risk
meningioma undergoing observation and in patients with intermediate- or high-risk
meningioma undergoing radiotherapy.

Secondary

- To study the concordance, or lack thereof, between central and parent institution
histopathologic diagnosis, grading, and subtyping.

- To estimate the rates of overall survival at 3 years in these patients.

- To estimate the incidence rates of acute and late adverse events ≥ grade 2 in patients
with intermediate- or high-risk meningioma undergoing radiotherapy.

- To evaluate MRI imaging predictors by central neuroradiology review at diagnosis, at any
failure, and at 3 years.

- To evaluate adherence to protocol-specific target and normal tissue radiotherapy
parameters.

This is a multicenter study. Patients are assigned to 1 of 3 groups according to risk.

After completion of study treatment, patients are followed up every 3-6 months for 3 years
and then annually for 10 years.

Inclusion Criteria:

1. A histologically documented World Health Organization (WHO) grade I, II, or III
meningioma, newly diagnosed or recurrent, and of any resection extent, confirmed by
central pathology review. Patients are partitioned according to three groupings: Group
I (low risk), Group II (intermediate risk), and Group III (high risk) as defined
below:

- Group I (low risk): Patients with a newly diagnosed WHO grade I meningioma that
has been gross totally resected (Simpson's grade I, II, or III resections, with
no residual nodular enhancement on postoperative imaging) or subtotally resected
(residual nodular enhancement or Simpson grade IV or V excision). The extent of
resection will be based upon the neurosurgeons' assessment and postoperative MR
imaging.

- Group II (intermediate risk): Patients with a newly diagnosed gross totally
resected WHO grade II meningioma or patients with a recurrent WHO grade I
meningioma irrespective of the resection extent. Resection extent will be
recorded on the same basis described above for the low-risk group.

- Group III (high risk): Patients with a newly diagnosed or a recurrent WHO grade
III meningioma of any resection extent; patients with a recurrent WHO grade II
meningioma of any resection extent; or patients with a newly diagnosed subtotally
resected WHO grade II meningioma. In the setting of a newly diagnosed meningioma,
the histologic diagnosis must have been reached within 6 months of Step 2
registration. Resection extent will be recorded on the same basis described above
for the low-risk group.

- 1.1 In the setting of a newly diagnosed meningioma, the histologic diagnosis must
have been reached within 24 weeks prior to Step 2 registration. In the setting of
a recurrent meningioma, there are no such time constraints. Additional resection
or biopsy is encouraged for patients with recurrence but is not requisite. If
further biopsy or resection is performed at recurrence, these specimens must be
submitted; submission of the original pathology specimens is encouraged but not
required. The diagnosis of recurrence solely on the basis of imaging findings is
permitted, but if no additional resection is performed, specimens from prior
resection must be submitted.

- 1.2 In cases of newly diagnosed or surgically treated recurrent meningioma, the
operating neurosurgeon must provide a Simpson grade for the degree of resection.

2. History/physical examination, including neurologic examination, within 8 weeks prior
to Step 2 registration

3. Zubrod Performance Status 0-1

4. Age ≥ 18

5. All patients must have a magnetic resonance imaging (MRI) scan within 12 weeks prior
to Step 2 registration. Both preoperative and postoperative MRIs are required for all
newly diagnosed patients in groups I, II, or III. In the setting of group II or III
patients with recurrent/progressive meningioma and without recent surgery, a
pre-operative study may not apply, although MRI documentation of recurrence or
progression is required. MRIs must include precontrast T1, T2, and flair images and
multiplanar (axial, sagittal, and coronal) postcontrast T1. The postoperative study
must be completed within 12 weeks of surgery.

- 5.1 Group I: All group I patients will have surgery. Preoperative and
postoperative MRIs are thus required in order to assess resection extent.

- 5.2 Group II: Surgery will be undertaken for the subgroup with a gross totally
resected WHO grade II meningioma. For these patients preoperative and
postoperative MRIs are necessitated. For the other subgroup with recurrent WHO
grade I meningioma, preoperative and postoperative MRIs are required if surgery
is undertaken for the recurrent/progressive tumor. However, only the follow-up
imaging documenting recurrence or progression will apply if further surgery is
not completed.

- 5.3 Group III: Surgery will be undertaken for the subgroup with a newly diagnosed
WHO grade III meningioma. For these patients preoperative and postoperative MRIs
are obligatory. For the subgroups with recurrent WHO grade II or III meningioma,
preoperative and postoperative MRIs are required if surgery is undertaken for the
recurrent/progressive tumor. However, only the follow-up imaging documenting
recurrence or progression will apply if further surgery is not completed.

6. For woman of childbearing potential who are intermediate or high risk:

- 6.1 Negative serum pregnancy test within 14 days prior to Step 2 registration

- 6.2 The patient must agree to practice adequate contraception from the time of
the negative serum pregnancy test throughout the entire course of EBRT.

7. Patient must sign study-specific informed consent prior to study entry

Exclusion Criteria:

1. Extracranial meningioma

2. Multiple meningiomas

3. Hemangiopericytoma

4. Major medical illnesses or psychiatric impairments which, in the investigators
opinion, will prevent administration or completion of the protocol therapy or preclude
informed consent

5. Previous radiation therapy to the scalp, cranium, brain, or skull base

6. Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free
for a minimum of 3 years (for example, carcinoma in situ of the breast, oral cavity,
or cervix are all permissible)

7. Patients with severe, active comorbidity including, but not restricted to:

- 7.1 Unstable angina and/or congestive heart failure requiring hospitalization at
the time of Step 2 registration

- 7.2 Transmural myocardial infarction within the last 6 months

- 7.3 Acute bacterial or fungal infection requiring intravenous antibiotics at the
time of Step 2 registration

- 7.4 Chronic obstructive pulmonary disease exacerbation or other respiratory
illness requiring hospitalization or precluding study therapy at the time of Step
2 registration

- 7.5 Hepatic insufficiency resulting in clinical jaundice and/or coagulation
defects. Note, however, that laboratory tests for liver function and coagulation
parameters are not required for entry into this protocol.

- 7.6 Acquired immune deficiency syndrome (AIDS) based upon current Centers for
Disease Control and Prevention (CDC) definition; note, however, that HIV testing
is not required for entry into this protocol. The need to exclude patients with
AIDS from this protocol is necessary because the treatments involved in this
protocol may be significantly immunosuppressive.

- 7.7 Active connective tissue disorders such as lupus or scleroderma if the
patient is intermediate or high risk

8. Inability to receive gadolinium