Observation or Radiation Therapy in Treating Patients With Grade I, Grade II, or Grade III Meningioma
Condition: Brain and Central Nervous System Tumors
MeSH terms: Meningioma; Nervous System Neoplasms; Central Nervous System Neoplasms
Intervention: 54 Gy radiotherapy; 60 Gy radiotherapy
Intervention description: External beam radiation therapy (EBRT) to a total dose of 54 Gy (RBE) in 30 fractions. 1.8 Gy (RBE) daily, 5 fractions per week, excluding weekends. 3D-CRT or IMRT or Proton allowed.; External beam radiation therapy using intensity-modulated radiation therapy (IMRT) to a total dose of 60 Gy in 30 fractions. 2.0 Gy daily, 5 fractions per week, excluding weekends.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 244.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: adult grade I meningioma; adult grade II meningioma; adult grade III meningioma; adult anaplastic meningioma; adult papillary meningioma; recurrent adult brain tumor

Summary:

      RATIONALE: Sometimes a tumor may not need treatment until it progresses. In this case,
      observation may be sufficient. Specialized radiation therapy that delivers a high dose of
      radiation directly to the tumor, such as 3-dimensional conformal radiation therapy and
      intensity-modulated radiation therapy, may kill more tumor cells and cause less damage to
      normal tissue. It is not yet known whether observation is more effective than radiation
      therapy in treating patients with meningioma.

      PURPOSE: This phase II trial is studying observation to see how well it works compared with
      radiation therapy in treating patients with grade I, grade II, or grade III meningioma.
    

Eligibility criteria:

        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