Observation or Radiation Therapy in Treating Patients With Newly Diagnosed Grade II Meningioma That Has Been Completely Removed by Surgery

PRIMARY OBJECTIVES:

I. To determine, in terms of progression-free survival (PFS), the extent of clinical benefit
of the addition of adjuvant radiotherapy (RT) to gross total resection (GTR) for patients
with newly diagnosed World Health Organization (WHO) grade II meningioma.

SECONDARY OBJECTIVES:

I. Overall survival (OS). II. Disease-specific survival (DSS). III. Toxicity (grade 3+,
exclusive of expected alopecia). IV. Neurocognitive function (NCF). V. Outcomes and patient
reported outcomes (PRO) measurements. VI. Adherence to protocol-specific target and normal
tissue parameters. VII. Concordance measurements of central versus parent-institution
pathology. VIII. Tissue microarray construction, and assessment of pHH3 mitotic index and
molecular correlates to OS.

OUTLINE: Patients are randomized to 1 of 2 arms after undergoing gross total resection.

ARM I: Patients undergo observation.

ARM II: Patients undergo radiation therapy 5 days a week over 6.5-7 weeks for a total of 33
fractions (59.4 Gy in 33 daily fractions of 1.8 Gy each).

After completion of study treatment, patients are followed up at 3, 6, and 12 months, every 6
months for year 2 and 3, then yearly for 10 years.

Inclusion Criteria:

- PRIOR TO STEP 1 REGISTRATION:

- The patient must have a newly diagnosed unifocal intracranial meningioma, gross
totally resected, and histologically confirmed as WHO grade II based upon pathology
findings at the enrolling institution; WHO grade will be assigned according to WHO
2016 criteria

- Gross total resection (GTR) will be interpreted as modified Simpson grade 1-3 without
gross residual dural-based or extradural tumor; GTR must be confirmed both by modified
Simpson grade and by post-operative magnetic resonance imaging (MRI) findings

- Step 1 registration must occur within 180 days of the initial surgery; within this 180
day interval, a second surgery is permitted in order to achieve GTR, but even with a
second surgery, step 1 registration must occur within 180 days of the initial
resection

- For step 1 registration the operating neurosurgeon must provide the modified Simpson
grade

- GTR must be confirmed on post-operative imaging following the most recent surgery;
submission of both pre-operative and post-operative MRIs is required for patients; if
a second surgery is performed, submission of post-operative MRI is required and
pre-operative MRI is required only if obtained; all sequences obtained in the pre- and
post-operative MR imaging are to be submitted to National Radiology Group (NRG)
Oncology for study registration; imaging subsequent to enrollment must include pre and
post gadolinium contrast-enhanced three-dimensional spoiled gradient (SPGR),
magnetization-prepared rapid gradient echo (MP-RAGE), or turbo field echo (TFE) MRI
scan and an axial T2 fluid attenuated inversion recovery (FLAIR) sequence; to yield
acceptable image quality, the gadolinium contrast-enhanced three-dimensional SPGR,
MP-RAGE, or TFE axial MRI scan should use the smallest possible axial slice thickness
not exceeding 1.5 mm; the post-operative MRI must be completed within sufficient time
to permit step 1 registration within 180 days of the initial resection; these same
conditions apply in the setting of a second surgical procedure, although if a second
surgery is completed, step 1 registration must still occur with 180 days of initial
surgery; computed tomography (CT) imaging is not required, but may be obtained if
desired clinically, for instance to assess calcifications or hyperostosis

- The patient or a legally authorized representative must provide study-specific
informed consent prior to study entry

- If the patient is a primary English speaker, the patient must participate in the NCF
and patient reported outcomes part of the study; if the patient is a primary French or
Spanish speaker, the patient must participate in the patient reported outcomes part of
the study

- NOTE: Central pathology review must occur between steps 1 and 2 of registration; once
appropriate pathology specimens are received, central pathology review will occur
within 15 days, and must confirm WHO grade II meningioma before the patient can
proceed to step 2 registration and randomization

- PRIOR TO STEP 2 REGISTRATION:

- Histologically confirmed diagnosis of WHO grade II meningioma confirmed by central
pathology review prior to step 2 registration

- History/physical examination, including neurologic examination within 60 days prior to
step 2 registration

- Post-operative Zubrod performance status 0-1 within 60 days prior to step 2
registration

- If the patient is a woman is of childbearing potential, a serum pregnancy test,
obtained within 14 days prior to step 2 registration, must be negative, and, if
randomized to receive radiation therapy, the woman must agree to use contraception

Exclusion Criteria:

- Optic nerve sheath meningioma, spinal or other extracranial meningioma, multiple
meningiomas, hemangiopericytoma

- Definitive evidence of metastatic meningioma

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

- Previous radiotherapy to the scalp, cranium, brain, or skull base and
radiation-induced meningiomas

- Major medical illnesses or psychiatric impairments, which in the investigators
opinion, will prevent administration or completion of the protocol therapy and/or
preclude informed consent; these include, but are not restricted to:

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

- Transmural myocardial infarction within the last 6 months prior to step 2
registration

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

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

- Type II neurofibromatosis (NF2)

- Ailments entailing substantial increases in sensitivity and side effect risk from
radiation therapy (ataxia telangiectasia, Nijmegen breakage syndrome, and human
immunodeficiency virus (HIV) with CD4 count < 200 cells/microliter); HIV testing
is not required for eligibility for this protocol, and known HIV positive
patients are eligible, provided they are under treatment with highly active
antiretroviral therapy (HAART) and have a CD4 count >= 200 cells/microliter
within 30 days prior to step 2 registration

- Inability to undergo MRI with and without contrast (e.g. claustrophobia, non-MRI
compatible implant or foreign body, etc) or receive gadolinium; note that
patients with severe claustrophobia are permitted on this study if they are
willing and able to undergo MRI with adequate sedation or anesthesia

- Pregnancy and/or nursing females