Comparing Radiation After Surgery to Observation After Surgery in Patients With Clinical Low-Risk, Molecular High-Risk Meningioma, and Evaluating Observation After Surgery in Patients With Clinical and Molecular Low-Risk Meningioma

Inclusion Criteria:

* Radiologically confirmed newly diagnosed or recurrent solitary (n=1) cranial World Health Organization (WHO) grade 1 meningioma post GTR or STR based on postoperative MRI findings, or newly diagnosed solitary WHO grade 2 meningioma post GTR based on postoperative MRI findings at the enrolling institution. Somatostatin receptor (SSTR)-directed positron emission tomography (PET) imaging may not be used to define extent of resection or meningioma number
* Histologically confirmed as WHO grade 1 or 2, based on pathology findings at the enrolling institution according to WHO 2021 criteria
* Initial surgery (GTR or STR) within 180 days prior to step 1 registration (within this 180-day period, a second surgery is permitted to achieve GTR):

  * GTR is defined as the absence of gross residual meningioma, as confirmed by postoperative MRI
  * STR is defined as the presence of gross residual meningioma, as confirmed by postoperative MRI
  * Surgeon-reported Simpson grade of resection, meningioma location, and any available SSTR-directed PET imaging studies will be assembled
* Postoperative MRI prior to step 1 registration. It is additionally required that all imaging sequences obtained in all preoperative and postoperative MRI, and any computed tomography (CT) or SSTR-direct PET imaging studies used for radiotherapy planning be submitted to NRG Oncology after step 1 registration. SSTR PET imaging may be used for radiotherapy planning to ensure all disease is encompassed in the clinical target volume (CTV) but may not be used to shrink the CTV or to supersede MRI-defined extent of resection or meningioma number
* NOTE: Central review for pathology, radiology, and gene expression profiling must occur between step 1 and step 2 of registration. Once appropriate pathology and imaging data are received, central pathology and radiology review will occur within 10 business days and must confirm WHO grade 1 meningioma after GTR or STR or WHO grade 2 meningioma after GTR. Gene expression profiling will occur within 30 business days of receiving appropriate pathology specimens. Central review for pathology, radiology, and gene expression must be completed before the patient can proceed to step 2 registration/randomization. For patients with central confirmation of clinical low-risk, molecular high-risk meningioma who will be eligible for cohort A randomization, central determination of 54 gray (Gy)/30 fractions (Fx) or 25Gy/5Fx radiotherapy and recommended radiotherapy treatment volumes will be provided prior to step 2 registration. See the study-specific biospecimen collection and submission manual on the Cancer Trials Support Unit (CTSU) protocol website for details of central pathology review and gene expression biomarker testing
* Age ≥ 18
* Central radiology confirmation of solitary (n=1) cranial meningioma on preoperative MRI and extent of resection (GTR or STR) on postoperative MRI
* Central histological pathology confirmation of newly diagnosed or recurrent WHO grade 1 meningioma after GTR or STR, or newly diagnosed WHO grade 2 meningioma after GTR, according to WHO 2021 criteria
* Central gene expression profiling for calculation of the gene expression risk score:

  * Cohort A: High gene expression risk score after GTR or STR, or intermediate gene expression risk score after STR
  * Cohort B: Low gene expression risk score after GTR or STR, or intermediate gene expression risk score after GTR
* Postoperative Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
* Not pregnant and not nursing

  \* Negative urine or serum pregnancy test (in persons of childbearing potential) within 14 days prior to step 2 registration. Childbearing potential is defined as any person who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) and who is not postmenopausal
* No prior high dose radiotherapy within the last 10 years to the region of the study tumor that would result in overlap of radiotherapy fields will be allowed. High dose radiotherapy is defined as an EQD2 of 45Gy or higher, as calculated with an alpha/beta ratio of 3. Patients with known or suspected radiation-induced meningioma are eligible
* New York Heart Association Functional Classification II or better (New York Heart Association \[NYHA\] Functional Classification III/IV are not eligible) (Note: Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification)
* No active infection currently requiring intravenous (IV) antibiotic management
* No known history of meningioma predisposition syndrome, such as neurofibromatosis type 2 (testing is not required)

Exclusion Criteria:

\-