Phase II Trial of Observation for Low-Risk Meningiomas and of Radiotherapy for Intermediate- and High-Risk Meningiomas
Overview
- Phase
- Phase 2
- Intervention
- Not specified
- Conditions
- Brain and Central Nervous System Tumors
- Sponsor
- Radiation Therapy Oncology Group
- Enrollment
- 244
- Locations
- 78
- Primary Endpoint
- Progression-free Survival Rate at 3 Years
- Status
- Completed
- Last Updated
- 2 years ago
Overview
Brief 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.
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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.
- •History/physical examination, including neurologic examination, within 8 weeks prior to Step 2 registration
- •Zubrod Performance Status 0-1
- •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 T
- •The postoperative study must be completed within 12 weeks of surgery.
Exclusion Criteria
- •Extracranial meningioma
- •Multiple meningiomas
- •Hemangiopericytoma
- •Major medical illnesses or psychiatric impairments which, in the investigators opinion, will prevent administration or completion of the protocol therapy or preclude informed consent
- •Previous radiation therapy to the scalp, cranium, brain, or skull base
- •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)
- •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
Outcomes
Primary Outcomes
Progression-free Survival Rate at 3 Years
Time Frame: From registration to 3 years
Progression was determined by central review of magnetic resonance imaging (MRI) exams and is defined as an increase in measurable tumor of greater than 20% in any diameter, or as new nodular enhancement in patients with no measurable tumor on initial postoperative imaging. In the absence of neurologic progression (NP), suspected imaging progression of less than 5 mm (maximum diameter) must be confirmed on two successive follow-up MRI studies, a minimum of 3 months apart. NP is defined as a new or progressive neurologic deficit attributed to the meningioma, with or without measurable meningioma growth. Progression-free survival (PFS) rates are estimated using the binomial method.
Secondary Outcomes
- Greatest Single Dimension From MRI as Assessed by Central Neuroradiology Review at Diagnosis, at Progression, and at 3 Years(Baseline, at time of first progression, and at 3 years)
- Histopathologic Correlates of PFS Including Light Microscopy, Immunohistochemical Analysis, and Microarray Analysis(From registration to 3 years)
- Number of Patients With Grades 2-5 Late Adverse Events in the Following Categories Individually and Combined: Neurology, Ocular/Visual, Dermatologic/Skin [Excluding Alopecia](Ninety-one days from start of radiation therapy to last follow-up. Maximum follow-up at time of analysis was 6.3 years.)
- Concordance Between Central and Parent Institution Histopathologic Grading/Subtyping(Baseline)
- Number of Patients With Grades 2-5 Acute Adverse Events in the Following Categories Individually and Combined: Neurology, Ocular/Visual, Dermatologic/Skin [Excluding Alopecia](From start of radiation to 90 days.)
- Overall Survival Rate at 3 Years(From registration to 3 years)
- Progression-free Survival Rate at 3 Years (Kaplan-Meier Method)(From registration to 3 years)
- Number of Participants Determined to Have MRI Imaging Features as Assessed by Central Neuroradiology Review at Diagnosis, at Progression, and at 3 Years(Baseline, at time of first progression, and at 3 years)
- Adherence to Protocol-specific Target and Normal Tissue Radiotherapy Parameters(After treatment delivery)
- Molecular Correlative Studies(From registration to 3 years)