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.
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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
244
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.
Arizona Oncology Services Foundation
Phoenix, Arizona, United States
Mayo Clinic Hospital
Phoenix, Arizona, United States
Mayo Clinic Scottsdale
Scottsdale, Arizona, United States
City of Hope Comprehensive Cancer Center
Duarte, California, United States
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, United States
Progression-free Survival Rate at 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.
Time frame: From registration to 3 years
Number of Patients With Grades 2-5 Acute Adverse Events in the Following Categories Individually and Combined: Neurology, Ocular/Visual, Dermatologic/Skin [Excluding Alopecia]
Grades 2-5 neurology, ocular/visual, dermatologic/skin \[excluding alopecia\] categories, individually and combined for acute adverse events as assessed by NCI Common Toxicity Criteria for Adverse Effects (CTCAE) v3.0 where the attribution is related to treatment as definite, probable, possible, or unknown. Adverse events are graded using CTCAE v3.0. Grade refers to the severity of the AE. The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE.
Time frame: From start of radiation to 90 days.
Number of Patients With Grades 2-5 Late Adverse Events in the Following Categories Individually and Combined: Neurology, Ocular/Visual, Dermatologic/Skin [Excluding Alopecia]
Grades 2-5 neurology, ocular/visual, dermatologic/skin \[excluding alopecia\] categories, individually and combined for acute adverse events as assessed by NCI Common Toxicity Criteria for Adverse Effects (CTCAE) v3.0 where the attribution is related to treatment as definite, probable, possible, or unknown. Late adverse events are those occurring more than 90 days from start of radiation therapy.
Time frame: Ninety-one days from start of radiation therapy to last follow-up. Maximum follow-up at time of analysis was 6.3 years.
Overall Survival Rate at 3 Years
Overall survival time is defined as time from randomization to date of death from any cause and is estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact.
Time frame: From registration to 3 years
Progression-free Survival Rate at 3 Years (Kaplan-Meier Method)
Progression was determined by central review of 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 time is defined as time from registration to the date of progression, death, or last known follow-up (censored). Progression-free survival rates are estimated using the Kaplan-Meier method.
Time frame: 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
MRI's were centrally reviewed by the study neuroradiology co-chairs for presence of edema, homogeneous enhancement, calcification, hyperostosis, and brain invasion. Data is presented for all risk groups combined, with time points presented in each column. Neither risk groups nor time points are compared.
Time frame: Baseline, at time of first progression, and at 3 years
Greatest Single Dimension From MRI as Assessed by Central Neuroradiology Review at Diagnosis, at Progression, and at 3 Years
MRI's were centrally reviewed by the study neuroradiology co-chairs. Data is presented for all risk groups combined, with time points presented in each column. Neither risk groups nor time points are compared.
Time frame: Baseline, at time of first progression, and at 3 years
Adherence to Protocol-specific Target and Normal Tissue Radiotherapy Parameters
The principle investigator performed a radiotherapy quality assurance (QA) review.
Time frame: After treatment delivery
Concordance Between Central and Parent Institution Histopathologic Grading/Subtyping
A pathology review was conducted both by the institution and centrally, with three possible choices for grade / subtype: World Health Organization (WHO) Grade I / benign; WHO grade II / atypical; WHO grade III / anaplastic. Data is presented for all risk groups combined.
Time frame: Baseline
Molecular Correlative Studies
Time frame: From registration to 3 years
Histopathologic Correlates of PFS Including Light Microscopy, Immunohistochemical Analysis, and Microarray Analysis
Time frame: From registration to 3 years
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Yale Cancer Center
New Haven, Connecticut, United States
University of Florida Shands Cancer Center
Gainesville, Florida, United States
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Miami, Florida, United States
Emory Crawford Long Hospital
Atlanta, Georgia, United States
Winship Cancer Institute of Emory University
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