Observation or Radiation Therapy in Treating Patients With Grade I, Grade II, or Grade III Meningioma

• Sponsor: Radiation Therapy Oncology Group (Other)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT00895622
• Collaborator: National Cancer Institute (NCI) (NIH), NRG Oncology (Other)
• Enrollment: 244
• Locations: 78
• Arms: 3
• Patients Per Site: 3.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Brain and Central Nervous System Tumors	Radiation: 54 Gy radiotherapy; Radiation: 60 Gy radiotherapy	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 244 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Trial of Observation for Low-Risk Meningiomas and of Radiotherapy for Intermediate- and High-Risk Meningiomas
• Study Start Date: Jun 1, 2009
• Actual Primary Completion Date: Sep 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
No Intervention: Low Risk No treatment given.
Experimental: Intermediate Risk 54 Gy radiotherapy	Radiation: 54 Gy radiotherapy; 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.; Other Names: external beam radiation therapy (EBRT) radiation therapy (RT) Proton therapy Three-dimensional conformal radiotherapy (3D-CRT) Intensity-modulated radiation therapy (IMRT)
Experimental: High Risk 60 Gy radiotherapy	Radiation: 60 Gy radiotherapy; 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.; Other Names: external beam radiation therapy (EBRT) radiation therapy Intensity-modulated radiation therapy (IMRT)

Outcome Measures

Primary Outcome Measures

1. Progression-free Survival Rate at 3 Years [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 Outcome Measures

1. 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.]

   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.

2. 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.]

   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.

3. Overall Survival Rate at 3 Years [From registration to 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.

4. Progression-free Survival Rate at 3 Years (Kaplan-Meier Method) [From registration to 3 years]

   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.

5. 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]

   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.

6. 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]

   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.

7. Adherence to Protocol-specific Target and Normal Tissue Radiotherapy Parameters [After treatment delivery]

   The principle investigator performed a radiotherapy quality assurance (QA) review.

8. Concordance Between Central and Parent Institution Histopathologic Grading/Subtyping [Baseline]

   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.

9. Molecular Correlative Studies [From registration to 3 years]

10. Histopathologic Correlates of PFS Including Light Microscopy, Immunohistochemical Analysis, and Microarray Analysis [From registration to 3 years]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

1. History/physical examination, including neurologic examination, within 8 weeks prior to Step 2 registration

2. Zubrod Performance Status 0-1

3. Age ≥ 18

4. 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.

1. 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.

1. 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

1. Inability to receive gadolinium

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arizona Oncology Services Foundation	Phoenix	Arizona	United States	85013
2	Mayo Clinic Hospital	Phoenix	Arizona	United States	85054
3	Mayo Clinic Scottsdale	Scottsdale	Arizona	United States	85259-5499
4	City of Hope Comprehensive Cancer Center	Duarte	California	United States	91010-3000
5	UCSF Helen Diller Family Comprehensive Cancer Center	San Francisco	California	United States	94115
6	Yale Cancer Center	New Haven	Connecticut	United States	06520-8028
7	University of Florida Shands Cancer Center	Gainesville	Florida	United States	32610-0232
8	Baptist-South Miami Regional Cancer Program	Miami	Florida	United States	33176
9	Emory Crawford Long Hospital	Atlanta	Georgia	United States	30308
10	Winship Cancer Institute of Emory University	Atlanta	Georgia	United States	30322
11	Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center	Savannah	Georgia	United States	31403-3089
12	Saint Alphonsus Cancer Care Center at Saint Alphonsus Regional Medical Center	Boise	Idaho	United States	83706
13	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois	United States	60611-3013
14	Methodist Cancer Center at Methodist Hospital	Indianapolis	Indiana	United States	46202
15	Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center	Kansas City	Kansas	United States	66160-7357
16	Kansas City Cancer Centers - Southwest	Overland Park	Kansas	United States	66210
17	CCOP - Kansas City	Prairie Village	Kansas	United States	66208
18	Norton Suburban Hospital	Louisville	Kentucky	United States	40207
19	Mary Bird Perkins Cancer Center - Baton Rouge	Baton Rouge	Louisiana	United States	70809
20	Maine Center for Cancer Medicine and Blood Disorders - Scarborough	Scarborough	Maine	United States	04074
21	Greenebaum Cancer Center at University of Maryland Medical Center	Baltimore	Maryland	United States	21201
22	Baystate Regional Cancer Program at D'Amour Center for Cancer Care	Springfield	Massachusetts	United States	01107
23	Josephine Ford Cancer Center at Henry Ford Hospital	Detroit	Michigan	United States	48202
24	Van Elslander Cancer Center at St. John Hospital and Medical Center	Grosse Pointe Woods	Michigan	United States	48236
25	West Michigan Cancer Center	Kalamazoo	Michigan	United States	49007-3731
26	Sparrow Regional Cancer Center	Lansing	Michigan	United States	48912-1811
27	St. Joseph Mercy Oakland	Pontiac	Michigan	United States	48341-2985
28	Mercy Regional Cancer Center at Mercy Hospital	Port Huron	Michigan	United States	48060
29	Seton Cancer Institute at Saint Mary's - Saginaw	Saginaw	Michigan	United States	48601
30	St. John Macomb Hospital	Warren	Michigan	United States	48093
31	Mayo Clinic Cancer Center	Rochester	Minnesota	United States	55905
32	Regions Hospital Cancer Care Center	Saint Paul	Minnesota	United States	55101
33	United Hospital	Saint Paul	Minnesota	United States	55102
34	Kansas City Cancer Centers - South	Kansas City	Missouri	United States	64131
35	Kansas City Cancer Centers - North	Kansas City	Missouri	United States	64154
36	Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis	Saint Louis	Missouri	United States	63110
37	Billings Clinic - Downtown	Billings	Montana	United States	59107-7000
38	Methodist Estabrook Cancer Center	Omaha	Nebraska	United States	68114
39	Nebraska Medical Center	Omaha	Nebraska	United States	68198
40	Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756-0002
41	Albert Einstein Cancer Center at Albert Einstein College of Medicine	Bronx	New York	United States	10461
42	CCOP - North Shore University Hospital	Manhasset	New York	United States	11030
43	Long Island Jewish Medical Center	New Hyde Park	New York	United States	11040
44	Highland Hospital of Rochester	Rochester	New York	United States	14620
45	James P. Wilmot Cancer Center at University of Rochester Medical Center	Rochester	New York	United States	14642
46	Blumenthal Cancer Center at Carolinas Medical Center	Charlotte	North Carolina	United States	28232-2861
47	Summa Center for Cancer Care at Akron City Hospital	Akron	Ohio	United States	44309-2090
48	Barberton Citizens Hospital	Barberton	Ohio	United States	44203
49	Case Comprehensive Cancer Center	Cleveland	Ohio	United States	44106-5065
50	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio	United States	44195
51	Riverside Methodist Hospital Cancer Care	Columbus	Ohio	United States	43214-3998
52	Grant Medical Center Cancer Care	Columbus	Ohio	United States	43215
53	Lake/University Ireland Cancer Center	Mentor	Ohio	United States	44060
54	Oklahoma University Cancer Institute	Oklahoma City	Oklahoma	United States	73104
55	Penn State Hershey Cancer Institute at Milton S. Hershey Medical Center	Hershey	Pennsylvania	United States	17033-0850
56	Kimmel Cancer Center at Thomas Jefferson University - Philadelphia	Philadelphia	Pennsylvania	United States	19107-5541
57	Gibbs Regional Cancer Center at Spartanburg Regional Medical Center	Spartanburg	South Carolina	United States	29303
58	University of Texas Medical Branch	Galveston	Texas	United States	77555-0361
59	M. D. Anderson Cancer Center at University of Texas	Houston	Texas	United States	77030-4009
60	Jon and Karen Huntsman Cancer Center at Intermountain Medical Center	Murray	Utah	United States	84157
61	Val and Ann Browning Cancer Center at McKay-Dee Hospital Center	Ogden	Utah	United States	84403
62	Dixie Regional Medical Center - East Campus	Saint George	Utah	United States	84770
63	Huntsman Cancer Institute at University of Utah	Salt Lake City	Utah	United States	84112
64	Norris Cotton Cancer Center - North	Saint Johnsbury	Vermont	United States	05819
65	Virginia Commonwealth University Massey Cancer Center	Richmond	Virginia	United States	23298-0037
66	University Cancer Center at University of Washington Medical Center	Seattle	Washington	United States	98195
67	St. Mary's Hospital Medical Center - Green Bay	Green Bay	Wisconsin	United States	54303
68	St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin	United States	54307-3508
69	Bay Area Cancer Care Center at Bay Area Medical Center	Marinette	Wisconsin	United States	54143
70	Community Memorial Hospital Cancer Care Center	Menomonee Falls	Wisconsin	United States	53051
71	Medical College of Wisconsin Cancer Center	Milwaukee	Wisconsin	United States	53226
72	Regional Cancer Center at Oconomowoc Memorial Hospital	Oconomowoc	Wisconsin	United States	53066
73	Door County Cancer Center at Door County Memorial Hospital	Sturgeon Bay	Wisconsin	United States	54235-1495
74	Waukesha Memorial Hospital Regional Cancer Center	Waukesha	Wisconsin	United States	53188
75	Cross Cancer Institute at University of Alberta	Edmonton	Alberta	Canada	T6G 1Z2
76	Ottawa Hospital Regional Cancer Centre - General Campus	Ottawa	Ontario	Canada	K1Y 4E9
77	Hopital Notre-Dame du CHUM	Montreal	Quebec	Canada	H2L 4M1
78	McGill Cancer Centre at McGill University	Montreal	Quebec	Canada	H2W 1S6

Sponsors and Collaborators

• Radiation Therapy Oncology Group
• National Cancer Institute (NCI)
• NRG Oncology

Investigators

• Principal Investigator: C. Leland Rogers, MD, Virginia Commonwealth University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Radiation Therapy Oncology Group
• ClinicalTrials.gov Identifier: NCT00895622
• Other Study ID Numbers: RTOG-0539; CDR0000641815
• First Posted: May 8, 2009
• Last Update Posted: Jun 10, 2021
• Last Verified: May 1, 2021

• Keywords provided by Radiation Therapy Oncology Group: adult grade I meningioma; adult grade II meningioma; adult grade III meningioma; adult anaplastic meningioma; adult papillary meningioma; recurrent adult brain tumor
• Additional relevant MeSH terms: Meningioma; Nervous System Neoplasms; Central Nervous System Neoplasms

Study Results

Participant Flow

Pre-assignment Detail	Two hundred forty-four patients registered for the first step registration which consisted of central pathology review confirmation of histology. One hundred seventy-eight continued on to the second step registration.

Arm/Group Title	Low Risk	Intermidiate Risk	High Risk
Arm/Group Description	No treatment given	54 Gy radiotherapy	60 Gy radiotherapy
Period Title: Overall Study
STARTED	65	56	57
COMPLETED	60	52	53
NOT COMPLETED	5	4	4

Baseline Characteristics

Arm/Group Title	Low Risk	Intermidiate Risk	High Risk	Total
Arm/Group Description	No treatment given	54 Gy radiotherapy	60 Gy radiotherapy	Total of all reporting groups
Overall Participants	60	52	53	165
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	56	53	62	56
Sex: Female, Male (Count of Participants)
Female	48 80%	32 61.5%	28 52.8%	108 65.5%
Male	12 20%	20 38.5%	25 47.2%	57 34.5%

Outcome Measures

1. Primary Outcome

Title	Progression-free Survival Rate at 3 Years
Description	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

Outcome Measure Data

Analysis Population Description

Eligible patients who started study treatment and evaluable for 3-year progression-free survival

Arm/Group Title	Low Risk	Intermidiate Risk	High Risk
Arm/Group Description	No treatment given	54 Gy radiotherapy	60 Gy radiotherapy
Measure Participants	51	48	51
Number (95% Confidence Interval) [percentage of participants]	92.2 153.7%	93.7 180.2%	58.8 110.9%

2. Secondary Outcome

Title	Number of Patients With Grades 2-5 Acute Adverse Events in the Following Categories Individually and Combined: Neurology, Ocular/Visual, Dermatologic/Skin [Excluding Alopecia]
Description	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.

Outcome Measure Data

Analysis Population Description

Eligible patients who started study treatment with acute AE assessed. Low risk patients are not reported since they did not receive any study treatment.

Arm/Group Title	Intermidiate Risk	High Risk
Arm/Group Description	54 Gy radiotherapy	60 Gy radiotherapy
Measure Participants	46	53
Grade 2	4 6.7%	3 5.8%
Grade 3	0 0%	2 3.8%
Grade 4	0 0%	0 0%
Grade 5	0 0%	0 0%
None Grade 2-5	42 70%	48 92.3%
Grade 2	1 1.7%	0 0%
Grade 3	0 0%	0 0%
Grade 4	0 0%	0 0%
Grade 5	0 0%	0 0%
None Grade 2-5	45 75%	53 101.9%
Grade 2	1 1.7%	2 3.8%
Grade 3	0 0%	0 0%
Grade 4	0 0%	0 0%
Grade 5	0 0%	0 0%
None Grade 2-5	45 75%	51 98.1%
Grade 2	5 8.3%	4 7.7%
Grade 3	0 0%	2 3.8%
Grade 4	0 0%	0 0%
Grade 5	0 0%	0 0%
None Grade 2-5	41 68.3%	47 90.4%

3. Secondary Outcome

Title	Number of Patients With Grades 2-5 Late Adverse Events in the Following Categories Individually and Combined: Neurology, Ocular/Visual, Dermatologic/Skin [Excluding Alopecia]
Description	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.

Outcome Measure Data

Analysis Population Description

Eligible patients who started study treatment with acute AE assessed. Low risk patients are not reported since they did not receive any study treatment.

Arm/Group Title	Intermidiate Risk	High Risk
Arm/Group Description	54 Gy radiotherapy	60 Gy radiotherapy
Measure Participants	51	51
Grade 2	12 20%	11 21.2%
Grade 3	0 0%	3 5.8%
Grade 4	0 0%	0 0%
Grade 5	0 0%	1 1.9%
None Grade 2-5	39 65%	36 69.2%
Grade 2	0 0%	0 0%
Grade 3	0 0%	0 0%
Grade 4	0 0%	0 0%
Grade 5	0 0%	0 0%
None Grade 2-5	51 85%	51 98.1%
Grade 2	1 1.7%	0 0%
Grade 3	0 0%	0 0%
Grade 4	0 0%	0 0%
Grade 5	0 0%	0 0%
None Grade 2-5	50 83.3%	51 98.1%
Grade 2	13 21.7%	11 21.2%
Grade 3	0 0%	3 5.8%
Grade 4	0 0%	0 0%
Grade 5	0 0%	1 1.9%
None Grade 2-5	38 63.3%	36 69.2%

4. Secondary Outcome

Title	Overall Survival Rate at 3 Years
Description	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

Outcome Measure Data

Analysis Population Description

Eligible patients who started study treatment

Arm/Group Title	Low Risk	Intermidiate Risk	High Risk
Arm/Group Description	No treatment given	54 Gy radiotherapy	60 Gy radiotherapy
Measure Participants	52	48	51
Number (95% Confidence Interval) [percentage of participants]	98.1 163.5%	95.8 184.2%	78.4 147.9%

5. Secondary Outcome

Title	Progression-free Survival Rate at 3 Years (Kaplan-Meier Method)
Description	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

Outcome Measure Data

Analysis Population Description

Eligible patients who started study treatment and evaluable for 3-year progression-free survival

Arm/Group Title	Low Risk	Intermidiate Risk	High Risk
Arm/Group Description	No treatment given	54 Gy radiotherapy	60 Gy radiotherapy
Measure Participants	60	52	53
Number (95% Confidence Interval) [percentage of participants]	91.4 152.3%	93.9 180.6%	59.2 111.7%

6. Secondary Outcome

Title	Number of Participants Determined to Have MRI Imaging Features as Assessed by Central Neuroradiology Review at Diagnosis, at Progression, and at 3 Years
Description	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

Outcome Measure Data

Analysis Population Description

Eligible participants who started study treatment, had a centrally reviewed MRI at the given time, and whose MRI was evaluable for the given feature

Arm/Group Title	MRI at Diagnosis	MRI at First Progression	MRI at 3 Years
Arm/Group Description
Measure Participants	148	23	79
Edema	76 126.7%	13 25%	15 28.3%
Homogeneous Enhancement	88 146.7%	9 17.3%	14 26.4%
Calcification	6 10%	0 0%	1 1.9%
Hyperostosis	17 28.3%	0 0%	1 1.9%
Brain Invasion	1 1.7%	0 0%	1 1.9%

7. Secondary Outcome

Title	Greatest Single Dimension From MRI as Assessed by Central Neuroradiology Review at Diagnosis, at Progression, and at 3 Years
Description	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

Outcome Measure Data

Analysis Population Description

Eligible participants who started study treatment, had a centrally reviewed MRI at the given time, and whose MRI was evaluable for tumor dimension.

Arm/Group Title	MRI at Diagnosis	MRI at First Progression	MRI at 3 Years
Arm/Group Description
Measure Participants	148	21	28
Median (Full Range) [milimeters]	42.7	34.7	29.0

8. Secondary Outcome

Title	Adherence to Protocol-specific Target and Normal Tissue Radiotherapy Parameters
Description	The principle investigator performed a radiotherapy quality assurance (QA) review.
Time Frame	After treatment delivery

Outcome Measure Data

Analysis Population Description

Eligible participants who started treatment and were centrally reviewed

Arm/Group Title	Intermidiate Risk	High Risk
Arm/Group Description	54 Gy radiotherapy	60 Gy radiotherapy
Measure Participants	44	46
Per protocol	36 60%	39 75%
Acceptable variation	4 6.7%	5 9.6%
Unacceptable deviation	2 3.3%	1 1.9%
Not evaluable	2 3.3%	1 1.9%

9. Secondary Outcome

Title	Concordance Between Central and Parent Institution Histopathologic Grading/Subtyping
Description	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

Outcome Measure Data

Analysis Population Description

Eligible patients with central and site reviews

Arm/Group Title	Central Review: Benign	Central Review: Atypical	Central Review: Anaplastic
Arm/Group Description
Measure Participants	76	71	25
Site Review: Benign	74 123.3%	9 17.3%	1 1.9%
Site Review: Atypical	2 3.3%	60 115.4%	8 15.1%
Site Review: Anaplastic	0 0%	2 3.8%	16 30.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Low Risk, Intermidiate Risk, High Risk
	Comments	The Kappa (κ) coefficient was used to assess the measure of agreement between the reviewers. κ can be interpreted as follows (κ / Agreement): < 0 / Less than chance agreement; 0.01-0.20 / Slight agreement; 0.21-0.40 / Fair agreement; 0.41-0.60 / Moderate agreement; 0.61-0.80 / Substantial agreement; 0.81-0.99 / Almost perfect agreement. The asymptotic test of the null hypothesis: κ=0 will be performed using the Z-statistic to determine the strength of agreement.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Z test
	Comments
Method of Estimation	Estimation Parameter	Kappa statistic
	Estimated Value	0.79
	Confidence Interval	(2-Sided) 95%; 0.71 to 0.87
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	Molecular Correlative Studies
Time Frame	From registration to 3 years

Outcome Measure Data

Analysis Population Description

The protocol did not provide sufficient detail to meet National Cancer Institute requirements for release of specimens from the NRG Oncology tissue bank for the protocol-specified analysis, therefore no assays were performed and no data were collected for this outcome measure. Specimen use will require federal approval and funding separate from this trial.

Arm/Group Title	Intermidiate Risk	High Risk
Arm/Group Description	54 Gy radiotherapy	60 Gy radiotherapy
Measure Participants	0	0

11. Secondary Outcome

Title	Histopathologic Correlates of PFS Including Light Microscopy, Immunohistochemical Analysis, and Microarray Analysis
Time Frame	From registration to 3 years

Outcome Measure Data

Analysis Population Description

The protocol did not provide sufficient detail to meet National Cancer Institute requirements for release of specimens from the NRG tissue bank for the protocol-specified analysis, therefore no assays were performed and no data were collected for this outcome measure. Specimen use will require federal approval and funding separate from this trial.

Arm/Group Title	Intermidiate Risk	High Risk
Arm/Group Description	54 Gy radiotherapy	60 Gy radiotherapy
Measure Participants	0	0

Adverse Events

Adverse Event Reporting Description	Eligible patients who started protocol treatment. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Arm/Group Title	Low Risk		Intermidiate Risk		High Risk
Arm/Group Description	No treatment given		54 Gy radiotherapy		60 Gy radiotherapy
All Cause Mortality
	Low Risk		Intermidiate Risk		High Risk
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	22/60 (36.7%)		47/52 (90.4%)		47/53 (88.7%)
Serious Adverse Events
	Low Risk		Intermidiate Risk		High Risk
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/60 (0%)		1/52 (1.9%)		5/53 (9.4%)
General disorders
Gait abnormal	0/60 (0%)		0/52 (0%)		1/53 (1.9%)
Pain [other]	0/60 (0%)		0/52 (0%)		1/53 (1.9%)
Infections and infestations
Soft tissue infection [with normal or Grade 1-2 ANC]	0/60 (0%)		0/52 (0%)		1/53 (1.9%)
Nervous system disorders
Central nervous system necrosis	0/60 (0%)		1/52 (1.9%)		1/53 (1.9%)
Neurological disorder NOS	0/60 (0%)		0/52 (0%)		1/53 (1.9%)
Peripheral sensory neuropathy	0/60 (0%)		0/52 (0%)		1/53 (1.9%)
Seizure	0/60 (0%)		0/52 (0%)		2/53 (3.8%)
Tremor	0/60 (0%)		0/52 (0%)		1/53 (1.9%)
Vascular disorders
Hypertension	0/60 (0%)		0/52 (0%)		1/53 (1.9%)
Other (Not Including Serious) Adverse Events
	Low Risk		Intermidiate Risk		High Risk
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	22/60 (36.7%)		47/52 (90.4%)		47/53 (88.7%)
Blood and lymphatic system disorders
Hemoglobin decreased	0/60 (0%)		1/52 (1.9%)		6/53 (11.3%)
Ear and labyrinth disorders
Hearing loss	0/60 (0%)		8/52 (15.4%)		4/53 (7.5%)
Tinnitus	0/60 (0%)		4/52 (7.7%)		0/53 (0%)
Eye disorders
Eye disorder	1/60 (1.7%)		5/52 (9.6%)		3/53 (5.7%)
Flashing vision	0/60 (0%)		3/52 (5.8%)		1/53 (1.9%)
Vision blurred	2/60 (3.3%)		7/52 (13.5%)		6/53 (11.3%)
Gastrointestinal disorders
Constipation	0/60 (0%)		4/52 (7.7%)		5/53 (9.4%)
Diarrhea	0/60 (0%)		4/52 (7.7%)		2/53 (3.8%)
Dyspepsia	0/60 (0%)		3/52 (5.8%)		2/53 (3.8%)
Nausea	0/60 (0%)		11/52 (21.2%)		11/53 (20.8%)
Vomiting	0/60 (0%)		5/52 (9.6%)		1/53 (1.9%)
General disorders
Edema limbs	0/60 (0%)		0/52 (0%)		4/53 (7.5%)
Fatigue	5/60 (8.3%)		34/52 (65.4%)		29/53 (54.7%)
Gait abnormal	0/60 (0%)		1/52 (1.9%)		5/53 (9.4%)
General symptom	0/60 (0%)		3/52 (5.8%)		0/53 (0%)
Injury, poisoning and procedural complications
Dermatitis radiation	0/60 (0%)		6/52 (11.5%)		9/53 (17%)
Radiation recall reaction (dermatologic)	0/60 (0%)		2/52 (3.8%)		8/53 (15.1%)
Investigations
Lymphocyte count decreased	0/60 (0%)		0/52 (0%)		4/53 (7.5%)
Platelet count decreased	1/60 (1.7%)		1/52 (1.9%)		4/53 (7.5%)
Weight loss	0/60 (0%)		5/52 (9.6%)		2/53 (3.8%)
Metabolism and nutrition disorders
Anorexia	0/60 (0%)		7/52 (13.5%)		6/53 (11.3%)
Blood glucose increased	1/60 (1.7%)		0/52 (0%)		7/53 (13.2%)
Serum albumin decreased	0/60 (0%)		0/52 (0%)		4/53 (7.5%)
Serum calcium decreased	0/60 (0%)		0/52 (0%)		4/53 (7.5%)
Serum potassium decreased	1/60 (1.7%)		0/52 (0%)		4/53 (7.5%)
Serum sodium decreased	0/60 (0%)		0/52 (0%)		3/53 (5.7%)
Musculoskeletal and connective tissue disorders
Back pain	2/60 (3.3%)		4/52 (7.7%)		3/53 (5.7%)
Muscle weakness	0/60 (0%)		0/52 (0%)		3/53 (5.7%)
Musculoskeletal disorder	0/60 (0%)		0/52 (0%)		5/53 (9.4%)
Neck pain	2/60 (3.3%)		3/52 (5.8%)		0/53 (0%)
Pain in extremity	1/60 (1.7%)		4/52 (7.7%)		2/53 (3.8%)
Nervous system disorders
Ataxia	1/60 (1.7%)		3/52 (5.8%)		3/53 (5.7%)
Central nervous system necrosis	0/60 (0%)		0/52 (0%)		3/53 (5.7%)
Cognitive disturbance	1/60 (1.7%)		3/52 (5.8%)		7/53 (13.2%)
Dizziness	5/60 (8.3%)		14/52 (26.9%)		9/53 (17%)
Headache	10/60 (16.7%)		25/52 (48.1%)		21/53 (39.6%)
Memory impairment	4/60 (6.7%)		8/52 (15.4%)		14/53 (26.4%)
Neurological disorder NOS	1/60 (1.7%)		1/52 (1.9%)		7/53 (13.2%)
Olfactory nerve disorder	0/60 (0%)		3/52 (5.8%)		0/53 (0%)
Peripheral motor neuropathy	1/60 (1.7%)		3/52 (5.8%)		3/53 (5.7%)
Peripheral sensory neuropathy	5/60 (8.3%)		6/52 (11.5%)		7/53 (13.2%)
Seizure	4/60 (6.7%)		7/52 (13.5%)		14/53 (26.4%)
Speech disorder	2/60 (3.3%)		3/52 (5.8%)		8/53 (15.1%)
Taste alteration	0/60 (0%)		3/52 (5.8%)		6/53 (11.3%)
Tremor	0/60 (0%)		1/52 (1.9%)		3/53 (5.7%)
Psychiatric disorders
Anxiety	3/60 (5%)		2/52 (3.8%)		3/53 (5.7%)
Depression	4/60 (6.7%)		4/52 (7.7%)		8/53 (15.1%)
Insomnia	2/60 (3.3%)		4/52 (7.7%)		2/53 (3.8%)
Renal and urinary disorders
Urinary frequency	0/60 (0%)		3/52 (5.8%)		2/53 (3.8%)
Urinary incontinence	0/60 (0%)		0/52 (0%)		6/53 (11.3%)
Skin and subcutaneous tissue disorders
Alopecia	0/60 (0%)		28/52 (53.8%)		32/53 (60.4%)
Dry skin	0/60 (0%)		1/52 (1.9%)		3/53 (5.7%)
Pruritus	0/60 (0%)		2/52 (3.8%)		5/53 (9.4%)
Rash desquamating	0/60 (0%)		0/52 (0%)		3/53 (5.7%)
Scalp pain	3/60 (5%)		0/52 (0%)		3/53 (5.7%)
Skin disorder	0/60 (0%)		2/52 (3.8%)		3/53 (5.7%)
Skin hyperpigmentation	0/60 (0%)		4/52 (7.7%)		5/53 (9.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

PI's are required to abide by the sponsor's publication guidelines which require review by coauthors and subsequent review and approval by the sponsor.