Benign Meningioma
Conditions
Keywords
sphenoid region, parasellar area, photon radiation therapy, proton radiation therapy
Brief summary
The purpose of this study is to determine the best radiation dose for participants with meningioma that has grown back after previous surgery, or which the surgeon has been unable to remove completely. This research study is designed to determine whether a higher dose of radiation will decrease the likelihood that the tumor will grow back, compared to the probability of re-growth that occurs after standard radiation doses.
Detailed description
* After initial interview and physical examination, an immobilization device (head mask, neck support, back support, etc.) will be made for the participant. A treatment planning CT will be performed and a radiation treatment plan will be based on this CT scan. * The radiation dose will usually be given once a day, five days per week. The radiation treatment will take between 7 and 8 1/2 weeks, including treatment planning. * Treatment doses will vary, and the dose each participant will receive will be made on the basis of random assignment. Participants will either receive the usual dose of 55.8 CGE in 31 treatments or 1.8 CGE, or 63 CGE in 35 treatments of 1.8 CGE.
Interventions
RADIATIONStandard Treatment
55.8 CGE in 31 treatments of 1.8 CGE given once a day, for five days each week. Treatment based upon a treatment planning CT.
RADIATIONHigher Dose
55.8 CGE in 31 treatments of 1.8 CGE given once a day, for five days each week. Treatment based upon a treatment planning CT.
Sponsors
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age 18 or over * Histological documentation of benign meningioma * Documentation by imaging studies (CT and/ or MRI) or residual or recurrent intracranial tumor * Karnofsky performance status of ≥ 70 * Study specific informed consent
Exclusion criteria
* Malignant meningiomas * Prior cranial irradiation, except treatment of localized skin cancer of the face or scalp * Patients having a concurrent primary cancer (except skin) * Patients having another cancer controlled \< 3 years * Pregnant patients
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival | 5, 10, 15 years | The number of participants surviving at the given time point. Progression free survival (PFS) is measured from the starting date of radiation therapy and analyzed by intention to treat. PFS is measured until the earlier, date of death or development of radiologic progression, and is otherwise censored at the last follow-up for progression-free patients still alive. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Acute Toxicities | 90 Days | The number of participants that experienced the specified acute toxicities (any grade) as assessed by Radiation Therapy Oncology Acute Morbidity Scoring Criteria. Acute toxicities were assessed from the start of treatment through day 90 of treatment. |
| Late Toxicities | 5 Years | The number of participants that experienced the specified late toxicities (any grade) as assessed by Radiation Therapy Oncology Group Late Effects Scale. |
| Local Failure Rate | 15 Years | The number of participants with local failure. Local failure is defined as radiologic progression seen on follow-up scans showing tumor margin(s) extending in any direction at least five mm beyond that seen on baseline scans. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Standard Treatment Standard radiation therapy: 55.8 CGE in 31 treatments of 1.8 CGE given once a day, for five days each week.
Standard Treatment: 55.8 CGE in 31 treatments of 1.8 CGE given once a day, for five days each week.
Treatment based upon a treatment planning CT. | 22 |
| Higher Dose Treatment 63 CGE in 35 treatments of 1.8 CGE given once a day, for five days of each week.
Higher Dose: 55.8 CGE in 31 treatments of 1.8 CGE given once a day, for five days each week. Treatment based upon a treatment planning CT. | 22 |
| Total | 44 |
Baseline characteristics
| Characteristic | Standard Treatment | Higher Dose Treatment | Total |
|---|---|---|---|
| Age, Continuous | 61 years | 50.5 years | 55.5 years |
| Clinical Target Volume | 49 Cubic Centimeters | 28 Cubic Centimeters | 38.5 Cubic Centimeters |
| Co-morbidities Coronary artery disease | 1 participants | 0 participants | 1 participants |
| Co-morbidities Diabetes mellitus | 0 participants | 4 participants | 4 participants |
| Co-morbidities Hyperlipidemia | 1 participants | 0 participants | 1 participants |
| Co-morbidities Hypertension | 3 participants | 6 participants | 9 participants |
| Co-morbidities One or more of the above | 4 participants | 6 participants | 10 participants |
| Gross Tumor Volume | 39.7 Cubic Centimeters | 13.2 Cubic Centimeters | 26.5 Cubic Centimeters |
| Radiation Indication Recurrent Disease | 11 Participants | 10 Participants | 21 Participants |
| Radiation Indication Sub-Total Resection, postoperative | 11 Participants | 12 Participants | 23 Participants |
| Region of Enrollment United States | 22 participants | 22 participants | 44 participants |
| Sex: Female, Male Female | 14 Participants | 15 Participants | 29 Participants |
| Sex: Female, Male Male | 8 Participants | 7 Participants | 15 Participants |
| Smoking Status Non-smoker | 11 Participants | 6 Participants | 17 Participants |
| Smoking Status Smoker | 9 Participants | 13 Participants | 22 Participants |
| Smoking Status Unknown | 2 Participants | 3 Participants | 5 Participants |
| Tumor Location Cavernous sinus | 3 Tumors | 8 Tumors | 11 Tumors |
| Tumor Location Cerebellar pontine angle | 3 Tumors | 1 Tumors | 4 Tumors |
| Tumor Location Clival/prepontine space | 3 Tumors | 1 Tumors | 4 Tumors |
| Tumor Location Olfactory groove | 1 Tumors | 0 Tumors | 1 Tumors |
| Tumor Location Optic canal | 0 Tumors | 1 Tumors | 1 Tumors |
| Tumor Location Sella/Parasella | 6 Tumors | 2 Tumors | 8 Tumors |
| Tumor Location Sphenoid wing | 7 Tumors | 8 Tumors | 15 Tumors |
| Tumor Location Tentorium | 0 Tumors | 1 Tumors | 1 Tumors |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 14 / 22 | 5 / 22 |
| other Total, other adverse events | 22 / 22 | 22 / 22 |
| serious Total, serious adverse events | 6 / 22 | 0 / 22 |
Outcome results
Primary
Progression Free Survival
The number of participants surviving at the given time point. Progression free survival (PFS) is measured from the starting date of radiation therapy and analyzed by intention to treat. PFS is measured until the earlier, date of death or development of radiologic progression, and is otherwise censored at the last follow-up for progression-free patients still alive.
Time frame: 5, 10, 15 years
Population: Progression free survival in the entire cohort and by radiation indication sub-groups
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Standard Treatment | Progression Free Survival | Entire Cohort: 10 Years | 86 percentage of participants surviving |
| Standard Treatment | Progression Free Survival | Subtotal Resection: 15 Years | 64 percentage of participants surviving |
| Standard Treatment | Progression Free Survival | Subtotal Resection: 5 Years | 100 percentage of participants surviving |
| Standard Treatment | Progression Free Survival | Recurrent Disease: 5 Years | 82 percentage of participants surviving |
| Standard Treatment | Progression Free Survival | Entire Cohort: 15 Years | 52 percentage of participants surviving |
| Standard Treatment | Progression Free Survival | Recurrent Disease: 10 Years | 82 percentage of participants surviving |
| Standard Treatment | Progression Free Survival | Subtotal Resection: 10 Years | 91 percentage of participants surviving |
| Standard Treatment | Progression Free Survival | Recurrent Disease: 15 Years | 65 percentage of participants surviving |
| Standard Treatment | Progression Free Survival | Entire Cohort: 5 Years | 91 percentage of participants surviving |
| Higher Dose Treatment | Progression Free Survival | Recurrent Disease: 15 Years | 100 percentage of participants surviving |
| Higher Dose Treatment | Progression Free Survival | Entire Cohort: 5 Years | 91 percentage of participants surviving |
| Higher Dose Treatment | Progression Free Survival | Entire Cohort: 10 Years | 81 percentage of participants surviving |
| Higher Dose Treatment | Progression Free Survival | Entire Cohort: 15 Years | 70 percentage of participants surviving |
| Higher Dose Treatment | Progression Free Survival | Subtotal Resection: 5 Years | 83 percentage of participants surviving |
| Higher Dose Treatment | Progression Free Survival | Subtotal Resection: 10 Years | 67 percentage of participants surviving |
| Higher Dose Treatment | Progression Free Survival | Subtotal Resection: 15 Years | 57 percentage of participants surviving |
| Higher Dose Treatment | Progression Free Survival | Recurrent Disease: 5 Years | 100 percentage of participants surviving |
| Higher Dose Treatment | Progression Free Survival | Recurrent Disease: 10 Years | 100 percentage of participants surviving |
Comparison: Null hypothesis: Progression free survival is not significantly different by dose level in the overall cohort.p-value: 0.234Log Rank
Comparison: Null hypothesis: Progression free survival is not significantly different by dose level in the subgroup receiving treatment due to a sub-total resectionp-value: 0.82Log Rank
Comparison: Null hypothesis: Progression free survival is not significantly different by dose level in the sub-group receiving treatment due to recurrent diseasep-value: 0.061Log Rank
Secondary
Acute Toxicities
The number of participants that experienced the specified acute toxicities (any grade) as assessed by Radiation Therapy Oncology Acute Morbidity Scoring Criteria. Acute toxicities were assessed from the start of treatment through day 90 of treatment.
Time frame: 90 Days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Standard Treatment | Acute Toxicities | Facial weakness | 2 participants |
| Standard Treatment | Acute Toxicities | Exophthalmos | 1 participants |
| Standard Treatment | Acute Toxicities | Ataxia | 1 participants |
| Standard Treatment | Acute Toxicities | Tinnitus | 0 participants |
| Standard Treatment | Acute Toxicities | Seizure | 1 participants |
| Standard Treatment | Acute Toxicities | Visual field deficit | 1 participants |
| Standard Treatment | Acute Toxicities | Headache | 3 participants |
| Standard Treatment | Acute Toxicities | Olfactory alteration | 1 participants |
| Standard Treatment | Acute Toxicities | Nausea | 9 participants |
| Standard Treatment | Acute Toxicities | Conjunctivitis | 1 participants |
| Standard Treatment | Acute Toxicities | Dizziness | 1 participants |
| Standard Treatment | Acute Toxicities | Gustation alteration | 3 participants |
| Standard Treatment | Acute Toxicities | Vertigo | 1 participants |
| Standard Treatment | Acute Toxicities | Ptosis | 0 participants |
| Standard Treatment | Acute Toxicities | Syncope | 1 participants |
| Standard Treatment | Acute Toxicities | Neuromotor deficit | 1 participants |
| Standard Treatment | Acute Toxicities | Depression | 0 participants |
| Standard Treatment | Acute Toxicities | Eye, other | 2 participants |
| Standard Treatment | Acute Toxicities | Neurocog deficit | 1 participants |
| Standard Treatment | Acute Toxicities | Weakness | 1 participants |
| Standard Treatment | Acute Toxicities | Endocrine deficit | 0 participants |
| Standard Treatment | Acute Toxicities | Diplopia | 2 participants |
| Standard Treatment | Acute Toxicities | Skin changes | 16 participants |
| Standard Treatment | Acute Toxicities | Facial numbness | 2 participants |
| Standard Treatment | Acute Toxicities | Alopecia | 7 participants |
| Standard Treatment | Acute Toxicities | Hearing loss | 1 participants |
| Standard Treatment | Acute Toxicities | Fatigue | 12 participants |
| Standard Treatment | Acute Toxicities | Vision loss | 2 participants |
| Higher Dose Treatment | Acute Toxicities | Fatigue | 10 participants |
| Higher Dose Treatment | Acute Toxicities | Vision loss | 1 participants |
| Higher Dose Treatment | Acute Toxicities | Visual field deficit | 0 participants |
| Higher Dose Treatment | Acute Toxicities | Diplopia | 0 participants |
| Higher Dose Treatment | Acute Toxicities | Ptosis | 1 participants |
| Higher Dose Treatment | Acute Toxicities | Exophthalmos | 0 participants |
| Higher Dose Treatment | Acute Toxicities | Conjunctivitis | 2 participants |
| Higher Dose Treatment | Acute Toxicities | Eye, other | 5 participants |
| Higher Dose Treatment | Acute Toxicities | Hearing loss | 2 participants |
| Higher Dose Treatment | Acute Toxicities | Tinnitus | 1 participants |
| Higher Dose Treatment | Acute Toxicities | Olfactory alteration | 1 participants |
| Higher Dose Treatment | Acute Toxicities | Gustation alteration | 1 participants |
| Higher Dose Treatment | Acute Toxicities | Neuromotor deficit | 0 participants |
| Higher Dose Treatment | Acute Toxicities | Weakness | 0 participants |
| Higher Dose Treatment | Acute Toxicities | Facial numbness | 1 participants |
| Higher Dose Treatment | Acute Toxicities | Facial weakness | 2 participants |
| Higher Dose Treatment | Acute Toxicities | Ataxia | 0 participants |
| Higher Dose Treatment | Acute Toxicities | Seizure | 1 participants |
| Higher Dose Treatment | Acute Toxicities | Headache | 8 participants |
| Higher Dose Treatment | Acute Toxicities | Nausea | 8 participants |
| Higher Dose Treatment | Acute Toxicities | Dizziness | 1 participants |
| Higher Dose Treatment | Acute Toxicities | Vertigo | 4 participants |
| Higher Dose Treatment | Acute Toxicities | Syncope | 0 participants |
| Higher Dose Treatment | Acute Toxicities | Depression | 3 participants |
| Higher Dose Treatment | Acute Toxicities | Neurocog deficit | 3 participants |
| Higher Dose Treatment | Acute Toxicities | Endocrine deficit | 1 participants |
| Higher Dose Treatment | Acute Toxicities | Skin changes | 18 participants |
| Higher Dose Treatment | Acute Toxicities | Alopecia | 11 participants |
Secondary
Late Toxicities
The number of participants that experienced the specified late toxicities (any grade) as assessed by Radiation Therapy Oncology Group Late Effects Scale.
Time frame: 5 Years
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Standard Treatment | Late Toxicities | Vision loss | 5 participants |
| Standard Treatment | Late Toxicities | Neuromotor deficit | 1 participants |
| Standard Treatment | Late Toxicities | Weakness | 1 participants |
| Standard Treatment | Late Toxicities | Facial numbness | 1 participants |
| Standard Treatment | Late Toxicities | Facial weakness | 4 participants |
| Standard Treatment | Late Toxicities | Ataxia | 2 participants |
| Standard Treatment | Late Toxicities | Fall | 0 participants |
| Standard Treatment | Late Toxicities | Dysarthria | 1 participants |
| Standard Treatment | Late Toxicities | Visual field deficit | 5 participants |
| Standard Treatment | Late Toxicities | Diplopia | 1 participants |
| Standard Treatment | Late Toxicities | Exophthalmos | 0 participants |
| Standard Treatment | Late Toxicities | Eye, other | 3 participants |
| Standard Treatment | Late Toxicities | Hearing loss | 6 participants |
| Standard Treatment | Late Toxicities | Tinnitus | 2 participants |
| Standard Treatment | Late Toxicities | Olfactory alteration | 0 participants |
| Standard Treatment | Late Toxicities | Gustation alteration | 0 participants |
| Standard Treatment | Late Toxicities | Dysphasia | 0 participants |
| Standard Treatment | Late Toxicities | Headache | 5 participants |
| Standard Treatment | Late Toxicities | Dizziness | 1 participants |
| Standard Treatment | Late Toxicities | Vertigo | 1 participants |
| Standard Treatment | Late Toxicities | Depression | 0 participants |
| Standard Treatment | Late Toxicities | Neurocognative deficit | 7 participants |
| Standard Treatment | Late Toxicities | Endocrine deficit | 7 participants |
| Standard Treatment | Late Toxicities | Osteoporosis | 0 participants |
| Standard Treatment | Late Toxicities | Cerebral edema | 1 participants |
| Standard Treatment | Late Toxicities | Brain atrophy | 0 participants |
| Standard Treatment | Late Toxicities | Skin changes | 1 participants |
| Standard Treatment | Late Toxicities | Alopecia | 0 participants |
| Standard Treatment | Late Toxicities | Fatigue | 4 participants |
| Higher Dose Treatment | Late Toxicities | Olfactory alteration | 2 participants |
| Higher Dose Treatment | Late Toxicities | Neurocognative deficit | 6 participants |
| Higher Dose Treatment | Late Toxicities | Neuromotor deficit | 0 participants |
| Higher Dose Treatment | Late Toxicities | Gustation alteration | 1 participants |
| Higher Dose Treatment | Late Toxicities | Weakness | 2 participants |
| Higher Dose Treatment | Late Toxicities | Brain atrophy | 1 participants |
| Higher Dose Treatment | Late Toxicities | Facial numbness | 4 participants |
| Higher Dose Treatment | Late Toxicities | Dysphasia | 1 participants |
| Higher Dose Treatment | Late Toxicities | Facial weakness | 2 participants |
| Higher Dose Treatment | Late Toxicities | Dysarthria | 0 participants |
| Higher Dose Treatment | Late Toxicities | Ataxia | 3 participants |
| Higher Dose Treatment | Late Toxicities | Endocrine deficit | 10 participants |
| Higher Dose Treatment | Late Toxicities | Fall | 3 participants |
| Higher Dose Treatment | Late Toxicities | Headache | 3 participants |
| Higher Dose Treatment | Late Toxicities | Cerebral edema | 0 participants |
| Higher Dose Treatment | Late Toxicities | Vision loss | 2 participants |
| Higher Dose Treatment | Late Toxicities | Alopecia | 2 participants |
| Higher Dose Treatment | Late Toxicities | Visual field deficit | 1 participants |
| Higher Dose Treatment | Late Toxicities | Dizziness | 0 participants |
| Higher Dose Treatment | Late Toxicities | Diplopia | 3 participants |
| Higher Dose Treatment | Late Toxicities | Osteoporosis | 1 participants |
| Higher Dose Treatment | Late Toxicities | Exophthalmos | 2 participants |
| Higher Dose Treatment | Late Toxicities | Vertigo | 1 participants |
| Higher Dose Treatment | Late Toxicities | Eye, other | 2 participants |
| Higher Dose Treatment | Late Toxicities | Skin changes | 1 participants |
| Higher Dose Treatment | Late Toxicities | Hearing loss | 4 participants |
| Higher Dose Treatment | Late Toxicities | Depression | 1 participants |
| Higher Dose Treatment | Late Toxicities | Tinnitus | 3 participants |
| Higher Dose Treatment | Late Toxicities | Fatigue | 3 participants |
Secondary
Local Failure Rate
The number of participants with local failure. Local failure is defined as radiologic progression seen on follow-up scans showing tumor margin(s) extending in any direction at least five mm beyond that seen on baseline scans.
Time frame: 15 Years
Population: Failure rates are shown by dose group in the overall study population and by treatment indication subgroups.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Standard Treatment | Local Failure Rate | Entire Cohort | 3 participants |
| Standard Treatment | Local Failure Rate | Post-operative subgroup | 0 participants |
| Standard Treatment | Local Failure Rate | Tumor recurrence subgroup | 3 participants |
| Higher Dose Treatment | Local Failure Rate | Entire Cohort | 2 participants |
| Higher Dose Treatment | Local Failure Rate | Post-operative subgroup | 1 participants |
| Higher Dose Treatment | Local Failure Rate | Tumor recurrence subgroup | 1 participants |