Brain Tumor, Central Nervous System Tumor
Conditions
Keywords
childhood oligodendroglioma, recurrent childhood cerebellar astrocytoma, recurrent childhood cerebral astrocytoma, childhood low-grade cerebral astrocytoma, recurrent childhood visual pathway and hypothalamic glioma, untreated childhood cerebellar astrocytoma, untreated childhood visual pathway and hypothalamic glioma
Brief summary
RATIONALE: Specialized radiation therapy that delivers radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. PURPOSE: This phase II trial is studying how well radiation therapy works in treating young patients with gliomas.
Detailed description
OBJECTIVES: Primary * Determine the marginal-failure rate in young patients with low-grade gliomas treated with reduced-field conformal radiotherapy. Secondary * Determine the progression-free survival, event-free survival, and overall survival rates of young patients treated with this regimen. * Determine quality of life of patients treated with this regimen. * Correlate MIB-1 labeling index with progression-free survival and overall survival of these patients. OUTLINE: This is a multicenter study. Patients undergo reduced-field conformal radiotherapy 5 days a week for 6 weeks in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at baseline or 6 weeks after completion of study treatment and then at 2 and 5 years (closed as of 10/27/2010). After completion of study treatment, patients are followed every 3 months for 2 years, every 6 months for 2 years, and then annually thereafter.
Interventions
Undergo 3D-CRT Undergo proton radiation therapy Undergo IMRT
Sponsors
Study design
Eligibility
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically confirmed\* low-grade glioma, including any of the following: * Juvenile pilocytic astrocytoma (JPA) or pleomorphic JPA * Diffuse astrocytoma, including any of the following subtypes: * Fibrillary astrocytoma * Gemistocytic astrocytoma * Subependymal giant cell astrocytoma * Pleomorphic xanthoastrocytoma * Low-grade oligoastrocytoma * Low-grade oligodendroglioma * Low-grade glioma not otherwise specified NOTE: \*Patients with chiasmatic lesions who have contiguous extension of tumor into other regions of the visual pathway by CT scan or MRI are eligible without histopathologic confirmation; repeat biopsy required for patients with recurrent tumors that enhance but whose initial tumor did not * Measurable disease by radiography * Meets any of the following criteria: * Progressive nonresectable disease * Any location in the brain * Patients with a less than gross total resection are eligible provided they are symptomatic from their tumor OR the risk from neurologic impairment with progression is high enough to warrant immediate treatment * Has undergone biopsy only * Must have received ≥ 1 course of prior chemotherapy (for patients \< 10 years of age) * Prior chemotherapy optional (for patients ≥ 10 years of age) * No type-1 neurofibromatosis * No evidence of leptomeningeal dissemination PATIENT CHARACTERISTICS: Age * 3 to 20 Performance status * ECOG 0-2 OR * Karnofsky 50-100% (for patients \> 16 years of age) OR * Lansky 50-100% (for patients ≤ 16 years of age) Life expectancy * At least 1 year Hematopoietic * Absolute neutrophil count ≥ 1,000/mm\^3 * Platelet count ≥ 100,000/mm\^3 (transfusion independent) * Hemoglobin ≥ 10.0 g/dL (transfusions allowed) Hepatic * Not specified Renal * Not specified Other * Not pregnant * Negative pregnancy test * Fertile patients must use effective contraception * Not in status epilepticus, coma, or requiring assisted ventilation prior to study entry * Patients with a seizure disorder are eligible provided they are on anticonvulsants AND disease is well controlled PRIOR CONCURRENT THERAPY: Biologic therapy * Not specified Chemotherapy * See Disease Characteristics * Recovered from prior chemotherapy * No concurrent chemotherapy Endocrine therapy * Concurrent dexamethasone allowed provided patient has been on a stable dose for ≥ 2 weeks prior to study entry * Concurrent dexamethasone allowed for symptoms of increased intracranial pressure Radiotherapy * No prior radiotherapy Surgery * See Disease Characteristics Other * No other concurrent anticancer therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Marginal-failure Rate | Up to 5 years | Patients who do not recur as well as those with either central or distant recurrence would be treatment successes for this endpoint. Monitoring will be based on a Bayesian rule, with binomial likelihood and a Beta on the parameter p, the proportion of failures that are marginal failures. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Event-free Survival Probability | 3 years | To estimate the event-free survival rate for patients with recurrent, progressive or symptomatic low-grade gliomas after treatment with reduced field conformal radiation |
| Overall Survival Probability | 3 years | To estimate the overall survival rate for patients with recurrent, progressive or symptomatic low-grade gliomas after treatment with reduced field conformal radiation. |
| Progression-free Survival Probability | 3 years | To estimate the progression-free survival rate for patients with recurrent, progressive or symptomatic low-grade gliomas after treatment with reduced field conformal radiation. |
| MIB-1 Labeling Index Using Immunohistochemical Techniques With the MIB-1 Antibody According to Established Methods | At baseline | The MIB-1 labeling Index will be calculated as the percentage of tumor nuclei that are immunoreactive. |
| Correlation MIB-1 Labeling Index With PFS | Up to 10 years | The primary methods of analysis will be via stratified Cox regression |
| Quality of Life (QOL) | Up to 5 years | QOL accessed using the Behavior Assessment System for Children (BASC), the Adaptive Behavior Assessment System (ABAS), the Behavior Rating Inventory of Executive Function (BRIEF), and the Symptom Checklist-90-R (SCL-90-R). |
Countries
Australia, Canada, New Zealand, Puerto Rico, Switzerland, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Reduced-field Conformal Radiation Therapy Patients undergo reduced-field conformal radiation therapy 5 days a week for 6 weeks in the absence of disease progression or unacceptable toxicity.
radiation therapy: Undergo 3D-CRT Undergo proton radiation therapy Undergo IMRT | 92 |
| Total | 92 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 7 |
| Overall Study | Ineligible | 7 |
| Overall Study | Lost to Follow-up | 18 |
| Overall Study | Withdrawal by Subject | 4 |
Baseline characteristics
| Characteristic | Reduced-field Conformal Radiation Therapy |
|---|---|
| Age, Categorical <=18 years | 86 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants |
| Age, Continuous | 13.6 Years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 82 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 9 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 6 Participants |
| Race (NIH/OMB) White | 75 Participants |
| Sex: Female, Male Female | 49 Participants |
| Sex: Female, Male Male | 43 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 5 / 85 |
| serious Total, serious adverse events | 5 / 85 |
Outcome results
Marginal-failure Rate
Patients who do not recur as well as those with either central or distant recurrence would be treatment successes for this endpoint. Monitoring will be based on a Bayesian rule, with binomial likelihood and a Beta on the parameter p, the proportion of failures that are marginal failures.
Time frame: Up to 5 years
Population: All evaluable patients were included in this analysis (n = 84). One eligible patient was deemed to be not evaluable due to progression during treatment, and was excluded from the analysis per protocol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Reduced-field Conformal Radiation Therapy | Marginal-failure Rate | 0 percentage of failure rate |
Correlation MIB-1 Labeling Index With PFS
The primary methods of analysis will be via stratified Cox regression
Time frame: Up to 10 years
Population: All eligible patients with MIB-1 data available were included in this analysis. Per protocol, patients were stratified by age and tumor location. Based on a predefined cutoff, patients were categorized as MIB high or low (high: \>= 2; low: \< 2). The hazard ratio below is for patients with MIB high (low is the reference level).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Reduced-field Conformal Radiation Therapy | Correlation MIB-1 Labeling Index With PFS | 1.08 Hazard ratio |
Event-free Survival Probability
To estimate the event-free survival rate for patients with recurrent, progressive or symptomatic low-grade gliomas after treatment with reduced field conformal radiation
Time frame: 3 years
Population: All eligible patients were included in the analysis, per protocol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Reduced-field Conformal Radiation Therapy | Event-free Survival Probability | 77.1 Percentage 3-year EFS rate |
MIB-1 Labeling Index Using Immunohistochemical Techniques With the MIB-1 Antibody According to Established Methods
The MIB-1 labeling Index will be calculated as the percentage of tumor nuclei that are immunoreactive.
Time frame: At baseline
Population: All eligible patients with MIB-1 labeling index available.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Reduced-field Conformal Radiation Therapy | MIB-1 Labeling Index Using Immunohistochemical Techniques With the MIB-1 Antibody According to Established Methods | 3.1 percentage of tumor nuclei |
Overall Survival Probability
To estimate the overall survival rate for patients with recurrent, progressive or symptomatic low-grade gliomas after treatment with reduced field conformal radiation.
Time frame: 3 years
Population: All eligible patients were included in the analysis, per protocol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Reduced-field Conformal Radiation Therapy | Overall Survival Probability | 94.0 Percentage 3-year OS rate |
Progression-free Survival Probability
To estimate the progression-free survival rate for patients with recurrent, progressive or symptomatic low-grade gliomas after treatment with reduced field conformal radiation.
Time frame: 3 years
Population: All eligible patients were included in the analysis, per protocol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Reduced-field Conformal Radiation Therapy | Progression-free Survival Probability | 77.1 Percentage 3-year PFS rate |
Quality of Life (QOL)
QOL accessed using the Behavior Assessment System for Children (BASC), the Adaptive Behavior Assessment System (ABAS), the Behavior Rating Inventory of Executive Function (BRIEF), and the Symptom Checklist-90-R (SCL-90-R).
Time frame: Up to 5 years
Population: The QOL assessments were removed from the protocol as part of Amendment #1A (as of 10/27/2010) due to extremely low compliance. No QOL data were available for statistical analysis.