Brain Tumor, Low Grade Glioma, Astrocytoma, Ependymoma, Ganglioglioma
Conditions
Keywords
proton radiotherapy
Brief summary
Some patients with brain tumors receive standard radiation to help prevent tumor growth. Although standard radiation kills tumor cells, it can also damage normal tissue in the process and lead to more side effects. This research study is looking at a different form of radiation called proton radiotherapy which helps spare normal tissues while delivering radiation to the tumor or tumor bed. Proton techniques irradiate 2-3 times less normal tissue then standard radiation. This therapy has been used in treatment of other cancers and information from those other research studies suggests that this therapy may help better target brain tumors then standard radiation.
Detailed description
\- Participants will receive proton radiotherapy at the Francis H. Burr Proton Therapy Center which is located at the Massachusetts General Hospital. They will receive the proton radiotherapy 5 days per week. The number of weeks the participant will be receiving proton radiotherapy depends upon the tumor type and location and how well they are tolerating the treatment. Participant's will have a physical exam weekly during proton radiotherapy treatment.
Interventions
RADIATIONProton radiotherapy
5 days a week
Sponsors
Dana-Farber Cancer Institute
National Cancer Institute (NCI)
Massachusetts General Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to 25 Years
Healthy volunteers
No
Inclusion criteria
* Biopsy proven low grade glioma or astrocytoma, ependymoma, craniopharyngioma, meningioma, neurocytoma, medulloblastoma or gangliogliomas or other rare tumor requiring tumor bed or tumor irradiation. Patients with a presumed diagnosis of optic glioma or gliomas based on imaging and clinical characteristics will also be allowed on this trial. * Patients with biopsy proven high grade glioma (excluding GBM) and a gross total resection and patients with non-disseminated atypical teratoid rhabdoid (ATRT) may also be included. * Pathologic diagnosis must be based on pathology or pathology review by Department of Pathology at MGH or another DF/HCC institution. * Age between 1-25 years. * Life expectancy of greater than 1 year. * ECOG Performance Status 0, 1, 2 or 3 or Lansky performance status 30 or greater. * Girls and women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation.
Exclusion criteria
* Participants who have had radiotherapy to the site to be treated. * Participants with known spinal or distant metastases. Patients with ependymoma, medulloblastoma or germinoma must have metastatic workup including spine MRI to rule out metastases. * Uncontrolled intercurrent illness that would limit compliance with study requirements. * Pregnant or breastfeeding women. * Patients who cannot participate in contributing to the neurocognitive outcomes due to severe neurologic impairment or language barrier (ie not English or Spanish speaking) will be excluded from this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Endocrine Dysfunction | 3- and 5- years post radiation treatment | Cumulative incidence (estimated percentage participants) that developed endocrine dysfunction at 3- and 5-years following completion of proton radiation therapy. |
| Neurocognitive Sequelae | From the start of radiation treatment (baseline) to study completion. Participants were assessed annually up to 5 years following treatment completion. The median follow-up is 4.7 years. | The overall change in neurocognitive outcomes between treatment and last-follow-up as assessed by Wechsler Intelligence Scale for Children version 4 (WISC-IV). The test measures the Full-Scale Intelligence Quotient (FSIQ) of children through four indices; the Verbal Comprehension Index (VCI), Perceptual Reasoning Index (PRI), working memory test, and a processing speed test. FSIQ and the four indices are all assessed on a bell curve scale with an average score of 100 and standard deviation of 15. Higher scores represent higher intelligence and lower scores represent reduced intelligence. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease Control | 3- and 5- years post radiation treatment | Three and 5 year local and distant disease control survival probabilities. Participants were assessed each follow-up and categorized in the following ways: 1) disease controlled no evidence of progression, 2) disease not controlled, tumor has progressed 3) patient has suffered a second malignancy (new tumor unrelated to the one the participant was treated for). Disease failure (recurrence of primary tumor) can occur locally (at or near the site of the original tumor), distally (located further away from the original tumor site), or both. Participants who did not fail locally or in a distant site were censored at the date of their last follow-up, including death due to other causes. Disease control shows the percent probability of remaining recurrence free (disease is controlled) in follow-up post radiation treatment completion. |
| Cumulative Incidence of Grade 3+ Toxicities | 3- and 5- years post radiation treatment | Percentage of participants who experienced a toxicity following completion of radiation treatment as measured by the NCI Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE 4.0) after the completion of radiation therapy. Cumulative incidence is shown at 3- and 5-years post treatment. The descriptions and grading scales found in the NCI Common Terminology Criteria |
| Cumulative Incidence of Ototoxicity | 3- and 5- years post radiation treatment | Cumulative incidence (estimated percentage participants) who experienced ototoxicity defined as either grade 3 or 4 hearing loss in either ear after the completion of radiation therapy in the overall participant population. Cumulative incidence and 95% confidence intervals are shown at 3- and 5-years post radiation treatment. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Proton Radiotherapy Proton Radiotherapy
Proton radiotherapy: 5 days a week | 100 |
| Total | 100 |
Baseline characteristics
| Characteristic | Proton Radiotherapy |
|---|---|
| Age, Continuous | 8.0 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 4 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 13 Participants |
| Race (NIH/OMB) White | 80 Participants |
| Region of Enrollment United States | 100 participants |
| Sex: Female, Male Female | 49 Participants |
| Sex: Female, Male Male | 51 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 15 / 100 |
| other Total, other adverse events | 98 / 100 |
| serious Total, serious adverse events | 2 / 100 |
Outcome results
Primary
Endocrine Dysfunction
Cumulative incidence (estimated percentage participants) that developed endocrine dysfunction at 3- and 5-years following completion of proton radiation therapy.
Time frame: 3- and 5- years post radiation treatment
Population: Patient population at risk of developing an endocrine dysfunction during follow-up
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Proton Radiotherapy | Endocrine Dysfunction | 3-Years post RT | 14.5 percentage of participants |
| Proton Radiotherapy | Endocrine Dysfunction | 5-Years post RT | 20.2 percentage of participants |
95% CI: [8.3, 22.3]
95% CI: [12.7, 28.9]
Primary
Neurocognitive Sequelae
The overall change in neurocognitive outcomes between treatment and last-follow-up as assessed by Wechsler Intelligence Scale for Children version 4 (WISC-IV). The test measures the Full-Scale Intelligence Quotient (FSIQ) of children through four indices; the Verbal Comprehension Index (VCI), Perceptual Reasoning Index (PRI), working memory test, and a processing speed test. FSIQ and the four indices are all assessed on a bell curve scale with an average score of 100 and standard deviation of 15. Higher scores represent higher intelligence and lower scores represent reduced intelligence.
Time frame: From the start of radiation treatment (baseline) to study completion. Participants were assessed annually up to 5 years following treatment completion. The median follow-up is 4.7 years.
Population: Patients who received neurocognitive testing at both baseline and post radiation treatment
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Proton Radiotherapy | Neurocognitive Sequelae | Baseline FSIQ | 99.2 score on a scale | Standard Deviation 14.8 |
| Proton Radiotherapy | Neurocognitive Sequelae | Latest Follow-up FSIQ | 100.3 score on a scale | Standard Deviation 16.2 |
p-value: 0.54395% CI: [-2.6, 4.9]t-test, 2 sided
Secondary
Cumulative Incidence of Grade 3+ Toxicities
Percentage of participants who experienced a toxicity following completion of radiation treatment as measured by the NCI Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE 4.0) after the completion of radiation therapy. Cumulative incidence is shown at 3- and 5-years post treatment. The descriptions and grading scales found in the NCI Common Terminology Criteria
Time frame: 3- and 5- years post radiation treatment
Population: Patients at risk of developing a grade 3 or higher toxicity following proton radiation
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Proton Radiotherapy | Cumulative Incidence of Grade 3+ Toxicities | 3-Years post RT | 12.2 percentage of participants |
| Proton Radiotherapy | Cumulative Incidence of Grade 3+ Toxicities | 5-Years post RT | 16.3 percentage of participants |
95% CI: [6.6, 19.5]
95% CI: [9.8, 24.3]
Secondary
Cumulative Incidence of Ototoxicity
Cumulative incidence (estimated percentage participants) who experienced ototoxicity defined as either grade 3 or 4 hearing loss in either ear after the completion of radiation therapy in the overall participant population. Cumulative incidence and 95% confidence intervals are shown at 3- and 5-years post radiation treatment.
Time frame: 3- and 5- years post radiation treatment
Population: Patients with audiograms completed at both baseline and follow-up and at risk of developing grade 3 or 4 high grade hearing loss in either ear after radiation treatment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Proton Radiotherapy | Cumulative Incidence of Ototoxicity | 3-Years post RT | 12.5 percentage of participants |
| Proton Radiotherapy | Cumulative Incidence of Ototoxicity | 5-Years post RT | 12.5 percentage of participants |
95% CI: [2.9, 29.5]
95% CI: [2.9, 29.5]
Secondary
Disease Control
Three and 5 year local and distant disease control survival probabilities. Participants were assessed each follow-up and categorized in the following ways: 1) disease controlled no evidence of progression, 2) disease not controlled, tumor has progressed 3) patient has suffered a second malignancy (new tumor unrelated to the one the participant was treated for). Disease failure (recurrence of primary tumor) can occur locally (at or near the site of the original tumor), distally (located further away from the original tumor site), or both. Participants who did not fail locally or in a distant site were censored at the date of their last follow-up, including death due to other causes. Disease control shows the percent probability of remaining recurrence free (disease is controlled) in follow-up post radiation treatment completion.
Time frame: 3- and 5- years post radiation treatment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Proton Radiotherapy | Disease Control | Local Control 3-Year post RT | 89.9 percent probability |
| Proton Radiotherapy | Disease Control | Local Control 5-Year post RT | 85.9 percent probability |
| Proton Radiotherapy | Disease Control | Distant Control 3-Year post RT | 97.0 percent probability |
| Proton Radiotherapy | Disease Control | Distant Control 5-Year post RT | 95.0 percent probability |
95% CI: [83.1, 94.9]
95% CI: [78.2, 91.9]
95% CI: [92.1, 99.2]
95% CI: [89.4, 98.1]