Brain Tumor, Medulloblastoma, Pineoblastoma
Conditions
Keywords
proton beam radiation
Brief summary
There are two types of external radiation treatments (proton beam and photon beam). As part of the participant's treatment, they will receive radiation to the entire central nervous system (CNS); this is known as craniospinal irradiation (CSI). In the past, photon radiation therapy has been used for CSI. In this study we will be examining the effects of proton beam radiation therapy. Studies have suggested that this kind of radiation can cause less damage to normal tissue than photon radiation therapy. The physical characteristics of proton beam radiation let the doctor safely deliver the amount of radiation delivered to the tumor that is normally delivered through standard therapy but spare more normal tissue in the process.
Detailed description
* Before beginning radiation therapy, participants will have scans done in order to prepare for the radiation treatment. Doctors will use information gathered from these scans to plan the best way to deliver radiation to the tumor. * The following procedures will be performed either before or during the radiotherapy: Hearing exam; neurocognitive exam; blood tests and cerebral spinal fluid test. * Not everyone who participates in this study will receive the same amount of proton radiation therapy. The length of time and amount of radiation received will depend upon the condition of the participant's disease. Radiation treatment will be given once a day, 5 days a week (Monday-Friday). The overall treatment course will be approximately 6 weeks.
Interventions
RADIATIONproton beam radiation
Given once a day, 5 days a week (Monday-Friday)
Sponsors
M.D. Anderson Cancer Center
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
3 Years to 25 Years
Healthy volunteers
No
Inclusion criteria
* Participants must have undergone biopsy or attempted surgical resection and must have histologically confirmed medulloblastoma or pineoblastoma. * Participants may have had a gross total resection, sub-total resection or biopsy only. * For patients with no prior chemotherapy, treatment must start within 35 days of definitive surgery or as indicated if enrolled on therapeutic study * Age range between 3 and 25 at the time of enrollment * Life expectancy of greater than 3 months * Blood laboratory values as outlined in the protocol * 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
* Patients with more than one previous chemotherapy regimen * Patients with recurrent or progressive disease after one or more regimens of pre-radiation chemotherapy * Patients with prior radiation therapy * Any major uncontrolled or poorly controlled intercurrent illness that would limit compliance with study requirements * Pregnant women
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 RT (radiation treatment) |
| 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 Effects | Baseline and Follow-up (median of 6 years) | Difference in Full-Scale Intelligence Quotient (FSIQ) between baseline and latest follow-up neurocognitive test. Tests used include WISC (Wechsler Intelligence Scale for Children) IV, WISC V, WAIS (Wechsler Adult Intelligence Scale) III, WAIS IV. The test measures the 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 |
|---|---|---|
| Progression Free Survival | 3- and 5-years post radiation treatment | 3- and 5-year progression free survival rate of pediatric medulloblastoma and pineoblastoma patients treated with proton CSI treatment. |
| Treatment Efficiency | 2 years | To modify the speed of treating patients requiring cranial spinal irradiation (CSI) and improve the safety of treating patients under anesthesia |
| Percentage of Participants Who Experienced an Acute Toxicity by Grade | 3 months after radiation therapy | All patients shall be assessed for acute toxicity on a weekly basis during craniospinal irradiation (CSI). Percentage of participants who experienced an acute toxicity by grade. Acute toxicities are graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Toxicities are graded on a scale of 1 to 5. A higher grade indicates a worse outcome with 1 being mild, 4 being life-threatening, and 5 being death. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Proton Beam Radiation Proton Beam Radiation
proton beam radiation: Given once a day, 5 days a week (Monday-Friday) | 90 |
| Total | 90 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 1 |
Baseline characteristics
| Characteristic | Proton Beam Radiation |
|---|---|
| Age, Continuous | 8.3 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 5 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 79 Participants |
| Region of Enrollment United States | 90 Participants |
| Sex: Female, Male Female | 36 Participants |
| Sex: Female, Male Male | 54 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 19 / 90 |
| other Total, other adverse events | 89 / 90 |
| serious Total, serious adverse events | 9 / 90 |
Outcome results
Primary
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 RT (radiation treatment)
Time frame: 3- and 5- years post radiation treatment
Population: Subset of study population that were at risk of developing a grade 3 or 4 hearing loss in either ear in follow-up after the completion of radiation therapy.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Proton Beam Radiation | Cumulative Incidence of Ototoxicity | 3-Years post RT (radiation treatment) | 26 percentage of participants |
| Proton Beam Radiation | Cumulative Incidence of Ototoxicity | 5-Years post RT | 27 percentage of participants |
95% CI: [16, 37]
95% CI: [17, 38]
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 Beam Radiation | Endocrine Dysfunction | 3-Years post RT | 46 percentage of participants |
| Proton Beam Radiation | Endocrine Dysfunction | 5-Years post RT | 67 percentage of participants |
95% CI: [34, 57]
95% CI: [54, 77]
Primary
Neurocognitive Effects
Difference in Full-Scale Intelligence Quotient (FSIQ) between baseline and latest follow-up neurocognitive test. Tests used include WISC (Wechsler Intelligence Scale for Children) IV, WISC V, WAIS (Wechsler Adult Intelligence Scale) III, WAIS IV. The test measures the 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: Baseline and Follow-up (median of 6 years)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Proton Beam Radiation | Neurocognitive Effects | Baseline FSIQ | 102.7 score on a scale | Standard Deviation 12.5 |
| Proton Beam Radiation | Neurocognitive Effects | Follow-up FSIQ | 91.7 score on a scale | Standard Deviation 20.5 |
p-value: 0.0102495% CI: [-19.2, -2.9]t-test, 2 sided
Secondary
Percentage of Participants Who Experienced an Acute Toxicity by Grade
All patients shall be assessed for acute toxicity on a weekly basis during craniospinal irradiation (CSI). Percentage of participants who experienced an acute toxicity by grade. Acute toxicities are graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Toxicities are graded on a scale of 1 to 5. A higher grade indicates a worse outcome with 1 being mild, 4 being life-threatening, and 5 being death.
Time frame: 3 months after radiation therapy
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Proton Beam Radiation | Percentage of Participants Who Experienced an Acute Toxicity by Grade | Grade 1 | 90 Participants |
| Proton Beam Radiation | Percentage of Participants Who Experienced an Acute Toxicity by Grade | Grade 2 | 84 Participants |
| Proton Beam Radiation | Percentage of Participants Who Experienced an Acute Toxicity by Grade | Grade 3 | 36 Participants |
| Proton Beam Radiation | Percentage of Participants Who Experienced an Acute Toxicity by Grade | Grade 4 | 12 Participants |
| Proton Beam Radiation | Percentage of Participants Who Experienced an Acute Toxicity by Grade | Grade 5 | 0 Participants |
Secondary
Progression Free Survival
3- and 5-year progression free survival rate of pediatric medulloblastoma and pineoblastoma patients treated with proton CSI treatment.
Time frame: 3- and 5-years post radiation treatment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Proton Beam Radiation | Progression Free Survival | 3-Year post RT | 83.2 percentage of participants |
| Proton Beam Radiation | Progression Free Survival | 5-Year post RT | 79.6 percentage of participants |
95% CI: [75.8, 91.3]
95% CI: [71.7, 88.5]
Secondary
Treatment Efficiency
To modify the speed of treating patients requiring cranial spinal irradiation (CSI) and improve the safety of treating patients under anesthesia
Time frame: 2 years
Population: It was not possible to change/alter any portion of the treatment process for those requiring CSI and therefore no patient had altered treatment times. Specifically, we were unable to speed the delivery of the radiation and make treatment scheduling slots shorter than they already were. With no changes in treatment speed across patients, potential outcomes in terms of safety and treatment efficiency could not be compared by treatment speed. This data will not be collected in the future.