Brain and Central Nervous System Tumors, Long-term Effects Secondary to Cancer Therapy in Children
Conditions
Keywords
long-term effects secondary to cancer therapy in children, untreated childhood medulloblastoma, untreated childhood pineoblastoma
Brief summary
RATIONALE: Specialized radiation therapy that delivers radiation directly to the area where a tumor was surgically removed may kill any remaining tumor cells and cause less damage to normal tissue. PURPOSE: This phase II trial is studying how well proton beam radiation therapy works in treating young patients who have undergone biopsy or surgery for medulloblastoma or pineoblastoma.
Detailed description
OBJECTIVES: * Determine the 3-year incidence and severity of ototoxicity in young patients with medulloblastoma or pineoblastoma treated with adjuvant proton beam craniospinal and posterior fossa radiotherapy. * Determine the incidence of primary hypothyroidism and other endocrine dysfunction (neuroendocrine and end organ) in patients treated with this regimen. * Determine the incidence and severity of neurocognitive abnormalities in patients treated with this regimen. * Determine the acute side effects of this regimen, including esophagitis, upper and lower gastrointestinal tract disease, and weight loss, in these patients. * Determine the 3-year progression-free survival rate of patients treated with this regimen. OUTLINE: Patients are stratified according to risk (standard vs high). Patients receive proton beam craniospinal and posterior fossa radiotherapy once daily 5 days a week for 6-8 weeks\*. NOTE: \*Unless otherwise specified by a co-existing protocol. Patients undergo neurocognitive evaluation at baseline or within 3 months after completion of radiotherapy and then at 1, 3, and 5 years. Patients also undergo endocrine evaluation at baseline and then annually for 5 years; and audiology evaluation at baseline, before each course of cisplatin-based chemotherapy (if receiving this), and then annually for 5 years. After completion of study treatment, patients are followed every 3-6 months for 2-5 years. PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study.
Interventions
RADIATIONradiation therapy
Radiation therapy with proton beam to standard doses
Sponsors
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 21 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically confirmed medulloblastoma or pineoblastoma * Standard-risk or high-risk disease * Must have undergone biopsy or attempted surgical resection of the tumor within the past 35 days * Requires craniospinal irradiation PATIENT CHARACTERISTICS: Age * 3 to 21 Performance status * Not specified Life expectancy * Not specified Hematopoietic * Not specified Hepatic * Not specified Renal * Not specified Other * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy * Not specified Chemotherapy * No more than 1 prior chemotherapy regimen * No prior IV or intrathecal methotrexate * No prior intrathecal thiotepa * Concurrent cisplatin-based chemotherapy, including chemotherapy administered on another study, allowed Endocrine therapy * Not specified Radiotherapy * No prior radiotherapy Surgery * See Disease Characteristics
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative Incidence of Ototoxicity | 3 Years, 5 years, 7 years, 10 years | Percentage participants who experienced ototoxicity as measured by Common Toxicity Criteria for Adverse Events (CTCAE) v3.0 after the completion of radiation therapy in the overall participant population and by baseline measure subgroups. Incidence is shown after follow-up of 3 years, 5 years, 7 years, and 10 years. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 5 Years | 5 years | Percentage of participants who experienced endocrine dysfunction (neuroendocrine and end organ defects) after 5 years of follow-up (as determined by CTCAE 3.0). Incidence is shown by hormone type and risk group. |
| Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 7 Years | 7 years | Percentage of participants who experienced endocrine dysfunction (neuroendocrine and end organ defects) after 7 years of follow-up, as determined by CTCAE 3.0. Incidence is shown by hormone type and risk group |
| Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 3 Years | 3 years | Percentage of participants who experienced endocrine dysfunction (neuroendocrine and end organ defects) after 3 years of follow-up (as determined by CTCAE 3.0). Incidence is grouped by hormone type and risk group |
| Progression Free Survival | 5 years, 7 years, 10 years | The percentage of participants with progression free survival after five, seven, and ten years in the overall population and by risk and histological group. |
| Overall Survival | 5 years, 7 years, 10 years | the percentage of participants surviving after five and seven years and at the end of follow-up in the overall population. Survival is shown by risk and histological group. |
| Mean Change Per-Year in Neurocognitive Outcomes | Baseline, 1, 3, 5, 7 years | The mean change per-year in neurocognitive outcomes as assessed by Wechsler Intelligence Scale for Children version 4 (WISC-IV). The test measures the Full Scale Intelligence Quotient (FSIQ) of children with the use of 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 that has an average score of 100 and standard deviation of 15 points in the general population, meaning on average 68% of test takers would be within +/- 15 points of 100 and 95% within +/- 30 points. Higher scores represent higher intelligence and lower score represent reduced intelligence. Participants were assessed for changes in score with the use of repeated testing during a median follow-up time of 5.2 years. Repeated measures were taken at baseline, 1, 3, 5, and 7 years or until the participant was not available for evaluation (whichever comes first). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Radiation Therapy radiation therapy: Radiation therapy with proton beam to standard doses | 59 |
| Total | 59 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 1 |
Baseline characteristics
| Characteristic | Radiation Therapy |
|---|---|
| Age, Continuous | 6.6 years |
| Age, Customized < 8 Years | 37 Participants |
| Age, Customized ≥ 8 Years | 22 Participants |
| Boost Dose >54 GyRBE | 2 Participants |
| Boost Dose 54 GyRBE | 57 Participants |
| Boost Field Posterior Fossa | 23 Participants |
| Boost Field Tumor Bed Involved Field | 36 Participants |
| Cisplatin Cumulative Dose ≤300 mg/m2 | 17 participants |
| Cisplatin Cumulative Dose >300 mg/m2 | 34 participants |
| Cochlear Mean Dose to Each Ear (D50) <30 GyRBE | 61 Ears |
| Cochlear Mean Dose to Each Ear (D50) ≥30 GyRBE | 57 Ears |
| Craniospinal Radiation Doses 18-27 GyRBE | 45 Participants |
| Craniospinal Radiation Doses 36 GyRBE | 14 Participants |
| Enrolled on a Children's Oncology Group Protocol No | 47 participants |
| Enrolled on a Children's Oncology Group Protocol Yes : A9961 | 1 participants |
| Enrolled on a Children's Oncology Group Protocol Yes : ACNS0331 | 8 participants |
| Enrolled on a Children's Oncology Group Protocol Yes : ACNS0332 | 2 participants |
| Enrolled on a Children's Oncology Group Protocol Yes : ACNS0334 | 1 participants |
| Histological Subtype (Dominant Pattern) Anaplastic or Large Cell Variant | 8 Participants |
| Histological Subtype (Dominant Pattern) Classic | 45 Participants |
| Histological Subtype (Dominant Pattern) Desmoplastic or Nodular Variant | 6 Participants |
| Hypothalamus Mean Dose (D50) <40 GyRBE | 37 Participants |
| Hypothalamus Mean Dose (D50) ≥40 GyRBE | 22 Participants |
| Posterior Fossa Syndrome No | 45 Participants |
| Posterior Fossa Syndrome Yes | 14 Participants |
| Region of Enrollment United States | 59 Participants |
| Risk Group High | 14 Participants |
| Risk Group Intermediate | 6 Participants |
| Risk Group Standard | 39 Participants |
| Sex: Female, Male Female | 26 Participants |
| Sex: Female, Male Male | 33 Participants |
| Use of Photons for <20% radiation dose No | 53 Participants |
| Use of Photons for <20% radiation dose Yes | 6 Participants |
| Ventriculoperitoneal Shunt No | 47 Participants |
| Ventriculoperitoneal Shunt Yes | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 13 / 59 |
| other Total, other adverse events | 59 / 59 |
| serious Total, serious adverse events | 13 / 59 |
Outcome results
Primary
Cumulative Incidence of Ototoxicity
Percentage participants who experienced ototoxicity as measured by Common Toxicity Criteria for Adverse Events (CTCAE) v3.0 after the completion of radiation therapy in the overall participant population and by baseline measure subgroups. Incidence is shown after follow-up of 3 years, 5 years, 7 years, and 10 years.
Time frame: 3 Years, 5 years, 7 years, 10 years
Population: The overall study population after the stated durations of follow-up. Follow-up is ongoing and data is not yet available for the 10 year time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Radiation Therapy - 3 Years Follow-up | Cumulative Incidence of Ototoxicity | Vetriculoperitoneal shunt | 22 percentage of participants |
| Radiation Therapy - 3 Years Follow-up | Cumulative Incidence of Ototoxicity | Female | 20 percentage of participants |
| Radiation Therapy - 3 Years Follow-up | Cumulative Incidence of Ototoxicity | Cisplatin total dose ≤300 mg/m2 | 18 percentage of participants |
| Radiation Therapy - 3 Years Follow-up | Cumulative Incidence of Ototoxicity | ≥8 years old | 6 percentage of participants |
| Radiation Therapy - 3 Years Follow-up | Cumulative Incidence of Ototoxicity | <8 years old | 15 percentage of participants |
| Radiation Therapy - 3 Years Follow-up | Cumulative Incidence of Ototoxicity | All Participants | 12 percentage of participants |
| Radiation Therapy - 3 Years Follow-up | Cumulative Incidence of Ototoxicity | Intermediate-high risk | 7 percentage of participants |
| Radiation Therapy - 3 Years Follow-up | Cumulative Incidence of Ototoxicity | Standard Risk | 15 percentage of participants |
| Radiation Therapy - 3 Years Follow-up | Cumulative Incidence of Ototoxicity | No vetriculoperitoneal shunt | 10 percentage of participants |
| Radiation Therapy - 3 Years Follow-up | Cumulative Incidence of Ototoxicity | Male | 4 percentage of participants |
| Radiation Therapy - 3 Years Follow-up | Cumulative Incidence of Ototoxicity | Cisplatin total dose >300 mg/m2 | 12 percentage of participants |
| Radiation Therapy - 5 Years Follow-up | Cumulative Incidence of Ototoxicity | <8 years old | 20 percentage of participants |
| Radiation Therapy - 5 Years Follow-up | Cumulative Incidence of Ototoxicity | All Participants | 16 percentage of participants |
| Radiation Therapy - 5 Years Follow-up | Cumulative Incidence of Ototoxicity | Standard Risk | 20 percentage of participants |
| Radiation Therapy - 5 Years Follow-up | Cumulative Incidence of Ototoxicity | Intermediate-high risk | 7 percentage of participants |
| Radiation Therapy - 5 Years Follow-up | Cumulative Incidence of Ototoxicity | Male | 4 percentage of participants |
| Radiation Therapy - 5 Years Follow-up | Cumulative Incidence of Ototoxicity | Female | 27 percentage of participants |
| Radiation Therapy - 5 Years Follow-up | Cumulative Incidence of Ototoxicity | ≥8 years old | 6 percentage of participants |
| Radiation Therapy - 5 Years Follow-up | Cumulative Incidence of Ototoxicity | Vetriculoperitoneal shunt | 22 percentage of participants |
| Radiation Therapy - 5 Years Follow-up | Cumulative Incidence of Ototoxicity | No vetriculoperitoneal shunt | 14 percentage of participants |
| Radiation Therapy - 5 Years Follow-up | Cumulative Incidence of Ototoxicity | Cisplatin total dose ≤300 mg/m2 | 18 percentage of participants |
| Radiation Therapy - 5 Years Follow-up | Cumulative Incidence of Ototoxicity | Cisplatin total dose >300 mg/m2 | 17 percentage of participants |
| Radiation Therapy - 7 Years Follow-up | Cumulative Incidence of Ototoxicity | Cisplatin total dose ≤300 mg/m2 | 18 percentage of participants |
| Radiation Therapy - 7 Years Follow-up | Cumulative Incidence of Ototoxicity | Vetriculoperitoneal shunt | 22 percentage of participants |
| Radiation Therapy - 7 Years Follow-up | Cumulative Incidence of Ototoxicity | Intermediate-high risk | 7 percentage of participants |
| Radiation Therapy - 7 Years Follow-up | Cumulative Incidence of Ototoxicity | All Participants | 16 percentage of participants |
| Radiation Therapy - 7 Years Follow-up | Cumulative Incidence of Ototoxicity | No vetriculoperitoneal shunt | 14 percentage of participants |
| Radiation Therapy - 7 Years Follow-up | Cumulative Incidence of Ototoxicity | Standard Risk | 20 percentage of participants |
| Radiation Therapy - 7 Years Follow-up | Cumulative Incidence of Ototoxicity | <8 years old | 20 percentage of participants |
| Radiation Therapy - 7 Years Follow-up | Cumulative Incidence of Ototoxicity | Female | 27 percentage of participants |
| Radiation Therapy - 7 Years Follow-up | Cumulative Incidence of Ototoxicity | Cisplatin total dose >300 mg/m2 | 17 percentage of participants |
| Radiation Therapy - 7 Years Follow-up | Cumulative Incidence of Ototoxicity | ≥8 years old | 6 percentage of participants |
| Radiation Therapy - 7 Years Follow-up | Cumulative Incidence of Ototoxicity | Male | 4 percentage of participants |
Secondary
Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 3 Years
Percentage of participants who experienced endocrine dysfunction (neuroendocrine and end organ defects) after 3 years of follow-up (as determined by CTCAE 3.0). Incidence is grouped by hormone type and risk group
Time frame: 3 years
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Radiation Therapy - 3 Years Follow-up | Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 3 Years | Adrenal or cortisol deficit | 5 percentage of participants |
| Radiation Therapy - 3 Years Follow-up | Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 3 Years | Thyroid deficiency | 12 percentage of participants |
| Radiation Therapy - 3 Years Follow-up | Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 3 Years | Any hormone deficit | 27 percentage of participants |
| Radiation Therapy - 3 Years Follow-up | Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 3 Years | Growth hormone deficit | 22 percentage of participants |
| Radiation Therapy - 3 Years Follow-up | Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 3 Years | Sex hormone deficit | 3 percentage of participants |
| Radiation Therapy - 5 Years Follow-up | Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 3 Years | Thyroid deficiency | 10 percentage of participants |
| Radiation Therapy - 5 Years Follow-up | Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 3 Years | Any hormone deficit | 28 percentage of participants |
| Radiation Therapy - 5 Years Follow-up | Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 3 Years | Growth hormone deficit | 23 percentage of participants |
| Radiation Therapy - 5 Years Follow-up | Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 3 Years | Adrenal or cortisol deficit | 3 percentage of participants |
| Radiation Therapy - 5 Years Follow-up | Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 3 Years | Sex hormone deficit | 3 percentage of participants |
| Radiation Therapy - 7 Years Follow-up | Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 3 Years | Sex hormone deficit | 5 percentage of participants |
| Radiation Therapy - 7 Years Follow-up | Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 3 Years | Adrenal or cortisol deficit | 10 percentage of participants |
| Radiation Therapy - 7 Years Follow-up | Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 3 Years | Any hormone deficit | 25 percentage of participants |
| Radiation Therapy - 7 Years Follow-up | Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 3 Years | Thyroid deficiency | 15 percentage of participants |
| Radiation Therapy - 7 Years Follow-up | Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 3 Years | Growth hormone deficit | 20 percentage of participants |
Secondary
Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 5 Years
Percentage of participants who experienced endocrine dysfunction (neuroendocrine and end organ defects) after 5 years of follow-up (as determined by CTCAE 3.0). Incidence is shown by hormone type and risk group.
Time frame: 5 years
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Radiation Therapy - 3 Years Follow-up | Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 5 Years | Adrenal or cortisol deficit | 9 percentage of participants |
| Radiation Therapy - 3 Years Follow-up | Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 5 Years | Thyroid deficiency | 21 percentage of participants |
| Radiation Therapy - 3 Years Follow-up | Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 5 Years | Any hormone deficit | 55 percentage of participants |
| Radiation Therapy - 3 Years Follow-up | Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 5 Years | Growth hormone deficit | 46 percentage of participants |
| Radiation Therapy - 3 Years Follow-up | Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 5 Years | Sex hormone deficit : Overall study population | 3 percentage of participants |
| Radiation Therapy - 5 Years Follow-up | Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 5 Years | Thyroid deficiency | 21 percentage of participants |
| Radiation Therapy - 5 Years Follow-up | Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 5 Years | Any hormone deficit | 58 percentage of participants |
| Radiation Therapy - 5 Years Follow-up | Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 5 Years | Growth hormone deficit | 50 percentage of participants |
| Radiation Therapy - 5 Years Follow-up | Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 5 Years | Adrenal or cortisol deficit | 3 percentage of participants |
| Radiation Therapy - 5 Years Follow-up | Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 5 Years | Sex hormone deficit : Overall study population | 3 percentage of participants |
| Radiation Therapy - 7 Years Follow-up | Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 5 Years | Sex hormone deficit : Overall study population | 5 percentage of participants |
| Radiation Therapy - 7 Years Follow-up | Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 5 Years | Adrenal or cortisol deficit | 20 percentage of participants |
| Radiation Therapy - 7 Years Follow-up | Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 5 Years | Any hormone deficit | 50 percentage of participants |
| Radiation Therapy - 7 Years Follow-up | Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 5 Years | Thyroid deficiency | 20 percentage of participants |
| Radiation Therapy - 7 Years Follow-up | Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 5 Years | Growth hormone deficit | 40 percentage of participants |
Secondary
Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 7 Years
Percentage of participants who experienced endocrine dysfunction (neuroendocrine and end organ defects) after 7 years of follow-up, as determined by CTCAE 3.0. Incidence is shown by hormone type and risk group
Time frame: 7 years
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Radiation Therapy - 3 Years Follow-up | Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 7 Years | Adrenal or cortisol deficit | 9 percentage of participants |
| Radiation Therapy - 3 Years Follow-up | Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 7 Years | Thyroid deficiency | 26 percentage of participants |
| Radiation Therapy - 3 Years Follow-up | Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 7 Years | Any hormone deficit | 63 percentage of participants |
| Radiation Therapy - 3 Years Follow-up | Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 7 Years | Growth hormone deficit | 55 percentage of participants |
| Radiation Therapy - 3 Years Follow-up | Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 7 Years | Sex hormone deficit : Overall study population | 3 percentage of participants |
| Radiation Therapy - 5 Years Follow-up | Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 7 Years | Thyroid deficiency | 25 percentage of participants |
| Radiation Therapy - 5 Years Follow-up | Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 7 Years | Any hormone deficit | 68 percentage of participants |
| Radiation Therapy - 5 Years Follow-up | Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 7 Years | Growth hormone deficit | 62 percentage of participants |
| Radiation Therapy - 5 Years Follow-up | Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 7 Years | Adrenal or cortisol deficit | 3 percentage of participants |
| Radiation Therapy - 5 Years Follow-up | Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 7 Years | Sex hormone deficit : Overall study population | 3 percentage of participants |
| Radiation Therapy - 7 Years Follow-up | Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 7 Years | Sex hormone deficit : Overall study population | 5 percentage of participants |
| Radiation Therapy - 7 Years Follow-up | Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 7 Years | Adrenal or cortisol deficit | 20 percentage of participants |
| Radiation Therapy - 7 Years Follow-up | Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 7 Years | Any hormone deficit | 50 percentage of participants |
| Radiation Therapy - 7 Years Follow-up | Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 7 Years | Thyroid deficiency | 29 percentage of participants |
| Radiation Therapy - 7 Years Follow-up | Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 7 Years | Growth hormone deficit | 40 percentage of participants |
Secondary
Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 7 Years
percentage of participants who experienced endocrine dysfunction (neuroendocrine and end organ defects) as determined by CTCAE 3.0) at year 3, year 5, and year 7 of follow-up.
Time frame: 3 years, 5 years, 7 years
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Radiation Therapy - 3 Years Follow-up | Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 7 Years | Adrenal or cortisol deficit | 5 percentage of participants |
| Radiation Therapy - 3 Years Follow-up | Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 7 Years | Thyroid deficiency | 12 percentage of participants |
| Radiation Therapy - 3 Years Follow-up | Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 7 Years | Any hormone deficit | 27 percentage of participants |
| Radiation Therapy - 3 Years Follow-up | Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 7 Years | Growth hormone deficit | 22 percentage of participants |
| Radiation Therapy - 3 Years Follow-up | Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 7 Years | Sex hormone deficit | 3 percentage of participants |
| Radiation Therapy - 5 Years Follow-up | Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 7 Years | Thyroid deficiency | 21 percentage of participants |
| Radiation Therapy - 5 Years Follow-up | Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 7 Years | Any hormone deficit | 55 percentage of participants |
| Radiation Therapy - 5 Years Follow-up | Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 7 Years | Growth hormone deficit | 46 percentage of participants |
| Radiation Therapy - 5 Years Follow-up | Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 7 Years | Adrenal or cortisol deficit | 9 percentage of participants |
| Radiation Therapy - 5 Years Follow-up | Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 7 Years | Sex hormone deficit | 3 percentage of participants |
| Radiation Therapy - 7 Years Follow-up | Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 7 Years | Sex hormone deficit | 3 percentage of participants |
| Radiation Therapy - 7 Years Follow-up | Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 7 Years | Adrenal or cortisol deficit | 9 percentage of participants |
| Radiation Therapy - 7 Years Follow-up | Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 7 Years | Any hormone deficit | 63 percentage of participants |
| Radiation Therapy - 7 Years Follow-up | Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 7 Years | Thyroid deficiency | 26 percentage of participants |
| Radiation Therapy - 7 Years Follow-up | Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 7 Years | Growth hormone deficit | 55 percentage of participants |
Secondary
Mean Change Per-Year in Neurocognitive Outcomes
The mean change per-year in neurocognitive outcomes as assessed by Wechsler Intelligence Scale for Children version 4 (WISC-IV). The test measures the Full Scale Intelligence Quotient (FSIQ) of children with the use of 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 that has an average score of 100 and standard deviation of 15 points in the general population, meaning on average 68% of test takers would be within +/- 15 points of 100 and 95% within +/- 30 points. Higher scores represent higher intelligence and lower score represent reduced intelligence. Participants were assessed for changes in score with the use of repeated testing during a median follow-up time of 5.2 years. Repeated measures were taken at baseline, 1, 3, 5, and 7 years or until the participant was not available for evaluation (whichever comes first).
Time frame: Baseline, 1, 3, 5, 7 years
Population: The study participants that were evaluated for changes in neurocognitive outcomes
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Radiation Therapy - 3 Years Follow-up | Mean Change Per-Year in Neurocognitive Outcomes | FSIQ | -1.5 units on a scale |
| Radiation Therapy - 3 Years Follow-up | Mean Change Per-Year in Neurocognitive Outcomes | VCI | -1.3 units on a scale |
| Radiation Therapy - 3 Years Follow-up | Mean Change Per-Year in Neurocognitive Outcomes | PRI | -.4 units on a scale |
| Radiation Therapy - 3 Years Follow-up | Mean Change Per-Year in Neurocognitive Outcomes | Working Memory | -0.8 units on a scale |
| Radiation Therapy - 3 Years Follow-up | Mean Change Per-Year in Neurocognitive Outcomes | Processing speed | -2.4 units on a scale |
Secondary
Overall Survival
the percentage of participants surviving after five and seven years and at the end of follow-up in the overall population. Survival is shown by risk and histological group.
Time frame: 5 years, 7 years, 10 years
Population: Follow-up for the 10 year follow-up is still ongoing and the data is not yet available.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Radiation Therapy - 3 Years Follow-up | Overall Survival | Standard Risk | 86 percentage of participants surviving |
| Radiation Therapy - 3 Years Follow-up | Overall Survival | Classic or desmoplastic histological subtype | 84 percentage of participants surviving |
| Radiation Therapy - 3 Years Follow-up | Overall Survival | Intermediate-high risk | 75 percentage of participants surviving |
| Radiation Therapy - 3 Years Follow-up | Overall Survival | Anaplastic or large cell histological subtype | 75 percentage of participants surviving |
| Radiation Therapy - 3 Years Follow-up | Overall Survival | All Participants | 83 percentage of participants surviving |
| Radiation Therapy - 5 Years Follow-up | Overall Survival | Anaplastic or large cell histological subtype | 75 percentage of participants surviving |
| Radiation Therapy - 5 Years Follow-up | Overall Survival | All Participants | 81 percentage of participants surviving |
| Radiation Therapy - 5 Years Follow-up | Overall Survival | Standard Risk | 86 percentage of participants surviving |
| Radiation Therapy - 5 Years Follow-up | Overall Survival | Intermediate-high risk | 68 percentage of participants surviving |
| Radiation Therapy - 5 Years Follow-up | Overall Survival | Classic or desmoplastic histological subtype | 82 percentage of participants surviving |
Secondary
Progression Free Survival
The percentage of participants with progression free survival after five, seven, and ten years in the overall population and by risk and histological group.
Time frame: 5 years, 7 years, 10 years
Population: Follow-up is ongoing and data is not yet available for the 10 year follow-up time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Radiation Therapy - 3 Years Follow-up | Progression Free Survival | Standard Risk | 85 percentage of participants surviving |
| Radiation Therapy - 3 Years Follow-up | Progression Free Survival | Classic or desmoplastic histological subtype | 80 percentage of participants surviving |
| Radiation Therapy - 3 Years Follow-up | Progression Free Survival | Intermediate-high risk | 70 percentage of participants surviving |
| Radiation Therapy - 3 Years Follow-up | Progression Free Survival | Anaplastic or large cell histological subtype | 75 percentage of participants surviving |
| Radiation Therapy - 3 Years Follow-up | Progression Free Survival | All Participants | 80 percentage of participants surviving |
| Radiation Therapy - 5 Years Follow-up | Progression Free Survival | Anaplastic or large cell histological subtype | 75 percentage of participants surviving |
| Radiation Therapy - 5 Years Follow-up | Progression Free Survival | All Participants | 75 percentage of participants surviving |
| Radiation Therapy - 5 Years Follow-up | Progression Free Survival | Standard Risk | 81 percentage of participants surviving |
| Radiation Therapy - 5 Years Follow-up | Progression Free Survival | Intermediate-high risk | 63 percentage of participants surviving |
| Radiation Therapy - 5 Years Follow-up | Progression Free Survival | Classic or desmoplastic histological subtype | 75 percentage of participants surviving |