Medulloblastoma
Conditions
Brief summary
This randomized phase III trial is studying how well standard-dose radiation therapy works compared to reduced-dose radiation therapy in children 3-7 years of age AND how well standard volume boost radiation therapy works compared to smaller volume boost radiation therapy when given together with chemotherapy in treating young patients who have undergone surgery for newly diagnosed standard-risk medulloblastoma. Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy, such as vincristine, cisplatin, lomustine, and cyclophosphamide, work in different ways to stop tumor cells from dividing so they stop growing or die. Giving radiation therapy with chemotherapy after surgery may kill any remaining tumor cells. It is not yet known whether standard-dose radiation therapy is more effective than reduced-dose radiation therapy when given together with chemotherapy after surgery in treating young patients with medulloblastoma.
Detailed description
PRIMARY OBJECTIVE: I. To determine whether reducing the craniospinal dose of radiation therapy to 18.00 Gy in children 3-7 years of age does not compromise event-free survival and overall survival as compared to treatment with 23.40 Gy of craniospinal radiation; and to determine if reducing the irradiated volume of the primary site tumor boost from the whole posterior fossa to the tumor bed only will not compromise event-free and overall survival. SECONDARY OBJECTIVES: I. To evaluate patterns of failure in children treated with an irradiation boost volume smaller than conventional posterior fossa volumes. II. To reduce the cognitive, auditory and endocrinologic effects of treatment of average-risk medulloblastoma by reducing the dose of craniospinal irradiation therapy. III. To determine if the audiologic and endocrinologic toxicity will be reduced with the use of limited tumor boost volume irradiation compared to patients treated with conventional target volumes of radiation. IV. To develop an optimal gene expression medulloblastoma outcome predictor, validated prospectively in a multi-institution randomized clinical trial. V. To improve compliance with long-term quality of life and functional status data submission by educating institutional nurses to administer and submit for analysis a battery of four instruments: Behavior Assessment System for Children- 2nd Edition (BASC-2), Adaptive Behavior Assessment System - 2nd Edition (ABAS-II), Behavior Rating Inventory of Executive Function (BRIEF), PedsQLTM 4.0. OUTLINE: Patients 3-7 years of age are randomized to 1 of 4 arms (Arm I-IV). Patients 8-21 years of age are randomized to 1 of 2 arms (Arm V or VI). Within 31 days after definitive surgery, all patients begin therapy. Patients undergo radiation therapy with doses according to their Arm randomization on days 1-5, 8-12, 15-19, 22-26, 29-33, 36-40, and 43-47 (weeks 0-6). All patients receive vincristine intravenously (IV) over 1 minute (or infusion via minibag as per institutional policy) on days 8, 15, 22, 29, 36, and 43 (weeks 1-6). ARM I: Patients 3-7 years of age undergo lowered dose craniospinal irradiation (LDCSI) with involved-field radiation therapy (IFRT) boost. ARM II: Patients 3-7 years of age undergo LDCSI with whole posterior fossa radiation therapy (PFRT) boost. ARM III: Patients 3-7 years of age undergo standard dose craniospinal irradiation (SDCSI) with IFRT boost. ARM IV: Patients 3-7 years of age undergo SDCSI with PFRT boost. ARM V: Patients 8-21 years of age undergo SDCSI with IFRT boost. ARM VI: Patients 8-21 years of age undergo SDCSI with PFRT boost. MAINTENANCE CHEMOTHERAPY: Beginning 4 weeks after completion of chemoradiotherapy, patients receive 2 different regimens of maintenance chemotherapy for a total of 9 courses. Each course in regimen A is 6 weeks (42 days) in duration. Each course in regimen B is 4 weeks (28 days) in duration. REGIMEN A (courses 1, 2, 4, 5, 7, and 8): Patients receive lomustine orally and cisplatin IV over 6 hours on day 1 and vincristine IV on days 1, 8, and 15 of weeks 11, 17, 27, 33, 43, and 49. REGIMEN B (courses 3, 6, and 9): Patients receive cyclophosphamide IV over 1 hour on days 1 and 2 and vincristine IV on days 1 and 8 of weeks 23, 39, and 55. Treatment continues in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at 3-6 months after completion of radiotherapy and at 3-4 years after study entry. Neurocognitive function may also be assessed. Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter. OUTLINE: Patients 3-7 years of age are randomized to 1 of 4 arms (Arm I-IV). Patients 8-21 years of age are randomized to 1 of 2 arms (Arm V or VI). Within 31 days after definitive surgery, all patients begin therapy. Patients undergo radiation therapy with doses according to their Arm randomization on days 1-5, 8-12, 15-19, 22-26, 29-33, 36-40, and 43-47 (weeks 0-6). All patients receive vincristine intravenously (IV) over 1 minute (or infusion via minibag as per institutional policy) on days 8, 15, 22, 29, 36, and 43 (weeks 1-6). ARM I: Patients 3-7 years of age undergo lowered dose craniospinal irradiation (LDCSI) with involved-field radiation therapy (IFRT) boost. ARM II: Patients 3-7 years of age undergo LDCSI with whole posterior fossa radiation therapy (PFRT) boost. ARM III: Patients 3-7 years of age undergo standard dose craniospinal irradiation (SDCSI) with IFRT boost. ARM IV: Patients 3-7 years of age undergo SDCSI with PFRT boost. ARM V: Patients 8-21 years of age undergo SDCSI with IFRT boost. ARM VI: Patients 8-21 years of age undergo SDCSI with PFRT boost. MAINTENANCE CHEMOTHERAPY: Beginning 4 weeks after completion of chemoradiotherapy, patients receive 2 different regimens of maintenance chemotherapy for a total of 9 courses. Each course in regimen A is 6 weeks (42 days) in duration. Each course in regimen B is 4 weeks (28 days) in duration. REGIMEN A (courses 1, 2, 4, 5, 7, and 8): Patients receive lomustine orally and cisplatin IV over 6 hours on day 1 and vincristine IV on days 1, 8, and 15 of weeks 11, 17, 27, 33, 43, and 49. REGIMEN B (courses 3, 6, and 9): Patients receive cyclophosphamide IV over 1 hour on days 1 and 2 and vincristine IV on days 1 and 8 of weeks 23, 39, and 55. Treatment continues in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at 3-6 months after completion of radiotherapy and at 3-4 years after study entry. Neurocognitive function may also be assessed. Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter.
Interventions
DRUGCisplatin
Given IV
RADIATIONCraniospinal Irradiation
Undergo craniospinal Irradiation
DRUGCyclophosphamide
Given IV
RADIATIONInvolved-Field Radiation Therapy
Undergo smaller volume boost (involved-field radiation therapy)
OTHERLaboratory Biomarker Analysis
Correlative studies
DRUGLomustine
Given orally
OTHERQuality-of-Life Assessment
Ancillary studies
RADIATIONRadiation Therapy
Undergo standard volume boost (whole posterior fossa radiation therapy)
DRUGVincristine Sulfate
Given IV
Sponsors
National Cancer Institute (NCI)
Children's Oncology Group
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Years to 21 Years
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed medulloblastoma located in the posterior fossa * Standard-risk disease * Minimal volume, non-disseminated disease, defined by the following: * Residual tumor ≤ 1.5 cm\^2 confirmed by MRI with contrast imaging within 21 days after surgery * No metastatic disease in the head, spine, or cerebrospinal fluid (CSF) confirmed by both of the following: * Enhanced MRI of the spine within 5 days before surgery OR within 28 days after surgery * Negative cytological examination of CSF after surgery, but before study enrollment * Brain stem involvement allowed * Performance status - Karnofsky 50-100% (\> 16 years of age) * Performance status - Lansky 30-100% (≤ 16 years of age) * Absolute neutrophil count \> 1,500/uL * Platelet count \> 100,000/uL (transfusion independent) * Hemoglobin \> 10 g/dL (transfusions allowed) * Bilirubin \< 1.5 times upper limit of normal (ULN) for age * AST or ALT \< 1.5 times ULN for age * Creatinine clearance OR radioisotope glomerular filtration rate \>= 70 mL/min/1.73m\^2 or a serum creatinine based on age/gender as follows: Age Maximum Serum Creatine (mg/dL) * 1month to \< 6 months male: 0.4 female: 0.4 * 6 months to \<1 year male: 0.5 female: 0.5 * 1 year to \< 2 years male: 0.6 female: 0.6 * 2 to \< 6 years male: 0.8 female: 0.8 * 6 to \< 10 years male: 1 female: 1 * 10 to \< 13 years male: 1.2 female: 1.2 * 13 to \< 16 years male: 1.5 female: 1.4 * \>= 16 years male: 1.7 female: 1.4 * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No prior chemotherapy * Prior corticosteroids allowed * No prior radiotherapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Event-free Survival (EFS) | Assessed at 3 years | EFS was defined as the time interval from date of study entry to date of disease progression, disease recurrence, second malignant neoplasm or death from any cause, whichever occurs first, or to the date of last follow-up for patients without events. EFS was estimated using the method of Kaplan and Meier. 3-year estimates are reported with 95% confidence intervals (CI's). |
| Overall Survival (OS) | 3 years | OS was defined as the time interval from date of study entry to date of death from any cause or to the date of last follow-up for survivors. OS was estimated using the method of Kaplan and Meier. 3-year estimates are reported with 95% CI's. For purposes of this analysis, arms I, III and V (involved field radiation therapy \[IFRT\]) are combined and compared to arms II, IV and VI (posterior fossa irradiation \[PFRT\]). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Non-posterior Fossa (NPF) Failure Rate | 3 years | NPF failure was defined as tumor recurrence within the neuroaxis but outside the radiation therapy clinical target volume (CTV). The cumulative incidence (CI) of NPF failure was estimated; 3-year estimates were reported with 95% confidence intervals. Patients with other failure types (e.g., LPF failure) and with other events prior to NPF failure (e.g., death, second malignancy) were considered as having competing events. |
| Post-treatment Endocrine Function by CSI Group | Up to 3 years | Post-treatment endocrine function was measured by laboratory assessment of the thyroid stimulating hormone (TSH). The mean TSH will be reported. |
| Post-treatment Grade 3+ Hearing Loss as Measured by Common Terminology Criteria for Adverse Events (CTCAE) Version (v)4 | Up to 3 years | Proportions of patients with grade 3+ hearing loss after the completion of therapy will be calculated and reported separately for low dose craniospinal irradiation (LDCSI) versus (vs.) standard dose craniospinal irradiation (SDCSI) patients. Eligible and evaluable patients 3-7 years of age will be used. |
| Post-treatment Neurocognitive Function as Measured by the Estimated Full-scale IQ (FSIQ) by CSI Group Within Time Window 1 (4 - 15 Months Post Diagnosis). | 4 -15 months post diagnosis | Post-treatment neurocognitive function was assessed. Full-scale IQ (FSIQ) is a representative measurement for neurocognitive function. FSIQ was measured by IQ tests. Assessments within the time window, from eligible and evaluable patients are reported. The time window is 4-15 months post diagnosis, only the assessments before progression date were reported. The Range of FSIQ is 50-150. A higher FSIQ is better. |
| Post-treatment Neurocognitive Function as Measured by the Estimated Full-scale IQ (FSIQ) by CSI Group Within Time Window 2 (27 - 48 Months Post Diagnosis) | 27 - 48 months post diagnosis | Post-treatment neurocognitive function was assessed. Full-scale IQ (FSIQ) is a representative measurement for neurocognitive function. FSIQ was measured by IQ tests. Assessments within the time window, from eligible and evaluable patients are reported. The time window is 27-48 months post diagnosis, only the assessments before progression date were reported. The range of FSIQ is 50 - 150. A higher FSIQ is better. |
| Post-treatment Neurocognitive Function as Measured by the Estimated Full-scale IQ (FSIQ) by CSI Group Within Time Window 3 (49 - 72 Months Post Diagnosis) | 49 - 72 months post diagnosis | Post-treatment neurocognitive function was assessed. Full-scale IQ (FSIQ) is a representative measurement for neurocognitive function. FSIQ was measured by IQ tests. Assessments within the time window, from eligible and evaluable patients are reported. The time window is 49-72 months post diagnosis, only the assessments before progression date were reported. The Range of FSIQ is 50-150. A higher FSIQ is better. |
| Incidence of Grade 3+ Hearing Loss at 1-year Post Treatment as Assessed by CTCAE v4 | Up to 3 years | Proportions of patients with grade 3+ hearing impairment as assessed by CTCAE v4 at 1-year post treatment were calculated. |
| Incidence of Endocrine Dysfunction as Measured by Growth Hormone Stimulation Tests at the Time of Completion of Therapy by Radiotherapy (RT) Group | Post-treatment up to 3 years | Endocrine dysfunction was assessed by growth hormone stimulation (GHS) tests. We report the percentage of patients with abnormal growth hormone stimulation tests. |
| Local Posterior Fossa (LPF) Failure Rate | 3 years | LPF failure was defined as tumor recurrence/progression within the tumor bed. The cumulative incidence (CI) of LPF failure was estimated; 3-year estimates were reported with 95% confidence intervals. Patients with other failure types (e.g., NPF) and with other events prior to LPF failure (e.g., death, second malignancy) were considered as having competing events. |
| Progression-free Survival (PFS) by Molecular Subgroup Based on Methylation Arrays | 3 years | PFS was defined as the time interval from date of study entry to disease progression, relapse or death due to cancer or to last follow-up. Second malignancies and deaths from causes clearly not associated with tumor progression or recurrence were censored. PFS was estimated using the method of Kaplan and Meier. 3-year estimates are reported with 95% CI's. |
| Post-treatment Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) by CSI Group Within Time Window 1 (4-15 Months Post Diagnosis) | 4 - 15 months post diagnosis | Metacognition index (MI) was measured by BRIEF test. Assessments within the time window, from eligible and evaluable patients are reported. If the patient had disease progression, only the assessments before progression date were reported. The MI is a standard T- score, and it ranges from 0 to 100. The higher score reported suggests a higher level of dysfunction. |
| Post-treatment Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) by CSI Group Within Time Window 2 (27-48 Months Post Diagnosis) | 27-48 months post diagnosis | Metacognition index (MI) was measured by BRIEF test. Assessments within the time window, from eligible and evaluable patients are reported. If the patient had disease progression, only the assessments before progression date were reported. The MI is a standard T- score, and it ranges from 0 to 100. The higher score reported suggests a higher level of dysfunction. |
| Post-treatment Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) by CSI Group Within Time Window 3 (49 - 72 Months Post Diagnosis) | 49 - 72 months post diagnosis | Metacognition index (MI) was measured by BRIEF test. Assessments within the time window, from eligible and evaluable patients are reported. If the patient had disease progression, only the assessments before progression date were reported. The MI is a standard T- score, and it ranges from 0 to 100. The higher score reported suggests a higher level of dysfunction. |
| Compliance Rates for All Eligible and Evaluable Patients Enrolled Within Time Window 1 (4-15 Months Post Diagnosis) | 4-15 months post diagnosis | Compliance rates are calculated to monitor the compliance with long-term quality of life and functional status data submission. A patient will be compliant if the patient has metacognition index score. Compliance rates will be assessed at each of the 3 neurocognitive/quality of life assessment time windows. All eligible and evaluable patients enrolled will be used. Patients removed from treatment prior to the time of neuropsychological assessment (for reasons such as disease progression, death, withdrawal of consent, etc.) will not be included in the denominator to assess the compliance rate. The time window is 4 - 15 months post diagnosis. |
| Compliance Rates for All Eligible and Evaluable Patients Enrolled Within Time Window 2 (27-48 Months Post Diagnosis) | 27-48 months post diagnosis | Compliance rates are calculated to monitor the compliance with long-term quality of life and functional status data submission. A patient will be compliant if the patient has metacognition index score. Compliance rates will be assessed at each of the 3 neurocognitive/quality of life assessment time windows. All eligible and evaluable patients enrolled will be used. Patients removed from treatment prior to the time of neuropsychological assessment (for reasons such as disease progression, death, withdrawal of consent, etc.) will not be included in the denominator to assess the compliance rate. The time window is 27 - 48 months post diagnosis. |
| Compliance Rates for All Eligible and Evaluable Patients Enrolled Within Time Window 3 (49 - 72 Months Post Diagnosis) | 49 - 72 months post diagnosis | Compliance rates are calculated to monitor the compliance with long-term quality of life and functional status data submission. A patient will be compliant if the patient has metacognition index score. Compliance rates will be assessed at each of the 3 neurocognitive/quality of life assessment time windows. All eligible and evaluable patients enrolled will be used. Patients removed from treatment prior to the time of neuropsychological assessment (for reasons such as disease progression, death, withdrawal of consent, etc.) will not be included in the denominator to assess the compliance rate. The time window is 49 - 72 months post diagnosis. |
| Overall Survival (OS) by Molecular Subgroup Based on Methylation Arrays | 3 years | OS was defined as the time interval from date of study entry to date of death from any cause or to date of last contact for survivors. OS was estimated using the method of Kaplan and Meier. 3-year estimates are reported with 95% CI's. |
| Non-local Posterior Fossa (NLPF) Failure Rate | 3 years | NLPF failure was defined as tumor recurrence/progression outside the radiation therapy clinical target volume boost (CTV-boost) but within the posterior fossa CTV (CTV-PF). The cumulative incidence (CI) of NLPF failure was estimated; 3-year estimates were reported with 95% confidence intervals. Patients with other failure types (e.g., NPF, LPF) and with other events prior to NLPF failure (e.g., death, second malignancy) were considered as having competing events. |
Countries
Australia, Canada, Netherlands, New Zealand, Puerto Rico, Switzerland, United States
Participant flow
Recruitment details
Participants 3-21 years of age were recruited at Children's Oncology Group institutions worldwide and at sites affiliated with the Dutch Childhood Oncology Group. The first patient was enrolled on April 30, 2004 and the last patient was enrolled on January 6, 2014.
Pre-assignment details
Patients were randomized to receive a smaller volume boost (radiation to tumor bed)(IFRT) or standard volume boost (radiation to the entire posterior fossa) (PFRT).Patients 3-7 years of age were also randomized to receive reduced-dose craniospinal radiation (LDCSI) or standard-dose craniospinal radiation (SDCSI).Patients 8 and older received SDCSI.
Participants by arm
| Arm | Count |
|---|---|
| Arm I (3-7 Years of Age, LDCSI, IFRT) Eligible patients 3-7 yrs of age, LDCSI, IFRT | 63 |
| Arm II (3-7 Years of Age, LDCSI, PFRT) Eligible patients 3-7 yrs of age, LDCSI, PFRT | 64 |
| Arm III (3-7 Years of Age, SDCSI, IFRT) Eligible patients 3-7 yrs of age, SDCSI, IFRT | 60 |
| Arm IV (3-7 Years of Age, SDCSI, PFRT) Eligible patients 3-7 yrs of age, SDCSI, PFRT | 58 |
| Arm V (8-21 Years of Age, SDCSI, IFRT) Eligible patients 8-21 yrs of age, SDCSI, IFRT | 130 |
| Arm VI (8-21 Years of Age, SDCSI, PFRT) Eligible patients 8-21 yrs of age, SDCSI, PFRT | 138 |
| Total | 513 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Excess residual disease | 2 | 2 | 1 | 1 | 1 | 4 |
| Overall Study | Lack of Efficacy | 2 | 4 | 6 | 3 | 4 | 3 |
| Overall Study | Lost to Follow-up | 0 | 1 | 0 | 0 | 1 | 0 |
| Overall Study | Patient ineligible | 1 | 0 | 3 | 7 | 17 | 8 |
| Overall Study | Physician Decision | 2 | 3 | 2 | 3 | 11 | 8 |
| Overall Study | Protocol Violation | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Pt transferred to inst w/out study open | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Reason not documented | 1 | 0 | 1 | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 4 | 5 | 7 | 8 |
Baseline characteristics
| Characteristic | Arm II (3-7 Years of Age, LDCSI, PFRT) | Arm III (3-7 Years of Age, SDCSI, IFRT) | Arm IV (3-7 Years of Age, SDCSI, PFRT) | Arm V (8-21 Years of Age, SDCSI, IFRT) | Arm VI (8-21 Years of Age, SDCSI, PFRT) | Arm I (3-7 Years of Age, LDCSI, IFRT) | Total |
|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 64 Participants | 60 Participants | 58 Participants | 120 Participants | 128 Participants | 63 Participants | 493 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants | 10 Participants | 10 Participants | 0 Participants | 20 Participants |
| Age, Continuous | 5.9 years | 5.9 years | 5.4 years | 12.4 years | 11.8 years | 5.9 years | 8.3 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 18 Participants | 8 Participants | 9 Participants | 19 Participants | 23 Participants | 10 Participants | 87 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 44 Participants | 50 Participants | 46 Participants | 110 Participants | 109 Participants | 51 Participants | 410 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 2 Participants | 3 Participants | 1 Participants | 6 Participants | 2 Participants | 16 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 2 Participants | 2 Participants | 4 Participants | 2 Participants | 0 Participants | 10 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 5 Participants | 3 Participants | 13 Participants | 9 Participants | 5 Participants | 41 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 5 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 9 Participants | 5 Participants | 3 Participants | 4 Participants | 7 Participants | 7 Participants | 35 Participants |
| Race (NIH/OMB) White | 48 Participants | 46 Participants | 48 Participants | 108 Participants | 120 Participants | 50 Participants | 420 Participants |
| Sex: Female, Male Female | 20 Participants | 20 Participants | 24 Participants | 53 Participants | 51 Participants | 16 Participants | 184 Participants |
| Sex: Female, Male Male | 44 Participants | 40 Participants | 34 Participants | 77 Participants | 87 Participants | 47 Participants | 329 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 60 / 63 | 61 / 64 | 55 / 60 | 53 / 58 | 123 / 130 | 135 / 138 |
| serious Total, serious adverse events | 7 / 63 | 7 / 64 | 6 / 60 | 3 / 58 | 16 / 130 | 18 / 138 |
Outcome results
Primary
Event-free Survival (EFS)
EFS was defined as the time interval from date of study entry to date of disease progression, disease recurrence, second malignant neoplasm or death from any cause, whichever occurs first, or to the date of last follow-up for patients without events. EFS was estimated using the method of Kaplan and Meier. 3-year estimates are reported with 95% confidence intervals (CI's).
Time frame: Assessed at 3 years
Population: Per protocol only eligible \& evaluable pts are included. Pts with anaplastic histology or disseminated/excess residual disease were not evaluable (NE). 26/23 IFRT/PFRT pts were NE, leaving 227 vs 237 for this comparison. The LD/SD CSI comparison was done only in pts 3-7 yrs of age. 11/8 LD/SDCSI pts were NE, leaving 116 vs 110 for this comparison.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Low-dose Craniospinal Radiation (LDSCI) | Event-free Survival (EFS) | LDCSI vs SDCSI | 76.3 probability of 3 year EFS |
| Standard-dose Craniospinal Radiation (SDCSI) | Event-free Survival (EFS) | LDCSI vs SDCSI | 84.9 probability of 3 year EFS |
| Involved Field Radiation (IFRT) | Event-free Survival (EFS) | IFRT vs PFRT | 85.8 probability of 3 year EFS |
| Posterior Fossa Radiation (PFRT) | Event-free Survival (EFS) | IFRT vs PFRT | 85.8 probability of 3 year EFS |
Comparison: The comparison is based on all eligible randomized patients 3-7 years of age without anaplastic histology or excess residual disease or disseminated disease by central review per the protocol document. Using a one-sided log rank test with type I error of 0.20, this study was designed to have power of 0.80 to detect a 10% reduction in cure rate due to the use of LDCSI compared to SDCSI.
Comparison: The comparison is based on all eligible randomized patients 3-21 years of age without anaplastic histology or excess residual disease or disseminated disease by central review as per the protocol document. Using a one-sided log rank test with type I error of 0.20, this study was designed with power of 0.94 to detect a 10% reduction in cure rate and power of 0.65 to detect a 5% reduction in cure rate, due to the use of IFRT compared to PFRT.
Primary
Overall Survival (OS)
OS was defined as the time interval from date of study entry to date of death from any cause or to the date of last follow-up for survivors. OS was estimated using the method of Kaplan and Meier. 3-year estimates are reported with 95% CI's. For purposes of this analysis, arms I, III and V (involved field radiation therapy \[IFRT\]) are combined and compared to arms II, IV and VI (posterior fossa irradiation \[PFRT\]).
Time frame: 3 years
Population: Per protocol only eligible \& evaluable pts were included.Pts with anaplastic histology or disseminated/excess residual disease were not evaluable (NE). 26/23 IFRT/PFRT pts were NE, leaving 227 vs 237 for this comparison. The LD/SD CSI comparison was done only in pts 3-7 yrs of age. 11/8 LD/SDCSI pts were NE, leaving 116 vs 110 for this comparison.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Low-dose Craniospinal Radiation (LDSCI) | Overall Survival (OS) | LDCSI vs SDCSI | 85.5 Probability of 3 yr OS rate |
| Standard-dose Craniospinal Radiation (SDCSI) | Overall Survival (OS) | LDCSI vs SDCSI | 90.4 Probability of 3 yr OS rate |
| Involved Field Radiation (IFRT) | Overall Survival (OS) | IFRT vs PFRT | 90.3 Probability of 3 yr OS rate |
| Posterior Fossa Radiation (PFRT) | Overall Survival (OS) | IFRT vs PFRT | 93.3 Probability of 3 yr OS rate |
Secondary
Compliance Rates for All Eligible and Evaluable Patients Enrolled Within Time Window 1 (4-15 Months Post Diagnosis)
Compliance rates are calculated to monitor the compliance with long-term quality of life and functional status data submission. A patient will be compliant if the patient has metacognition index score. Compliance rates will be assessed at each of the 3 neurocognitive/quality of life assessment time windows. All eligible and evaluable patients enrolled will be used. Patients removed from treatment prior to the time of neuropsychological assessment (for reasons such as disease progression, death, withdrawal of consent, etc.) will not be included in the denominator to assess the compliance rate. The time window is 4 - 15 months post diagnosis.
Time frame: 4-15 months post diagnosis
Population: All eligible and evaluable patients enrolled. Patients removed from treatment prior to the time of neuropsychological assessment (for reasons such as disease progression, death, withdrawal of consent, etc.) will not be included in the denominator to assess the compliance rate.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low-dose Craniospinal Radiation (LDSCI) | Compliance Rates for All Eligible and Evaluable Patients Enrolled Within Time Window 1 (4-15 Months Post Diagnosis) | 58 Percentage of Participants |
Secondary
Compliance Rates for All Eligible and Evaluable Patients Enrolled Within Time Window 2 (27-48 Months Post Diagnosis)
Compliance rates are calculated to monitor the compliance with long-term quality of life and functional status data submission. A patient will be compliant if the patient has metacognition index score. Compliance rates will be assessed at each of the 3 neurocognitive/quality of life assessment time windows. All eligible and evaluable patients enrolled will be used. Patients removed from treatment prior to the time of neuropsychological assessment (for reasons such as disease progression, death, withdrawal of consent, etc.) will not be included in the denominator to assess the compliance rate. The time window is 27 - 48 months post diagnosis.
Time frame: 27-48 months post diagnosis
Population: All eligible and evaluable patients enrolled. Patients removed from treatment prior to the time of neuropsychological assessment (for reasons such as disease progression, death, withdrawal of consent, etc.) will not be included in the denominator to assess the compliance rate.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low-dose Craniospinal Radiation (LDSCI) | Compliance Rates for All Eligible and Evaluable Patients Enrolled Within Time Window 2 (27-48 Months Post Diagnosis) | 32 Percentage of Participants |
Secondary
Compliance Rates for All Eligible and Evaluable Patients Enrolled Within Time Window 3 (49 - 72 Months Post Diagnosis)
Compliance rates are calculated to monitor the compliance with long-term quality of life and functional status data submission. A patient will be compliant if the patient has metacognition index score. Compliance rates will be assessed at each of the 3 neurocognitive/quality of life assessment time windows. All eligible and evaluable patients enrolled will be used. Patients removed from treatment prior to the time of neuropsychological assessment (for reasons such as disease progression, death, withdrawal of consent, etc.) will not be included in the denominator to assess the compliance rate. The time window is 49 - 72 months post diagnosis.
Time frame: 49 - 72 months post diagnosis
Population: All eligible and evaluable patients enrolled. Patients removed from treatment prior to the time of neuropsychological assessment (for reasons such as disease progression, death, withdrawal of consent, etc.) will not be included in the denominator to assess the compliance rate.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low-dose Craniospinal Radiation (LDSCI) | Compliance Rates for All Eligible and Evaluable Patients Enrolled Within Time Window 3 (49 - 72 Months Post Diagnosis) | 69 Percentage of Participants |
Secondary
Incidence of Endocrine Dysfunction as Measured by Growth Hormone Stimulation Tests at the Time of Completion of Therapy by Radiotherapy (RT) Group
Endocrine dysfunction was assessed by growth hormone stimulation (GHS) tests. We report the percentage of patients with abnormal growth hormone stimulation tests.
Time frame: Post-treatment up to 3 years
Population: Only eligible \& evaluable patients 3-7 years of age were included. Patients with anaplastic histology or disseminated/excess residual disease were not evaluable (NE). Availability of growth hormone stimulation test results were very limited. Only 3 out of 464 eligible and evaluable patients had this data available (2 PFRT patients and 1 IFRT).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low-dose Craniospinal Radiation (LDSCI) | Incidence of Endocrine Dysfunction as Measured by Growth Hormone Stimulation Tests at the Time of Completion of Therapy by Radiotherapy (RT) Group | 0.0 Percentage of patients |
| Standard-dose Craniospinal Radiation (SDCSI) | Incidence of Endocrine Dysfunction as Measured by Growth Hormone Stimulation Tests at the Time of Completion of Therapy by Radiotherapy (RT) Group | 50.0 Percentage of patients |
Secondary
Incidence of Grade 3+ Hearing Loss at 1-year Post Treatment as Assessed by CTCAE v4
Proportions of patients with grade 3+ hearing impairment as assessed by CTCAE v4 at 1-year post treatment were calculated.
Time frame: Up to 3 years
Population: Eligible \& evaluable pts were included. Pts with anaplastic histology or disseminated/excess residual disease were not evaluable(NE). 26/23 IFRT/PFRT pts were NE, leaving 227 vs 237 eligible/evaluable pts. However some pts (28/22) weren't followed for at least 1-yr post-off tx (e.g., withdrew consent for FU or died), leaving 199 IFRT/215 PFRT pts.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low-dose Craniospinal Radiation (LDSCI) | Incidence of Grade 3+ Hearing Loss at 1-year Post Treatment as Assessed by CTCAE v4 | 8 Percentage of pts with g3+ hearing loss |
| Standard-dose Craniospinal Radiation (SDCSI) | Incidence of Grade 3+ Hearing Loss at 1-year Post Treatment as Assessed by CTCAE v4 | 8 Percentage of pts with g3+ hearing loss |
Secondary
Local Posterior Fossa (LPF) Failure Rate
LPF failure was defined as tumor recurrence/progression within the tumor bed. The cumulative incidence (CI) of LPF failure was estimated; 3-year estimates were reported with 95% confidence intervals. Patients with other failure types (e.g., NPF) and with other events prior to LPF failure (e.g., death, second malignancy) were considered as having competing events.
Time frame: 3 years
Population: Eligible and evaluable patients 3-21 yrs of age are included. Patients with anaplastic histology or disseminated/excess residual disease were not evaluable (NE). Arms I/III/V \[IFRT\] are combined \& arms II/IV/VI \[PFRT\] are combined. 26 \& 23 IFRT \& PFRT pts were NE and were excluded, leaving 227 and 237 eligible and evaluable pts.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low-dose Craniospinal Radiation (LDSCI) | Local Posterior Fossa (LPF) Failure Rate | 1.4 percentage 3 yr cumulative incidence |
| Standard-dose Craniospinal Radiation (SDCSI) | Local Posterior Fossa (LPF) Failure Rate | 2.7 percentage 3 yr cumulative incidence |
Secondary
Non-local Posterior Fossa (NLPF) Failure Rate
NLPF failure was defined as tumor recurrence/progression outside the radiation therapy clinical target volume boost (CTV-boost) but within the posterior fossa CTV (CTV-PF). The cumulative incidence (CI) of NLPF failure was estimated; 3-year estimates were reported with 95% confidence intervals. Patients with other failure types (e.g., NPF, LPF) and with other events prior to NLPF failure (e.g., death, second malignancy) were considered as having competing events.
Time frame: 3 years
Population: Eligible and evaluable patients 3-21 yrs of age are included. Patients with anaplastic histology or disseminated/excess residual disease were not evaluable (NE). Arms I/III/V \[IFRT\] are combined \& arms II/IV/VI \[PFRT\] are combined. 26 \& 23 IFRT \& PFRT pts were NE and were excluded, leaving 227 and 237 eligible and evaluable pts.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low-dose Craniospinal Radiation (LDSCI) | Non-local Posterior Fossa (NLPF) Failure Rate | 6.9 Percentage of 3 yr cumulative incidence |
| Standard-dose Craniospinal Radiation (SDCSI) | Non-local Posterior Fossa (NLPF) Failure Rate | 2.7 Percentage of 3 yr cumulative incidence |
Secondary
Non-posterior Fossa (NPF) Failure Rate
NPF failure was defined as tumor recurrence within the neuroaxis but outside the radiation therapy clinical target volume (CTV). The cumulative incidence (CI) of NPF failure was estimated; 3-year estimates were reported with 95% confidence intervals. Patients with other failure types (e.g., LPF failure) and with other events prior to NPF failure (e.g., death, second malignancy) were considered as having competing events.
Time frame: 3 years
Population: Eligible and evaluable patients 3-21 yrs of age are included. Patients with anaplastic histology or disseminated/excess residual disease were not evaluable (NE). Arms I/III/V \[IFRT\] are combined \& arms II/IV/VI \[PFRT\] are combined. 26 \& 23 IFRT \& PFRT pts were NE and were excluded, leaving 227 and 237 eligible and evaluable pts.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low-dose Craniospinal Radiation (LDSCI) | Non-posterior Fossa (NPF) Failure Rate | 5.1 Percentage of 3 yr cumulative incidence |
| Standard-dose Craniospinal Radiation (SDCSI) | Non-posterior Fossa (NPF) Failure Rate | 6.2 Percentage of 3 yr cumulative incidence |
Secondary
Overall Survival (OS) by Molecular Subgroup Based on Methylation Arrays
OS was defined as the time interval from date of study entry to date of death from any cause or to date of last contact for survivors. OS was estimated using the method of Kaplan and Meier. 3-year estimates are reported with 95% CI's.
Time frame: 3 years
Population: 355 patients were classified into one of the medulloblastoma subgroups by methylation arrays and included in this analysis; 74 were Group 3 medulloblastoma, 154 were Group 4 medulloblastoma, 64 were SHH medulloblastoma, and 63 were WNT medulloblastoma patients.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low-dose Craniospinal Radiation (LDSCI) | Overall Survival (OS) by Molecular Subgroup Based on Methylation Arrays | 76.3 Percent probability of overall survival |
| Standard-dose Craniospinal Radiation (SDCSI) | Overall Survival (OS) by Molecular Subgroup Based on Methylation Arrays | 97.3 Percent probability of overall survival |
| Involved Field Radiation (IFRT) | Overall Survival (OS) by Molecular Subgroup Based on Methylation Arrays | 92.0 Percent probability of overall survival |
| Posterior Fossa Radiation (PFRT) | Overall Survival (OS) by Molecular Subgroup Based on Methylation Arrays | 98.3 Percent probability of overall survival |
Secondary
Post-treatment Endocrine Function by CSI Group
Post-treatment endocrine function was measured by laboratory assessment of the thyroid stimulating hormone (TSH). The mean TSH will be reported.
Time frame: Up to 3 years
Population: Only eligible \& evaluable pts 3-7 years of age were included. Pts with anaplastic histology or disseminated/excess residual disease were not evaluable (NE). 11 and 8 LDSCI and SDCSI pts were NE, respectively, leaving 116 vs 110 for this comparison. Of these, 89 LDSCI and 79 SDCSI pts had post-treatment TSH values available and were included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low-dose Craniospinal Radiation (LDSCI) | Post-treatment Endocrine Function by CSI Group | 5.3 uU/ml | Standard Deviation 5.6 |
| Standard-dose Craniospinal Radiation (SDCSI) | Post-treatment Endocrine Function by CSI Group | 6.1 uU/ml | Standard Deviation 5.3 |
Secondary
Post-treatment Grade 3+ Hearing Loss as Measured by Common Terminology Criteria for Adverse Events (CTCAE) Version (v)4
Proportions of patients with grade 3+ hearing loss after the completion of therapy will be calculated and reported separately for low dose craniospinal irradiation (LDCSI) versus (vs.) standard dose craniospinal irradiation (SDCSI) patients. Eligible and evaluable patients 3-7 years of age will be used.
Time frame: Up to 3 years
Population: Only eligible \& evaluable pts 3-7 years of age are included since only younger pts were randomized to either LD or SD CSI. 11 and 8 LDCSI and SDCSI pts respectively were not evaluable due to anaplastic disease or excess residual/disseminated disease, leaving 116 vs 110 patients for this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low-dose Craniospinal Radiation (LDSCI) | Post-treatment Grade 3+ Hearing Loss as Measured by Common Terminology Criteria for Adverse Events (CTCAE) Version (v)4 | 11 Percentage of pts with g3+ hearing loss |
| Standard-dose Craniospinal Radiation (SDCSI) | Post-treatment Grade 3+ Hearing Loss as Measured by Common Terminology Criteria for Adverse Events (CTCAE) Version (v)4 | 11 Percentage of pts with g3+ hearing loss |
Secondary
Post-treatment Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) by CSI Group Within Time Window 1 (4-15 Months Post Diagnosis)
Metacognition index (MI) was measured by BRIEF test. Assessments within the time window, from eligible and evaluable patients are reported. If the patient had disease progression, only the assessments before progression date were reported. The MI is a standard T- score, and it ranges from 0 to 100. The higher score reported suggests a higher level of dysfunction.
Time frame: 4 - 15 months post diagnosis
Population: Only eligible \& evaluable patients 3-7 years of age with MI values within time window were included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low-dose Craniospinal Radiation (LDSCI) | Post-treatment Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) by CSI Group Within Time Window 1 (4-15 Months Post Diagnosis) | 50.7 T-score | Standard Deviation 11.1 |
| Standard-dose Craniospinal Radiation (SDCSI) | Post-treatment Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) by CSI Group Within Time Window 1 (4-15 Months Post Diagnosis) | 51.3 T-score | Standard Deviation 9.6 |
Secondary
Post-treatment Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) by CSI Group Within Time Window 2 (27-48 Months Post Diagnosis)
Metacognition index (MI) was measured by BRIEF test. Assessments within the time window, from eligible and evaluable patients are reported. If the patient had disease progression, only the assessments before progression date were reported. The MI is a standard T- score, and it ranges from 0 to 100. The higher score reported suggests a higher level of dysfunction.
Time frame: 27-48 months post diagnosis
Population: Only eligible \& evaluable patients 3-7 years of age with MI values within time window were included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low-dose Craniospinal Radiation (LDSCI) | Post-treatment Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) by CSI Group Within Time Window 2 (27-48 Months Post Diagnosis) | 51.4 T-score | Standard Deviation 10.6 |
| Standard-dose Craniospinal Radiation (SDCSI) | Post-treatment Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) by CSI Group Within Time Window 2 (27-48 Months Post Diagnosis) | 55.0 T-score | Standard Deviation 9.9 |
Secondary
Post-treatment Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) by CSI Group Within Time Window 3 (49 - 72 Months Post Diagnosis)
Metacognition index (MI) was measured by BRIEF test. Assessments within the time window, from eligible and evaluable patients are reported. If the patient had disease progression, only the assessments before progression date were reported. The MI is a standard T- score, and it ranges from 0 to 100. The higher score reported suggests a higher level of dysfunction.
Time frame: 49 - 72 months post diagnosis
Population: Only eligible \& evaluable patients 3-7 years of age with MI values within time window were included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low-dose Craniospinal Radiation (LDSCI) | Post-treatment Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) by CSI Group Within Time Window 3 (49 - 72 Months Post Diagnosis) | 54.1 T-score | Standard Deviation 10.7 |
| Standard-dose Craniospinal Radiation (SDCSI) | Post-treatment Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) by CSI Group Within Time Window 3 (49 - 72 Months Post Diagnosis) | 58.6 T-score | Standard Deviation 11.3 |
Secondary
Post-treatment Neurocognitive Function as Measured by the Estimated Full-scale IQ (FSIQ) by CSI Group Within Time Window 1 (4 - 15 Months Post Diagnosis).
Post-treatment neurocognitive function was assessed. Full-scale IQ (FSIQ) is a representative measurement for neurocognitive function. FSIQ was measured by IQ tests. Assessments within the time window, from eligible and evaluable patients are reported. The time window is 4-15 months post diagnosis, only the assessments before progression date were reported. The Range of FSIQ is 50-150. A higher FSIQ is better.
Time frame: 4 -15 months post diagnosis
Population: Only eligible \& evaluable patients 3-7 years of age with FSIQ observations within time window were included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low-dose Craniospinal Radiation (LDSCI) | Post-treatment Neurocognitive Function as Measured by the Estimated Full-scale IQ (FSIQ) by CSI Group Within Time Window 1 (4 - 15 Months Post Diagnosis). | 93.8 Scores on a scale | Standard Deviation 14.4 |
| Standard-dose Craniospinal Radiation (SDCSI) | Post-treatment Neurocognitive Function as Measured by the Estimated Full-scale IQ (FSIQ) by CSI Group Within Time Window 1 (4 - 15 Months Post Diagnosis). | 96.2 Scores on a scale | Standard Deviation 15 |
Secondary
Post-treatment Neurocognitive Function as Measured by the Estimated Full-scale IQ (FSIQ) by CSI Group Within Time Window 2 (27 - 48 Months Post Diagnosis)
Post-treatment neurocognitive function was assessed. Full-scale IQ (FSIQ) is a representative measurement for neurocognitive function. FSIQ was measured by IQ tests. Assessments within the time window, from eligible and evaluable patients are reported. The time window is 27-48 months post diagnosis, only the assessments before progression date were reported. The range of FSIQ is 50 - 150. A higher FSIQ is better.
Time frame: 27 - 48 months post diagnosis
Population: Only eligible \& evaluable patients 3-7 years of age with FSIQ observations within time window were included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low-dose Craniospinal Radiation (LDSCI) | Post-treatment Neurocognitive Function as Measured by the Estimated Full-scale IQ (FSIQ) by CSI Group Within Time Window 2 (27 - 48 Months Post Diagnosis) | 92.2 Scores on a scale | Standard Deviation 12.5 |
| Standard-dose Craniospinal Radiation (SDCSI) | Post-treatment Neurocognitive Function as Measured by the Estimated Full-scale IQ (FSIQ) by CSI Group Within Time Window 2 (27 - 48 Months Post Diagnosis) | 90.5 Scores on a scale | Standard Deviation 13.3 |
Secondary
Post-treatment Neurocognitive Function as Measured by the Estimated Full-scale IQ (FSIQ) by CSI Group Within Time Window 3 (49 - 72 Months Post Diagnosis)
Post-treatment neurocognitive function was assessed. Full-scale IQ (FSIQ) is a representative measurement for neurocognitive function. FSIQ was measured by IQ tests. Assessments within the time window, from eligible and evaluable patients are reported. The time window is 49-72 months post diagnosis, only the assessments before progression date were reported. The Range of FSIQ is 50-150. A higher FSIQ is better.
Time frame: 49 - 72 months post diagnosis
Population: Eligible and evaluable patients are reported.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low-dose Craniospinal Radiation (LDSCI) | Post-treatment Neurocognitive Function as Measured by the Estimated Full-scale IQ (FSIQ) by CSI Group Within Time Window 3 (49 - 72 Months Post Diagnosis) | 90.5 Scores on a scale | Standard Deviation 15.4 |
| Standard-dose Craniospinal Radiation (SDCSI) | Post-treatment Neurocognitive Function as Measured by the Estimated Full-scale IQ (FSIQ) by CSI Group Within Time Window 3 (49 - 72 Months Post Diagnosis) | 86.4 Scores on a scale | Standard Deviation 13.5 |
Secondary
Progression-free Survival (PFS) by Molecular Subgroup Based on Methylation Arrays
PFS was defined as the time interval from date of study entry to disease progression, relapse or death due to cancer or to last follow-up. Second malignancies and deaths from causes clearly not associated with tumor progression or recurrence were censored. PFS was estimated using the method of Kaplan and Meier. 3-year estimates are reported with 95% CI's.
Time frame: 3 years
Population: 355 patients were classified into one of the medulloblastoma subgroups by methylation arrays and included in this analysis; 74 were Group 3 medulloblastoma, 154 were Group 4 medulloblastoma, 64 were SHH medulloblastoma, and 63 were WNT medulloblastoma patients.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low-dose Craniospinal Radiation (LDSCI) | Progression-free Survival (PFS) by Molecular Subgroup Based on Methylation Arrays | 70.6 Percentage probability of PFS |
| Standard-dose Craniospinal Radiation (SDCSI) | Progression-free Survival (PFS) by Molecular Subgroup Based on Methylation Arrays | 90.6 Percentage probability of PFS |
| Involved Field Radiation (IFRT) | Progression-free Survival (PFS) by Molecular Subgroup Based on Methylation Arrays | 90.4 Percentage probability of PFS |
| Posterior Fossa Radiation (PFRT) | Progression-free Survival (PFS) by Molecular Subgroup Based on Methylation Arrays | 98.4 Percentage probability of PFS |