Comparison of Radiation Therapy Regimens in Combination With Chemotherapy in Treating Young Patients With Newly Diagnosed Standard-Risk Medulloblastoma
Official Title
A Study Evaluating Limited Target Volume Boost Irradiation and Reduced Dose Craniospinal Radiotherapy (18.00 Gy) and Chemotherapy in Children With Newly Diagnosed Standard Risk Medulloblastoma: A Phase III Double Randomized Trial
Acronym
Not provided
Organization
Children's Oncology GroupNETWORK
Status Module
Record Verification Date
May 2026
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Apr 30, 2004Actual
Primary Completion Date
Mar 31, 2016Actual
Completion Date
Dec 31, 2024Actual
First Submitted Date
Jun 14, 2004
First Submission Date that Met QC Criteria
Jun 15, 2004
First Posted Date
Jun 16, 2004Estimated
Results Waived
Not provided
Results First Submitted Date
Feb 22, 2017
Results First Submitted that Met QC Criteria
May 16, 2017
Results First Posted Date
Jun 14, 2017Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
May 14, 2026
Last Update Posted Date
Jun 9, 2026Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Children's Oncology GroupNETWORK
Collaborators
Name
Class
National Cancer Institute (NCI)
NIH
Oversight Module
No data available
No data is available for this block.
Description Module
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.
Conditions Module
Conditions
Medulloblastoma
Keywords
Not provided
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 3
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
549Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Arm I (3-7 years of age, LDCSI, IFRT)
Experimental
See Detailed Description (Arm I)
Drug: Cisplatin
Radiation: Craniospinal Irradiation
Drug: Cyclophosphamide
Radiation: Involved-Field Radiation Therapy
Other: Laboratory Biomarker Analysis
Drug: Lomustine
Other: Quality-of-Life Assessment
Drug: Vincristine Sulfate
Arm II (3-7 years of age, LDCSI, PFRT)
Experimental
See Detailed Description (Arm II)
Drug: Cisplatin
Radiation: Craniospinal Irradiation
Drug: Cyclophosphamide
Other: Laboratory Biomarker Analysis
Drug: Lomustine
Other: Quality-of-Life Assessment
Radiation: Radiation Therapy
Drug: Vincristine Sulfate
Arm III (3-7 years of age, SDCSI, IFRT)
Experimental
See Detailed Description (Arm III)
Drug: Cisplatin
Radiation: Craniospinal Irradiation
Drug: Cyclophosphamide
Radiation: Involved-Field Radiation Therapy
Other: Laboratory Biomarker Analysis
Drug: Lomustine
Other: Quality-of-Life Assessment
Drug: Vincristine Sulfate
Arm IV (3-7 years of age, SDCSI, PFRT)
Active Comparator
See Detailed Description (Arm IV)
Interventions
Name
Type
Description
Arm Group Labels
Other Names
Cisplatin
Drug
Given IV
Arm I (3-7 years of age, LDCSI, IFRT)
Arm II (3-7 years of age, LDCSI, PFRT)
Arm III (3-7 years of age, SDCSI, IFRT)
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
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).
Assessed at 3 years
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]).
3 years
Secondary Outcomes
Measure
Description
Time Frame
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.
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
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)
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.
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.
Undergo standard volume boost (whole posterior fossa radiation therapy)
Arm II (3-7 years of age, LDCSI, PFRT)
Arm IV (3-7 years of age, SDCSI, PFRT)
Arm VI (8-21 years of age, SDCSI, PFRT)
Cancer Radiotherapy
Energy Type
ENERGY_TYPE
Irradiate
Irradiated
Irradiation
Radiation
Radiation Therapy, NOS
Radiotherapeutics
Radiotherapy
RT
Therapy, Radiation
Vincristine Sulfate
Drug
Given IV
Arm I (3-7 years of age, LDCSI, IFRT)
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)
Kyocristine
Leurocristine Sulfate
Leurocristine, sulfate
Oncovin
Vincasar
Vincosid
Vincrex
Vincristine, sulfate
3 years
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.
3 years
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.
3 years
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.
Up to 3 years
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.
Up to 3 years
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.
4 -15 months post diagnosis
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.
27 - 48 months post diagnosis
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.
49 - 72 months post diagnosis
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.
Up to 3 years
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.
Post-treatment up to 3 years
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.
3 years
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.
3 years
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.
4 - 15 months post diagnosis
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.
27-48 months post diagnosis
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.
49 - 72 months post diagnosis
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.
4-15 months post diagnosis
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.
27-48 months post diagnosis
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.
49 - 72 months post diagnosis
Birmingham
Alabama
35233
United States
Phoenix Childrens Hospital
Phoenix
Arizona
85016
United States
Banner University Medical Center - Tucson
Tucson
Arizona
85719
United States
Kaiser Permanente Downey Medical Center
Downey
California
90242
United States
Loma Linda University Medical Center
Loma Linda
California
92354
United States
Miller Children's and Women's Hospital Long Beach
Long Beach
California
90806
United States
Children's Hospital Los Angeles
Los Angeles
California
90027
United States
Cedars-Sinai Medical Center
Los Angeles
California
90048
United States
Valley Children's Hospital
Madera
California
93636
United States
UCSF Benioff Children's Hospital Oakland
Oakland
California
94609
United States
Kaiser Permanente-Oakland
Oakland
California
94611
United States
Children's Hospital of Orange County
Orange
California
92868
United States
Lucile Packard Children's Hospital Stanford University
Palo Alto
California
94304
United States
Sutter Medical Center Sacramento
Sacramento
California
95816
United States
University of California Davis Comprehensive Cancer Center
Sacramento
California
95817
United States
Rady Children's Hospital - San Diego
San Diego
California
92123
United States
UCSF Medical Center-Parnassus
San Francisco
California
94143
United States
UCSF Medical Center-Mission Bay
San Francisco
California
94158
United States
Santa Barbara Cottage Hospital
Santa Barbara
California
93102
United States
Children's Hospital Colorado
Aurora
Colorado
80045
United States
Connecticut Children's Medical Center
Hartford
Connecticut
06106
United States
Yale University
New Haven
Connecticut
06520
United States
Alfred I duPont Hospital for Children
Wilmington
Delaware
19803
United States
MedStar Georgetown University Hospital
Washington D.C.
District of Columbia
20007
United States
Children's National Medical Center
Washington D.C.
District of Columbia
20010
United States
Broward Health Medical Center
Fort Lauderdale
Florida
33316
United States
Lee Memorial Health System
Fort Myers
Florida
33901
United States
Golisano Children's Hospital of Southwest Florida
Fort Myers
Florida
33908
United States
UF Health Cancer Institute - Gainesville
Gainesville
Florida
32610
United States
Memorial Regional Hospital/Joe DiMaggio Children's Hospital
Hollywood
Florida
33021
United States
Nemours Children's Clinic-Jacksonville
Jacksonville
Florida
32207
United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami
Florida
33136
United States
Nicklaus Children's Hospital
Miami
Florida
33155
United States
AdventHealth Orlando
Orlando
Florida
32803
United States
Arnold Palmer Hospital for Children
Orlando
Florida
32806
United States
Nemours Children's Clinic - Orlando
Orlando
Florida
32806
United States
Orlando Health Cancer Institute
Orlando
Florida
32806
United States
Nemours Children's Hospital
Orlando
Florida
32827
United States
Nemours Children's Clinic - Pensacola
Pensacola
Florida
32504
United States
Johns Hopkins All Children's Hospital
St. Petersburg
Florida
33701
United States
Saint Joseph's Hospital/Children's Hospital-Tampa
Tampa
Florida
33607
United States
Saint Mary's Medical Center
West Palm Beach
Florida
33407
United States
Children's Healthcare of Atlanta - Arthur M Blank Hospital
Atlanta
Georgia
30329
United States
Augusta University Medical Center
Augusta
Georgia
30912
United States
Memorial Health University Medical Center
Savannah
Georgia
31404
United States
University of Hawaii Cancer Center
Honolulu
Hawaii
96813
United States
Kapiolani Medical Center for Women and Children
Honolulu
Hawaii
96826
United States
Tripler Army Medical Center
Honolulu
Hawaii
96859
United States
Saint Luke's Cancer Institute - Boise
Boise
Idaho
83712
United States
Lurie Children's Hospital-Chicago
Chicago
Illinois
60611
United States
University of Illinois
Chicago
Illinois
60612
United States
University of Chicago Comprehensive Cancer Center
Chicago
Illinois
60637
United States
Loyola University Medical Center
Maywood
Illinois
60153
United States
Advocate Children's Hospital-Oak Lawn
Oak Lawn
Illinois
60453
United States
Advocate Children's Hospital-Park Ridge
Park Ridge
Illinois
60068
United States
Advocate Lutheran General Hospital
Park Ridge
Illinois
60068
United States
Saint Jude Midwest Affiliate
Peoria
Illinois
61637
United States
Southern Illinois University School of Medicine
Springfield
Illinois
62702
United States
Riley Hospital for Children
Indianapolis
Indiana
46202
United States
Ascension Saint Vincent Indianapolis Hospital
Indianapolis
Indiana
46260
United States
Blank Children's Hospital
Des Moines
Iowa
50309
United States
University of Iowa/Holden Comprehensive Cancer Center
Iowa City
Iowa
52242
United States
University of Kentucky/Markey Cancer Center
Lexington
Kentucky
40536
United States
Norton Children's Hospital
Louisville
Kentucky
40202
United States
Tulane University School of Medicine
New Orleans
Louisiana
70112
United States
Children's Hospital New Orleans
New Orleans
Louisiana
70118
United States
Eastern Maine Medical Center
Bangor
Maine
04401
United States
Maine Children's Cancer Program
Scarborough
Maine
04074
United States
University of Maryland/Greenebaum Cancer Center
Baltimore
Maryland
21201
United States
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore
Maryland
21287
United States
Walter Reed National Military Medical Center
Bethesda
Maryland
20889-5600
United States
Tufts Children's Hospital
Boston
Massachusetts
02111
United States
Massachusetts General Hospital Cancer Center
Boston
Massachusetts
02114
United States
Dana-Farber Cancer Institute
Boston
Massachusetts
02215
United States
C S Mott Children's Hospital
Ann Arbor
Michigan
48109
United States
Wayne State University/Karmanos Cancer Institute
Detroit
Michigan
48201
United States
Henry Ford Health Saint John Hospital
Detroit
Michigan
48236
United States
Michigan State University
East Lansing
Michigan
48823
United States
Hurley Medical Center
Flint
Michigan
48503
United States
Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital
Grand Rapids
Michigan
49503
United States
Bronson Methodist Hospital
Kalamazoo
Michigan
49007
United States
Kalamazoo Center for Medical Studies
Kalamazoo
Michigan
49008
United States
Children's Hospitals and Clinics of Minnesota - Minneapolis
Minneapolis
Minnesota
55404
United States
University of Minnesota/Masonic Cancer Center
Minneapolis
Minnesota
55455
United States
Mayo Clinic in Rochester
Rochester
Minnesota
55905
United States
Children's Hospital and Clinic-Saint Paul
Saint Paul
Minnesota
55102
United States
University of Mississippi Medical Center
Jackson
Mississippi
39216
United States
Children's Mercy Hospitals and Clinics
Kansas City
Missouri
64108
United States
Cardinal Glennon Children's Medical Center
St Louis
Missouri
63104
United States
Washington University School of Medicine
St Louis
Missouri
63110
United States
Children's Hospital and Medical Center of Omaha
Omaha
Nebraska
68114
United States
University of Nebraska Medical Center
Omaha
Nebraska
68198
United States
Nevada Cancer Research Foundation NCORP
Las Vegas
Nevada
89120
United States
Alliance for Childhood Diseases/Cure 4 the Kids Foundation
Las Vegas
Nevada
89135
United States
Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
Lebanon
New Hampshire
03756
United States
Hackensack University Medical Center
Hackensack
New Jersey
07601
United States
Morristown Medical Center
Morristown
New Jersey
07960
United States
Saint Peter's University Hospital
New Brunswick
New Jersey
08901
United States
Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
New Brunswick
New Jersey
08903
United States
Newark Beth Israel Medical Center
Newark
New Jersey
07112
United States
Saint Joseph's Regional Medical Center
Paterson
New Jersey
07503
United States
Overlook Hospital
Summit
New Jersey
07902
United States
University of New Mexico Cancer Center
Albuquerque
New Mexico
87106
United States
Albany Medical Center
Albany
New York
12208
United States
Roswell Park Cancer Institute
Buffalo
New York
14263
United States
NYU Langone Hospital - Long Island
Mineola
New York
11501
United States
The Steven and Alexandra Cohen Children's Medical Center of New York
New Hyde Park
New York
11040
United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York
New York
10016
United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York
New York
10032
United States
University of Rochester
Rochester
New York
14642
United States
State University of New York Upstate Medical University
Data Available: Individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive
FG002
Arm III (3-7 Yrs of Age, SDCSI, IFRT)
Patients 3-7 years of age, SDCSI, IFRT
FG003
Arm IV (3-7 Yrs of Age, SDCSI, PFRT)
Patients 3-7 years of age, SDCSI, PFRT
FG004
Arm V (8-21 Yrs of Age, SDCSI, IFRT)
Patients 8-21 years of age, SDCSI, IFRT
FG005
Arm VI (8-21 Yrs of Age, SDCSI, PFRT)
Patients 8-21 yrs of age, SDCSI, PFRT
FG00064 subjects
FG00164 subjects
FG00263 subjects
FG00365 subjects
FG004147 subjects
FG005146 subjects
COMPLETED
FG00052 subjects
FG00154 subjects
FG00246 subjects
FG00346 subjects
FG004105 subjects
FG005115 subjects
NOT COMPLETED
FG00012 subjects
FG00110 subjects
FG00217 subjects
FG00319 subjects
FG00442 subjects
FG00531 subjects
Type
Comment
Reasons
Adverse Event
FG0001 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
Lack of Efficacy
FG0002 subjects
FG0014 subjects
FG0026 subjects
FG0033 subjects
FG004
Lost to Follow-up
FG0000 subjects
FG0011 subjects
FG0020 subjects
FG0030 subjects
FG004
Physician Decision
FG0002 subjects
FG0013 subjects
FG0022 subjects
FG0033 subjects
FG004
Protocol Violation
FG0001 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Withdrawal by Subject
FG0001 subjects
FG0010 subjects
FG0024 subjects
FG0035 subjects
FG004
Patient ineligible
FG0001 subjects
FG0010 subjects
FG0023 subjects
FG0037 subjects
FG004
Excess residual disease
FG0002 subjects
FG0012 subjects
FG0021 subjects
FG0031 subjects
FG004
Reason not documented
FG0001 subjects
FG0010 subjects
FG0021 subjects
FG0030 subjects
FG004
Pt transferred to inst w/out study open
FG0001 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Only eligible patients are included in each of the 6 groups for baseline characteristics.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Arm I (3-7 Years of Age, LDCSI, IFRT)
Eligible patients 3-7 yrs of age, LDCSI, IFRT
BG001
Arm II (3-7 Years of Age, LDCSI, PFRT)
Eligible patients 3-7 yrs of age, LDCSI, PFRT
BG002
Arm III (3-7 Years of Age, SDCSI, IFRT)
Eligible patients 3-7 yrs of age, SDCSI, IFRT
BG003
Arm IV (3-7 Years of Age, SDCSI, PFRT)
Eligible patients 3-7 yrs of age, SDCSI, PFRT
BG004
Arm V (8-21 Years of Age, SDCSI, IFRT)
Eligible patients 8-21 yrs of age, SDCSI, IFRT
BG005
Arm VI (8-21 Years of Age, SDCSI, PFRT)
Eligible patients 8-21 yrs of age, SDCSI, PFRT
BG006
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG00063
BG00164
BG00260
BG00358
BG004130
BG005138
BG006513
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Categorical
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
<=18 years
BG00063
BG00164
BG00260
BG003
Age, Continuous
Median
Full Range
years
Title
Denominators
Categories
Title
Measurements
BG0005.9(3.2 to 7.8)
BG0015.9(3.3 to 7.9)
BG002
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG00016
BG00120
BG002
Ethnicity (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Hispanic or Latino
BG00010
BG00118
BG002
Race (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
American Indian or Alaska Native
BG0000
BG0010
BG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
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).
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.
Posted
Number
95% Confidence Interval
probability of 3 year EFS
Assessed at 3 years
ID
Title
Description
OG000
Low-dose Craniospinal Radiation (LDSCI)
Includes eligible patients 3-7 years of age without anaplastic histology or evidence of disseminated or ERD based on central review and randomized to one of the LDCSI arms (Arms I and II)
OG001
Standard-dose Craniospinal Radiation (SDCSI)
Includes eligible patients 3-7 years of age without anaplastic histology or evidence of disseminated or ERD based on central review and randomized to one of the SDCSI arms (Arms III and IV)
OG002
Involved Field Radiation (IFRT)
Includes eligible patients without anaplastic histology or evidence of disseminated or ERD based on central review and randomized to one of the IFRT arms (I, III, V).
OG003
Posterior Fossa Radiation (PFRT)
Includes eligible patients without anaplastic histology or evidence of disseminated or ERD based on central review and randomized to one of the PFRT arms (II, IV, VI).
Units
Counts
Participants
OG000116
OG001110
OG002227
OG003
Title
Denominators
Categories
LDCSI vs SDCSI
ParticipantsOG000116
ParticipantsOG001110
ParticipantsOG0020
ParticipantsOG003
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
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.
Hazard Ratio (HR)
1.5
1-Sided
80
1.9
Non-Inferiority
A hazard ratio of 1.6 is used as the non-inferiority margin. For the final analysis of comparing LDCSI vs. SDCSI, a one-sided 80% upper confidence limit of the hazard ratio based on a stratified approach will be estimated (stratified by RT group (IFRT vs. PFRT)). If the upper confidence limit is lower than 1.6, LDCSI would be deemed to be non-inferior. If not, non-inferiority would not be established.
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]).
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.
Posted
Number
95% Confidence Interval
Probability of 3 yr OS rate
3 years
ID
Title
Description
OG000
Low-dose Craniospinal Radiation (LDSCI)
Includes eligible patients 3-7 years of age without anaplastic histology or evidence of disseminated or ERD based on central review and randomized to one of the LDCSI arms (Treatment Arms I or II)
OG001
Standard-dose Craniospinal Radiation (SDCSI)
Includes eligible patients 3-7 years of age without anaplastic histology or evidence of disseminated or ERD based on central review and randomized to one of the SDCSI arms (Treatment Arms III or IV)
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.
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.
Posted
Number
95% Confidence Interval
percentage 3 yr cumulative incidence
3 years
ID
Title
Description
OG000
Involved Field Radiation (IFRT)
Includes eligible patients 3-21 years of age without anaplastic histology or evidence of disseminated or ERD based on central review and randomized to one of the IFRT arms (Treatment Arms I, III, V)
OG001
Posterior Fossa Radiation (PFRT)
Includes eligible patients 3-21 years of age without anaplastic histology or evidence of disseminated or ERD based on central review and randomized to one of the PFRT arms (Treatment Arms II, IV, VI)
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.
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.
Posted
Number
95% Confidence Interval
Percentage of 3 yr cumulative incidence
3 years
ID
Title
Description
OG000
Involved Field Radiation (IFRT)
Includes eligible patients 3-21 years of age without anaplastic histology or evidence of disseminated or ERD based on central review and randomized to one of the IFRT arms (Treatment Arms I, III, V)
OG001
Posterior Fossa Radiation (PFRT)
Includes eligible patients 3-21 years of age without anaplastic histology or evidence of disseminated or ERD based on central review and randomized to one of the PFRT arms (Treatment Arms II, IV, VI).
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.
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.
Posted
Number
95% Confidence Interval
Percentage of 3 yr cumulative incidence
3 years
ID
Title
Description
OG000
Involved Field Radiation (IFRT)
Includes eligible patients 3-21 years of age without anaplastic histology or evidence of disseminated or ERD based on central review and randomized to one of the IFRT arms (Treatment Arms I, III, V).
OG001
Posterior Fossa Radiation (PFRT)
Includes eligible patients 3-21 years of age without anaplastic histology or evidence of disseminated or ERD based on central review and randomized to one of the PFRT arms (Treatment Arms II, IV, VI).
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.
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.
Posted
Mean
Standard Deviation
uU/ml
Up to 3 years
ID
Title
Description
OG000
Low-dose Craniospinal Radiation (LDSCI)
Includes eligible patients 3-7 years of age without anaplastic histology or evidence of disseminated or ERD based on central review and randomized to one of the LDCSI arms (Treatment Arms I or II) and with a post-treatment TSH value.
OG001
Standard-dose Craniospinal Radiation (SDCSI)
Includes eligible patients 3-7 years of age without anaplastic histology or evidence of disseminated or ERD based on central review and randomized to one of the SDCSI arms (Treatment Arms III or IV) and with a post-treatment TSH value.
Units
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.
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.
Posted
Number
Percentage of pts with g3+ hearing loss
Up to 3 years
ID
Title
Description
OG000
Low-dose Craniospinal Radiation (LDSCI)
Includes eligible patients 3-7 years of age without anaplastic histology or evidence of disseminated or ERD based on central review and randomized to one of the LDCSI arms (Treatment Arms I or II)
OG001
Standard-dose Craniospinal Radiation (SDCSI)
Includes eligible patients 3-7 years of age without anaplastic histology or evidence of disseminated or ERD based on central review and randomized to one of the SDCSI arms (Treatment Arms III or IV)
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.
Only eligible & evaluable patients 3-7 years of age with FSIQ observations within time window were included.
Posted
Mean
Standard Deviation
Scores on a scale
4 -15 months post diagnosis
ID
Title
Description
OG000
Low-dose Craniospinal Radiation (LDSCI)
Includes eligible patients 3-7 years of age without anaplastic histology or evidence of disseminated or ERD based on central review and randomized to one of the LDCSI arms (Treatment Arms I or II) and with a post-treatment TSH value.
OG001
Standard-dose Craniospinal Radiation (SDCSI)
Includes eligible patients 3-7 years of age without anaplastic histology or evidence of disseminated or ERD based on central review and randomized to one of the SDCSI arms (Treatment Arms III or IV) and with a post-treatment TSH value.
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.
Only eligible & evaluable patients 3-7 years of age with FSIQ observations within time window were included.
Posted
Mean
Standard Deviation
Scores on a scale
27 - 48 months post diagnosis
ID
Title
Description
OG000
Low-dose Craniospinal Radiation (LDSCI)
Includes eligible patients 3-7 years of age without anaplastic histology or evidence of disseminated or ERD based on central review and randomized to one of the LDCSI arms (Treatment Arms I or II) and with a post-treatment TSH value.
OG001
Standard-dose Craniospinal Radiation (SDCSI)
Includes eligible patients 3-7 years of age without anaplastic histology or evidence of disseminated or ERD based on central review and randomized to one of the SDCSI arms (Treatment Arms III or IV) and with a post-treatment TSH value.
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.
Eligible and evaluable patients are reported.
Posted
Mean
Standard Deviation
Scores on a scale
49 - 72 months post diagnosis
ID
Title
Description
OG000
Low-dose Craniospinal Radiation (LDSCI)
Includes eligible patients 3-7 years of age without anaplastic histology or evidence of disseminated or ERD based on central review and randomized to one of the LDCSI arms (Treatment Arms I or II) and with a post-treatment TSH value.
OG001
Standard-dose Craniospinal Radiation (SDCSI)
Includes eligible patients 3-7 years of age without anaplastic histology or evidence of disseminated or ERD based on central review and randomized to one of the SDCSI arms (Treatment Arms III or IV) and with a post-treatment TSH value.
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.
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.
Posted
Number
Percentage of pts with g3+ hearing loss
Up to 3 years
ID
Title
Description
OG000
Involved Field Radiation (IFRT)
Includes eligible patients 3-21 years of age without anaplastic histology or evidence of disseminated or ERD based on central review and randomized to one of the IFRT arms (Treatment Arms I, III, V).
OG001
Posterior Fossa Radiation (PFRT)
Includes eligible patients 3-21 years of age without anaplastic histology or evidence of disseminated or ERD based on central review and randomized to one of the PFRT arms (Treatment Arms II, IV, VI).
Units
Counts
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.
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).
Posted
Number
95% Confidence Interval
Percentage of patients
Post-treatment up to 3 years
ID
Title
Description
OG000
Involved Field Radiation (IFRT)
Includes eligible patients 3-21 years of age without anaplastic histology or evidence of disseminated or ERD based on central review and randomized to one of the IFRT arms (Treatment Arms I, III, V)
OG001
Posterior Fossa Radiation (PFRT)
Includes eligible patients 3-21 years of age without anaplastic histology or evidence of disseminated or ERD based on central review and randomized to one of the PFRT arms (Treatment Arms II, IV, VI)
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.
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.
Posted
Number
95% Confidence Interval
Percent probability of overall survival
3 years
ID
Title
Description
OG000
Group 3 Medulloblastoma
Includes eligible patients 3-21 years of age without anaplastic histology or evidence of disseminated or ERD based on central review and classified as Group 3 medulloblastoma by methylation arrays
OG001
Group 4 Medulloblastoma
Includes eligible patients 3-21 years of age without anaplastic histology or evidence of disseminated or ERD based on central review and classified as Group 4 medulloblastoma by methylation arrays
OG002
Sonic Hedgehog (SHH) Medulloblastoma
Includes eligible patients 3-21 years of age without anaplastic histology or evidence of disseminated or ERD based on central review and classified as SHH medulloblastoma by methylation arrays
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.
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.
Posted
Number
95% Confidence Interval
Percentage probability of PFS
3 years
ID
Title
Description
OG000
Group 3 Medulloblastoma
Includes eligible patients 3-21 years of age without anaplastic histology or evidence of disseminated or ERD based on central review and classified as Group 3 medulloblastoma by methylation arrays
OG001
Group 4 Medulloblastoma
Includes eligible patients 3-21 years of age without anaplastic histology or evidence of disseminated or ERD based on central review and classified as Group 4 medulloblastoma by methylation arrays
OG002
Sonic Hedgehog (SHH) Medulloblastoma
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.
Only eligible & evaluable patients 3-7 years of age with MI values within time window were included.
Posted
Mean
Standard Deviation
T-score
4 - 15 months post diagnosis
ID
Title
Description
OG000
Low-dose Craniospinal Radiation (LDSCI)
Includes eligible patients 3-7 years of age without anaplastic histology or evidence of disseminated or ERD based on central review and randomized to one of the LDCSI arms (Treatment Arms I or II) and with a post-treatment TSH value.
OG001
Standard-dose Craniospinal Radiation (SDCSI)
Includes eligible patients 3-7 years of age without anaplastic histology or evidence of disseminated or ERD based on central review and randomized to one of the SDCSI arms (Treatment Arms III or IV) and with a post-treatment TSH value.
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.
Only eligible & evaluable patients 3-7 years of age with MI values within time window were included.
Posted
Mean
Standard Deviation
T-score
27-48 months post diagnosis
ID
Title
Description
OG000
Low-dose Craniospinal Radiation (LDSCI)
Includes eligible patients 3-7 years of age without anaplastic histology or evidence of disseminated or ERD based on central review and randomized to one of the LDCSI arms (Treatment Arms I or II) and with a post-treatment TSH value.
OG001
Standard-dose Craniospinal Radiation (SDCSI)
Includes eligible patients 3-7 years of age without anaplastic histology or evidence of disseminated or ERD based on central review and randomized to one of the SDCSI arms (Treatment Arms III or IV) and with a post-treatment TSH value.
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.
Only eligible & evaluable patients 3-7 years of age with MI values within time window were included.
Posted
Mean
Standard Deviation
T-score
49 - 72 months post diagnosis
ID
Title
Description
OG000
Low-dose Craniospinal Radiation (LDSCI)
Includes eligible patients 3-7 years of age without anaplastic histology or evidence of disseminated or ERD based on central review and randomized to one of the LDCSI arms (Treatment Arms I or II) and with a post-treatment TSH value.
OG001
Standard-dose Craniospinal Radiation (SDCSI)
Includes eligible patients 3-7 years of age without anaplastic histology or evidence of disseminated or ERD based on central review and randomized to one of the SDCSI arms (Treatment Arms III or IV) and with a post-treatment TSH value.
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.
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.
Posted
Number
95% Confidence Interval
Percentage of Participants
4-15 months post diagnosis
ID
Title
Description
OG000
Eligible and Evaluable Patients
All eligible and evaluable patients enrolled on ACNS0331
Units
Counts
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.
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.
Posted
Number
95% Confidence Interval
Percentage of Participants
27-48 months post diagnosis
ID
Title
Description
OG000
Eligible and Evaluable Patients
All eligible and evaluable patients enrolled on ACNS0331
Units
Counts
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.
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.
Posted
Number
95% Confidence Interval
Percentage of Participants
49 - 72 months post diagnosis
ID
Title
Description
OG000
Eligible and Evaluable Patients
All eligible and evaluable patients enrolled on ACNS0331
Units
Counts
Participants
Time Frame
Not provided
Description
All adverse events (grade 1 and higher) for all eligible patients (n=513) were included in this analysis. Serious AE's were based on whether an AdEERS report was filed OR whether the AE was a grade 5 AE (resulting in death). Of note, there was no other variable in the study database to indicate whether an AE was "serious" or not.
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.
Hazard Ratio (HR)
1.0
1-Sided
94
1.3
Non-Inferiority
A hazard ratio of 1.6 is used as the non-inferiority margin. For the final analysis comparing IFRT vs. PFRT, a one-sided 94% upper confidence limit of the hazard ratio based on a stratified approach will be estimated (stratified by age group and RT group (LDCSI vs. SDCSI)). If the upper confidence limit is lower than 1.6, IFRT would be deemed to be non-inferior. If not, non-inferiority would not be established.
OG002
Involved Field Radiation (IFRT)
Includes eligible patients 3-21 years of age without anaplastic histology or evidence of disseminated or ERD based on central review and randomized to one of the IFRT arms (Treatment Arms I, III, V)
OG003
Posterior Fossa Radiation (PFRT)
Includes eligible patients 3-21 years of age without anaplastic histology or evidence of disseminated or ERD based on central review and randomized to one of the PFRT arms (Treatment Arms II, IV, VI)
Units
Counts
Participants
OG000116
OG001110
OG002227
OG003237
Title
Denominators
Categories
IFRT vs PFRT
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG002227
ParticipantsOG003237
Title
Measurements
OG00290.3(86.2 to 94.4)
OG00393.3(90.0 to 96.6)
LDCSI vs SDCSI
ParticipantsOG000116
ParticipantsOG001110
ParticipantsOG0020
ParticipantsOG0030
Units
Counts
Participants
OG000227
OG001237
Title
Denominators
Categories
Title
Measurements
OG0001.4(0.0 to 2.89)
OG0012.7(0.6 to 4.9)
Units
Counts
Participants
OG000227
OG001237
Title
Denominators
Categories
Title
Measurements
OG0006.9(3.5 to 10.3)
OG0012.7(0.6 to 4.8)
Units
Counts
Participants
OG000227
OG001237
Title
Denominators
Categories
Title
Measurements
OG0005.1(2.2 to 8.0)
OG0016.2(3.0 to 9.4)
Counts
Participants
OG00089
OG00179
Title
Denominators
Categories
Title
Measurements
OG0005.3± 5.6
OG0016.1± 5.3
Units
Counts
Participants
OG000116
OG001110
Title
Denominators
Categories
Title
Measurements
OG00011
OG00111
Units
Counts
Participants
OG00056
OG00152
Title
Denominators
Categories
Title
Measurements
OG00093.8± 14.4
OG00196.2± 15.0
Units
Counts
Participants
OG00035
OG00134
Title
Denominators
Categories
Title
Measurements
OG00092.2± 12.5
OG00190.5± 13.3
Units
Counts
Participants
OG00023
OG00122
Title
Denominators
Categories
Title
Measurements
OG00090.5± 15.4
OG00186.4± 13.5
Participants
OG000199
OG001215
Title
Denominators
Categories
Title
Measurements
OG0008
OG0018
Units
Counts
Participants
OG0001
OG0012
Title
Denominators
Categories
Title
Measurements
OG0000.0(0.0 to 95.0)
OG00150.0(2.5 to 97.5)
OG003
Wingless (WNT) Medulloblastoma
Includes eligible patients 3-21 years of age without anaplastic histology or evidence of disseminated or ERD based on central review and classified as WNT medulloblastoma by methylation arrays
Units
Counts
Participants
OG00074
OG001154
OG00264
OG00363
Title
Denominators
Categories
Title
Measurements
OG00076.3(66.5 to 86.1)
OG00197.3(94.8 to 99.8)
OG00292.0(85.1 to 98.9)
OG00398.3(95.0 to 100.0)
Includes eligible patients 3-21 years of age without anaplastic histology or evidence of disseminated or ERD based on central review and classified as SHH medulloblastoma by methylation arrays
OG003
Wingless (WNT) Medulloblastoma
Includes eligible patients 3-21 years of age without anaplastic histology or evidence of disseminated or ERD based on central review and classified as WNT medulloblastoma by methylation arrays