Brain and Central Nervous System Tumors
Conditions
Keywords
untreated childhood medulloblastoma, untreated childhood supratentorial primitive neuroectodermal tumor, untreated childhood pineoblastoma, childhood atypical teratoid/rhabdoid tumor, childhood choroid plexus tumor, childhood high grade glioma, newly diagnosed childhood ependymoma
Brief summary
RATIONALE: In this study a combination of anti-cancer drugs (chemotherapy) is used to treat brain tumors in young children. Using chemotherapy gives the brain more time to develop before radiation is given. The chemotherapy in this study includes the drug methotrexate. This drug was an important part of the two clinical trials which resulted in the best survival results for children less than 3 years of age with medulloblastoma. Most patients treated on this trial will also receive radiation which is carefully targeted to the area of the tumor. This type of radiation (focal conformal or proton beam radiotherapy) may result in fewer problems with thinking and learning than radiation to the whole brain and spinal cord. PURPOSE: This clinical trial is studying how well giving combination chemotherapy together with radiation therapy works in treating young patients with newly diagnosed central nervous system tumors.
Detailed description
All patients with medulloblastoma who were diagnosed prior to their 3rd birthday will contribute to both the biology and therapeutic primary objectives of this protocol. Furthermore patients who were ≥3 and \<5 years old at the time of diagnosis will also be included in the cohort for these primary objectives as long as they meet the eligibility criteria as outlined in Amendment 8.0 of this protocol. Patients in the 3-5 year old age cohort who enrolled on previous versions of this protocol and who do not meet the criteria as outlined in Amendment 8.0 of this protocol will be excluded from the outcome analyses of the biology and therapeutic primary objectives of the protocol. OBJECTIVES: Primary * To identify patterns of methylation profiling that are associated with progression-free survival among young pediatric patients with medulloblastoma treated with risk-adapted therapy. * To estimate the event-free survival distribution of young medulloblastoma patients treated with risk-adapted therapy. Secondary * To perform high-resolution genome-wide analyses of chromosomal abnormalities and gene expression patterns, and evaluate the relationship of these to other clinicopathological variables. * To evaluate specific tumor types for molecular abnormalities with suspected prognostic or therapeutic significance. * To evaluate the feasibility of collecting frozen and fixed tumor samples for analysis using high-resolution molecular biology tools. * To estimate the event-free and overall survival of patients treated with the proposed risk-adapted therapy regimen, and to descriptively compare these survival rates to historical controls. * To estimate the rates of local and distant disease progression in patients treated with focal radiotherapy (RT) to the post-operative tumor bed using a 5 mm clinical target volume margin. * To estimate the objective response rate (sustained for 8 weeks) to induction chemotherapy including high-dose intravenous methotrexate for patients with residual or metastatic disease. * To evaluate the feasibility and toxicity of administering low-dose intravenous vinblastine in conjunction with induction chemotherapy to patients with metastatic disease. * To evaluate the feasibility and toxicity of administering consolidation therapy including cyclophosphamide and pharmacokinetically targeted topotecan to patients with metastatic disease, and to estimate the sustained (for 8 weeks) objective response rate (complete response and partial response) to such therapy in patients with measurable residual disease after induction. * To evaluate the feasibility and toxicity of administering oral maintenance therapy in young children. * To use quantitative magnetic resonance (MR) measures (volumetric, diffusion, and perfusion) of young brain tumor patients receiving chemotherapy including high-dose intravenous methotrexate to assess impact of treatment on developing brain. * To investigate the feasibility of using PET as an in-vivo dosimetric and distal edge verification system for patients treated with proton beam therapy (for participants enrolled at St Jude only). OUTLINE: This is a multicenter study. Patients are stratified according to disease risk (low-risk vs intermediate-risk vs high-risk). Therapy consists of risk adapted induction, consolidation and maintenance chemotherapy. Focal irradiation is given to intermediate risk patients who have reached at least 12 months of age upon completion of induction. Intermediate risk patients who have not will receive low risk chemotherapy to delay RT until the age of 12 months. Patients may consent to provide tumor tissue and blood samples for biological studies. Tumor tissues are analyzed for the activation of the wnt signaling pathway (β-catenin), activation of the shh signaling pathway (Gli-1/SFRP1), and ERBB2; validation of novel patterns of gene expression via immunohistochemical (IHC) analysis; loss of chromosomes 6, 8p, 9q22, isochromosome 17q; amplification of MYCC, MYCN, and MYCL; validation of genetic abnormalities via interphase fluorescence in situ hybridization (iFISH); construction of gene expression profiles via microarray analysis; single nucleotide polymorphism (SNP) analysis for DNA purity and integrity using UV spectrophotometry and agarose gel electrophoresis; amplification of DNA via PCR and a combination of previously published and 'in-house' generated primers; potential oncogenes and tumor suppressor genes via DNA sequence analysis; expression of a number of cell signal proteins implicated in the biology of medulloblastoma via western blot; expression of additional proteins encoded by genes associated through SNP and gene expression array analysis with clinical disease behavior; and differential expression pattern of genes detected using microarray analysis via RT-PCR. DNA extraction and construction of tissue microarrays (TMAs) from tumor tissue will also be used for future IHC and FISH analysis. Blood samples are analyzed for constitutional DNA from patients whose tumors contain gene mutations via sequence analysis of constitutional DNA; cyclophosphamide and its metabolites via liquid chromatography mass spectroscopy method; topotecan lactone via isocratic high-performance liquid chromatography assay with fluorescence detection; and alpha-1-acid glycoprotein (AAGP) concentrations via immunoturbidimetric assay. After completion of study treatment, patients are followed every 6 months for 5 years.
Interventions
DRUGLow-Risk Therapy
Induction will be followed by further conventional chemotherapy with carboplatin, cyclophosphamide, and etoposide. After consolidation, patients will receive 6 cycles of oral maintenance chemotherapy with cyclophosphamide, topotecan, and depending on the diagnosis, either erlotinib or etoposide (VP-16).
DRUGInduction Chemotherapy
All patients will receive 4 identical cycles of induction chemotherapy including highdose (5 g/m2 or 2.5g/m2 for patients less than or equal to 31 days of age at enrollment) intravenous methotrexate and standard dose vincristine, cisplatin, and cyclophosphamide.
DRUGHigh-Risk Therapy
High risk patients will also receive vinblastine with each course of induction chemotherapy. Induction will be followed by either chemotherapy with targeted intravenous topotecan and cyclophosphamide or optional craniospinal irradiation (CSI). CSI will be offered only to patients who reach 3 years of age by the end of induction only. After consolidation, all patients will receive 6 cycles of oral maintenance chemotherapy with cyclophosphamide, topotecan, and depending on the diagnosis, either erlotinib or etoposide (VP-16).
DRUGIntermediate-Risk Therapy
Induction will be followed by consolidation focal radiotherapy (RT) to the tumor bed. Patients less than 12 months old upon completion of induction will receive low risk chemotherapy to delay RT until the age of 12 months. After consolidation, patients will receive 6 cycles of oral maintenance chemotherapy with cyclophosphamide, topotecan, and depending on the diagnosis, either erlotinib or etoposide (VP-16). Note: The option to receive focal proton beam irradiation was suspended 10/29/2015. Focal photon beam irradiation continues as part of the treatment plan.
Sponsors
St. Jude Children's Research Hospital
University of Florida
National Cancer Institute (NCI)
The Pew Charitable Trusts
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 5 Years
Healthy volunteers
No
Inclusion criteria
Histologically confirmed newly diagnosed CNS tumors of any of the following : * Medulloblastoma (all histologic subtypes, including medullomyoblastoma and melanotic medulloblastoma) * Supratentorial primitive neuroectodermal tumor (PNET) (including CNS neuroblastoma or ganglioneuroblastoma, medulloepithelioma, and ependymoblastoma) * Pineoblastoma * Atypical teratoid rhabdoid tumor (ATRT) * Choroid plexus carcinoma * High grade glioma (including anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic ganglioglioma, pleomorphic xanthoastrocytoma with anaplastic features, high-grade astroblastoma , anaplastic pilocytic astrocytoma, malignant glioneuronal tumor, glioblastoma multiforme), or gliosarcoma, * Ependymoma (including all ependymoma histological variants) * Age \< 3 years at time of diagnosis for all histological diagnosis. Medulloblastoma patients ≥ 3 and \< 5years old at diagnosis who have non-metastatic disease with no more than 1cm2 of residual tumor are also eligible. * Meets criteria for 1 of the following risk groups: * Low-risk group: * Histologically confirmed nodular desmoplastic medulloblastoma, including medulloblastoma with extensive nodularity * Focal areas of anaplasia or other atypical features suggesting more aggressive phenotype in a tumor otherwise considered nodular desmoplastic should be treated on the intermediate-risk group, with final risk stratification at the discretion of principal investigator and study pathologist * No evidence of CNS metastasis 7 to 28 days after surgery by MRI and cytologic examination of lumbar cerebrospinal fluid (CSF) * Ventricular CSF from a shunt or Ommaya reservoir may be used to rule out M1 disease when lumbar puncture is medically contraindicated * Intermediate-risk group assignment when there is no other evidence of metastasis and CSF sampling is not possible * Gross total resection, defined as residual tumor or imaging abnormality (not definitive for residual tumor) with a size of \< 1 cm2 confirmed on postoperative CT scan or MRI * Brain stem invasion by the tumor in the absence of imaging evidence of residual tumor (tumor size \< 1 cm2) and otherwise meets criteria for the low-risk group, the patient will be classified as low-risk * Desmoplastic medulloblastoma patients who are ≥3 -\<5 years of age will NOT be eligible for the low risk arm of the protocol. * Intermediate-risk group: * Histologically confirmed nodular desmoplastic medulloblastoma with less than gross total resection and no evidence of metastasis * Any eligible histologic diagnosis other than desmoplastic medulloblastoma with no evidence of CNS metastasis * Medulloblastoma patients who are ≥3 and \< 5 yrs of age irrespective of histology and with no evidence of CNS metastasis * High-risk group: * Any eligible histologic diagnosis with evidence of CNS metastasis * Patients with extraneural metastasis are eligible for treatment on the high-risk group PATIENT CHARACTERISTICS: * Lansky performance status ≥ 30 (except for posterior fossa syndrome) * WBC \> 2,000/mm3 * Platelets \> 50,000/mm3 (without support) * Hemoglobin \> 8 g/dL (with or without support) * ANC \> 500/mm3 * Serum creatinine \< 3 times upper limit of normal (ULN) * ALT \< 5 times ULN * Total bilirubin \< 3 times ULN PRIOR CONCURRENT THERAPY: * See Disease Characteristics * No more than 31 days since prior definitive surgery * No prior radiotherapy or chemotherapy other than corticosteroid therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Probability of Progression-free Survival (PFS) for Medulloblastoma Patients | From date on treatment until date of first progression or relapse or disease related death or date of last contact, estimated at 1 year after treatment | Progression was defined as 25% increase in the size of any measurable lesion; the appearance of a new lesion; or the conversion of negative cerebrospinal fluid (CSF) cytology to positive. Defined as the time interval from date on treatment until the date of first progression, medulloblastoma-related death or date of last contact for patients who have not experienced an event. All eligible medulloblastoma patients who received any methotrexate are included in this analysis. |
| Percent Probability of Progression-free Survival (PFS) for Medulloblastoma Patients by DNA Methylation Subgroup | From date on treatment to date of first progression or relapse or disease related death or date of last contact, estimated at 1 year after treatment | Defined as the time interval from date on treatment until the date of first progression, medulloblastoma-related death or date of last contact for patients who have not experienced an event. Eligible medulloblastoma patients who received any methotrexate and had molecularly confirmed medulloblastoma are included in this analysis. Five patients were excluded as 3 had no archival tissue available and 2 were found to not be medulloblastoma by methylation profile. |
| Percent Probability of Event-free Survival (EFS) for Medulloblastoma Patients | From date on treatment to date of first progression, relapse, second malignancy or death from any cause or to date of last contact, estimated at 1 year after | Defined as the time interval from date on treatment until the date of first progression, second malignancy or death due to any cause; or date of last contact for patients who have not experienced an event. All eligible medulloblastoma patients who received any methotrexate are included in this analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Chromosomal Abnormalities | Based on samples obtained at the time of initial surgery or repeat surgery prior to treatment | Amplifications and deletions (gains and losses) for chromosomes of interest are shown in the table of measured values. |
| Numbers of Patients With Gene Alterations | Based on samples obtained at the time of initial surgery or repeat surgery prior to treatment | Gene alterations, which include single nucleotide variants (SNPs), amplifications, deletions, translocations, indels, and germline alterations are shown for specific genes of interest in the results table. |
| Numbers of Patients With Molecular Abnormalities by Tumor Type | Based on samples obtained at the time of initial surgery or repeat surgery prior to treatment | Alterations included single nucleotide variants (SNPs), amplifications, deletions, translocations, indels, and germline alterations. Cytogenetic information shows gains and losses as specified in the table of measured values. |
| Number of Successful Collections for Frozen and Fixed Tumor Samples | Based on samples obtained at the time of initial surgery or repeat surgery prior to treatment | Successful collections will be defined as the number of patients who have frozen/fixed tumor samples available. |
| Event-free Survival (EFS) Compared to Historical Controls | From date on treatment until date of first event (progression, second malignancy or death) or until date of last contact, assessed up to 10 years | EFS was measured from the date of initial treatment to the earliest date of disease progression, second malignancy or death for patients who fail; and to the date of last contact for patients who remain at risk for failure. 1-year EFS estimates are reported by risk group. EFS was compared to St. Jude historical cohorts by risk group using hazard ratios with 95% confidence intervals. |
| Overall Survival (OS) Compared to Historical Controls | 1 year after treatment initiation of last patient | OS was measured from the date of initial treatment to date of death or to date of last contact for survivors. 1-year OS estimates were reported by risk group. OS was compared to St. Jude historical cohorts by risk group using hazard ratios with 95% confidence intervals. |
| Percentage of Patients With Objective Responses Rate to Induction Chemotherapy | From on-study date to 2 months after completion of induction chemotherapy (up to 4 months after on-study date) | For patients treated in the intermediate and high risk strata with residual or metastatic disease we will estimate the stratum-specific objective response rate (complete response (CR) or partial response \[ PR\]). All patients who receive at least 1 -dose of methotrexate are evaluable for response. Objective responses must be sustained for at least eight weeks. |
| Feasibility and Toxicity of Administering Vinblastine With Induction Chemotherapy for Patients With Metastatic Disease as Measured by the Percentage of Courses Delayed for More Than 7 Days Due to Toxicity | From on-study date up to 4 months after on-study date | For the subset of patients with metastatic disease (high-risk group patients), during induction, the proportion percentage of courses during which subsequent chemotherapy administration was delayed for more than 7 days due to toxicity will be calculated. Patients were to receive 4 courses of induction and then consolidation chemotherapy. |
| Feasibility and Toxicity of Administering Consolidation Therapy Including Cyclophosphamide and Pharmacokinetically Targeted Topotecan to Patients With Metastatic Disease Based on the Percentage of Courses Delayed for More Than 7 Days Due to Toxicity | At completion of consolidation therapy (up to 6 months after on-study date) | For the subset of patients with metastatic disease (high-risk group patients), during consolidation, we will calculate the number and proportion of courses during which subsequent chemotherapy administration was delayed for more than 7 days due to toxicity. Patients were to received 2 courses of consolidation chemotherapy and then maintenance therapy. |
| Percent of Patients With Sustained Objective Responses Rate After Consolidation | 8 weeks after completion of consolidation therapy (up to 8 months after on-study date) | For patients enrolled on the high-risk arm with measurable residual disease after induction treated with consolidation therapy, we will estimate the objective response (complete response (CR)/partial response (PR)) rate after consolidation therapy with a 95% confidence interval. Objective responses must be sustained for at least eight weeks. All patients who receive at least 1 dose of cyclophosphamide or topotecan during consolidation are evaluable for response. |
| Feasibility and Toxicity of Administering Oral Maintenance Therapy in Children <3 Years of Age as Measured by the Percentage of Total Scheduled Maintenance Doses Received | From start of oral maintenance therapy (approximately 6 months after on-study date) to completion of oral maintenance therapy (up to 1 year after on-study date) | These data are based on patient diaries. For children \<3 years of age, we will calculate the percentage of total scheduled doses each patient received per course for each of the oral maintenance courses and report the overall average number percentage of doses received per course across patients. If patients received all planned doses, their percentage would be 100%. If the average percentage was less than 75%, then feasibility would be in question. |
| Percent of PET Scans With Loss of Signal Intensity | Up to 3 times during RT consolidation | Measures will be analyzed for intermediate risk participants who receive proton beam therapy (PBT) and who consent. This objective aims to assess the feasibility of using post-proton beam therapy (PBT) positron emission tomography (PET) as an in-vivo dosimetric and distal edge verification system in this patient population. To quantify the decay in signal, 134 scans from 53 patients were analyzed by recording the mean activation value (MAV), the average recorded PET signal from activation, within the target volume. With each patient being given the same dose, the percent standard deviation in the MAV can serve as a quantitative representation of signal loss due to radioactive decay. |
| Concentration of Cerebrospinal Fluid Neurotransmitters | Baseline, at the completion of therapy, and every 12 months up to 36 months after off therapy date | Concentrations of various neurotransmitters in cerebrospinal fluid were measured at 5 timepoints. The median concentration of each neurotransmitter at each time point was calculated and provided with a full range. |
| Number and Type of Genetic Polymorphisms | At study enrollment (Day 0) | Types of genetic polymorphisms of neurotransmitters were examined. We studied 3 genetic polymorphisms; these were types of genetic polymorphisms involved in dopamine metabolism. They were as follows: rs6323, rs4680, and rs6280. |
| Pharmacogenetic Variation on Central Nervous System Transmitters | At study enrollment (Day 0) | Frequencies of genetic polymorphisms were reported. |
| Number of Participants With Endocrinopathy | End of induction therapy (approximately 16 weeks from start of treatment), end of therapy (approximately 48 weeks from start of treatment), and 6, 12, 24, 36, 48, and 60 months off therapy | Endocrine screening and growth hormone (GH) testing were done in consenting intermediate risk patients at the end of induction therapy, the end of all therapy, and at 6, 12, 24, 36, 48, and 60 months off therapy. Endocrinopathy was defined as the presence of central hypothyroidism (free T4 concentration below normal with low or normal TSH concentration), growth hormone deficiency (peak growth hormone concentration below 5 ng/mL on dynamic testing), or ACTH deficiency (cortisol concentration below 14 ug/dL after low dose cosyntropin stimulation). Numbers of participants with endocrinopathy at each time point are reported. Please note the small numbers of participants with available data. |
| Growth Hormone Secretion | End of induction therapy (approximately 16 weeks from start of treatment), end of therapy (approximately 48 weeks from start of treatment), and 6, 12, 24, 36, 48, and 60 months off therapy | Growth hormone secretion was measured in consenting intermediate risk patients at the end of induction therapy, the end of all therapy, and at 6, 12, 24, 36, 48, and 60 months off therapy. Mean growth hormone secretion values are reported by assessment time point. Please note the small numbers of participants with available data. |
| Methotrexate Clearance in Induction Cycle 1 | Pre-infusion and 6, 23, 42, 66 hours from start of Methotrexate (MTX) | Methotrexate plasma concentration-time data are collected after the start of methotrexate infusion in induction cycle 1. Population parameters and inter-subject variability are estimated. Individual estimates of methotrexate clearance are obtained using post hoc analysis. |
| Methotrexate Clearance in Induction Cycle 2 | Pre-infusion and 6, 23, 42, 66 hours from start of MTX | Methotrexate plasma concentration-time data are collected after the start of methotrexate infusion in induction cycle 2. Population parameters and inter-subject variability are estimated. Individual estimates of methotrexate clearance are obtained using post hoc analysis. |
| Methotrexate Clearance in Induction Cycle 3 | Pre-infusion and 6, 23, 42, 66 hours from start of MTX | Methotrexate plasma concentration-time data are collected after the start of methotrexate infusion in induction cycle 3. Population parameters and inter-subject variability are estimated. Individual estimates of methotrexate clearance are obtained using post hoc analysis. |
| Methotrexate Clearance in Induction Cycle 4 | Pre-infusion and 6, 23, 42, 66 hours from start of MTX | Methotrexate plasma concentration-time data are collected after the start of methotrexate infusion in induction cycle 4. Population parameters and inter-subject variability are estimated. Individual estimates of methotrexate clearance are obtained using post hoc analysis. |
| Methotrexate Volume of Central Compartment in Induction Cycle 1 | Pre-infusion and 6, 23, 42, 66 hours from start of MTX | Methotrexate plasma concentration-time data are collected after the start of methotrexate infusion in induction cycle 1. Population parameters and inter-subject variability are estimated. Individual estimates of methotrexate volume of central compartment are obtained using post hoc analysis. |
| Methotrexate Volume of Central Compartment in Induction Cycle 2 | Pre-infusion and 6, 23, 42, 66 hours from start of MTX | Methotrexate plasma concentration-time data are collected after the start of methotrexate infusion in induction cycle 2. Population parameters and inter-subject variability are estimated. Individual estimates of methotrexate volume of central compartment are obtained using post hoc analysis. |
| Methotrexate Volume of Central Compartment in Induction Cycle 3 | Pre-infusion and 6, 23, 42, 66 hours from start of MTX | Methotrexate plasma concentration-time data are collected after the start of methotrexate infusion in induction cycle 3. Population parameters and inter-subject variability are estimated. Individual estimates of methotrexate volume of central compartment are obtained using post hoc analysis. |
| Methotrexate AUC0-66h in Induction Cycle 1 | Pre-infusion and 6, 23, 42, 66 hours from start of MTX | Methotrexate plasma concentration-time data are collected after the start of methotrexate infusion in induction cycle 1. Population parameters and inter-subject variability are estimated. Individual estimates of methotrexate AUC0-66h (area under concentration curve from time 0 to 66 hours post-dose) are obtained using post hoc analysis. |
| Methotrexate AUC0-66h in Induction Cycle 2 | Pre-infusion and 6, 23, 42, 66 hours from start of MTX | Methotrexate plasma concentration-time data are collected after the start of methotrexate infusion in induction cycle 2. Population parameters and inter-subject variability are estimated. Individual estimates of methotrexate AUC0-66h (area under concentration curve from time 0 to 66 hours post-dose) are obtained using post hoc analysis. |
| Methotrexate Volume of Central Compartment in Induction Cycle 4 | Pre-infusion and 6, 23, 42, 66 hours from start of MTX | Methotrexate plasma concentration-time data are collected after the start of methotrexate infusion in induction cycle 4. Population parameters and inter-subject variability are estimated. Individual estimates of methotrexate volume of central compartment are obtained using post hoc analysis. |
| Methotrexate AUC0-66h in Induction Cycle 3 | Pre-infusion and 6, 23, 42, 66 hours from start of MTX | Methotrexate plasma concentration-time data are collected after the start of methotrexate infusion in induction cycle 3. Population parameters and inter-subject variability are estimated. Individual estimates of methotrexate AUC0-66h (area under concentration curve from time 0 to 66 hours post-dose) are obtained using post hoc analysis. |
| Methotrexate AUC0-66h in Induction Cycle 4 | Pre-infusion and 6, 23, 42, 66 hours from start of MTX | Methotrexate plasma concentration-time data are collected after the start of methotrexate infusion in induction cycle 4. Population parameters and inter-subject variability are estimated. Individual estimates of methotrexate AUC0-66h (area under concentration curve from time 0 to 66 hours post-dose) are obtained using post hoc analysis. |
| Methotrexate Concentration at 42 Hours Post-dose in Induction Cycle 1 | 42 hours from start of MTX | Methotrexate plasma concentration-time data are collected after the start of methotrexate infusion in induction cycle 1. Population parameters and inter-subject variability are estimated. Individual estimates of methotrexate concentration at 42 hours post-dose are obtained using post hoc analysis. |
| Methotrexate Concentration at 42 Hours Post-dose in Induction Cycle 2 | 42 hours from start of MTX | Methotrexate plasma concentration-time data are collected after the start of methotrexate infusion in induction cycle 2. Population parameters and inter-subject variability are estimated. Individual estimates of methotrexate concentration at 42 hours post-dose are obtained using post hoc analysis. |
| Methotrexate Concentration at 42 Hours Post-dose in Induction Cycle 3 | 42 hours from start of MTX | Methotrexate plasma concentration-time data are collected after the start of methotrexate infusion in induction cycle 3. Population parameters and inter-subject variability are estimated. Individual estimates of methotrexate concentration at 42 hours post-dose are obtained using post hoc analysis. |
| Methotrexate Concentration at 42 Hours Post-dose in Induction Cycle 4 | 42 hours from start of MTX | Methotrexate plasma concentration-time data are collected after the start of methotrexate infusion in induction cycle 4. Population parameters and inter-subject variability are estimated. Individual estimates of methotrexate concentration at 42 hours post-dose are obtained using post hoc analysis. |
| Cyclophosphamide Clearance in Induction Chemotherapy | Pre-infusion, end of infusion, 3, 6, and 24 hours from end of cyclophosphamide infusion | Cyclophosphamide plasma concentration-time data are collected on day 9 in one cycle of induction chemotherapy. Individual estimates of cyclophosphamide clearance are obtained using post hoc analysis. |
| Cyclophosphamide Clearance in Consolidation Chemotherapy Cycle 1 | Pre-infusion, end of infusion, 3, 6, and 24 hours from end of cyclophosphamide infusion | Cyclophosphamide plasma concentration-time data are collected in consolidation cycle 1. Individual estimates of cyclophosphamide clearance are obtained using post hoc analysis. |
| Cyclophosphamide Clearance in Consolidation Chemotherapy Cycle 2 | Pre-infusion, end of infusion, 3, 6, and 24 hours from end of cyclophosphamide infusion | Cyclophosphamide plasma concentration-time data are collected in consolidation cycle 2. Individual estimates of cyclophosphamide clearance are obtained using post hoc analysis. |
| Cyclophosphamide Apparent Oral Clearance in Maintenance Chemotherapy Cycle A1 | Pre-dose, 0.5, 1.75, 3 and 6 hours post-dose | Cyclophosphamide plasma concentration-time data are collected on day 1 of maintenance cycle A1. Individual estimates of cyclophosphamide apparent oral clearance are obtained using post hoc analysis. |
| Cyclophosphamide AUC0-24h in Induction Chemotherapy | Pre-infusion, end of infusion, 3, 6, and 24 hours from end of cyclophosphamide infusion | Cyclophosphamide plasma concentration-time data are collected on day 9 in one cycle of induction chemotherapy. Individual estimates of cyclophosphamide AUC0-24h (area under concentration curve from time 0 to 24 hours post-dose) are obtained using post hoc analysis. |
| Cyclophosphamide AUC0-24h in Consolidation Chemotherapy Cycle 1 | Pre-infusion, end of infusion, 3, 6, and 24 hours from end of cyclophosphamide infusion | Cyclophosphamide plasma concentration-time data are collected in consolidation cycle 1. Individual estimates of cyclophosphamide AUC0-24h (area under concentration curve from time 0 to 24 hours post-dose) are obtained using post hoc analysis. |
| 4-OH Cyclophosphamide AUC0-24h in Consolidation Chemotherapy Cycle 1 | Pre-infusion, end of infusion, 3, 6, and 24 hours from end of cyclophosphamide infusion | 4-OH cyclophosphamide plasma concentration-time data are collected in consolidation cycle 1. Individual estimates of 4-OH cyclophosphamide AUC0-24h (area under concentration curve from time 0 to 24 hours post- dose) are obtained using post hoc analysis. |
| Cyclophosphamide AUC0-24h in Consolidation Chemotherapy Cycle 2 | Pre-infusion, end of infusion, 3, 6, and 24 hours from end of cyclophosphamide infusion | Cyclophosphamide plasma concentration-time data are collected in consolidation cycle 2. Individual estimates of cyclophosphamide AUC0-24h (area under concentration curve from time 0 to 24 hours post-dose) are obtained using post hoc analysis. |
| Cyclophosphamide AUC0-24h in Maintenance Chemotherapy Cycle A1 | Pre-dose, 0.5, 1.75, 3, 6, and 24 hours post-dose | Cyclophosphamide plasma concentration-time data are collected on day 1 of maintenance cycle A1. Individual estimates of cyclophosphamide AUC0-24h are obtained using post hoc analysis. |
| 4-OH Cyclophosphamide AUC0-24h in Induction Chemotherapy | Pre-infusion, end of infusion, 3, 6, and 24 hours from end of cyclophosphamide infusion | 4-OH cyclophosphamide plasma concentration-time data are collected on day 9 in one cycle of induction chemotherapy. Individual estimates of 4-OH cyclophosphamide AUC0-24h (area under concentration curve from time 0 to 24 hours post-dose) are obtained using post hoc analysis. |
| 4-OH Cyclophosphamide AUC0-24h in Consolidation Chemotherapy Cycle 2 | Pre-infusion, end of infusion, 3, 6, and 24 hours from end of cyclophosphamide infusion | 4-OH cyclophosphamide plasma concentration-time data are collected in consolidation cycle 2. Individual estimates of 4-OH cyclophosphamide AUC0-24h (area under concentration curve from time 0 to 24 hours post- dose) are obtained using post hoc analysis. |
| 4-OH Cyclophosphamide AUC0-24h in Maintenance Chemotherapy Cycle A1 | Pre-dose, 0.5, 1.75, 3, 6, and 24 hours post-dose | 4-OH cyclophosphamide plasma concentration-time data are collected on day 1 of maintenance cycle A1. Individual estimates of 4-OH cyclophosphamide AUC0-24h (area under concentration curve from time 0 to 24 hours post-dose) are obtained using post hoc analysis. |
| CEPM AUC0-24h in Induction Chemotherapy | Pre-infusion, end of infusion, 3, 6, and 24 hours from end of cyclophosphamide infusion | Carboxyethylphosphoramide mustard (CEPM) plasma concentration-time data are collected on day 9 in one induction cycle. Individual estimates of CEPM AUC0-24h (area under concentration curve from time 0 to 24 hours post-dose) are obtained using post hoc analysis. |
| CEPM AUC0-24h in Consolidation Chemotherapy Cycle 1 | Pre-infusion, end of infusion, 3, 6, and 24 hours from end of cyclophosphamide infusion | Carboxyethylphosphoramide mustard (CEPM) plasma concentration-time data are collected in consolidation cycle 1. Individual estimates of CEPM AUC0-24h (area under concentration curve from time 0 to 24 hours post- dose) are obtained using post hoc analysis. |
| CEPM AUC0-24h in Consolidation Chemotherapy Cycle 2 | Pre-infusion, end of infusion, 3, 6, and 24 hours from end of cyclophosphamide infusion | Carboxyethylphosphoramide mustard (CEPM) plasma concentration-time data are collected in consolidation cycle 2. Individual estimates of CEPM AUC0-24h (area under concentration curve from time 0 to 24 hours post- dose) are obtained using post hoc analysis. |
| CEPM AUC0-24h in Maintenance Chemotherapy Cycle A1 | Pre-dose, 0.5, 1.75, 3, 6, and 24 hours post-dose | Carboxyethylphosphoramide mustard (CEPM) plasma concentration-time data are collected on day 1 of maintenance cycle A1. Individual estimates of CEPM AUC0-24h (area under concentration curve from time 0 to 24 hours post-dose) are obtained using post hoc analysis. |
| Participants With Empirical Dosage Achieving Target System Exposure of Intravenous Topotecan | Pre-infusion, 5 min., 1, and 3 hours from end of infusion | Number of participants who successfully achieve target systemic exposure of intravenous topotecan after an empiric dosage during consolidation phase of therapy are reported. |
| Participants With PK-guided Dosage Adjustment Achieving Target System Exposure of Intravenous Topotecan | Pre-infusion, 5 min., 1, and 3 hours from end of infusion | Number of participants who successfully achieve target systemic exposure of intravenous topotecan after a pharmacokinetic-guided dosage adjustment during consolidation phase of therapy are reported. |
| Topotecan Clearance in Consolidation Chemotherapy | Pre-infusion, 5 min., 1, and 3 hours from end of infusion | Topotecan plasma concentration-time data are collected on day 1 of consolidation cycle 1 after a single IV dose. Individual estimates of topotecan clearance are obtained using post hoc analysis. |
| Topotecan Apparent Oral Clearance in Maintenance Chemotherapy | Pre-dose, 0.25, 1.5 and 6 hours post-dose | Topotecan plasma concentration-time data are collected on day 1 of maintenance cycle A1 after a single oral dose. Individual estimates of topotecan apparent oral clearance are obtained using post hoc analysis. |
| Topotecan AUC0-24h in Consolidation Chemotherapy | Pre-infusion, 5 min., 1, 3, and 24 hours from end of infusion | Topotecan plasma concentration-time data are collected on day 1 of consolidation cycle 1 after a single IV dose. Individual estimates of topotecan AUC0-24h (area under concentration curve from time 0 to 24 hours post- dose) are obtained using post hoc analysis. |
| Topotecan AUC0-24h in Maintenance Chemotherapy | Pre-dose, 0.25, 1.5, 6, and 24 hours post-dose | Topotecan plasma concentration-time data are collected on day 1 of maintenance cycle A1 after a single oral dose. Individual estimates of topotecan AUC0-24h (area under concentration curve from time 0 to 24 hours post- dose) are obtained using post hoc analysis. |
| Erlotinib Apparent Oral Clearance | Pre-dose, 1, 2, 4, 8, and 24 hours post-dose | Erlotinib plasma concentration-time data are collected on day 1 of maintenance cycle B2. Individual estimates of erlotinib apparent oral clearance are obtained using post hoc analysis. |
| Erlotinib Apparent Volume of Central Compartment | Pre-dose, 1, 2, 4, 8, and 24 hours post-dose | Erlotinib plasma concentration-time data are collected on day 1 of maintenance cycle B2. Individual estimates of erlotinib apparent volume of central compartment are obtained using post hoc analysis. |
| Erlotinib AUC0-24h | Pre-dose, 1, 2, 4, 8, and 24 hours post-dose | Erlotinib plasma concentration-time data are collected on day 1 of maintenance cycle B2. Individual estimates of erlotinib AUC0-24h (area under concentration curve from 0 to 24 hours post-dose) are obtained using post hoc analysis. |
| OSI-420 AUC0-24h | Pre-dose, 1, 2, 4, 8, and 24 hours post-dose | Erlotinib metabolite OSI-420 plasma concentration-time data are collected on day 1 of maintenance cycle B2. Individual estimates of OSI-420 AUC0-24h (area under concentration curve from 0 to 24 hours post-dose) are obtained using post hoc analysis. |
| Rate of Local Disease Progression | 1 year after completion of radiation therapy for last patient | Local failure was defined as the interval from end of RT to date of local failure (or combined local + distant failure). Competing events were distant failure or second malignancy. Patients without an event were censored at date of last contact. The 1-year cumulative incidence was estimated and reported with a 95% confidence interval. |
| Rate of Distant Disease Progression | 1 year after completion of radiation therapy for last patient | Distant failure was defined as the interval from end of RT to date of distant failure (or combined local + distant failure). Competing events were local failure or second malignancy. Patients without an event were censored at date of last contact. The 1-year cumulative incidence was estimated and reported with a 95% confidence interval. |
| Neurocognitive Performance Related to Global Cognitive Functioning as Measured by Cognitive Composite Scores and Estimated IQ Scores | Baseline, prior to maintenance therapy, completion of therapy, and 12 months, 24 months, 36 months, 48 months, and 60 months off therapy | Global cognitive functioning was measured based on Cognitive Composite Scores from the Bayley III instrument for subjects \<3 years of age and on estimated IQ scores from the Stanford Binet V instrument for subjects ≥3 years of age. Higher scores indicate better performance. The normative mean is 100 with a standard deviation of 15. |
| Neurocognitive Performance Related to Attention as Measured by Attention Problems T-scores | Baseline, prior to maintenance therapy, completion of therapy, and 12 months, 24 months, 36 months, 48 months, and 60 months off therapy | Scores measuring attention were obtained from the Attention Problems T-score on the BASC-2 instrument which is a parent report. Higher scores indicate more attention problems. The normative mean is 50 with a standard deviation of 10. |
| Neurocognitive Performance Related to Processing Speed as Measured by Visual Matching Standard Scores | Baseline, prior to maintenance therapy, completion of therapy, and 12 months, 24 months, 36 months, 48 months, and 60 months off therapy | Scores measuring processing speed were obtained based on the visual matching standard score from the Woodcock Johnson III instrument. Higher scores indicate better performance. The normative mean is 100 with a standard deviation of 15. |
| Neurocognitive Performance Related to Executive Functioning as Measured by Global Executive Composite T-scores | Baseline, prior to maintenance therapy, completion of therapy, and 12 months, 24 months, 36 months, 48 months, and 60 months off therapy | Scores measuring executive functioning were obtained from Global Executive Composite (GEC) T-scores, which were obtained from the Behavior Rating Inventory of Executive Function (BRIEF) instrument which is a parent report. Higher scores indicate more problems. The normative mean is 50 with a standard deviation of 10. |
| Neurocognitive Performance Related to Working Memory as Measured by Working Memory T-scores | Baseline, prior to maintenance therapy, completion of therapy, and 12 months, 24 months, 36 months, 48 months, and 60 months off therapy | Scores measuring working memory were obtained from Working Memory T-scores, which were obtained from the Behavior Rating Inventory of Executive Function (BRIEF) instrument which is a parent report. Higher scores indicate more problems. The normative mean is 50 with a standard deviation of 10. |
| Neurocognitive Performance Related to Verbal Fluency as Measured by Retrieval Fluency Standard Scores | Baseline, prior to maintenance therapy, completion of therapy, and 12 months, 24 months, 36 months, 48 months, and 60 months off therapy | Scores measuring verbal fluency were obtained from Retrieval Fluency standard scores on the Woodcock Johnson III instrument. Higher scores indicate better performance. The normative mean is 100 with a standard deviation of 15. |
| Neurocognitive Performance Related to Visual-spatial Reasoning as Measured by Visual Motor Integration (VMI) T-scores | Baseline, prior to maintenance therapy, completion of therapy, and 12 months, 24 months, 36 months, 48 months, and 60 months off therapy | Scores measuring visual-spatial reasoning were obtained from VMI T-scores on the Beery VMI instrument. Higher scores indicate better performance. The normative mean is 50 with standard deviation of 10. |
| Neurocognitive Performance Related to Visual-spatial Reasoning as Measured by Visual Perception T-scores | Baseline, prior to maintenance therapy, completion of therapy, and 12 months, 24 months, 36 months, 48 months, and 60 months off therapy | Scores measuring visual-spatial reasoning were obtained from Visual Perception T-scores on the Beery Visual Motor Integration (VMI) instrument. Higher scores indicate better performance. The normative mean is 50 with a standard deviation of 10. |
| Change in Neurostructure, Especially White Matter Volume and Integrity | From baseline (month 0) to 60 months (therapy duration lasted approximately 48 weeks or 11 months) | Quantitative MRI measures Fractional Anisotropy (FA) change per month in right frontal-lobe over time in each risk group will be assessed using a random effects model incorporating various covariates. Covariates to be considered include age at diagnosis, time since diagnosis and risk-arm. Differences in quantitative MRI measures of neurostructure volume and integrity between patient groups will be evaluated as a metric of structural neurotoxicity of therapy. Fractional anisotropy (FA) is a scalar unitless measure that quantifies the degree of anisotropy of a diffusion process, particularly in the context of diffusion tensor imaging (DTI) used in MRI scans. FA values range from 0 to 1 |
| Change in Quantitative Magnetic Resonance (MR) Measures in the Frontal Lobe | From baseline (month 0) to 60 months (therapy duration lasted approximately 48 weeks or 11 months) | Quantitative MRI measures Fractional Anisotropy (FA) change per month in frontal lobe over time in each risk group will be assessed using a random effects model incorporating various covariates. Covariates to be considered include age at diagnosis, time since diagnosis and risk-arm. Differences in quantitative MRI measures of neurostructure volume and integrity between patient groups will be evaluated as a metric of structural neurotoxicity of therapy. Fractional anisotropy (FA) is a scalar unitless measure that quantifies the degree of anisotropy of a diffusion process, particularly in the context of diffusion tensor imaging (DTI) used in MRI scans. FA values range from 0 to 1 |
| Change in Quantitative MR Measures in the Right Frontal-parietal Regions | From baseline (month 0) to 60 months (therapy duration lasted approximately 48 weeks or 11 months) | Quantitative MRI measures Fractional Anisotropy (FA) change per month in right frontal-parietal region over time in each risk group will be assessed using a random effects model incorporating various covariates. Covariates to be considered include age at diagnosis, time since diagnosis and risk-arm. Differences in quantitative MRI measures of neurostructure volume and integrity between patient groups will be evaluated as a metric of structural neurotoxicity of therapy. Fractional anisotropy (FA) is a scalar unitless measure that quantifies the degree of anisotropy of a diffusion process, particularly in the context of diffusion tensor imaging (DTI) used in MRI scans. FA values range from 0 to 1 |
Countries
Australia, United States
Contacts
STUDY_CHAIRAmar Gajjar, MD
St. Jude Children's Research Hospital
Participant flow
Recruitment details
293 participants were enrolled between December 17, 2007 and April 19, 2017.
Pre-assignment details
Of the 293 participants enrolled, 3 were ineligible and removed from study, leaving 290 eligible patients. Eighty-one (81) of the 290 eligible patients enrolled had histologically confirmed medulloblastoma; medulloblastoma patients are the focus of the primary study objectives.
Participants by arm
| Arm | Count |
|---|---|
| Low-Risk Group Patients with gross total resection (GTR)/no evidence of metastatic (M0) medulloblastoma, nodular desmoplastic or high grade glioma histology will receive induction chemotherapy and low-risk therapy. | 57 |
| Intermediate-Risk Group Patients with M0 medulloblastoma or nodular desmoplastic histology with less than a GTR, other histologic diagnoses with no metastatic disease, will receive induction chemotherapy and intermediate-risk therapy. | 156 |
| High-Risk Group Patients with central nervous system (CNS) metastatic disease will receive induction chemotherapy and high-risk therapy. | 77 |
| Total | 290 |
Baseline characteristics
| Characteristic | High-Risk Group | Total | Intermediate-Risk Group | Low-Risk Group |
|---|---|---|---|---|
| Age, Continuous | 19.3 months STANDARD_DEVIATION 10.4 | 20.8 months STANDARD_DEVIATION 11.9 | 21.9 months | 16.1 months |
| Race/Ethnicity, Customized Ethnicity Mexican/Chicano | 2 Participants | 7 Participants | 5 Participants | 0 Participants |
| Race/Ethnicity, Customized Ethnicity Non Spanish speaking, Non Hispanic | 64 Participants | 231 Participants | 120 Participants | 47 Participants |
| Race/Ethnicity, Customized Ethnicity NOS Spanish, Hispanic, Latino | 7 Participants | 30 Participants | 16 Participants | 7 Participants |
| Race/Ethnicity, Customized Ethnicity Puerto Rican | 1 Participants | 4 Participants | 2 Participants | 1 Participants |
| Race/Ethnicity, Customized Ethnicity South or Central American | 0 Participants | 2 Participants | 2 Participants | 0 Participants |
| Race/Ethnicity, Customized Ethnicity Unknown | 3 Participants | 16 Participants | 11 Participants | 2 Participants |
| Race/Ethnicity, Customized Race American Indian/Alaskan Native | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Race American Indian/Alaskan/White | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Asian | 1 Participants | 10 Participants | 6 Participants | 3 Participants |
| Race/Ethnicity, Customized Race Asian and White | 2 Participants | 4 Participants | 2 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Black | 10 Participants | 30 Participants | 14 Participants | 6 Participants |
| Race/Ethnicity, Customized Race Black and White | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Multiple Race (NOS) | 1 Participants | 9 Participants | 7 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Other | 1 Participants | 7 Participants | 4 Participants | 2 Participants |
| Race/Ethnicity, Customized Race Pacific Islander | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Unknown | 1 Participants | 6 Participants | 3 Participants | 2 Participants |
| Race/Ethnicity, Customized Race White | 61 Participants | 220 Participants | 118 Participants | 41 Participants |
| Sex: Female, Male Female | 43 Participants | 131 Participants | 66 Participants | 22 Participants |
| Sex: Female, Male Male | 34 Participants | 159 Participants | 90 Participants | 35 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 10 / 57 | 58 / 156 | 49 / 77 |
| other Total, other adverse events | 55 / 57 | 145 / 156 | 70 / 76 |
| serious Total, serious adverse events | 3 / 57 | 7 / 156 | 5 / 76 |
Outcome results
Primary
Percent Probability of Event-free Survival (EFS) for Medulloblastoma Patients
Defined as the time interval from date on treatment until the date of first progression, second malignancy or death due to any cause; or date of last contact for patients who have not experienced an event. All eligible medulloblastoma patients who received any methotrexate are included in this analysis.
Time frame: From date on treatment to date of first progression, relapse, second malignancy or death from any cause or to date of last contact, estimated at 1 year after
Population: Eligible medulloblastoma patients (n=81) were included. EFS estimates are reported by risk group.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low-Risk Group | Percent Probability of Event-free Survival (EFS) for Medulloblastoma Patients | 73.9 Percent Probability |
| Intermediate-Risk Group | Percent Probability of Event-free Survival (EFS) for Medulloblastoma Patients | 46.9 Percent Probability |
| High-Risk Group | Percent Probability of Event-free Survival (EFS) for Medulloblastoma Patients | 30.8 Percent Probability |
Primary
Percent Probability of Progression-free Survival (PFS) for Medulloblastoma Patients
Progression was defined as 25% increase in the size of any measurable lesion; the appearance of a new lesion; or the conversion of negative cerebrospinal fluid (CSF) cytology to positive. Defined as the time interval from date on treatment until the date of first progression, medulloblastoma-related death or date of last contact for patients who have not experienced an event. All eligible medulloblastoma patients who received any methotrexate are included in this analysis.
Time frame: From date on treatment until date of first progression or relapse or disease related death or date of last contact, estimated at 1 year after treatment
Population: All eligible medulloblastoma patients started methotrexate and were included (n=81). PFS estimates are reported by risk group.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low-Risk Group | Percent Probability of Progression-free Survival (PFS) for Medulloblastoma Patients | 73.9 Percent Probability |
| Intermediate-Risk Group | Percent Probability of Progression-free Survival (PFS) for Medulloblastoma Patients | 46.9 Percent Probability |
| High-Risk Group | Percent Probability of Progression-free Survival (PFS) for Medulloblastoma Patients | 30.8 Percent Probability |
Primary
Percent Probability of Progression-free Survival (PFS) for Medulloblastoma Patients by DNA Methylation Subgroup
Defined as the time interval from date on treatment until the date of first progression, medulloblastoma-related death or date of last contact for patients who have not experienced an event. Eligible medulloblastoma patients who received any methotrexate and had molecularly confirmed medulloblastoma are included in this analysis. Five patients were excluded as 3 had no archival tissue available and 2 were found to not be medulloblastoma by methylation profile.
Time frame: From date on treatment to date of first progression or relapse or disease related death or date of last contact, estimated at 1 year after treatment
Population: Eligible patients with molecularly confirmed medulloblastoma (n=76) were included. PFS estimates are reported by methylation subgroup and risk group. There were no low-risk group 3 or group 4 patients.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low-Risk Group | Percent Probability of Progression-free Survival (PFS) for Medulloblastoma Patients by DNA Methylation Subgroup | 73.9 Percent Probability |
| Intermediate-Risk Group | Percent Probability of Progression-free Survival (PFS) for Medulloblastoma Patients by DNA Methylation Subgroup | 50.0 Percent Probability |
| High-Risk Group | Percent Probability of Progression-free Survival (PFS) for Medulloblastoma Patients by DNA Methylation Subgroup | 54.5 Percent Probability |
| Intermediate-risk Group 3 Patients | Percent Probability of Progression-free Survival (PFS) for Medulloblastoma Patients by DNA Methylation Subgroup | 30.8 Percent Probability |
| High-risk Group 3 Patients | Percent Probability of Progression-free Survival (PFS) for Medulloblastoma Patients by DNA Methylation Subgroup | 9.1 Percent Probability |
| Intermediate-risk Group 4 Patients | Percent Probability of Progression-free Survival (PFS) for Medulloblastoma Patients by DNA Methylation Subgroup | 62.5 Percent Probability |
| High-risk Group 4 Patients | Percent Probability of Progression-free Survival (PFS) for Medulloblastoma Patients by DNA Methylation Subgroup | 50.0 Percent Probability |
Secondary
4-OH Cyclophosphamide AUC0-24h in Consolidation Chemotherapy Cycle 1
4-OH cyclophosphamide plasma concentration-time data are collected in consolidation cycle 1. Individual estimates of 4-OH cyclophosphamide AUC0-24h (area under concentration curve from time 0 to 24 hours post- dose) are obtained using post hoc analysis.
Time frame: Pre-infusion, end of infusion, 3, 6, and 24 hours from end of cyclophosphamide infusion
Population: Eligible patients who received cyclophosphamide during consolidation cycle 1 and had samples collected for PK analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Low-Risk Group | 4-OH Cyclophosphamide AUC0-24h in Consolidation Chemotherapy Cycle 1 | 96.8 µmol·h/L |
| Intermediate-Risk Group | 4-OH Cyclophosphamide AUC0-24h in Consolidation Chemotherapy Cycle 1 | 48.7 µmol·h/L |
| High-Risk Group | 4-OH Cyclophosphamide AUC0-24h in Consolidation Chemotherapy Cycle 1 | 39.8 µmol·h/L |
Secondary
4-OH Cyclophosphamide AUC0-24h in Consolidation Chemotherapy Cycle 2
4-OH cyclophosphamide plasma concentration-time data are collected in consolidation cycle 2. Individual estimates of 4-OH cyclophosphamide AUC0-24h (area under concentration curve from time 0 to 24 hours post- dose) are obtained using post hoc analysis.
Time frame: Pre-infusion, end of infusion, 3, 6, and 24 hours from end of cyclophosphamide infusion
Population: Eligible patients who received cyclophosphamide during consolidation cycle 2 and had samples collected for PK analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Low-Risk Group | 4-OH Cyclophosphamide AUC0-24h in Consolidation Chemotherapy Cycle 2 | 95.9 µmol·h/L |
| Intermediate-Risk Group | 4-OH Cyclophosphamide AUC0-24h in Consolidation Chemotherapy Cycle 2 | 49.5 µmol·h/L |
| High-Risk Group | 4-OH Cyclophosphamide AUC0-24h in Consolidation Chemotherapy Cycle 2 | 43.5 µmol·h/L |
Secondary
4-OH Cyclophosphamide AUC0-24h in Induction Chemotherapy
4-OH cyclophosphamide plasma concentration-time data are collected on day 9 in one cycle of induction chemotherapy. Individual estimates of 4-OH cyclophosphamide AUC0-24h (area under concentration curve from time 0 to 24 hours post-dose) are obtained using post hoc analysis.
Time frame: Pre-infusion, end of infusion, 3, 6, and 24 hours from end of cyclophosphamide infusion
Population: Eligible patients who received cyclophosphamide during a cycle of induction therapy and had samples collected for PK analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Low-Risk Group | 4-OH Cyclophosphamide AUC0-24h in Induction Chemotherapy | 116.4 µmol·h/L |
| Intermediate-Risk Group | 4-OH Cyclophosphamide AUC0-24h in Induction Chemotherapy | 111.3 µmol·h/L |
| High-Risk Group | 4-OH Cyclophosphamide AUC0-24h in Induction Chemotherapy | 109.1 µmol·h/L |
Secondary
4-OH Cyclophosphamide AUC0-24h in Maintenance Chemotherapy Cycle A1
4-OH cyclophosphamide plasma concentration-time data are collected on day 1 of maintenance cycle A1. Individual estimates of 4-OH cyclophosphamide AUC0-24h (area under concentration curve from time 0 to 24 hours post-dose) are obtained using post hoc analysis.
Time frame: Pre-dose, 0.5, 1.75, 3, 6, and 24 hours post-dose
Population: Eligible patients who received cyclophosphamide during maintenance cycle A1 and had samples collected for PK analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Low-Risk Group | 4-OH Cyclophosphamide AUC0-24h in Maintenance Chemotherapy Cycle A1 | 1.98 µmol·h/L |
| Intermediate-Risk Group | 4-OH Cyclophosphamide AUC0-24h in Maintenance Chemotherapy Cycle A1 | 1.96 µmol·h/L |
| High-Risk Group | 4-OH Cyclophosphamide AUC0-24h in Maintenance Chemotherapy Cycle A1 | 1.82 µmol·h/L |
Secondary
CEPM AUC0-24h in Consolidation Chemotherapy Cycle 1
Carboxyethylphosphoramide mustard (CEPM) plasma concentration-time data are collected in consolidation cycle 1. Individual estimates of CEPM AUC0-24h (area under concentration curve from time 0 to 24 hours post- dose) are obtained using post hoc analysis.
Time frame: Pre-infusion, end of infusion, 3, 6, and 24 hours from end of cyclophosphamide infusion
Population: Eligible patients who received cyclophosphamide during consolidation cycle 1 and had samples collected for PK analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Low-Risk Group | CEPM AUC0-24h in Consolidation Chemotherapy Cycle 1 | 128.9 µmol·h/L |
| Intermediate-Risk Group | CEPM AUC0-24h in Consolidation Chemotherapy Cycle 1 | 62.2 µmol·h/L |
| High-Risk Group | CEPM AUC0-24h in Consolidation Chemotherapy Cycle 1 | 51.8 µmol·h/L |
Secondary
CEPM AUC0-24h in Consolidation Chemotherapy Cycle 2
Carboxyethylphosphoramide mustard (CEPM) plasma concentration-time data are collected in consolidation cycle 2. Individual estimates of CEPM AUC0-24h (area under concentration curve from time 0 to 24 hours post- dose) are obtained using post hoc analysis.
Time frame: Pre-infusion, end of infusion, 3, 6, and 24 hours from end of cyclophosphamide infusion
Population: Eligible patients who received cyclophosphamide during consolidation cycle 2 and had samples collected for PK analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Low-Risk Group | CEPM AUC0-24h in Consolidation Chemotherapy Cycle 2 | 132.7 µmol·h/L |
| Intermediate-Risk Group | CEPM AUC0-24h in Consolidation Chemotherapy Cycle 2 | 46.8 µmol·h/L |
| High-Risk Group | CEPM AUC0-24h in Consolidation Chemotherapy Cycle 2 | 44.0 µmol·h/L |
Secondary
CEPM AUC0-24h in Induction Chemotherapy
Carboxyethylphosphoramide mustard (CEPM) plasma concentration-time data are collected on day 9 in one induction cycle. Individual estimates of CEPM AUC0-24h (area under concentration curve from time 0 to 24 hours post-dose) are obtained using post hoc analysis.
Time frame: Pre-infusion, end of infusion, 3, 6, and 24 hours from end of cyclophosphamide infusion
Population: Eligible patients who received cyclophosphamide during a cycle of induction therapy and had samples collected for PK analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Low-Risk Group | CEPM AUC0-24h in Induction Chemotherapy | 140.2 µmol·h/L |
| Intermediate-Risk Group | CEPM AUC0-24h in Induction Chemotherapy | 137.8 µmol·h/L |
| High-Risk Group | CEPM AUC0-24h in Induction Chemotherapy | 135.3 µmol·h/L |
Secondary
CEPM AUC0-24h in Maintenance Chemotherapy Cycle A1
Carboxyethylphosphoramide mustard (CEPM) plasma concentration-time data are collected on day 1 of maintenance cycle A1. Individual estimates of CEPM AUC0-24h (area under concentration curve from time 0 to 24 hours post-dose) are obtained using post hoc analysis.
Time frame: Pre-dose, 0.5, 1.75, 3, 6, and 24 hours post-dose
Population: Eligible patients who received cyclophosphamide during maintenance cycle A1 and had samples collected for PK analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Low-Risk Group | CEPM AUC0-24h in Maintenance Chemotherapy Cycle A1 | 1.59 µmol·h/L |
| Intermediate-Risk Group | CEPM AUC0-24h in Maintenance Chemotherapy Cycle A1 | 1.65 µmol·h/L |
| High-Risk Group | CEPM AUC0-24h in Maintenance Chemotherapy Cycle A1 | 1.41 µmol·h/L |
Secondary
Change in Neurostructure, Especially White Matter Volume and Integrity
Quantitative MRI measures Fractional Anisotropy (FA) change per month in left occipital lobe over time in each risk group will be assessed using a random effects model incorporating various covariates. Covariates to be considered include age at diagnosis, time since diagnosis and risk-arm. Differences in quantitative MRI measures of neurostructure volume and integrity between patient groups will be evaluated as a metric of structural neurotoxicity of therapy. Fractional anisotropy (FA) is a scalar unitless measure that quantifies the degree of anisotropy of a diffusion process, particularly in the context of diffusion tensor imaging (DTI) used in MRI scans. FA values range from 0 to 1
Time frame: From baseline (month 0) to 60 months (therapy duration lasted approximately 48 weeks or 11 months)
Population: Eligible infratentorial medulloblastoma, ependymoma, and pineoblastoma patients(n=75) were included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low-Risk Group | Change in Neurostructure, Especially White Matter Volume and Integrity | 0.0021 Change in FA per month |
| Intermediate-Risk Group | Change in Neurostructure, Especially White Matter Volume and Integrity | 0.0020 Change in FA per month |
| High-Risk Group | Change in Neurostructure, Especially White Matter Volume and Integrity | 0.0015 Change in FA per month |
Secondary
Change in Neurostructure, Especially White Matter Volume and Integrity
Quantitative MRI measures Fractional Anisotropy (FA) change per month in left parietal lobe over time in each risk group will be assessed using a random effects model incorporating various covariates. Covariates to be considered include age at diagnosis, time since diagnosis and risk-arm. Differences in quantitative MRI measures of neurostructure volume and integrity between patient groups will be evaluated as a metric of structural neurotoxicity of therapy. Fractional anisotropy (FA) is a scalar unitless measure that quantifies the degree of anisotropy of a diffusion process, particularly in the context of diffusion tensor imaging (DTI) used in MRI scans. FA values range from 0 to 1
Time frame: From baseline (month 0) to 60 months (therapy duration lasted approximately 48 weeks or 11 months)
Population: Eligible infratentorial medulloblastoma, ependymoma, and pineoblastoma patients(n=75) were included
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low-Risk Group | Change in Neurostructure, Especially White Matter Volume and Integrity | 0.0016 Change in FA per month |
| Intermediate-Risk Group | Change in Neurostructure, Especially White Matter Volume and Integrity | 0.0014 Change in FA per month |
| High-Risk Group | Change in Neurostructure, Especially White Matter Volume and Integrity | 0.0016 Change in FA per month |
Secondary
Change in Neurostructure, Especially White Matter Volume and Integrity
Quantitative MRI measures Fractional Anisotropy (FA) change per month in right parietal lobe over time in each risk group will be assessed using a random effects model incorporating various covariates. Covariates to be considered include age at diagnosis, time since diagnosis and risk-arm. Differences in quantitative MRI measures of neurostructure volume and integrity between patient groups will be evaluated as a metric of structural neurotoxicity of therapy. Fractional anisotropy (FA) is a scalar unitless measure that quantifies the degree of anisotropy of a diffusion process, particularly in the context of diffusion tensor imaging (DTI) used in MRI scans. FA values range from 0 to 1
Time frame: From baseline (month 0) to 60 months (therapy duration lasted approximately 48 weeks or 11 months)
Population: Eligible infratentorial medulloblastoma, ependymoma, and pineoblastoma patients(n=75) were included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low-Risk Group | Change in Neurostructure, Especially White Matter Volume and Integrity | 0.0015 Change in FA per month |
| Intermediate-Risk Group | Change in Neurostructure, Especially White Matter Volume and Integrity | 0.0014 Change in FA per month |
| High-Risk Group | Change in Neurostructure, Especially White Matter Volume and Integrity | 0.0016 Change in FA per month |
Secondary
Change in Neurostructure, Especially White Matter Volume and Integrity
Quantitative MRI measures Fractional Anisotropy (FA) change per month in right occipital lobe over time in each risk group will be assessed using a random effects model incorporating various covariates. Covariates to be considered include age at diagnosis, time since diagnosis and risk-arm. Differences in quantitative MRI measures of neurostructure volume and integrity between patient groups will be evaluated as a metric of structural neurotoxicity of therapy. Fractional anisotropy (FA) is a scalar unitless measure that quantifies the degree of anisotropy of a diffusion process, particularly in the context of diffusion tensor imaging (DTI) used in MRI scans. FA values range from 0 to 1
Time frame: From baseline (month 0) to 60 months (therapy duration lasted approximately 48 weeks or 11 months)
Population: Eligible infratentorial medulloblastoma, ependymoma, and pineoblastoma patients(n=75) were included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low-Risk Group | Change in Neurostructure, Especially White Matter Volume and Integrity | 0.0016 Change in FA per month |
| Intermediate-Risk Group | Change in Neurostructure, Especially White Matter Volume and Integrity | 0.0015 Change in FA per month |
| High-Risk Group | Change in Neurostructure, Especially White Matter Volume and Integrity | 0.0013 Change in FA per month |
Secondary
Change in Neurostructure, Especially White Matter Volume and Integrity
Quantitative MRI measures Fractional Anisotropy (FA) change per month in left frontal lobe over time in each risk group will be assessed using a random effects model incorporating various covariates. Covariates to be considered include age at diagnosis, time since diagnosis and risk-arm. Differences in quantitative MRI measures of neurostructure volume and integrity between patient groups will be evaluated as a metric of structural neurotoxicity of therapy. Fractional anisotropy (FA) is a scalar unitless measure that quantifies the degree of anisotropy of a diffusion process, particularly in the context of diffusion tensor imaging (DTI) used in MRI scans. FA values range from 0 to 1
Time frame: From baseline (month 0) to 60 months (therapy duration lasted approximately 48 weeks or 11 months)
Population: Eligible infratentorial medulloblastoma, ependymoma, and pineoblastoma patients(n=75) were included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low-Risk Group | Change in Neurostructure, Especially White Matter Volume and Integrity | 0.0019 change in FA per month |
| Intermediate-Risk Group | Change in Neurostructure, Especially White Matter Volume and Integrity | 0.0017 change in FA per month |
| High-Risk Group | Change in Neurostructure, Especially White Matter Volume and Integrity | 0.0017 change in FA per month |
Secondary
Change in Neurostructure, Especially White Matter Volume and Integrity
Quantitative MRI measures Fractional Anisotropy (FA) change per month in right frontal-lobe over time in each risk group will be assessed using a random effects model incorporating various covariates. Covariates to be considered include age at diagnosis, time since diagnosis and risk-arm. Differences in quantitative MRI measures of neurostructure volume and integrity between patient groups will be evaluated as a metric of structural neurotoxicity of therapy. Fractional anisotropy (FA) is a scalar unitless measure that quantifies the degree of anisotropy of a diffusion process, particularly in the context of diffusion tensor imaging (DTI) used in MRI scans. FA values range from 0 to 1
Time frame: From baseline (month 0) to 60 months (therapy duration lasted approximately 48 weeks or 11 months)
Population: Eligible infratentorial medulloblastoma, ependymoma, and pineoblastoma patients(n=75) were included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low-Risk Group | Change in Neurostructure, Especially White Matter Volume and Integrity | 0.0019 Change in FA per month |
| Intermediate-Risk Group | Change in Neurostructure, Especially White Matter Volume and Integrity | 0.0016 Change in FA per month |
| High-Risk Group | Change in Neurostructure, Especially White Matter Volume and Integrity | 0.0017 Change in FA per month |
Secondary
Change in Neurostructure, Especially White Matter Volume and Integrity
Quantitative MRI measures Fractional Anisotropy (FA) change per month in right temporal lobe over time in each risk group will be assessed using a random effects model incorporating various covariates. Covariates to be considered include age at diagnosis, time since diagnosis and risk-arm. Differences in quantitative MRI measures of neurostructure volume and integrity between patient groups will be evaluated as a metric of structural neurotoxicity of therapy. Fractional anisotropy (FA) is a scalar unitless measure that quantifies the degree of anisotropy of a diffusion process, particularly in the context of diffusion tensor imaging (DTI) used in MRI scans. FA values range from 0 to 1
Time frame: From baseline (month 0) to 60 months (therapy duration lasted approximately 48 weeks or 11 months)
Population: Eligible infratentorial medulloblastoma, ependymoma, and pineoblastoma patients(n=75) were included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low-Risk Group | Change in Neurostructure, Especially White Matter Volume and Integrity | 0.0014 Change in FA per month |
| Intermediate-Risk Group | Change in Neurostructure, Especially White Matter Volume and Integrity | 0.0013 Change in FA per month |
| High-Risk Group | Change in Neurostructure, Especially White Matter Volume and Integrity | 0.0013 Change in FA per month |
Secondary
Change in Neurostructure, Especially White Matter Volume and Integrity
Quantitative MRI measures Fractional Anisotropy (FA) change per month in left temporal lobe over time in each risk group will be assessed using a random effects model incorporating various covariates. Covariates to be considered include age at diagnosis, time since diagnosis and risk-arm. Differences in quantitative MRI measures of neurostructure volume and integrity between patient groups will be evaluated as a metric of structural neurotoxicity of therapy. Fractional anisotropy (FA) is a scalar unitless measure that quantifies the degree of anisotropy of a diffusion process, particularly in the context of diffusion tensor imaging (DTI) used in MRI scans. FA values range from 0 to 1
Time frame: From baseline (month 0) to 60 months (therapy duration lasted approximately 48 weeks or 11 months)
Population: Eligible infratentorial medulloblastoma, ependymoma, and pineoblastoma patients(n=75) were included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low-Risk Group | Change in Neurostructure, Especially White Matter Volume and Integrity | 0.0014 Change in FA per month |
| Intermediate-Risk Group | Change in Neurostructure, Especially White Matter Volume and Integrity | 0.0013 Change in FA per month |
| High-Risk Group | Change in Neurostructure, Especially White Matter Volume and Integrity | 0.0014 Change in FA per month |
Secondary
Change in Quantitative Magnetic Resonance (MR) Measures in the Frontal Lobe
Quantitative MRI measures Fractional Anisotropy (FA) change per month in frontal lobe over time in each risk group will be assessed using a random effects model incorporating various covariates. Covariates to be considered include age at diagnosis, time since diagnosis and risk-arm. Differences in quantitative MRI measures of neurostructure volume and integrity between patient groups will be evaluated as a metric of structural neurotoxicity of therapy. Fractional anisotropy (FA) is a scalar unitless measure that quantifies the degree of anisotropy of a diffusion process, particularly in the context of diffusion tensor imaging (DTI) used in MRI scans. FA values range from 0 to 1
Time frame: From baseline (month 0) to 60 months (therapy duration lasted approximately 48 weeks or 11 months)
Population: Eligible infratentorial medulloblastoma, ependymoma, and pineoblastoma patients(n=75) were included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low-Risk Group | Change in Quantitative Magnetic Resonance (MR) Measures in the Frontal Lobe | 0.0019 Change in FA per month |
| Intermediate-Risk Group | Change in Quantitative Magnetic Resonance (MR) Measures in the Frontal Lobe | 0.0017 Change in FA per month |
| High-Risk Group | Change in Quantitative Magnetic Resonance (MR) Measures in the Frontal Lobe | 0.0017 Change in FA per month |
Secondary
Change in Quantitative MR Measures in the Right Frontal-parietal Regions
Quantitative MRI measures Fractional Anisotropy (FA) change per month in right frontal-parietal region over time in each risk group will be assessed using a random effects model incorporating various covariates. Covariates to be considered include age at diagnosis, time since diagnosis and risk-arm. Differences in quantitative MRI measures of neurostructure volume and integrity between patient groups will be evaluated as a metric of structural neurotoxicity of therapy. Fractional anisotropy (FA) is a scalar unitless measure that quantifies the degree of anisotropy of a diffusion process, particularly in the context of diffusion tensor imaging (DTI) used in MRI scans. FA values range from 0 to 1
Time frame: From baseline (month 0) to 60 months (therapy duration lasted approximately 48 weeks or 11 months)
Population: Eligible infratentorial medulloblastoma, ependymoma, and pineoblastoma patients(n=75) were included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low-Risk Group | Change in Quantitative MR Measures in the Right Frontal-parietal Regions | 0.0017 Change in FA per month |
| Intermediate-Risk Group | Change in Quantitative MR Measures in the Right Frontal-parietal Regions | 0.0015 Change in FA per month |
| High-Risk Group | Change in Quantitative MR Measures in the Right Frontal-parietal Regions | 0.0016 Change in FA per month |
Secondary
Concentration of Cerebrospinal Fluid Neurotransmitters
Concentrations of various neurotransmitters in cerebrospinal fluid were measured at 5 timepoints. The median concentration of each neurotransmitter at each time point was calculated and provided with a full range.
Time frame: Baseline, at the completion of therapy, and every 12 months up to 36 months after off therapy date
Population: Eligible patients who had cerebrospinal fluid neurotransmitter studies performed. Seventeen patients had studies performed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Low-Risk Group | Concentration of Cerebrospinal Fluid Neurotransmitters | Dopamine concentration at baseline | 3.16 ng/ml |
| Low-Risk Group | Concentration of Cerebrospinal Fluid Neurotransmitters | Dopamine concentration at completion of treatment | 3.70 ng/ml |
| Low-Risk Group | Concentration of Cerebrospinal Fluid Neurotransmitters | Dopamine concentration at 12 months off treatment | 6.43 ng/ml |
| Low-Risk Group | Concentration of Cerebrospinal Fluid Neurotransmitters | Dopamine concentration at 24 months off treatment | 4.46 ng/ml |
| Low-Risk Group | Concentration of Cerebrospinal Fluid Neurotransmitters | Dopamine concentration at 36 months off treatment | 4.05 ng/ml |
| Low-Risk Group | Concentration of Cerebrospinal Fluid Neurotransmitters | 3,4-dihydroxyphenylacetic acid concentration at baseline | 2.56 ng/ml |
| Low-Risk Group | Concentration of Cerebrospinal Fluid Neurotransmitters | 3,4-dihydroxyphenylacetic acid concentration at completion of treatment | 1.62 ng/ml |
| Low-Risk Group | Concentration of Cerebrospinal Fluid Neurotransmitters | 3,4-dihydroxyphenylacetic acid concentration at 12 months off treatment | 1.04 ng/ml |
| Low-Risk Group | Concentration of Cerebrospinal Fluid Neurotransmitters | 3,4-dihydroxyphenylacetic acid concentration at 24 months off treatment | 1.52 ng/ml |
| Low-Risk Group | Concentration of Cerebrospinal Fluid Neurotransmitters | 3,4-dihydroxyphenylacetic acid concentration at 36 months off treatment | 1.00 ng/ml |
| Low-Risk Group | Concentration of Cerebrospinal Fluid Neurotransmitters | Hydroxytryptamine concentration at baseline | 2.38 ng/ml |
| Low-Risk Group | Concentration of Cerebrospinal Fluid Neurotransmitters | Hydroxytryptamine concentration at completion of treatment | 2.01 ng/ml |
| Low-Risk Group | Concentration of Cerebrospinal Fluid Neurotransmitters | Hydroxytryptamine concentration at 12 months off treatment | 2.00 ng/ml |
| Low-Risk Group | Concentration of Cerebrospinal Fluid Neurotransmitters | Hydroxytryptamine concentration at 24 months off treatment | 2.44 ng/ml |
| Low-Risk Group | Concentration of Cerebrospinal Fluid Neurotransmitters | Hydroxytryptamine concentration at 36 months off treatment | 1.62 ng/ml |
| Low-Risk Group | Concentration of Cerebrospinal Fluid Neurotransmitters | Hydroxyindoleacetic acid concentration at baseline | 52.03 ng/ml |
| Low-Risk Group | Concentration of Cerebrospinal Fluid Neurotransmitters | Hydroxyindoleacetic acid concentration at completion of treatment | 52.72 ng/ml |
| Low-Risk Group | Concentration of Cerebrospinal Fluid Neurotransmitters | Hydroxyindoleacetic acid concentration at 12 months off treatment | 35.72 ng/ml |
| Low-Risk Group | Concentration of Cerebrospinal Fluid Neurotransmitters | Hydroxyindoleacetic acid concentration at 24 months off treatment | 33.98 ng/ml |
| Low-Risk Group | Concentration of Cerebrospinal Fluid Neurotransmitters | Hydroxyindoleacetic acid concentration at 36 months off treatment | 31.56 ng/ml |
| Low-Risk Group | Concentration of Cerebrospinal Fluid Neurotransmitters | Homovanillic acid concentration at baseline | 82.44 ng/ml |
| Low-Risk Group | Concentration of Cerebrospinal Fluid Neurotransmitters | Homovanillic acid concentration at completion of treatment | 114.13 ng/ml |
| Low-Risk Group | Concentration of Cerebrospinal Fluid Neurotransmitters | Homovanillic acid concentration at 12 months off treatment | 68.28 ng/ml |
| Low-Risk Group | Concentration of Cerebrospinal Fluid Neurotransmitters | Homovanillic acid concentration at 24 months off treatment | 88.27 ng/ml |
| Low-Risk Group | Concentration of Cerebrospinal Fluid Neurotransmitters | Homovanillic acid concentration at 36 months off treatment | 79.78 ng/ml |
Secondary
Cyclophosphamide Apparent Oral Clearance in Maintenance Chemotherapy Cycle A1
Cyclophosphamide plasma concentration-time data are collected on day 1 of maintenance cycle A1. Individual estimates of cyclophosphamide apparent oral clearance are obtained using post hoc analysis.
Time frame: Pre-dose, 0.5, 1.75, 3 and 6 hours post-dose
Population: Eligible patients who received cyclophosphamide during maintenance cycle A1 and had samples collected for PK analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Low-Risk Group | Cyclophosphamide Apparent Oral Clearance in Maintenance Chemotherapy Cycle A1 | 2.95 L/h/m^2 |
| Intermediate-Risk Group | Cyclophosphamide Apparent Oral Clearance in Maintenance Chemotherapy Cycle A1 | 2.83 L/h/m^2 |
| High-Risk Group | Cyclophosphamide Apparent Oral Clearance in Maintenance Chemotherapy Cycle A1 | 2.74 L/h/m^2 |
Secondary
Cyclophosphamide AUC0-24h in Consolidation Chemotherapy Cycle 1
Cyclophosphamide plasma concentration-time data are collected in consolidation cycle 1. Individual estimates of cyclophosphamide AUC0-24h (area under concentration curve from time 0 to 24 hours post-dose) are obtained using post hoc analysis.
Time frame: Pre-infusion, end of infusion, 3, 6, and 24 hours from end of cyclophosphamide infusion
Population: Eligible patients who received cyclophosphamide during consolidation cycle 1 and had samples collected for PK analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Low-Risk Group | Cyclophosphamide AUC0-24h in Consolidation Chemotherapy Cycle 1 | 1968 µmol·h/L |
| Intermediate-Risk Group | Cyclophosphamide AUC0-24h in Consolidation Chemotherapy Cycle 1 | 1504 µmol·h/L |
| High-Risk Group | Cyclophosphamide AUC0-24h in Consolidation Chemotherapy Cycle 1 | 868 µmol·h/L |
Secondary
Cyclophosphamide AUC0-24h in Consolidation Chemotherapy Cycle 2
Cyclophosphamide plasma concentration-time data are collected in consolidation cycle 2. Individual estimates of cyclophosphamide AUC0-24h (area under concentration curve from time 0 to 24 hours post-dose) are obtained using post hoc analysis.
Time frame: Pre-infusion, end of infusion, 3, 6, and 24 hours from end of cyclophosphamide infusion
Population: Eligible patients who received cyclophosphamide during consolidation cycle 2 and had samples collected for PK analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Low-Risk Group | Cyclophosphamide AUC0-24h in Consolidation Chemotherapy Cycle 2 | 1966 µmol·h/L |
| Intermediate-Risk Group | Cyclophosphamide AUC0-24h in Consolidation Chemotherapy Cycle 2 | 799 µmol·h/L |
| High-Risk Group | Cyclophosphamide AUC0-24h in Consolidation Chemotherapy Cycle 2 | 899 µmol·h/L |
Secondary
Cyclophosphamide AUC0-24h in Induction Chemotherapy
Cyclophosphamide plasma concentration-time data are collected on day 9 in one cycle of induction chemotherapy. Individual estimates of cyclophosphamide AUC0-24h (area under concentration curve from time 0 to 24 hours post-dose) are obtained using post hoc analysis.
Time frame: Pre-infusion, end of infusion, 3, 6, and 24 hours from end of cyclophosphamide infusion
Population: Eligible patients who received cyclophosphamide during a cycle of induction therapy and had samples collected for PK analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Low-Risk Group | Cyclophosphamide AUC0-24h in Induction Chemotherapy | 2070 µmol·h/L |
| Intermediate-Risk Group | Cyclophosphamide AUC0-24h in Induction Chemotherapy | 2150 µmol·h/L |
| High-Risk Group | Cyclophosphamide AUC0-24h in Induction Chemotherapy | 2105 µmol·h/L |
Secondary
Cyclophosphamide AUC0-24h in Maintenance Chemotherapy Cycle A1
Cyclophosphamide plasma concentration-time data are collected on day 1 of maintenance cycle A1. Individual estimates of cyclophosphamide AUC0-24h are obtained using post hoc analysis.
Time frame: Pre-dose, 0.5, 1.75, 3, 6, and 24 hours post-dose
Population: Eligible patients who received cyclophosphamide during maintenance cycle A1 and had samples collected for PK analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Low-Risk Group | Cyclophosphamide AUC0-24h in Maintenance Chemotherapy Cycle A1 | 39.9 µmol·h/L |
| Intermediate-Risk Group | Cyclophosphamide AUC0-24h in Maintenance Chemotherapy Cycle A1 | 38.7 µmol·h/L |
| High-Risk Group | Cyclophosphamide AUC0-24h in Maintenance Chemotherapy Cycle A1 | 42.2 µmol·h/L |
Secondary
Cyclophosphamide Clearance in Consolidation Chemotherapy Cycle 1
Cyclophosphamide plasma concentration-time data are collected in consolidation cycle 1. Individual estimates of cyclophosphamide clearance are obtained using post hoc analysis.
Time frame: Pre-infusion, end of infusion, 3, 6, and 24 hours from end of cyclophosphamide infusion
Population: Eligible patients who received cyclophosphamide during consolidation cycle 1 and had samples collected for PK analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Low-Risk Group | Cyclophosphamide Clearance in Consolidation Chemotherapy Cycle 1 | 2.39 L/h/m^2 |
| Intermediate-Risk Group | Cyclophosphamide Clearance in Consolidation Chemotherapy Cycle 1 | 2.08 L/h/m^2 |
| High-Risk Group | Cyclophosphamide Clearance in Consolidation Chemotherapy Cycle 1 | 2.43 L/h/m^2 |
Secondary
Cyclophosphamide Clearance in Consolidation Chemotherapy Cycle 2
Cyclophosphamide plasma concentration-time data are collected in consolidation cycle 2. Individual estimates of cyclophosphamide clearance are obtained using post hoc analysis.
Time frame: Pre-infusion, end of infusion, 3, 6, and 24 hours from end of cyclophosphamide infusion
Population: Eligible patients who received cyclophosphamide during consolidation cycle 2 and had samples collected for PK analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Low-Risk Group | Cyclophosphamide Clearance in Consolidation Chemotherapy Cycle 2 | 2.48 L/h/m^2 |
| Intermediate-Risk Group | Cyclophosphamide Clearance in Consolidation Chemotherapy Cycle 2 | 2.55 L/h/m^2 |
| High-Risk Group | Cyclophosphamide Clearance in Consolidation Chemotherapy Cycle 2 | 2.37 L/h/m^2 |
Secondary
Cyclophosphamide Clearance in Induction Chemotherapy
Cyclophosphamide plasma concentration-time data are collected on day 9 in one cycle of induction chemotherapy. Individual estimates of cyclophosphamide clearance are obtained using post hoc analysis.
Time frame: Pre-infusion, end of infusion, 3, 6, and 24 hours from end of cyclophosphamide infusion
Population: Eligible patients who received cyclophosphamide during a cycle of induction therapy and had samples collected for PK analysis..
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Low-Risk Group | Cyclophosphamide Clearance in Induction Chemotherapy | 2.40 L/h/m^2 |
| Intermediate-Risk Group | Cyclophosphamide Clearance in Induction Chemotherapy | 2.23 L/h/m^2 |
| High-Risk Group | Cyclophosphamide Clearance in Induction Chemotherapy | 2.25 L/h/m^2 |
Secondary
Erlotinib Apparent Oral Clearance
Erlotinib plasma concentration-time data are collected on day 1 of maintenance cycle B2. Individual estimates of erlotinib apparent oral clearance are obtained using post hoc analysis.
Time frame: Pre-dose, 1, 2, 4, 8, and 24 hours post-dose
Population: Eligible patients who received oral erlotinib during maintenance therapy cycle B2 and had samples collected for PK analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Low-Risk Group | Erlotinib Apparent Oral Clearance | 6.53 L/h/m^2 |
| Intermediate-Risk Group | Erlotinib Apparent Oral Clearance | 7.79 L/h/m^2 |
| High-Risk Group | Erlotinib Apparent Oral Clearance | 8.40 L/h/m^2 |
Secondary
Erlotinib Apparent Volume of Central Compartment
Erlotinib plasma concentration-time data are collected on day 1 of maintenance cycle B2. Individual estimates of erlotinib apparent volume of central compartment are obtained using post hoc analysis.
Time frame: Pre-dose, 1, 2, 4, 8, and 24 hours post-dose
Population: Eligible patients who received oral erlotinib during maintenance therapy cycle B2 and had samples collected for PK analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Low-Risk Group | Erlotinib Apparent Volume of Central Compartment | 72.9 L/m^2 |
| Intermediate-Risk Group | Erlotinib Apparent Volume of Central Compartment | 61.7 L/m^2 |
| High-Risk Group | Erlotinib Apparent Volume of Central Compartment | 104.8 L/m^2 |
Secondary
Erlotinib AUC0-24h
Erlotinib plasma concentration-time data are collected on day 1 of maintenance cycle B2. Individual estimates of erlotinib AUC0-24h (area under concentration curve from 0 to 24 hours post-dose) are obtained using post hoc analysis.
Time frame: Pre-dose, 1, 2, 4, 8, and 24 hours post-dose
Population: Eligible patients who received oral erlotinib during maintenance therapy cycle B2 and had samples collected for PK analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Low-Risk Group | Erlotinib AUC0-24h | 31.0 µmol·h/L |
| Intermediate-Risk Group | Erlotinib AUC0-24h | 23.5 µmol·h/L |
| High-Risk Group | Erlotinib AUC0-24h | 22.0 µmol·h/L |
Secondary
Event-free Survival (EFS) Compared to Historical Controls
EFS was measured from the date of initial treatment to the earliest date of disease progression, second malignancy or death for patients who fail; and to the date of last contact for patients who remain at risk for failure. 1-year EFS estimates are reported by risk group. EFS was compared to St. Jude historical cohorts by risk group using hazard ratios with 95% confidence intervals.
Time frame: From date on treatment until date of first event (progression, second malignancy or death) or until date of last contact, assessed up to 10 years
Population: Eligible medulloblastoma patients who received any methotrexate were included in this analysis. Hazard ratios with 95% confidence intervals are reported and compare SJYC07 patients to historical controls in each risk group. As there were too few low-risk historical controls, no hazard ratio is included for the low-risk group.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low-Risk Group | Event-free Survival (EFS) Compared to Historical Controls | 73.9 Percent probability |
| Intermediate-Risk Group | Event-free Survival (EFS) Compared to Historical Controls | 46.9 Percent probability |
| High-Risk Group | Event-free Survival (EFS) Compared to Historical Controls | 30.8 Percent probability |
Comparison: The historical control included 10 medulloblastoma patients treated during 1998-2006 who would have been classified as intermediate risk according to SJYC07 criteria (section 13.1.3 of protocol).95% CI: [1.17, 21.23]
Comparison: The historical control included 14 medulloblastoma patients treated during 1998-2006 who would have been classified as high risk according to SJYC07 criteria (section 13.1.3 of protocol).95% CI: [0.4, 1.84]
Secondary
Feasibility and Toxicity of Administering Consolidation Therapy Including Cyclophosphamide and Pharmacokinetically Targeted Topotecan to Patients With Metastatic Disease Based on the Percentage of Courses Delayed for More Than 7 Days Due to Toxicity
For the subset of patients with metastatic disease (high-risk group patients), during consolidation, we will calculate the number and proportion of courses during which subsequent chemotherapy administration was delayed for more than 7 days due to toxicity. Patients were to received 2 courses of consolidation chemotherapy and then maintenance therapy.
Time frame: At completion of consolidation therapy (up to 6 months after on-study date)
Population: Eligible high-risk group patients who started therapy were included. Course 2 of consolidation and the 1st course of maintenance were used in this analysis and assessed for delays \>7 days due to toxicity. Of the 76 high-risk patients that started induction therapy, 50 started consolidation (with 47 courses included in this analysis).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low-Risk Group | Feasibility and Toxicity of Administering Consolidation Therapy Including Cyclophosphamide and Pharmacokinetically Targeted Topotecan to Patients With Metastatic Disease Based on the Percentage of Courses Delayed for More Than 7 Days Due to Toxicity | 2.6 Percentage of courses delayed |
Secondary
Feasibility and Toxicity of Administering Oral Maintenance Therapy in Children <3 Years of Age as Measured by the Percentage of Total Scheduled Maintenance Doses Received
These data are based on patient diaries. For children \<3 years of age, we will calculate the percentage of total scheduled doses each patient received per course for each of the oral maintenance courses and report the overall average number percentage of doses received per course across patients. If patients received all planned doses, their percentage would be 100%. If the average percentage was less than 75%, then feasibility would be in question.
Time frame: From start of oral maintenance therapy (approximately 6 months after on-study date) to completion of oral maintenance therapy (up to 1 year after on-study date)
Population: Eligible patients less than 3 years of age (n=273) constituted the study population for this analysis; 167 of these patients started the first course of maintenance and were included in this analysis (50 low-risk, 87 intermediate-risk, and 30 high-risk patients).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low-Risk Group | Feasibility and Toxicity of Administering Oral Maintenance Therapy in Children <3 Years of Age as Measured by the Percentage of Total Scheduled Maintenance Doses Received | 96 Percentage of scheduled doses received | Standard Deviation 8 |
| Intermediate-Risk Group | Feasibility and Toxicity of Administering Oral Maintenance Therapy in Children <3 Years of Age as Measured by the Percentage of Total Scheduled Maintenance Doses Received | 91 Percentage of scheduled doses received | Standard Deviation 23 |
| High-Risk Group | Feasibility and Toxicity of Administering Oral Maintenance Therapy in Children <3 Years of Age as Measured by the Percentage of Total Scheduled Maintenance Doses Received | 98 Percentage of scheduled doses received | Standard Deviation 4 |
Secondary
Feasibility and Toxicity of Administering Vinblastine With Induction Chemotherapy for Patients With Metastatic Disease as Measured by the Percentage of Courses Delayed for More Than 7 Days Due to Toxicity
For the subset of patients with metastatic disease (high-risk group patients), during induction, the proportion percentage of courses during which subsequent chemotherapy administration was delayed for more than 7 days due to toxicity will be calculated. Patients were to receive 4 courses of induction and then consolidation chemotherapy.
Time frame: From on-study date up to 4 months after on-study date
Population: Eligible high-risk group patients who started therapy were included in this analysis (n=76). 1 patient enrolled on the high-risk arm did not start therapy due to early disease progression and was excluded. Courses 2-4 of induction and the 1st consolidation course were used in this analysis. 76 patients (with 263 courses) were included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low-Risk Group | Feasibility and Toxicity of Administering Vinblastine With Induction Chemotherapy for Patients With Metastatic Disease as Measured by the Percentage of Courses Delayed for More Than 7 Days Due to Toxicity | 3.8 Percentage of courses delayed |
Secondary
Growth Hormone Secretion
Growth hormone secretion was measured in consenting intermediate risk patients at the end of induction therapy, the end of all therapy, and at 6, 12, 24, 36, 48, and 60 months off therapy. Mean growth hormone secretion values are reported by assessment time point. Please note the small numbers of participants with available data.
Time frame: End of induction therapy (approximately 16 weeks from start of treatment), end of therapy (approximately 48 weeks from start of treatment), and 6, 12, 24, 36, 48, and 60 months off therapy
Population: Growth hormone secretion was measured in consenting intermediate risk patients. No Intermediate Risk patients had data available at 12, 36, 48, and 60 months off therapy.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Intermediate-Risk Group | Growth Hormone Secretion | End of induction | 15.3 ng/mL | Standard Deviation 9.7 |
| Intermediate-Risk Group | Growth Hormone Secretion | 24-months off therapy | 9.2 ng/mL | Standard Deviation 6.5 |
| Intermediate-Risk Group | Growth Hormone Secretion | End of therapy | 13.4 ng/mL | Standard Deviation 6.2 |
| Intermediate-Risk Group | Growth Hormone Secretion | 6-months off therapy | 7.3 ng/mL | Standard Deviation 2.9 |
Secondary
Methotrexate AUC0-66h in Induction Cycle 1
Methotrexate plasma concentration-time data are collected after the start of methotrexate infusion in induction cycle 1. Population parameters and inter-subject variability are estimated. Individual estimates of methotrexate AUC0-66h (area under concentration curve from time 0 to 66 hours post-dose) are obtained using post hoc analysis.
Time frame: Pre-infusion and 6, 23, 42, 66 hours from start of MTX
Population: Eligible patients who received methotrexate during induction cycle 1 and had samples collected for PK analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Low-Risk Group | Methotrexate AUC0-66h in Induction Cycle 1 | 1797 µmol·h/L |
| Intermediate-Risk Group | Methotrexate AUC0-66h in Induction Cycle 1 | 1813 µmol·h/L |
| High-Risk Group | Methotrexate AUC0-66h in Induction Cycle 1 | 1821 µmol·h/L |
Secondary
Methotrexate AUC0-66h in Induction Cycle 2
Methotrexate plasma concentration-time data are collected after the start of methotrexate infusion in induction cycle 2. Population parameters and inter-subject variability are estimated. Individual estimates of methotrexate AUC0-66h (area under concentration curve from time 0 to 66 hours post-dose) are obtained using post hoc analysis.
Time frame: Pre-infusion and 6, 23, 42, 66 hours from start of MTX
Population: Eligible patients who received methotrexate during induction cycle 2 and had samples collected for PK analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Low-Risk Group | Methotrexate AUC0-66h in Induction Cycle 2 | 1900 µmol·h/L |
| Intermediate-Risk Group | Methotrexate AUC0-66h in Induction Cycle 2 | 1902 µmol·h/L |
| High-Risk Group | Methotrexate AUC0-66h in Induction Cycle 2 | 1879 µmol·h/L |
Secondary
Methotrexate AUC0-66h in Induction Cycle 3
Methotrexate plasma concentration-time data are collected after the start of methotrexate infusion in induction cycle 3. Population parameters and inter-subject variability are estimated. Individual estimates of methotrexate AUC0-66h (area under concentration curve from time 0 to 66 hours post-dose) are obtained using post hoc analysis.
Time frame: Pre-infusion and 6, 23, 42, 66 hours from start of MTX
Population: Eligible patients who received methotrexate during induction cycle 3 and had samples collected for PK analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Low-Risk Group | Methotrexate AUC0-66h in Induction Cycle 3 | 1872 µmol·h/L |
| Intermediate-Risk Group | Methotrexate AUC0-66h in Induction Cycle 3 | 1879 µmol·h/L |
| High-Risk Group | Methotrexate AUC0-66h in Induction Cycle 3 | 1831 µmol·h/L |
Secondary
Methotrexate AUC0-66h in Induction Cycle 4
Methotrexate plasma concentration-time data are collected after the start of methotrexate infusion in induction cycle 4. Population parameters and inter-subject variability are estimated. Individual estimates of methotrexate AUC0-66h (area under concentration curve from time 0 to 66 hours post-dose) are obtained using post hoc analysis.
Time frame: Pre-infusion and 6, 23, 42, 66 hours from start of MTX
Population: Eligible patients who received methotrexate during induction cycle 4 and had samples collected for PK analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Low-Risk Group | Methotrexate AUC0-66h in Induction Cycle 4 | 1804 µmol·h/L |
| Intermediate-Risk Group | Methotrexate AUC0-66h in Induction Cycle 4 | 1841 µmol·h/L |
| High-Risk Group | Methotrexate AUC0-66h in Induction Cycle 4 | 1886 µmol·h/L |
Secondary
Methotrexate Clearance in Induction Cycle 1
Methotrexate plasma concentration-time data are collected after the start of methotrexate infusion in induction cycle 1. Population parameters and inter-subject variability are estimated. Individual estimates of methotrexate clearance are obtained using post hoc analysis.
Time frame: Pre-infusion and 6, 23, 42, 66 hours from start of Methotrexate (MTX)
Population: Eligible patients who received methotrexate during induction cycle 1 and had samples collected for PK analysis
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Low-Risk Group | Methotrexate Clearance in Induction Cycle 1 | 5.69 L/h/m^2 |
| Intermediate-Risk Group | Methotrexate Clearance in Induction Cycle 1 | 6.06 L/h/m^2 |
| High-Risk Group | Methotrexate Clearance in Induction Cycle 1 | 5.65 L/h/m^2 |
Secondary
Methotrexate Clearance in Induction Cycle 2
Methotrexate plasma concentration-time data are collected after the start of methotrexate infusion in induction cycle 2. Population parameters and inter-subject variability are estimated. Individual estimates of methotrexate clearance are obtained using post hoc analysis.
Time frame: Pre-infusion and 6, 23, 42, 66 hours from start of MTX
Population: Eligible patients who received methotrexate during induction cycle 2 and had samples collected for PK analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Low-Risk Group | Methotrexate Clearance in Induction Cycle 2 | 5.47 L/h/m^2 |
| Intermediate-Risk Group | Methotrexate Clearance in Induction Cycle 2 | 5.70 L/h/m^2 |
| High-Risk Group | Methotrexate Clearance in Induction Cycle 2 | 5.70 L/h/m^2 |
Secondary
Methotrexate Clearance in Induction Cycle 3
Methotrexate plasma concentration-time data are collected after the start of methotrexate infusion in induction cycle 3. Population parameters and inter-subject variability are estimated. Individual estimates of methotrexate clearance are obtained using post hoc analysis.
Time frame: Pre-infusion and 6, 23, 42, 66 hours from start of MTX
Population: Eligible patients who received methotrexate during induction cycle 3 and had samples collected for PK analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Low-Risk Group | Methotrexate Clearance in Induction Cycle 3 | 5.68 L/h/m^2 |
| Intermediate-Risk Group | Methotrexate Clearance in Induction Cycle 3 | 5.78 L/h/m^2 |
| High-Risk Group | Methotrexate Clearance in Induction Cycle 3 | 5.81 L/h/m^2 |
Secondary
Methotrexate Clearance in Induction Cycle 4
Methotrexate plasma concentration-time data are collected after the start of methotrexate infusion in induction cycle 4. Population parameters and inter-subject variability are estimated. Individual estimates of methotrexate clearance are obtained using post hoc analysis.
Time frame: Pre-infusion and 6, 23, 42, 66 hours from start of MTX
Population: Eligible patients who received methotrexate during induction cycle 4 and had samples collected for PK analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Low-Risk Group | Methotrexate Clearance in Induction Cycle 4 | 5.75 L/h/m^2 |
| Intermediate-Risk Group | Methotrexate Clearance in Induction Cycle 4 | 5.89 L/h/m^2 |
| High-Risk Group | Methotrexate Clearance in Induction Cycle 4 | 5.79 L/h/m^2 |
Secondary
Methotrexate Concentration at 42 Hours Post-dose in Induction Cycle 1
Methotrexate plasma concentration-time data are collected after the start of methotrexate infusion in induction cycle 1. Population parameters and inter-subject variability are estimated. Individual estimates of methotrexate concentration at 42 hours post-dose are obtained using post hoc analysis.
Time frame: 42 hours from start of MTX
Population: Eligible patients who received methotrexate during induction cycle 1 and had samples collected for PK analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Low-Risk Group | Methotrexate Concentration at 42 Hours Post-dose in Induction Cycle 1 | 0.49 µmol/L |
| Intermediate-Risk Group | Methotrexate Concentration at 42 Hours Post-dose in Induction Cycle 1 | 0.57 µmol/L |
| High-Risk Group | Methotrexate Concentration at 42 Hours Post-dose in Induction Cycle 1 | 0.61 µmol/L |
Secondary
Methotrexate Concentration at 42 Hours Post-dose in Induction Cycle 2
Methotrexate plasma concentration-time data are collected after the start of methotrexate infusion in induction cycle 2. Population parameters and inter-subject variability are estimated. Individual estimates of methotrexate concentration at 42 hours post-dose are obtained using post hoc analysis.
Time frame: 42 hours from start of MTX
Population: Eligible patients who received methotrexate during induction cycle 2 and had samples collected for PK analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Low-Risk Group | Methotrexate Concentration at 42 Hours Post-dose in Induction Cycle 2 | 0.75 µmol/L |
| Intermediate-Risk Group | Methotrexate Concentration at 42 Hours Post-dose in Induction Cycle 2 | 0.72 µmol/L |
| High-Risk Group | Methotrexate Concentration at 42 Hours Post-dose in Induction Cycle 2 | 0.69 µmol/L |
Secondary
Methotrexate Concentration at 42 Hours Post-dose in Induction Cycle 3
Methotrexate plasma concentration-time data are collected after the start of methotrexate infusion in induction cycle 3. Population parameters and inter-subject variability are estimated. Individual estimates of methotrexate concentration at 42 hours post-dose are obtained using post hoc analysis.
Time frame: 42 hours from start of MTX
Population: Eligible patients who received methotrexate during induction cycle 3 and had samples collected for PK analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Low-Risk Group | Methotrexate Concentration at 42 Hours Post-dose in Induction Cycle 3 | 0.65 µmol/L |
| Intermediate-Risk Group | Methotrexate Concentration at 42 Hours Post-dose in Induction Cycle 3 | 0.70 µmol/L |
| High-Risk Group | Methotrexate Concentration at 42 Hours Post-dose in Induction Cycle 3 | 0.58 µmol/L |
Secondary
Methotrexate Concentration at 42 Hours Post-dose in Induction Cycle 4
Methotrexate plasma concentration-time data are collected after the start of methotrexate infusion in induction cycle 4. Population parameters and inter-subject variability are estimated. Individual estimates of methotrexate concentration at 42 hours post-dose are obtained using post hoc analysis.
Time frame: 42 hours from start of MTX
Population: Eligible patients who received methotrexate during induction cycle 4 and had samples collected for PK analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Low-Risk Group | Methotrexate Concentration at 42 Hours Post-dose in Induction Cycle 4 | 0.64 µmol/L |
| Intermediate-Risk Group | Methotrexate Concentration at 42 Hours Post-dose in Induction Cycle 4 | 0.64 µmol/L |
| High-Risk Group | Methotrexate Concentration at 42 Hours Post-dose in Induction Cycle 4 | 0.55 µmol/L |
Secondary
Methotrexate Volume of Central Compartment in Induction Cycle 1
Methotrexate plasma concentration-time data are collected after the start of methotrexate infusion in induction cycle 1. Population parameters and inter-subject variability are estimated. Individual estimates of methotrexate volume of central compartment are obtained using post hoc analysis.
Time frame: Pre-infusion and 6, 23, 42, 66 hours from start of MTX
Population: Eligible patients who received methotrexate during induction cycle 1 and had samples collected for PK analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Low-Risk Group | Methotrexate Volume of Central Compartment in Induction Cycle 1 | 11.63 L/m^2 |
| Intermediate-Risk Group | Methotrexate Volume of Central Compartment in Induction Cycle 1 | 13.70 L/m^2 |
| High-Risk Group | Methotrexate Volume of Central Compartment in Induction Cycle 1 | 13.25 L/m^2 |
Secondary
Methotrexate Volume of Central Compartment in Induction Cycle 2
Methotrexate plasma concentration-time data are collected after the start of methotrexate infusion in induction cycle 2. Population parameters and inter-subject variability are estimated. Individual estimates of methotrexate volume of central compartment are obtained using post hoc analysis.
Time frame: Pre-infusion and 6, 23, 42, 66 hours from start of MTX
Population: Eligible patients who received methotrexate during induction cycle 2 and had samples collected for PK analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Low-Risk Group | Methotrexate Volume of Central Compartment in Induction Cycle 2 | 13.77 L/m^2 |
| Intermediate-Risk Group | Methotrexate Volume of Central Compartment in Induction Cycle 2 | 13.73 L/m^2 |
| High-Risk Group | Methotrexate Volume of Central Compartment in Induction Cycle 2 | 13.62 L/m^2 |
Secondary
Methotrexate Volume of Central Compartment in Induction Cycle 3
Methotrexate plasma concentration-time data are collected after the start of methotrexate infusion in induction cycle 3. Population parameters and inter-subject variability are estimated. Individual estimates of methotrexate volume of central compartment are obtained using post hoc analysis.
Time frame: Pre-infusion and 6, 23, 42, 66 hours from start of MTX
Population: Eligible patients who received methotrexate during induction cycle 3 and had samples collected for PK analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Low-Risk Group | Methotrexate Volume of Central Compartment in Induction Cycle 3 | 12.70 L/m^2 |
| Intermediate-Risk Group | Methotrexate Volume of Central Compartment in Induction Cycle 3 | 13.55 L/m^2 |
| High-Risk Group | Methotrexate Volume of Central Compartment in Induction Cycle 3 | 13.87 L/m^2 |
Secondary
Methotrexate Volume of Central Compartment in Induction Cycle 4
Methotrexate plasma concentration-time data are collected after the start of methotrexate infusion in induction cycle 4. Population parameters and inter-subject variability are estimated. Individual estimates of methotrexate volume of central compartment are obtained using post hoc analysis.
Time frame: Pre-infusion and 6, 23, 42, 66 hours from start of MTX
Population: Eligible patients who received methotrexate during induction cycle 4 and had samples collected for PK analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Low-Risk Group | Methotrexate Volume of Central Compartment in Induction Cycle 4 | 12.64 L/m^2 |
| Intermediate-Risk Group | Methotrexate Volume of Central Compartment in Induction Cycle 4 | 13.31 L/m^2 |
| High-Risk Group | Methotrexate Volume of Central Compartment in Induction Cycle 4 | 13.68 L/m^2 |
Secondary
Neurocognitive Performance Related to Attention as Measured by Attention Problems T-scores
Scores measuring attention were obtained from the Attention Problems T-score on the BASC-2 instrument which is a parent report. Higher scores indicate more attention problems. The normative mean is 50 with a standard deviation of 10.
Time frame: Baseline, prior to maintenance therapy, completion of therapy, and 12 months, 24 months, 36 months, 48 months, and 60 months off therapy
Population: Eligible patients with scores at any of the data collection timepoints were included. Sample sizes differ across timepoints as not all subjects had scores for all timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low-Risk Group | Neurocognitive Performance Related to Attention as Measured by Attention Problems T-scores | Baseline | 51.7 score on a scale | Standard Deviation 10.9 |
| Low-Risk Group | Neurocognitive Performance Related to Attention as Measured by Attention Problems T-scores | Prior to Maintenance Therapy | 53.5 score on a scale | Standard Deviation 9.5 |
| Low-Risk Group | Neurocognitive Performance Related to Attention as Measured by Attention Problems T-scores | Completion of Therapy | 52.6 score on a scale | Standard Deviation 8.6 |
| Low-Risk Group | Neurocognitive Performance Related to Attention as Measured by Attention Problems T-scores | 12 Months Off Therapy | 56.2 score on a scale | Standard Deviation 10.1 |
| Low-Risk Group | Neurocognitive Performance Related to Attention as Measured by Attention Problems T-scores | 24 Months Off Therapy | 54.5 score on a scale | Standard Deviation 10.6 |
| Low-Risk Group | Neurocognitive Performance Related to Attention as Measured by Attention Problems T-scores | 36 Months Off Therapy | 53.3 score on a scale | Standard Deviation 8.3 |
| Low-Risk Group | Neurocognitive Performance Related to Attention as Measured by Attention Problems T-scores | 48 Months Off Therapy | 56.4 score on a scale | Standard Deviation 10.4 |
| Low-Risk Group | Neurocognitive Performance Related to Attention as Measured by Attention Problems T-scores | 60 Months Off Therapy | 51.9 score on a scale | Standard Deviation 11.5 |
| Intermediate-Risk Group | Neurocognitive Performance Related to Attention as Measured by Attention Problems T-scores | Completion of Therapy | 50.9 score on a scale | Standard Deviation 9.4 |
| Intermediate-Risk Group | Neurocognitive Performance Related to Attention as Measured by Attention Problems T-scores | 48 Months Off Therapy | 55.5 score on a scale | Standard Deviation 10.1 |
| Intermediate-Risk Group | Neurocognitive Performance Related to Attention as Measured by Attention Problems T-scores | 12 Months Off Therapy | 53.9 score on a scale | Standard Deviation 10.2 |
| Intermediate-Risk Group | Neurocognitive Performance Related to Attention as Measured by Attention Problems T-scores | 24 Months Off Therapy | 55.3 score on a scale | Standard Deviation 10.1 |
| Intermediate-Risk Group | Neurocognitive Performance Related to Attention as Measured by Attention Problems T-scores | 36 Months Off Therapy | 55.1 score on a scale | Standard Deviation 9.8 |
| Intermediate-Risk Group | Neurocognitive Performance Related to Attention as Measured by Attention Problems T-scores | Baseline | 49.6 score on a scale | Standard Deviation 9.5 |
| Intermediate-Risk Group | Neurocognitive Performance Related to Attention as Measured by Attention Problems T-scores | Prior to Maintenance Therapy | 51.3 score on a scale | Standard Deviation 9.9 |
| Intermediate-Risk Group | Neurocognitive Performance Related to Attention as Measured by Attention Problems T-scores | 60 Months Off Therapy | 57.7 score on a scale | Standard Deviation 12 |
| High-Risk Group | Neurocognitive Performance Related to Attention as Measured by Attention Problems T-scores | Completion of Therapy | 43.3 score on a scale | Standard Deviation 12.7 |
| High-Risk Group | Neurocognitive Performance Related to Attention as Measured by Attention Problems T-scores | Prior to Maintenance Therapy | 52.4 score on a scale | Standard Deviation 4.6 |
| High-Risk Group | Neurocognitive Performance Related to Attention as Measured by Attention Problems T-scores | Baseline | 49.2 score on a scale | Standard Deviation 9.1 |
| High-Risk Group | Neurocognitive Performance Related to Attention as Measured by Attention Problems T-scores | 12 Months Off Therapy | 53.9 score on a scale | Standard Deviation 13 |
| High-Risk Group | Neurocognitive Performance Related to Attention as Measured by Attention Problems T-scores | 48 Months Off Therapy | 55.3 score on a scale | Standard Deviation 10.3 |
| High-Risk Group | Neurocognitive Performance Related to Attention as Measured by Attention Problems T-scores | 36 Months Off Therapy | 53.3 score on a scale | Standard Deviation 12.2 |
| High-Risk Group | Neurocognitive Performance Related to Attention as Measured by Attention Problems T-scores | 24 Months Off Therapy | 49.8 score on a scale | Standard Deviation 12.6 |
| High-Risk Group | Neurocognitive Performance Related to Attention as Measured by Attention Problems T-scores | 60 Months Off Therapy | 58.8 score on a scale | Standard Deviation 12.5 |
Secondary
Neurocognitive Performance Related to Executive Functioning as Measured by Global Executive Composite T-scores
Scores measuring executive functioning were obtained from Global Executive Composite (GEC) T-scores, which were obtained from the Behavior Rating Inventory of Executive Function (BRIEF) instrument which is a parent report. Higher scores indicate more problems. The normative mean is 50 with a standard deviation of 10.
Time frame: Baseline, prior to maintenance therapy, completion of therapy, and 12 months, 24 months, 36 months, 48 months, and 60 months off therapy
Population: Eligible patients with scores at any of the data collection timepoints were included. Sample sizes differ across timepoints as not all subjects had scores for all timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low-Risk Group | Neurocognitive Performance Related to Executive Functioning as Measured by Global Executive Composite T-scores | 60 Months Off Therapy | 55.1 score on a scale | Standard Deviation 11.8 |
| Low-Risk Group | Neurocognitive Performance Related to Executive Functioning as Measured by Global Executive Composite T-scores | Baseline | 59.2 score on a scale | Standard Deviation 16 |
| Low-Risk Group | Neurocognitive Performance Related to Executive Functioning as Measured by Global Executive Composite T-scores | 12 Months Off Therapy | 57.9 score on a scale | Standard Deviation 13.7 |
| Low-Risk Group | Neurocognitive Performance Related to Executive Functioning as Measured by Global Executive Composite T-scores | 48 Months Off Therapy | 60.3 score on a scale | Standard Deviation 16.8 |
| Low-Risk Group | Neurocognitive Performance Related to Executive Functioning as Measured by Global Executive Composite T-scores | Prior to Maintenance Therapy | 54.3 score on a scale | Standard Deviation 9.9 |
| Low-Risk Group | Neurocognitive Performance Related to Executive Functioning as Measured by Global Executive Composite T-scores | 24 Months Off Therapy | 59.9 score on a scale | Standard Deviation 16.5 |
| Low-Risk Group | Neurocognitive Performance Related to Executive Functioning as Measured by Global Executive Composite T-scores | Completion of Therapy | 55.3 score on a scale | Standard Deviation 11.9 |
| Low-Risk Group | Neurocognitive Performance Related to Executive Functioning as Measured by Global Executive Composite T-scores | 36 Months Off Therapy | 55.7 score on a scale | Standard Deviation 12.8 |
| Intermediate-Risk Group | Neurocognitive Performance Related to Executive Functioning as Measured by Global Executive Composite T-scores | Prior to Maintenance Therapy | 52.5 score on a scale | Standard Deviation 12.3 |
| Intermediate-Risk Group | Neurocognitive Performance Related to Executive Functioning as Measured by Global Executive Composite T-scores | Baseline | 49.6 score on a scale | Standard Deviation 9.7 |
| Intermediate-Risk Group | Neurocognitive Performance Related to Executive Functioning as Measured by Global Executive Composite T-scores | 48 Months Off Therapy | 55.6 score on a scale | Standard Deviation 11.7 |
| Intermediate-Risk Group | Neurocognitive Performance Related to Executive Functioning as Measured by Global Executive Composite T-scores | 60 Months Off Therapy | 58.3 score on a scale | Standard Deviation 15 |
| Intermediate-Risk Group | Neurocognitive Performance Related to Executive Functioning as Measured by Global Executive Composite T-scores | 36 Months Off Therapy | 57.7 score on a scale | Standard Deviation 11.8 |
| Intermediate-Risk Group | Neurocognitive Performance Related to Executive Functioning as Measured by Global Executive Composite T-scores | Completion of Therapy | 50.6 score on a scale | Standard Deviation 10.1 |
| Intermediate-Risk Group | Neurocognitive Performance Related to Executive Functioning as Measured by Global Executive Composite T-scores | 12 Months Off Therapy | 56.5 score on a scale | Standard Deviation 14.3 |
| Intermediate-Risk Group | Neurocognitive Performance Related to Executive Functioning as Measured by Global Executive Composite T-scores | 24 Months Off Therapy | 55.1 score on a scale | Standard Deviation 13.6 |
| High-Risk Group | Neurocognitive Performance Related to Executive Functioning as Measured by Global Executive Composite T-scores | 60 Months Off Therapy | 55.2 score on a scale | Standard Deviation 13.4 |
| High-Risk Group | Neurocognitive Performance Related to Executive Functioning as Measured by Global Executive Composite T-scores | Baseline | 52.4 score on a scale | Standard Deviation 13.1 |
| High-Risk Group | Neurocognitive Performance Related to Executive Functioning as Measured by Global Executive Composite T-scores | Prior to Maintenance Therapy | 49.3 score on a scale | Standard Deviation 11.9 |
| High-Risk Group | Neurocognitive Performance Related to Executive Functioning as Measured by Global Executive Composite T-scores | Completion of Therapy | 45.3 score on a scale | Standard Deviation 14.7 |
| High-Risk Group | Neurocognitive Performance Related to Executive Functioning as Measured by Global Executive Composite T-scores | 12 Months Off Therapy | 60.1 score on a scale | Standard Deviation 20 |
| High-Risk Group | Neurocognitive Performance Related to Executive Functioning as Measured by Global Executive Composite T-scores | 24 Months Off Therapy | 52.1 score on a scale | Standard Deviation 9.6 |
| High-Risk Group | Neurocognitive Performance Related to Executive Functioning as Measured by Global Executive Composite T-scores | 36 Months Off Therapy | 58.2 score on a scale | Standard Deviation 11.1 |
| High-Risk Group | Neurocognitive Performance Related to Executive Functioning as Measured by Global Executive Composite T-scores | 48 Months Off Therapy | 49.5 score on a scale | Standard Deviation 10.6 |
Secondary
Neurocognitive Performance Related to Global Cognitive Functioning as Measured by Cognitive Composite Scores and Estimated IQ Scores
Global cognitive functioning was measured based on Cognitive Composite Scores from the Bayley III instrument for subjects \<3 years of age and on estimated IQ scores from the Stanford Binet V instrument for subjects ≥3 years of age. Higher scores indicate better performance. The normative mean is 100 with a standard deviation of 15.
Time frame: Baseline, prior to maintenance therapy, completion of therapy, and 12 months, 24 months, 36 months, 48 months, and 60 months off therapy
Population: Eligible patients with scores at any of the data collection timepoints were included. Sample sizes differ across timepoints as not all subjects had scores for all timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low-Risk Group | Neurocognitive Performance Related to Global Cognitive Functioning as Measured by Cognitive Composite Scores and Estimated IQ Scores | Completion of Therapy | 85.8 score on a scale | Standard Deviation 17.5 |
| Low-Risk Group | Neurocognitive Performance Related to Global Cognitive Functioning as Measured by Cognitive Composite Scores and Estimated IQ Scores | 36 Months Off Therapy | 92.4 score on a scale | Standard Deviation 26 |
| Low-Risk Group | Neurocognitive Performance Related to Global Cognitive Functioning as Measured by Cognitive Composite Scores and Estimated IQ Scores | 24 Months Off Therapy | 97.6 score on a scale | Standard Deviation 16.7 |
| Low-Risk Group | Neurocognitive Performance Related to Global Cognitive Functioning as Measured by Cognitive Composite Scores and Estimated IQ Scores | 12 Months Off Therapy | 89.2 score on a scale | Standard Deviation 21.3 |
| Low-Risk Group | Neurocognitive Performance Related to Global Cognitive Functioning as Measured by Cognitive Composite Scores and Estimated IQ Scores | 60 Months Off Therapy | 82.0 score on a scale | Standard Deviation 25.6 |
| Low-Risk Group | Neurocognitive Performance Related to Global Cognitive Functioning as Measured by Cognitive Composite Scores and Estimated IQ Scores | Prior to Maintenance Therapy | 91.1 score on a scale | Standard Deviation 16.8 |
| Low-Risk Group | Neurocognitive Performance Related to Global Cognitive Functioning as Measured by Cognitive Composite Scores and Estimated IQ Scores | Baseline | 88.6 score on a scale | Standard Deviation 17.6 |
| Low-Risk Group | Neurocognitive Performance Related to Global Cognitive Functioning as Measured by Cognitive Composite Scores and Estimated IQ Scores | 48 Months Off Therapy | 85.3 score on a scale | Standard Deviation 24.1 |
| Intermediate-Risk Group | Neurocognitive Performance Related to Global Cognitive Functioning as Measured by Cognitive Composite Scores and Estimated IQ Scores | 60 Months Off Therapy | 85.3 score on a scale | Standard Deviation 17.9 |
| Intermediate-Risk Group | Neurocognitive Performance Related to Global Cognitive Functioning as Measured by Cognitive Composite Scores and Estimated IQ Scores | Baseline | 91.0 score on a scale | Standard Deviation 15.4 |
| Intermediate-Risk Group | Neurocognitive Performance Related to Global Cognitive Functioning as Measured by Cognitive Composite Scores and Estimated IQ Scores | Prior to Maintenance Therapy | 92.3 score on a scale | Standard Deviation 15.1 |
| Intermediate-Risk Group | Neurocognitive Performance Related to Global Cognitive Functioning as Measured by Cognitive Composite Scores and Estimated IQ Scores | Completion of Therapy | 93.4 score on a scale | Standard Deviation 15.3 |
| Intermediate-Risk Group | Neurocognitive Performance Related to Global Cognitive Functioning as Measured by Cognitive Composite Scores and Estimated IQ Scores | 12 Months Off Therapy | 89.9 score on a scale | Standard Deviation 15.6 |
| Intermediate-Risk Group | Neurocognitive Performance Related to Global Cognitive Functioning as Measured by Cognitive Composite Scores and Estimated IQ Scores | 24 Months Off Therapy | 89.4 score on a scale | Standard Deviation 19 |
| Intermediate-Risk Group | Neurocognitive Performance Related to Global Cognitive Functioning as Measured by Cognitive Composite Scores and Estimated IQ Scores | 36 Months Off Therapy | 89.9 score on a scale | Standard Deviation 16.2 |
| Intermediate-Risk Group | Neurocognitive Performance Related to Global Cognitive Functioning as Measured by Cognitive Composite Scores and Estimated IQ Scores | 48 Months Off Therapy | 91.3 score on a scale | Standard Deviation 18.4 |
| High-Risk Group | Neurocognitive Performance Related to Global Cognitive Functioning as Measured by Cognitive Composite Scores and Estimated IQ Scores | 24 Months Off Therapy | 77.7 score on a scale | Standard Deviation 21 |
| High-Risk Group | Neurocognitive Performance Related to Global Cognitive Functioning as Measured by Cognitive Composite Scores and Estimated IQ Scores | Baseline | 87.4 score on a scale | Standard Deviation 22.3 |
| High-Risk Group | Neurocognitive Performance Related to Global Cognitive Functioning as Measured by Cognitive Composite Scores and Estimated IQ Scores | 36 Months Off Therapy | 81.3 score on a scale | Standard Deviation 17.4 |
| High-Risk Group | Neurocognitive Performance Related to Global Cognitive Functioning as Measured by Cognitive Composite Scores and Estimated IQ Scores | Prior to Maintenance Therapy | 94.8 score on a scale | Standard Deviation 19 |
| High-Risk Group | Neurocognitive Performance Related to Global Cognitive Functioning as Measured by Cognitive Composite Scores and Estimated IQ Scores | 60 Months Off Therapy | 71.5 score on a scale | Standard Deviation 18.4 |
| High-Risk Group | Neurocognitive Performance Related to Global Cognitive Functioning as Measured by Cognitive Composite Scores and Estimated IQ Scores | 12 Months Off Therapy | 83.3 score on a scale | Standard Deviation 18.3 |
| High-Risk Group | Neurocognitive Performance Related to Global Cognitive Functioning as Measured by Cognitive Composite Scores and Estimated IQ Scores | Completion of Therapy | 76.8 score on a scale | Standard Deviation 18.6 |
| High-Risk Group | Neurocognitive Performance Related to Global Cognitive Functioning as Measured by Cognitive Composite Scores and Estimated IQ Scores | 48 Months Off Therapy | 85.2 score on a scale | Standard Deviation 27.4 |
Secondary
Neurocognitive Performance Related to Processing Speed as Measured by Visual Matching Standard Scores
Scores measuring processing speed were obtained based on the visual matching standard score from the Woodcock Johnson III instrument. Higher scores indicate better performance. The normative mean is 100 with a standard deviation of 15.
Time frame: Baseline, prior to maintenance therapy, completion of therapy, and 12 months, 24 months, 36 months, 48 months, and 60 months off therapy
Population: Eligible patients with scores at any of the data collection timepoints were included. Sample sizes differ across timepoints as not all subjects had scores for all timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low-Risk Group | Neurocognitive Performance Related to Processing Speed as Measured by Visual Matching Standard Scores | Baseline | 119.0 score on a scale | — |
| Low-Risk Group | Neurocognitive Performance Related to Processing Speed as Measured by Visual Matching Standard Scores | Prior to Maintenance Therapy | 89.0 score on a scale | — |
| Low-Risk Group | Neurocognitive Performance Related to Processing Speed as Measured by Visual Matching Standard Scores | Completion of Therapy | 105.3 score on a scale | Standard Deviation 20.2 |
| Low-Risk Group | Neurocognitive Performance Related to Processing Speed as Measured by Visual Matching Standard Scores | 12 Months Off Therapy | 96.8 score on a scale | Standard Deviation 9.8 |
| Low-Risk Group | Neurocognitive Performance Related to Processing Speed as Measured by Visual Matching Standard Scores | 24 Months Off Therapy | 98.4 score on a scale | Standard Deviation 16.6 |
| Low-Risk Group | Neurocognitive Performance Related to Processing Speed as Measured by Visual Matching Standard Scores | 36 Months Off Therapy | 101.6 score on a scale | Standard Deviation 15.8 |
| Low-Risk Group | Neurocognitive Performance Related to Processing Speed as Measured by Visual Matching Standard Scores | 48 Months Off Therapy | 93.2 score on a scale | Standard Deviation 23.9 |
| Low-Risk Group | Neurocognitive Performance Related to Processing Speed as Measured by Visual Matching Standard Scores | 60 Months Off Therapy | 86.3 score on a scale | Standard Deviation 36.2 |
| Intermediate-Risk Group | Neurocognitive Performance Related to Processing Speed as Measured by Visual Matching Standard Scores | Completion of Therapy | 100.2 score on a scale | Standard Deviation 15.2 |
| Intermediate-Risk Group | Neurocognitive Performance Related to Processing Speed as Measured by Visual Matching Standard Scores | 12 Months Off Therapy | 93.1 score on a scale | Standard Deviation 13.3 |
| Intermediate-Risk Group | Neurocognitive Performance Related to Processing Speed as Measured by Visual Matching Standard Scores | 24 Months Off Therapy | 90.2 score on a scale | Standard Deviation 15.3 |
| Intermediate-Risk Group | Neurocognitive Performance Related to Processing Speed as Measured by Visual Matching Standard Scores | 36 Months Off Therapy | 89.7 score on a scale | Standard Deviation 20.2 |
| Intermediate-Risk Group | Neurocognitive Performance Related to Processing Speed as Measured by Visual Matching Standard Scores | Baseline | 96.5 score on a scale | Standard Deviation 11 |
| Intermediate-Risk Group | Neurocognitive Performance Related to Processing Speed as Measured by Visual Matching Standard Scores | Prior to Maintenance Therapy | 97.6 score on a scale | Standard Deviation 12.3 |
| Intermediate-Risk Group | Neurocognitive Performance Related to Processing Speed as Measured by Visual Matching Standard Scores | 60 Months Off Therapy | 84.6 score on a scale | Standard Deviation 17.1 |
| Intermediate-Risk Group | Neurocognitive Performance Related to Processing Speed as Measured by Visual Matching Standard Scores | 48 Months Off Therapy | 87.6 score on a scale | Standard Deviation 14.7 |
| High-Risk Group | Neurocognitive Performance Related to Processing Speed as Measured by Visual Matching Standard Scores | Prior to Maintenance Therapy | 109.5 score on a scale | Standard Deviation 2.1 |
| High-Risk Group | Neurocognitive Performance Related to Processing Speed as Measured by Visual Matching Standard Scores | 12 Months Off Therapy | 71.0 score on a scale | — |
| High-Risk Group | Neurocognitive Performance Related to Processing Speed as Measured by Visual Matching Standard Scores | 48 Months Off Therapy | 78.7 score on a scale | Standard Deviation 17 |
| High-Risk Group | Neurocognitive Performance Related to Processing Speed as Measured by Visual Matching Standard Scores | Baseline | 107.0 score on a scale | — |
| High-Risk Group | Neurocognitive Performance Related to Processing Speed as Measured by Visual Matching Standard Scores | 24 Months Off Therapy | 89.3 score on a scale | Standard Deviation 13.3 |
| High-Risk Group | Neurocognitive Performance Related to Processing Speed as Measured by Visual Matching Standard Scores | 60 Months Off Therapy | 65.0 score on a scale | — |
| High-Risk Group | Neurocognitive Performance Related to Processing Speed as Measured by Visual Matching Standard Scores | 36 Months Off Therapy | 89.8 score on a scale | Standard Deviation 12.4 |
Secondary
Neurocognitive Performance Related to Verbal Fluency as Measured by Retrieval Fluency Standard Scores
Scores measuring verbal fluency were obtained from Retrieval Fluency standard scores on the Woodcock Johnson III instrument. Higher scores indicate better performance. The normative mean is 100 with a standard deviation of 15.
Time frame: Baseline, prior to maintenance therapy, completion of therapy, and 12 months, 24 months, 36 months, 48 months, and 60 months off therapy
Population: Eligible patients with scores at any of the data collection timepoints were included. Sample sizes differ across timepoints as not all subjects had scores for all timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low-Risk Group | Neurocognitive Performance Related to Verbal Fluency as Measured by Retrieval Fluency Standard Scores | 60 Months Off Therapy | 81.9 score on a scale | Standard Deviation 22.1 |
| Low-Risk Group | Neurocognitive Performance Related to Verbal Fluency as Measured by Retrieval Fluency Standard Scores | 24 Months Off Therapy | 98.8 score on a scale | Standard Deviation 9.7 |
| Low-Risk Group | Neurocognitive Performance Related to Verbal Fluency as Measured by Retrieval Fluency Standard Scores | Baseline | 117.0 score on a scale | — |
| Low-Risk Group | Neurocognitive Performance Related to Verbal Fluency as Measured by Retrieval Fluency Standard Scores | 48 Months Off Therapy | 77.1 score on a scale | Standard Deviation 16 |
| Low-Risk Group | Neurocognitive Performance Related to Verbal Fluency as Measured by Retrieval Fluency Standard Scores | 36 Months Off Therapy | 100.2 score on a scale | Standard Deviation 13.3 |
| Low-Risk Group | Neurocognitive Performance Related to Verbal Fluency as Measured by Retrieval Fluency Standard Scores | Prior to Maintenance Therapy | 97.0 score on a scale | Standard Deviation 5.7 |
| Low-Risk Group | Neurocognitive Performance Related to Verbal Fluency as Measured by Retrieval Fluency Standard Scores | 12 Months Off Therapy | 94.8 score on a scale | Standard Deviation 11.4 |
| Low-Risk Group | Neurocognitive Performance Related to Verbal Fluency as Measured by Retrieval Fluency Standard Scores | Completion of Therapy | 90.0 score on a scale | Standard Deviation 13.2 |
| Intermediate-Risk Group | Neurocognitive Performance Related to Verbal Fluency as Measured by Retrieval Fluency Standard Scores | 24 Months Off Therapy | 82.5 score on a scale | Standard Deviation 20.6 |
| Intermediate-Risk Group | Neurocognitive Performance Related to Verbal Fluency as Measured by Retrieval Fluency Standard Scores | Baseline | 87.7 score on a scale | Standard Deviation 18.4 |
| Intermediate-Risk Group | Neurocognitive Performance Related to Verbal Fluency as Measured by Retrieval Fluency Standard Scores | Prior to Maintenance Therapy | 89.4 score on a scale | Standard Deviation 13.4 |
| Intermediate-Risk Group | Neurocognitive Performance Related to Verbal Fluency as Measured by Retrieval Fluency Standard Scores | Completion of Therapy | 95.3 score on a scale | Standard Deviation 14.4 |
| Intermediate-Risk Group | Neurocognitive Performance Related to Verbal Fluency as Measured by Retrieval Fluency Standard Scores | 12 Months Off Therapy | 86.1 score on a scale | Standard Deviation 19.9 |
| Intermediate-Risk Group | Neurocognitive Performance Related to Verbal Fluency as Measured by Retrieval Fluency Standard Scores | 36 Months Off Therapy | 88.1 score on a scale | Standard Deviation 24.9 |
| Intermediate-Risk Group | Neurocognitive Performance Related to Verbal Fluency as Measured by Retrieval Fluency Standard Scores | 48 Months Off Therapy | 88.7 score on a scale | Standard Deviation 16 |
| Intermediate-Risk Group | Neurocognitive Performance Related to Verbal Fluency as Measured by Retrieval Fluency Standard Scores | 60 Months Off Therapy | 87.9 score on a scale | Standard Deviation 16.4 |
| High-Risk Group | Neurocognitive Performance Related to Verbal Fluency as Measured by Retrieval Fluency Standard Scores | 60 Months Off Therapy | 70.3 score on a scale | Standard Deviation 23.7 |
| High-Risk Group | Neurocognitive Performance Related to Verbal Fluency as Measured by Retrieval Fluency Standard Scores | 48 Months Off Therapy | 95.7 score on a scale | Standard Deviation 15 |
| High-Risk Group | Neurocognitive Performance Related to Verbal Fluency as Measured by Retrieval Fluency Standard Scores | 12 Months Off Therapy | 87.0 score on a scale | Standard Deviation 1.4 |
| High-Risk Group | Neurocognitive Performance Related to Verbal Fluency as Measured by Retrieval Fluency Standard Scores | 36 Months Off Therapy | 81.4 score on a scale | Standard Deviation 14.9 |
| High-Risk Group | Neurocognitive Performance Related to Verbal Fluency as Measured by Retrieval Fluency Standard Scores | 24 Months Off Therapy | 90.8 score on a scale | Standard Deviation 4.6 |
Secondary
Neurocognitive Performance Related to Visual-spatial Reasoning as Measured by Visual Motor Integration (VMI) T-scores
Scores measuring visual-spatial reasoning were obtained from VMI T-scores on the Beery VMI instrument. Higher scores indicate better performance. The normative mean is 50 with standard deviation of 10.
Time frame: Baseline, prior to maintenance therapy, completion of therapy, and 12 months, 24 months, 36 months, 48 months, and 60 months off therapy
Population: Eligible patients with scores at any of the data collection timepoints were included. Sample sizes differ across timepoints as not all subjects had scores for all timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low-Risk Group | Neurocognitive Performance Related to Visual-spatial Reasoning as Measured by Visual Motor Integration (VMI) T-scores | Baseline | 62.0 score on a scale | — |
| Low-Risk Group | Neurocognitive Performance Related to Visual-spatial Reasoning as Measured by Visual Motor Integration (VMI) T-scores | Prior to Maintenance Therapy | 39.0 score on a scale | Standard Deviation 17 |
| Low-Risk Group | Neurocognitive Performance Related to Visual-spatial Reasoning as Measured by Visual Motor Integration (VMI) T-scores | Completion Of Therapy | 40.0 score on a scale | Standard Deviation 13.6 |
| Low-Risk Group | Neurocognitive Performance Related to Visual-spatial Reasoning as Measured by Visual Motor Integration (VMI) T-scores | 12 Months Off Therapy | 43.1 score on a scale | Standard Deviation 18.2 |
| Low-Risk Group | Neurocognitive Performance Related to Visual-spatial Reasoning as Measured by Visual Motor Integration (VMI) T-scores | 24 Months Off Therapy | 48.2 score on a scale | Standard Deviation 11.5 |
| Low-Risk Group | Neurocognitive Performance Related to Visual-spatial Reasoning as Measured by Visual Motor Integration (VMI) T-scores | 36 Months Off Therapy | 45.6 score on a scale | Standard Deviation 14.1 |
| Low-Risk Group | Neurocognitive Performance Related to Visual-spatial Reasoning as Measured by Visual Motor Integration (VMI) T-scores | 48 Months Off Therapy | 44.2 score on a scale | Standard Deviation 23.5 |
| Low-Risk Group | Neurocognitive Performance Related to Visual-spatial Reasoning as Measured by Visual Motor Integration (VMI) T-scores | 60 Months Off Therapy | 39.4 score on a scale | Standard Deviation 16.7 |
| Intermediate-Risk Group | Neurocognitive Performance Related to Visual-spatial Reasoning as Measured by Visual Motor Integration (VMI) T-scores | Completion Of Therapy | 48.5 score on a scale | Standard Deviation 8.6 |
| Intermediate-Risk Group | Neurocognitive Performance Related to Visual-spatial Reasoning as Measured by Visual Motor Integration (VMI) T-scores | 48 Months Off Therapy | 43.6 score on a scale | Standard Deviation 7.3 |
| Intermediate-Risk Group | Neurocognitive Performance Related to Visual-spatial Reasoning as Measured by Visual Motor Integration (VMI) T-scores | 12 Months Off Therapy | 43.8 score on a scale | Standard Deviation 11.1 |
| Intermediate-Risk Group | Neurocognitive Performance Related to Visual-spatial Reasoning as Measured by Visual Motor Integration (VMI) T-scores | 24 Months Off Therapy | 43.6 score on a scale | Standard Deviation 10.3 |
| Intermediate-Risk Group | Neurocognitive Performance Related to Visual-spatial Reasoning as Measured by Visual Motor Integration (VMI) T-scores | 36 Months Off Therapy | 41.3 score on a scale | Standard Deviation 8.9 |
| Intermediate-Risk Group | Neurocognitive Performance Related to Visual-spatial Reasoning as Measured by Visual Motor Integration (VMI) T-scores | Baseline | 47.5 score on a scale | Standard Deviation 16.3 |
| Intermediate-Risk Group | Neurocognitive Performance Related to Visual-spatial Reasoning as Measured by Visual Motor Integration (VMI) T-scores | Prior to Maintenance Therapy | 44.6 score on a scale | Standard Deviation 12.6 |
| Intermediate-Risk Group | Neurocognitive Performance Related to Visual-spatial Reasoning as Measured by Visual Motor Integration (VMI) T-scores | 60 Months Off Therapy | 40.6 score on a scale | Standard Deviation 9.2 |
| High-Risk Group | Neurocognitive Performance Related to Visual-spatial Reasoning as Measured by Visual Motor Integration (VMI) T-scores | Completion Of Therapy | 46.0 score on a scale | — |
| High-Risk Group | Neurocognitive Performance Related to Visual-spatial Reasoning as Measured by Visual Motor Integration (VMI) T-scores | Prior to Maintenance Therapy | 53.0 score on a scale | Standard Deviation 0 |
| High-Risk Group | Neurocognitive Performance Related to Visual-spatial Reasoning as Measured by Visual Motor Integration (VMI) T-scores | Baseline | 37.3 score on a scale | Standard Deviation 11.9 |
| High-Risk Group | Neurocognitive Performance Related to Visual-spatial Reasoning as Measured by Visual Motor Integration (VMI) T-scores | 12 Months Off Therapy | 39.0 score on a scale | Standard Deviation 9.2 |
| High-Risk Group | Neurocognitive Performance Related to Visual-spatial Reasoning as Measured by Visual Motor Integration (VMI) T-scores | 48 Months Off Therapy | 44.3 score on a scale | Standard Deviation 10.1 |
| High-Risk Group | Neurocognitive Performance Related to Visual-spatial Reasoning as Measured by Visual Motor Integration (VMI) T-scores | 36 Months Off Therapy | 36.8 score on a scale | Standard Deviation 13.6 |
| High-Risk Group | Neurocognitive Performance Related to Visual-spatial Reasoning as Measured by Visual Motor Integration (VMI) T-scores | 24 Months Off Therapy | 32.0 score on a scale | Standard Deviation 16 |
| High-Risk Group | Neurocognitive Performance Related to Visual-spatial Reasoning as Measured by Visual Motor Integration (VMI) T-scores | 60 Months Off Therapy | 34.0 score on a scale | Standard Deviation 15.7 |
Secondary
Neurocognitive Performance Related to Visual-spatial Reasoning as Measured by Visual Perception T-scores
Scores measuring visual-spatial reasoning were obtained from Visual Perception T-scores on the Beery Visual Motor Integration (VMI) instrument. Higher scores indicate better performance. The normative mean is 50 with a standard deviation of 10.
Time frame: Baseline, prior to maintenance therapy, completion of therapy, and 12 months, 24 months, 36 months, 48 months, and 60 months off therapy
Population: Eligible patients with scores at any of the data collection timepoints were included. Sample sizes differ across timepoints as not all subjects had scores for all timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low-Risk Group | Neurocognitive Performance Related to Visual-spatial Reasoning as Measured by Visual Perception T-scores | Baseline | 66.0 score on a scale | — |
| Low-Risk Group | Neurocognitive Performance Related to Visual-spatial Reasoning as Measured by Visual Perception T-scores | Prior to Maintenance Therapy | 32.0 score on a scale | Standard Deviation 7.1 |
| Low-Risk Group | Neurocognitive Performance Related to Visual-spatial Reasoning as Measured by Visual Perception T-scores | Completion of Therapy | 39.0 score on a scale | Standard Deviation 16.4 |
| Low-Risk Group | Neurocognitive Performance Related to Visual-spatial Reasoning as Measured by Visual Perception T-scores | 12 Months Off Therapy | 42.3 score on a scale | Standard Deviation 14.7 |
| Low-Risk Group | Neurocognitive Performance Related to Visual-spatial Reasoning as Measured by Visual Perception T-scores | 24 Months Off Therapy | 43.4 score on a scale | Standard Deviation 15 |
| Low-Risk Group | Neurocognitive Performance Related to Visual-spatial Reasoning as Measured by Visual Perception T-scores | 36 Months Off Therapy | 51.2 score on a scale | Standard Deviation 17.8 |
| Low-Risk Group | Neurocognitive Performance Related to Visual-spatial Reasoning as Measured by Visual Perception T-scores | 48 Months Off Therapy | 48.6 score on a scale | Standard Deviation 24.9 |
| Low-Risk Group | Neurocognitive Performance Related to Visual-spatial Reasoning as Measured by Visual Perception T-scores | 60 Months Off Therapy | 43.1 score on a scale | Standard Deviation 18.8 |
| Intermediate-Risk Group | Neurocognitive Performance Related to Visual-spatial Reasoning as Measured by Visual Perception T-scores | Completion of Therapy | 39.8 score on a scale | Standard Deviation 12.3 |
| Intermediate-Risk Group | Neurocognitive Performance Related to Visual-spatial Reasoning as Measured by Visual Perception T-scores | 48 Months Off Therapy | 46.1 score on a scale | Standard Deviation 11.3 |
| Intermediate-Risk Group | Neurocognitive Performance Related to Visual-spatial Reasoning as Measured by Visual Perception T-scores | 12 Months Off Therapy | 41.0 score on a scale | Standard Deviation 14.5 |
| Intermediate-Risk Group | Neurocognitive Performance Related to Visual-spatial Reasoning as Measured by Visual Perception T-scores | 24 Months Off Therapy | 40.1 score on a scale | Standard Deviation 13.4 |
| Intermediate-Risk Group | Neurocognitive Performance Related to Visual-spatial Reasoning as Measured by Visual Perception T-scores | 36 Months Off Therapy | 41.0 score on a scale | Standard Deviation 13.6 |
| Intermediate-Risk Group | Neurocognitive Performance Related to Visual-spatial Reasoning as Measured by Visual Perception T-scores | Baseline | 31.6 score on a scale | Standard Deviation 12.2 |
| Intermediate-Risk Group | Neurocognitive Performance Related to Visual-spatial Reasoning as Measured by Visual Perception T-scores | Prior to Maintenance Therapy | 40.2 score on a scale | Standard Deviation 12.2 |
| Intermediate-Risk Group | Neurocognitive Performance Related to Visual-spatial Reasoning as Measured by Visual Perception T-scores | 60 Months Off Therapy | 42.3 score on a scale | Standard Deviation 13.3 |
| High-Risk Group | Neurocognitive Performance Related to Visual-spatial Reasoning as Measured by Visual Perception T-scores | Completion of Therapy | 18.5 score on a scale | Standard Deviation 26.2 |
| High-Risk Group | Neurocognitive Performance Related to Visual-spatial Reasoning as Measured by Visual Perception T-scores | Prior to Maintenance Therapy | 56.0 score on a scale | Standard Deviation 8.5 |
| High-Risk Group | Neurocognitive Performance Related to Visual-spatial Reasoning as Measured by Visual Perception T-scores | Baseline | 33.7 score on a scale | Standard Deviation 9.5 |
| High-Risk Group | Neurocognitive Performance Related to Visual-spatial Reasoning as Measured by Visual Perception T-scores | 12 Months Off Therapy | 33.0 score on a scale | — |
| High-Risk Group | Neurocognitive Performance Related to Visual-spatial Reasoning as Measured by Visual Perception T-scores | 48 Months Off Therapy | 42.7 score on a scale | Standard Deviation 8.3 |
| High-Risk Group | Neurocognitive Performance Related to Visual-spatial Reasoning as Measured by Visual Perception T-scores | 36 Months Off Therapy | 48.8 score on a scale | Standard Deviation 18.7 |
| High-Risk Group | Neurocognitive Performance Related to Visual-spatial Reasoning as Measured by Visual Perception T-scores | 24 Months Off Therapy | 32.0 score on a scale | Standard Deviation 8.9 |
| High-Risk Group | Neurocognitive Performance Related to Visual-spatial Reasoning as Measured by Visual Perception T-scores | 60 Months Off Therapy | 36.0 score on a scale | Standard Deviation 12.7 |
Secondary
Neurocognitive Performance Related to Working Memory as Measured by Working Memory T-scores
Scores measuring working memory were obtained from Working Memory T-scores, which were obtained from the Behavior Rating Inventory of Executive Function (BRIEF) instrument which is a parent report. Higher scores indicate more problems. The normative mean is 50 with a standard deviation of 10.
Time frame: Baseline, prior to maintenance therapy, completion of therapy, and 12 months, 24 months, 36 months, 48 months, and 60 months off therapy
Population: Eligible patients with scores at any of the data collection timepoints were included. Sample sizes differ across timepoints as not all subjects had scores for all timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low-Risk Group | Neurocognitive Performance Related to Working Memory as Measured by Working Memory T-scores | Completion of Therapy | 60.8 score on a scale | Standard Deviation 14.9 |
| Low-Risk Group | Neurocognitive Performance Related to Working Memory as Measured by Working Memory T-scores | 48 Months Off Therapy | 60.9 score on a scale | Standard Deviation 16.1 |
| Low-Risk Group | Neurocognitive Performance Related to Working Memory as Measured by Working Memory T-scores | 60 Months Off Therapy | 56.8 score on a scale | Standard Deviation 13.3 |
| Low-Risk Group | Neurocognitive Performance Related to Working Memory as Measured by Working Memory T-scores | 12 Months Off Therapy | 64.4 score on a scale | Standard Deviation 16.1 |
| Low-Risk Group | Neurocognitive Performance Related to Working Memory as Measured by Working Memory T-scores | Baseline | 63.2 score on a scale | Standard Deviation 16 |
| Low-Risk Group | Neurocognitive Performance Related to Working Memory as Measured by Working Memory T-scores | Prior to Maintenance Therapy | 58.7 score on a scale | Standard Deviation 10.7 |
| Low-Risk Group | Neurocognitive Performance Related to Working Memory as Measured by Working Memory T-scores | 24 Months Off Therapy | 63.6 score on a scale | Standard Deviation 17.8 |
| Low-Risk Group | Neurocognitive Performance Related to Working Memory as Measured by Working Memory T-scores | 36 Months Off Therapy | 59.3 score on a scale | Standard Deviation 13.9 |
| Intermediate-Risk Group | Neurocognitive Performance Related to Working Memory as Measured by Working Memory T-scores | 24 Months Off Therapy | 59.4 score on a scale | Standard Deviation 14.7 |
| Intermediate-Risk Group | Neurocognitive Performance Related to Working Memory as Measured by Working Memory T-scores | Baseline | 51.6 score on a scale | Standard Deviation 10.8 |
| Intermediate-Risk Group | Neurocognitive Performance Related to Working Memory as Measured by Working Memory T-scores | 48 Months Off Therapy | 60.0 score on a scale | Standard Deviation 13.1 |
| Intermediate-Risk Group | Neurocognitive Performance Related to Working Memory as Measured by Working Memory T-scores | Completion of Therapy | 54.9 score on a scale | Standard Deviation 11.1 |
| Intermediate-Risk Group | Neurocognitive Performance Related to Working Memory as Measured by Working Memory T-scores | Prior to Maintenance Therapy | 55.5 score on a scale | Standard Deviation 13.3 |
| Intermediate-Risk Group | Neurocognitive Performance Related to Working Memory as Measured by Working Memory T-scores | 60 Months Off Therapy | 60.6 score on a scale | Standard Deviation 14.3 |
| Intermediate-Risk Group | Neurocognitive Performance Related to Working Memory as Measured by Working Memory T-scores | 36 Months Off Therapy | 62.0 score on a scale | Standard Deviation 14.2 |
| Intermediate-Risk Group | Neurocognitive Performance Related to Working Memory as Measured by Working Memory T-scores | 12 Months Off Therapy | 60.4 score on a scale | Standard Deviation 14.5 |
| High-Risk Group | Neurocognitive Performance Related to Working Memory as Measured by Working Memory T-scores | Prior to Maintenance Therapy | 54.1 score on a scale | Standard Deviation 11.1 |
| High-Risk Group | Neurocognitive Performance Related to Working Memory as Measured by Working Memory T-scores | Baseline | 57.0 score on a scale | Standard Deviation 13.6 |
| High-Risk Group | Neurocognitive Performance Related to Working Memory as Measured by Working Memory T-scores | 12 Months Off Therapy | 67.7 score on a scale | Standard Deviation 22.3 |
| High-Risk Group | Neurocognitive Performance Related to Working Memory as Measured by Working Memory T-scores | 24 Months Off Therapy | 55.4 score on a scale | Standard Deviation 13.3 |
| High-Risk Group | Neurocognitive Performance Related to Working Memory as Measured by Working Memory T-scores | 36 Months Off Therapy | 61.7 score on a scale | Standard Deviation 8.6 |
| High-Risk Group | Neurocognitive Performance Related to Working Memory as Measured by Working Memory T-scores | 48 Months Off Therapy | 54.5 score on a scale | Standard Deviation 12.8 |
| High-Risk Group | Neurocognitive Performance Related to Working Memory as Measured by Working Memory T-scores | 60 Months Off Therapy | 61.0 score on a scale | Standard Deviation 15.3 |
| High-Risk Group | Neurocognitive Performance Related to Working Memory as Measured by Working Memory T-scores | Completion of Therapy | 49.0 score on a scale | Standard Deviation 16.8 |
Secondary
Number and Type of Genetic Polymorphisms
Types of genetic polymorphisms of neurotransmitters were examined. We studied 3 genetic polymorphisms; these were types of genetic polymorphisms involved in dopamine metabolism. They were as follows: rs6323, rs4680, and rs6280.
Time frame: At study enrollment (Day 0)
Population: Three genetic polymorphisms involved in dopamine metabolism (rs6323, rs4680, and rs6280) were studied in 17 patients with CNS neurotransmitter studies.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Low-Risk Group | Number and Type of Genetic Polymorphisms | rs6280 | 17 Participants |
| Low-Risk Group | Number and Type of Genetic Polymorphisms | rs6323 | 17 Participants |
| Low-Risk Group | Number and Type of Genetic Polymorphisms | rs4680 | 17 Participants |
Secondary
Number of Participants With Chromosomal Abnormalities
Amplifications and deletions (gains and losses) for chromosomes of interest are shown in the table of measured values.
Time frame: Based on samples obtained at the time of initial surgery or repeat surgery prior to treatment
Population: Eligible medulloblastoma patients (n=81) were included in these analyses. 23 of 23 low risk patients had data available for this objective, as did 27/32 and 24/26 intermediate and high risk patients.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Low-Risk Group | Number of Participants With Chromosomal Abnormalities | chr2p gain/amplification | 5 Participants |
| Low-Risk Group | Number of Participants With Chromosomal Abnormalities | chr2p loss/deletion | 0 Participants |
| Low-Risk Group | Number of Participants With Chromosomal Abnormalities | chr2q gain/amplification | 5 Participants |
| Low-Risk Group | Number of Participants With Chromosomal Abnormalities | chr2q loss/deletion | 0 Participants |
| Low-Risk Group | Number of Participants With Chromosomal Abnormalities | chr6p gain/amplification | 1 Participants |
| Low-Risk Group | Number of Participants With Chromosomal Abnormalities | chr9p loss/deletion | 4 Participants |
| Low-Risk Group | Number of Participants With Chromosomal Abnormalities | chr9q gain/amplification | 2 Participants |
| Low-Risk Group | Number of Participants With Chromosomal Abnormalities | chr9q loss/deletion | 6 Participants |
| Low-Risk Group | Number of Participants With Chromosomal Abnormalities | chr10p gain/amplification | 0 Participants |
| Low-Risk Group | Number of Participants With Chromosomal Abnormalities | chr10p loss/deletion | 0 Participants |
| Low-Risk Group | Number of Participants With Chromosomal Abnormalities | chr10q gain/amplification | 0 Participants |
| Low-Risk Group | Number of Participants With Chromosomal Abnormalities | chr10q loss/deletion | 3 Participants |
| Low-Risk Group | Number of Participants With Chromosomal Abnormalities | chr20p gain/amplification | 0 Participants |
| Low-Risk Group | Number of Participants With Chromosomal Abnormalities | chr20p loss/deletion | 2 Participants |
| Low-Risk Group | Number of Participants With Chromosomal Abnormalities | chr20q gain/amplification | 0 Participants |
| Low-Risk Group | Number of Participants With Chromosomal Abnormalities | chr20q loss/deletion | 1 Participants |
| Low-Risk Group | Number of Participants With Chromosomal Abnormalities | chr6q gain/amplification | 1 Participants |
| Low-Risk Group | Number of Participants With Chromosomal Abnormalities | chr6p loss/deletion | 0 Participants |
| Low-Risk Group | Number of Participants With Chromosomal Abnormalities | chr6q loss/deletion | 0 Participants |
| Low-Risk Group | Number of Participants With Chromosomal Abnormalities | chr8p gain/amplification | 1 Participants |
| Low-Risk Group | Number of Participants With Chromosomal Abnormalities | chr8p loss/deletion | 0 Participants |
| Low-Risk Group | Number of Participants With Chromosomal Abnormalities | chr8q gain/amplification | 1 Participants |
| Low-Risk Group | Number of Participants With Chromosomal Abnormalities | chr8q loss/deletion | 0 Participants |
| Low-Risk Group | Number of Participants With Chromosomal Abnormalities | chr9p gain/amplification | 4 Participants |
| Intermediate-Risk Group | Number of Participants With Chromosomal Abnormalities | chr10p gain/amplification | 0 Participants |
| Intermediate-Risk Group | Number of Participants With Chromosomal Abnormalities | chr2p gain/amplification | 1 Participants |
| Intermediate-Risk Group | Number of Participants With Chromosomal Abnormalities | chr8p gain/amplification | 2 Participants |
| Intermediate-Risk Group | Number of Participants With Chromosomal Abnormalities | chr20p gain/amplification | 0 Participants |
| Intermediate-Risk Group | Number of Participants With Chromosomal Abnormalities | chr2p loss/deletion | 2 Participants |
| Intermediate-Risk Group | Number of Participants With Chromosomal Abnormalities | chr8q gain/amplification | 3 Participants |
| Intermediate-Risk Group | Number of Participants With Chromosomal Abnormalities | chr6q gain/amplification | 3 Participants |
| Intermediate-Risk Group | Number of Participants With Chromosomal Abnormalities | chr2q gain/amplification | 1 Participants |
| Intermediate-Risk Group | Number of Participants With Chromosomal Abnormalities | chr10q gain/amplification | 0 Participants |
| Intermediate-Risk Group | Number of Participants With Chromosomal Abnormalities | chr9p gain/amplification | 6 Participants |
| Intermediate-Risk Group | Number of Participants With Chromosomal Abnormalities | chr2q loss/deletion | 2 Participants |
| Intermediate-Risk Group | Number of Participants With Chromosomal Abnormalities | chr20p loss/deletion | 4 Participants |
| Intermediate-Risk Group | Number of Participants With Chromosomal Abnormalities | chr8q loss/deletion | 5 Participants |
| Intermediate-Risk Group | Number of Participants With Chromosomal Abnormalities | chr6p gain/amplification | 3 Participants |
| Intermediate-Risk Group | Number of Participants With Chromosomal Abnormalities | chr6q loss/deletion | 0 Participants |
| Intermediate-Risk Group | Number of Participants With Chromosomal Abnormalities | chr10p loss/deletion | 5 Participants |
| Intermediate-Risk Group | Number of Participants With Chromosomal Abnormalities | chr6p loss/deletion | 0 Participants |
| Intermediate-Risk Group | Number of Participants With Chromosomal Abnormalities | chr9p loss/deletion | 0 Participants |
| Intermediate-Risk Group | Number of Participants With Chromosomal Abnormalities | chr20q gain/amplification | 0 Participants |
| Intermediate-Risk Group | Number of Participants With Chromosomal Abnormalities | chr10q loss/deletion | 7 Participants |
| Intermediate-Risk Group | Number of Participants With Chromosomal Abnormalities | chr9q gain/amplification | 1 Participants |
| Intermediate-Risk Group | Number of Participants With Chromosomal Abnormalities | chr8p loss/deletion | 6 Participants |
| Intermediate-Risk Group | Number of Participants With Chromosomal Abnormalities | chr20q loss/deletion | 3 Participants |
| Intermediate-Risk Group | Number of Participants With Chromosomal Abnormalities | chr9q loss/deletion | 5 Participants |
| High-Risk Group | Number of Participants With Chromosomal Abnormalities | chr20q loss/deletion | 5 Participants |
| High-Risk Group | Number of Participants With Chromosomal Abnormalities | chr10p gain/amplification | 0 Participants |
| High-Risk Group | Number of Participants With Chromosomal Abnormalities | chr10p loss/deletion | 7 Participants |
| High-Risk Group | Number of Participants With Chromosomal Abnormalities | chr6q loss/deletion | 2 Participants |
| High-Risk Group | Number of Participants With Chromosomal Abnormalities | chr10q gain/amplification | 0 Participants |
| High-Risk Group | Number of Participants With Chromosomal Abnormalities | chr8q gain/amplification | 0 Participants |
| High-Risk Group | Number of Participants With Chromosomal Abnormalities | chr10q loss/deletion | 9 Participants |
| High-Risk Group | Number of Participants With Chromosomal Abnormalities | chr20p gain/amplification | 0 Participants |
| High-Risk Group | Number of Participants With Chromosomal Abnormalities | chr8p gain/amplification | 0 Participants |
| High-Risk Group | Number of Participants With Chromosomal Abnormalities | chr20p loss/deletion | 5 Participants |
| High-Risk Group | Number of Participants With Chromosomal Abnormalities | chr8q loss/deletion | 7 Participants |
| High-Risk Group | Number of Participants With Chromosomal Abnormalities | chr20q gain/amplification | 0 Participants |
| High-Risk Group | Number of Participants With Chromosomal Abnormalities | chr9q loss/deletion | 5 Participants |
| High-Risk Group | Number of Participants With Chromosomal Abnormalities | chr2p gain/amplification | 6 Participants |
| High-Risk Group | Number of Participants With Chromosomal Abnormalities | chr8p loss/deletion | 8 Participants |
| High-Risk Group | Number of Participants With Chromosomal Abnormalities | chr2p loss/deletion | 0 Participants |
| High-Risk Group | Number of Participants With Chromosomal Abnormalities | chr2q gain/amplification | 6 Participants |
| High-Risk Group | Number of Participants With Chromosomal Abnormalities | chr2q loss/deletion | 0 Participants |
| High-Risk Group | Number of Participants With Chromosomal Abnormalities | chr6p gain/amplification | 3 Participants |
| High-Risk Group | Number of Participants With Chromosomal Abnormalities | chr9p gain/amplification | 3 Participants |
| High-Risk Group | Number of Participants With Chromosomal Abnormalities | chr9p loss/deletion | 3 Participants |
| High-Risk Group | Number of Participants With Chromosomal Abnormalities | chr6p loss/deletion | 2 Participants |
| High-Risk Group | Number of Participants With Chromosomal Abnormalities | chr9q gain/amplification | 1 Participants |
| High-Risk Group | Number of Participants With Chromosomal Abnormalities | chr6q gain/amplification | 3 Participants |
Secondary
Number of Participants With Endocrinopathy
Endocrine screening and growth hormone (GH) testing were done in consenting intermediate risk patients at the end of induction therapy, the end of all therapy, and at 6, 12, 24, 36, 48, and 60 months off therapy. Endocrinopathy was defined as the presence of central hypothyroidism (free T4 concentration below normal with low or normal TSH concentration), growth hormone deficiency (peak growth hormone concentration below 5 ng/mL on dynamic testing), or ACTH deficiency (cortisol concentration below 14 ug/dL after low dose cosyntropin stimulation). Numbers of participants with endocrinopathy at each time point are reported. Please note the small numbers of participants with available data.
Time frame: End of induction therapy (approximately 16 weeks from start of treatment), end of therapy (approximately 48 weeks from start of treatment), and 6, 12, 24, 36, 48, and 60 months off therapy
Population: Endocrine screening and growth hormone (GH) testing were done in consenting intermediate risk patients.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Intermediate-Risk Group | Number of Participants With Endocrinopathy | End of induction-number with endocrinopathy | 0 participants |
| Intermediate-Risk Group | Number of Participants With Endocrinopathy | 48-months off therapy-number with endocrinopathy | 0 participants |
| Intermediate-Risk Group | Number of Participants With Endocrinopathy | 60-months off therapy-number with endocrinopathy | 1 participants |
| Intermediate-Risk Group | Number of Participants With Endocrinopathy | End of therapy-number with endocrinopathy | 0 participants |
| Intermediate-Risk Group | Number of Participants With Endocrinopathy | 6-months off therapy-number with endocrinopathy | 0 participants |
| Intermediate-Risk Group | Number of Participants With Endocrinopathy | 12-months off therapy-number with endocrinopathy | 0 participants |
| Intermediate-Risk Group | Number of Participants With Endocrinopathy | 24-months off therapy-number with endocrinopathy | 2 participants |
| Intermediate-Risk Group | Number of Participants With Endocrinopathy | 36-months off therapy-number with endocrinopathy | 0 participants |
Secondary
Number of Successful Collections for Frozen and Fixed Tumor Samples
Successful collections will be defined as the number of patients who have frozen/fixed tumor samples available.
Time frame: Based on samples obtained at the time of initial surgery or repeat surgery prior to treatment
Population: All eligible patients enrolled (n=290) were included in this analysis. The numbers of patients with pre-study samples were considered for these results.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Low-Risk Group | Number of Successful Collections for Frozen and Fixed Tumor Samples | Number with frozen tumor tissue | 27 Participants |
| Low-Risk Group | Number of Successful Collections for Frozen and Fixed Tumor Samples | Number with fixed tumor tissue | 54 Participants |
| Intermediate-Risk Group | Number of Successful Collections for Frozen and Fixed Tumor Samples | Number with frozen tumor tissue | 73 Participants |
| Intermediate-Risk Group | Number of Successful Collections for Frozen and Fixed Tumor Samples | Number with fixed tumor tissue | 153 Participants |
| High-Risk Group | Number of Successful Collections for Frozen and Fixed Tumor Samples | Number with frozen tumor tissue | 32 Participants |
| High-Risk Group | Number of Successful Collections for Frozen and Fixed Tumor Samples | Number with fixed tumor tissue | 71 Participants |
Secondary
Numbers of Patients With Gene Alterations
Gene alterations, which include single nucleotide variants (SNPs), amplifications, deletions, translocations, indels, and germline alterations are shown for specific genes of interest in the results table.
Time frame: Based on samples obtained at the time of initial surgery or repeat surgery prior to treatment
Population: Eligible medulloblastoma patients (n=81) were included in these analyses. Not all patients had data available for each gene.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Low-Risk Group | Numbers of Patients With Gene Alterations | BCOR alteration | 1 Participants |
| Low-Risk Group | Numbers of Patients With Gene Alterations | SUFU alteration | 6 Participants |
| Low-Risk Group | Numbers of Patients With Gene Alterations | BRCA2 alteration | 0 Participants |
| Low-Risk Group | Numbers of Patients With Gene Alterations | SMO alteration | 2 Participants |
| Low-Risk Group | Numbers of Patients With Gene Alterations | KMT2D alteration | 5 Participants |
| Low-Risk Group | Numbers of Patients With Gene Alterations | SMARCA4 alteration | 2 Participants |
| Low-Risk Group | Numbers of Patients With Gene Alterations | MYCN alteration | 0 Participants |
| Low-Risk Group | Numbers of Patients With Gene Alterations | TP53 alteration | 0 Participants |
| Low-Risk Group | Numbers of Patients With Gene Alterations | PTEN alteration | 1 Participants |
| Low-Risk Group | Numbers of Patients With Gene Alterations | PTCH1 alteration | 7 Participants |
| Low-Risk Group | Numbers of Patients With Gene Alterations | GLI2 alteration | 0 Participants |
| Intermediate-Risk Group | Numbers of Patients With Gene Alterations | KMT2D alteration | 1 Participants |
| Intermediate-Risk Group | Numbers of Patients With Gene Alterations | SMARCA4 alteration | 1 Participants |
| Intermediate-Risk Group | Numbers of Patients With Gene Alterations | TP53 alteration | 0 Participants |
| Intermediate-Risk Group | Numbers of Patients With Gene Alterations | MYCN alteration | 1 Participants |
| Intermediate-Risk Group | Numbers of Patients With Gene Alterations | PTCH1 alteration | 4 Participants |
| Intermediate-Risk Group | Numbers of Patients With Gene Alterations | SUFU alteration | 1 Participants |
| Intermediate-Risk Group | Numbers of Patients With Gene Alterations | SMO alteration | 0 Participants |
| Intermediate-Risk Group | Numbers of Patients With Gene Alterations | BCOR alteration | 0 Participants |
| Intermediate-Risk Group | Numbers of Patients With Gene Alterations | PTEN alteration | 0 Participants |
| Intermediate-Risk Group | Numbers of Patients With Gene Alterations | BRCA2 alteration | 0 Participants |
| Intermediate-Risk Group | Numbers of Patients With Gene Alterations | GLI2 alteration | 0 Participants |
| High-Risk Group | Numbers of Patients With Gene Alterations | BRCA2 alteration | 0 Participants |
| High-Risk Group | Numbers of Patients With Gene Alterations | BCOR alteration | 0 Participants |
| High-Risk Group | Numbers of Patients With Gene Alterations | MYCN alteration | 1 Participants |
| High-Risk Group | Numbers of Patients With Gene Alterations | SMARCA4 alteration | 0 Participants |
| High-Risk Group | Numbers of Patients With Gene Alterations | PTEN alteration | 0 Participants |
| High-Risk Group | Numbers of Patients With Gene Alterations | TP53 alteration | 0 Participants |
| High-Risk Group | Numbers of Patients With Gene Alterations | KMT2D alteration | 3 Participants |
| High-Risk Group | Numbers of Patients With Gene Alterations | GLI2 alteration | 0 Participants |
| High-Risk Group | Numbers of Patients With Gene Alterations | SUFU alteration | 1 Participants |
| High-Risk Group | Numbers of Patients With Gene Alterations | SMO alteration | 1 Participants |
| High-Risk Group | Numbers of Patients With Gene Alterations | PTCH1 alteration | 3 Participants |
Secondary
Numbers of Patients With Molecular Abnormalities by Tumor Type
Alterations included single nucleotide variants (SNPs), amplifications, deletions, translocations, indels, and germline alterations. Cytogenetic information shows gains and losses as specified in the table of measured values.
Time frame: Based on samples obtained at the time of initial surgery or repeat surgery prior to treatment
Population: Eligible patients with molecularly confirmed medulloblastoma (n=76) were included in these analyses. Not all patients had data available for each gene.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Low-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | TP53 alteration | 0 Participants |
| Low-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr6q gain/amplification | 1 Participants |
| Low-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr10p gain/amplification | 0 Participants |
| Low-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr8q gain/amplification | 1 Participants |
| Low-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | PTEN alteration | 1 Participants |
| Low-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr8p loss/deletion | 0 Participants |
| Low-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr10q loss/deletion | 3 Participants |
| Low-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | SMARCA4 alteration | 2 Participants |
| Low-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr6q loss/deletion | 0 Participants |
| Low-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | PTCH1 alteration | 7 Participants |
| Low-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | BRCA2 alteration | 0 Participants |
| Low-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr20q loss/deletion | 1 Participants |
| Low-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr2q gain/amplification | 5 Participants |
| Low-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr10q gain/amplification | 0 Participants |
| Low-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | GLI2 alteration | 0 Participants |
| Low-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr8p gain/amplification | 1 Participants |
| Low-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr20p gain/amplification | 0 Participants |
| Low-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr9q gain/amplification | 2 Participants |
| Low-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | SUFU alteration | 6 Participants |
| Low-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr9p loss/deletion | 4 Participants |
| Low-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr20q gain/amplification | 0 Participants |
| Low-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr2p gain/amplification | 5 Participants |
| Low-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr6p gain/amplification | 1 Participants |
| Low-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr10p loss/deletion | 0 Participants |
| Low-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | KMT2D alteration | 5 Participants |
| Low-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr2p loss/deletion | 0 Participants |
| Low-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr9p gain/amplification | 4 Participants |
| Low-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr20p loss/deletion | 2 Participants |
| Low-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | MYCN amplification | 0 Participants |
| Low-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr6p loss/deletion | 0 Participants |
| Low-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr9q loss/deletion | 6 Participants |
| Low-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | SMO alteration | 2 Participants |
| Low-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr8q loss/deletion | 0 Participants |
| Low-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | BCOR alteration | 1 Participants |
| Low-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr2q loss/deletion | 0 Participants |
| Intermediate-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr20q loss/deletion | 0 Participants |
| Intermediate-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr10p gain/amplification | 0 Participants |
| Intermediate-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr20p gain/amplification | 0 Participants |
| Intermediate-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr10p loss/deletion | 0 Participants |
| Intermediate-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr2q loss/deletion | 0 Participants |
| Intermediate-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr10q loss/deletion | 2 Participants |
| Intermediate-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr10q gain/amplification | 0 Participants |
| Intermediate-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr2p gain/amplification | 0 Participants |
| Intermediate-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr6p gain/amplification | 0 Participants |
| Intermediate-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | MYCN amplification | 1 Participants |
| Intermediate-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr6p loss/deletion | 0 Participants |
| Intermediate-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | TP53 alteration | 0 Participants |
| Intermediate-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr6q gain/amplification | 0 Participants |
| Intermediate-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | SMARCA4 alteration | 0 Participants |
| Intermediate-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr6q loss/deletion | 0 Participants |
| Intermediate-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | GLI2 alteration | 0 Participants |
| Intermediate-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr8p gain/amplification | 0 Participants |
| Intermediate-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | BRCA2 alteration | 0 Participants |
| Intermediate-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr8p loss/deletion | 0 Participants |
| Intermediate-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | PTEN alteration | 0 Participants |
| Intermediate-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr8q gain/amplification | 0 Participants |
| Intermediate-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr2q gain/amplification | 0 Participants |
| Intermediate-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | BCOR alteration | 0 Participants |
| Intermediate-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr8q loss/deletion | 0 Participants |
| Intermediate-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | SMO alteration | 0 Participants |
| Intermediate-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr9p gain/amplification | 4 Participants |
| Intermediate-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr2p loss/deletion | 0 Participants |
| Intermediate-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | KMT2D alteration | 1 Participants |
| Intermediate-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr9p loss/deletion | 0 Participants |
| Intermediate-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | SUFU alteration | 1 Participants |
| Intermediate-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr9q gain/amplification | 0 Participants |
| Intermediate-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr20q gain/amplification | 0 Participants |
| Intermediate-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | PTCH1 alteration | 4 Participants |
| Intermediate-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr9q loss/deletion | 5 Participants |
| Intermediate-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr20p loss/deletion | 1 Participants |
| High-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | SMO alteration | 1 Participants |
| High-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr20q loss/deletion | 1 Participants |
| High-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr10p gain/amplification | 0 Participants |
| High-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr8q loss/deletion | 0 Participants |
| High-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr2q gain/amplification | 4 Participants |
| High-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr9q gain/amplification | 1 Participants |
| High-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr6p loss/deletion | 0 Participants |
| High-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | KMT2D alteration | 3 Participants |
| High-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | MYCN amplification | 0 Participants |
| High-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr9q loss/deletion | 2 Participants |
| High-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr9p gain/amplification | 3 Participants |
| High-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr10q loss/deletion | 1 Participants |
| High-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr10q gain/amplification | 0 Participants |
| High-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr6p gain/amplification | 0 Participants |
| High-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | SUFU alteration | 1 Participants |
| High-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr2p gain/amplification | 4 Participants |
| High-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr20p loss/deletion | 1 Participants |
| High-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr8p gain/amplification | 0 Participants |
| High-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | GLI2 alteration | 0 Participants |
| High-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | BRCA2 alteration | 0 Participants |
| High-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr9p loss/deletion | 0 Participants |
| High-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr6q loss/deletion | 0 Participants |
| High-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | SMARCA4 alteration | 0 Participants |
| High-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr20q gain/amplification | 0 Participants |
| High-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr8p loss/deletion | 0 Participants |
| High-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | PTEN alteration | 0 Participants |
| High-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr10p loss/deletion | 0 Participants |
| High-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr20p gain/amplification | 0 Participants |
| High-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | BCOR alteration | 0 Participants |
| High-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr6q gain/amplification | 0 Participants |
| High-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr2p loss/deletion | 0 Participants |
| High-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr8q gain/amplification | 0 Participants |
| High-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | PTCH1 alteration | 3 Participants |
| High-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr2q loss/deletion | 0 Participants |
| High-Risk Group | Numbers of Patients With Molecular Abnormalities by Tumor Type | TP53 alteration | 0 Participants |
| Intermediate-risk Group 3 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr8p loss/deletion | 2 Participants |
| Intermediate-risk Group 3 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr2p loss/deletion | 1 Participants |
| Intermediate-risk Group 3 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr2q gain/amplification | 0 Participants |
| Intermediate-risk Group 3 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr2q loss/deletion | 1 Participants |
| Intermediate-risk Group 3 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr6p gain/amplification | 2 Participants |
| Intermediate-risk Group 3 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr6p loss/deletion | 0 Participants |
| Intermediate-risk Group 3 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr6q gain/amplification | 2 Participants |
| Intermediate-risk Group 3 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr6q loss/deletion | 0 Participants |
| Intermediate-risk Group 3 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr8p gain/amplification | 1 Participants |
| Intermediate-risk Group 3 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr8q gain/amplification | 2 Participants |
| Intermediate-risk Group 3 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr8q loss/deletion | 1 Participants |
| Intermediate-risk Group 3 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr9p gain/amplification | 1 Participants |
| Intermediate-risk Group 3 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr9p loss/deletion | 0 Participants |
| Intermediate-risk Group 3 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr9q gain/amplification | 0 Participants |
| Intermediate-risk Group 3 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr9q loss/deletion | 0 Participants |
| Intermediate-risk Group 3 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr10p gain/amplification | 0 Participants |
| Intermediate-risk Group 3 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr10p loss/deletion | 5 Participants |
| Intermediate-risk Group 3 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr10q gain/amplification | 0 Participants |
| Intermediate-risk Group 3 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr10q loss/deletion | 5 Participants |
| Intermediate-risk Group 3 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr20p gain/amplification | 0 Participants |
| Intermediate-risk Group 3 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr20p loss/deletion | 3 Participants |
| Intermediate-risk Group 3 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | PTCH1 alteration | 0 Participants |
| Intermediate-risk Group 3 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | SUFU alteration | 0 Participants |
| Intermediate-risk Group 3 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | KMT2D alteration | 0 Participants |
| Intermediate-risk Group 3 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | SMO alteration | 0 Participants |
| Intermediate-risk Group 3 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | BCOR alteration | 0 Participants |
| Intermediate-risk Group 3 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | PTEN alteration | 0 Participants |
| Intermediate-risk Group 3 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | BRCA2 alteration | 0 Participants |
| Intermediate-risk Group 3 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | GLI2 alteration | 0 Participants |
| Intermediate-risk Group 3 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | SMARCA4 alteration | 1 Participants |
| Intermediate-risk Group 3 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | TP53 alteration | 0 Participants |
| Intermediate-risk Group 3 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | MYCN amplification | 0 Participants |
| Intermediate-risk Group 3 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr2p gain/amplification | 0 Participants |
| Intermediate-risk Group 3 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr20q gain/amplification | 0 Participants |
| Intermediate-risk Group 3 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr20q loss/deletion | 3 Participants |
| High-risk Group 3 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr8q gain/amplification | 0 Participants |
| High-risk Group 3 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr2p loss/deletion | 0 Participants |
| High-risk Group 3 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr20q gain/amplification | 0 Participants |
| High-risk Group 3 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | BCOR alteration | 0 Participants |
| High-risk Group 3 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr10p gain/amplification | 0 Participants |
| High-risk Group 3 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr6p loss/deletion | 2 Participants |
| High-risk Group 3 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr9p loss/deletion | 3 Participants |
| High-risk Group 3 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr8p loss/deletion | 7 Participants |
| High-risk Group 3 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | SMARCA4 alteration | 0 Participants |
| High-risk Group 3 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr2p gain/amplification | 1 Participants |
| High-risk Group 3 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | PTEN alteration | 0 Participants |
| High-risk Group 3 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr20p loss/deletion | 4 Participants |
| High-risk Group 3 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr6q gain/amplification | 3 Participants |
| High-risk Group 3 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | GLI2 alteration | 0 Participants |
| High-risk Group 3 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | SUFU alteration | 0 Participants |
| High-risk Group 3 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr8p gain/amplification | 0 Participants |
| High-risk Group 3 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr6q loss/deletion | 2 Participants |
| High-risk Group 3 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | BRCA2 alteration | 0 Participants |
| High-risk Group 3 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr9q loss/deletion | 3 Participants |
| High-risk Group 3 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr20q loss/deletion | 4 Participants |
| High-risk Group 3 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr9q gain/amplification | 0 Participants |
| High-risk Group 3 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr9p gain/amplification | 0 Participants |
| High-risk Group 3 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr2q loss/deletion | 0 Participants |
| High-risk Group 3 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr2q gain/amplification | 1 Participants |
| High-risk Group 3 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | KMT2D alteration | 0 Participants |
| High-risk Group 3 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr10q loss/deletion | 8 Participants |
| High-risk Group 3 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | MYCN amplification | 1 Participants |
| High-risk Group 3 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr10p loss/deletion | 7 Participants |
| High-risk Group 3 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr8q loss/deletion | 6 Participants |
| High-risk Group 3 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr6p gain/amplification | 3 Participants |
| High-risk Group 3 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | PTCH1 alteration | 0 Participants |
| High-risk Group 3 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | SMO alteration | 0 Participants |
| High-risk Group 3 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr20p gain/amplification | 0 Participants |
| High-risk Group 3 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | TP53 alteration | 0 Participants |
| High-risk Group 3 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr10q gain/amplification | 0 Participants |
| Intermediate-risk Group 4 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr20p gain/amplification | 0 Participants |
| Intermediate-risk Group 4 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr9q loss/deletion | 0 Participants |
| Intermediate-risk Group 4 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr9q gain/amplification | 1 Participants |
| Intermediate-risk Group 4 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | PTCH1 alteration | 0 Participants |
| Intermediate-risk Group 4 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr9p loss/deletion | 0 Participants |
| Intermediate-risk Group 4 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr2q gain/amplification | 0 Participants |
| Intermediate-risk Group 4 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | SUFU alteration | 0 Participants |
| Intermediate-risk Group 4 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr9p gain/amplification | 1 Participants |
| Intermediate-risk Group 4 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | KMT2D alteration | 0 Participants |
| Intermediate-risk Group 4 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr8q loss/deletion | 4 Participants |
| Intermediate-risk Group 4 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr20q loss/deletion | 0 Participants |
| Intermediate-risk Group 4 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | SMO alteration | 0 Participants |
| Intermediate-risk Group 4 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr8q gain/amplification | 0 Participants |
| Intermediate-risk Group 4 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | BCOR alteration | 0 Participants |
| Intermediate-risk Group 4 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr8p loss/deletion | 4 Participants |
| Intermediate-risk Group 4 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr20q gain/amplification | 0 Participants |
| Intermediate-risk Group 4 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | PTEN alteration | 0 Participants |
| Intermediate-risk Group 4 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr8p gain/amplification | 0 Participants |
| Intermediate-risk Group 4 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | BRCA2 alteration | 0 Participants |
| Intermediate-risk Group 4 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr6q loss/deletion | 0 Participants |
| Intermediate-risk Group 4 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | GLI2 alteration | 0 Participants |
| Intermediate-risk Group 4 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr6q gain/amplification | 1 Participants |
| Intermediate-risk Group 4 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr2p loss/deletion | 1 Participants |
| Intermediate-risk Group 4 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | SMARCA4 alteration | 0 Participants |
| Intermediate-risk Group 4 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr6p loss/deletion | 0 Participants |
| Intermediate-risk Group 4 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | TP53 alteration | 0 Participants |
| Intermediate-risk Group 4 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr6p gain/amplification | 1 Participants |
| Intermediate-risk Group 4 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | MYCN amplification | 0 Participants |
| Intermediate-risk Group 4 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr2q loss/deletion | 1 Participants |
| Intermediate-risk Group 4 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr10q gain/amplification | 0 Participants |
| Intermediate-risk Group 4 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr10p loss/deletion | 0 Participants |
| Intermediate-risk Group 4 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr2p gain/amplification | 0 Participants |
| Intermediate-risk Group 4 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr10q loss/deletion | 0 Participants |
| Intermediate-risk Group 4 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr10p gain/amplification | 0 Participants |
| Intermediate-risk Group 4 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr20p loss/deletion | 0 Participants |
| High-risk Group 4 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr10p gain/amplification | 0 Participants |
| High-risk Group 4 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | BCOR alteration | 0 Participants |
| High-risk Group 4 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr8p loss/deletion | 1 Participants |
| High-risk Group 4 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | SMO alteration | 0 Participants |
| High-risk Group 4 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr9q loss/deletion | 0 Participants |
| High-risk Group 4 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | TP53 alteration | 0 Participants |
| High-risk Group 4 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr6p gain/amplification | 0 Participants |
| High-risk Group 4 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr9p loss/deletion | 0 Participants |
| High-risk Group 4 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr8q gain/amplification | 0 Participants |
| High-risk Group 4 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr20q loss/deletion | 0 Participants |
| High-risk Group 4 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | KMT2D alteration | 0 Participants |
| High-risk Group 4 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr20p gain/amplification | 0 Participants |
| High-risk Group 4 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | MYCN amplification | 0 Participants |
| High-risk Group 4 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr2q loss/deletion | 0 Participants |
| High-risk Group 4 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr10q loss/deletion | 0 Participants |
| High-risk Group 4 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr8q loss/deletion | 1 Participants |
| High-risk Group 4 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | SUFU alteration | 0 Participants |
| High-risk Group 4 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr10p loss/deletion | 0 Participants |
| High-risk Group 4 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr9p gain/amplification | 0 Participants |
| High-risk Group 4 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | BRCA2 alteration | 0 Participants |
| High-risk Group 4 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr6q loss/deletion | 0 Participants |
| High-risk Group 4 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | PTCH1 alteration | 0 Participants |
| High-risk Group 4 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr20q gain/amplification | 0 Participants |
| High-risk Group 4 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr2p loss/deletion | 0 Participants |
| High-risk Group 4 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr8p gain/amplification | 0 Participants |
| High-risk Group 4 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr9q gain/amplification | 0 Participants |
| High-risk Group 4 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | GLI2 alteration | 0 Participants |
| High-risk Group 4 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr6q gain/amplification | 0 Participants |
| High-risk Group 4 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr10q gain/amplification | 0 Participants |
| High-risk Group 4 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | PTEN alteration | 0 Participants |
| High-risk Group 4 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr20p loss/deletion | 0 Participants |
| High-risk Group 4 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr2p gain/amplification | 0 Participants |
| High-risk Group 4 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr2q gain/amplification | 0 Participants |
| High-risk Group 4 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | SMARCA4 alteration | 0 Participants |
| High-risk Group 4 Patients | Numbers of Patients With Molecular Abnormalities by Tumor Type | chr6p loss/deletion | 0 Participants |
Secondary
OSI-420 AUC0-24h
Erlotinib metabolite OSI-420 plasma concentration-time data are collected on day 1 of maintenance cycle B2. Individual estimates of OSI-420 AUC0-24h (area under concentration curve from 0 to 24 hours post-dose) are obtained using post hoc analysis.
Time frame: Pre-dose, 1, 2, 4, 8, and 24 hours post-dose
Population: Eligible patients who received oral erlotinib during maintenance therapy cycle B2 and had samples collected for PK analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Low-Risk Group | OSI-420 AUC0-24h | 2.17 µmol·h/L |
| Intermediate-Risk Group | OSI-420 AUC0-24h | 1.81 µmol·h/L |
| High-Risk Group | OSI-420 AUC0-24h | 1.62 µmol·h/L |
Secondary
Overall Survival (OS) Compared to Historical Controls
OS was measured from the date of initial treatment to date of death or to date of last contact for survivors. 1-year OS estimates were reported by risk group. OS was compared to St. Jude historical cohorts by risk group using hazard ratios with 95% confidence intervals.
Time frame: 1 year after treatment initiation of last patient
Population: Eligible medulloblastoma patients who received any methotrexate were included in this analysis. Hazard ratios with 95% confidence intervals are reported and compare SJYC07 patients to historical controls in each risk group. As there were too few low-risk historical controls, no hazard ratio is included for the low-risk group.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low-Risk Group | Overall Survival (OS) Compared to Historical Controls | 100 Percent probability |
| Intermediate-Risk Group | Overall Survival (OS) Compared to Historical Controls | 84.4 Percent probability |
| High-Risk Group | Overall Survival (OS) Compared to Historical Controls | 61.5 Percent probability |
Comparison: The historical control included 10 medulloblastoma patients treated during 1998-2006 who would have been classified as intermediate risk according to SJYC07 criteria (section 13.1.3 of protocol).95% CI: [0.42, 8.22]
Comparison: The historical control included 14 medulloblastoma patients treated during 1998-2006 who would have been classified as high risk according to SJYC07 criteria (section 13.1.3 of protocol).95% CI: [0.31, 1.79]
Secondary
Participants With Empirical Dosage Achieving Target System Exposure of Intravenous Topotecan
Number of participants who successfully achieve target systemic exposure of intravenous topotecan after an empiric dosage during consolidation phase of therapy are reported.
Time frame: Pre-infusion, 5 min., 1, and 3 hours from end of infusion
Population: Eligible patients who received topotecan with empirical dosage during consolidation therapy were included in this analysis. Per protocol, low-risk and intermediate-risk patients did not receive topotecan during consolidation unless they experienced disease progression during induction. One such intermediate-risk patient was included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low-Risk Group | Participants With Empirical Dosage Achieving Target System Exposure of Intravenous Topotecan | 0 participants |
| Intermediate-Risk Group | Participants With Empirical Dosage Achieving Target System Exposure of Intravenous Topotecan | 8 participants |
Secondary
Participants With PK-guided Dosage Adjustment Achieving Target System Exposure of Intravenous Topotecan
Number of participants who successfully achieve target systemic exposure of intravenous topotecan after a pharmacokinetic-guided dosage adjustment during consolidation phase of therapy are reported.
Time frame: Pre-infusion, 5 min., 1, and 3 hours from end of infusion
Population: Eligible patients who received topotecan with PK-guided dosage adjustment during consolidation therapy were included in this analysis. Per protocol, low-risk and intermediate-risk patients did not receive topotecan during consolidation unless they experienced disease progression during induction. One such intermediate-risk patient was included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low-Risk Group | Participants With PK-guided Dosage Adjustment Achieving Target System Exposure of Intravenous Topotecan | 1 participants |
| Intermediate-Risk Group | Participants With PK-guided Dosage Adjustment Achieving Target System Exposure of Intravenous Topotecan | 20 participants |
Secondary
Percentage of Patients With Objective Responses Rate to Induction Chemotherapy
For patients treated in the intermediate and high risk strata with residual or metastatic disease we will estimate the stratum-specific objective response rate (complete response (CR) or partial response \[ PR\]). All patients who receive at least 1 -dose of methotrexate are evaluable for response. Objective responses must be sustained for at least eight weeks.
Time frame: From on-study date to 2 months after completion of induction chemotherapy (up to 4 months after on-study date)
Population: Eligible intermediate and high risk group patients who received at least 1 dose of methotrexate were included in this analysis. One of the high risk patients did not start therapy and was excluded.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low-Risk Group | Percentage of Patients With Objective Responses Rate to Induction Chemotherapy | 58.3 Percentage of patients |
| Intermediate-Risk Group | Percentage of Patients With Objective Responses Rate to Induction Chemotherapy | 21.1 Percentage of patients |
Secondary
Percent of Patients With Sustained Objective Responses Rate After Consolidation
For patients enrolled on the high-risk arm with measurable residual disease after induction treated with consolidation therapy, we will estimate the objective response (complete response (CR)/partial response (PR)) rate after consolidation therapy with a 95% confidence interval. Objective responses must be sustained for at least eight weeks. All patients who receive at least 1 dose of cyclophosphamide or topotecan during consolidation are evaluable for response.
Time frame: 8 weeks after completion of consolidation therapy (up to 8 months after on-study date)
Population: Of the 50 high-risk patients that started consolidation chemotherapy, 38 had measurable residual disease after induction and were included in this result.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low-Risk Group | Percent of Patients With Sustained Objective Responses Rate After Consolidation | 13.2 percentage of participants |
Secondary
Percent of PET Scans With Loss of Signal Intensity
Measures will be analyzed for intermediate risk participants who receive proton beam therapy (PBT) and who consent. This objective aims to assess the feasibility of using post-proton beam therapy (PBT) positron emission tomography (PET) as an in-vivo dosimetric and distal edge verification system in this patient population. To quantify the decay in signal, 134 scans from 53 patients were analyzed by recording the mean activation value (MAV), the average recorded PET signal from activation, within the target volume. With each patient being given the same dose, the percent standard deviation in the MAV can serve as a quantitative representation of signal loss due to radioactive decay.
Time frame: Up to 3 times during RT consolidation
Population: Intermediate risk patients treated at St. Jude were eligible to receive proton beam therapy through referral to the University of Florida Proton Therapy Institute. Patients electing to receive PBT and post-treatment PET scans after the delivery of one treatment beam were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low-Risk Group | Percent of PET Scans With Loss of Signal Intensity | 60 mean activation value (MAV) | Standard Deviation 27 |
Secondary
Pharmacogenetic Variation on Central Nervous System Transmitters
Frequencies of genetic polymorphisms were reported.
Time frame: At study enrollment (Day 0)
Population: Eligible patients who had neurotransmitter studies performed. Seventeen patients had studies performed.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Low-Risk Group | Pharmacogenetic Variation on Central Nervous System Transmitters | Genetic Polymorphisms for dopamine receptor D (DRD3) rs6280 | GG | 0 Participants |
| Low-Risk Group | Pharmacogenetic Variation on Central Nervous System Transmitters | Genetic Polymorphisms for monoamine oxidase A (MAOA) rs6323 | AA | 0 Participants |
| Low-Risk Group | Pharmacogenetic Variation on Central Nervous System Transmitters | Genetic Polymorphisms for monoamine oxidase A (MAOA) rs6323 | AG | 0 Participants |
| Low-Risk Group | Pharmacogenetic Variation on Central Nervous System Transmitters | Genetic Polymorphisms for monoamine oxidase A (MAOA) rs6323 | CC | 0 Participants |
| Low-Risk Group | Pharmacogenetic Variation on Central Nervous System Transmitters | Genetic Polymorphisms for monoamine oxidase A (MAOA) rs6323 | GG | 2 Participants |
| Low-Risk Group | Pharmacogenetic Variation on Central Nervous System Transmitters | Genetic Polymorphisms for monoamine oxidase A (MAOA) rs6323 | TC | 0 Participants |
| Low-Risk Group | Pharmacogenetic Variation on Central Nervous System Transmitters | Genetic Polymorphisms for monoamine oxidase A (MAOA) rs6323 | TG | 2 Participants |
| Low-Risk Group | Pharmacogenetic Variation on Central Nervous System Transmitters | Genetic Polymorphisms for monoamine oxidase A (MAOA) rs6323 | TT | 13 Participants |
| Low-Risk Group | Pharmacogenetic Variation on Central Nervous System Transmitters | Genetic Polymorphisms for catecholamine-O-methyltransferase (COMT) rs4680 | AA | 5 Participants |
| Low-Risk Group | Pharmacogenetic Variation on Central Nervous System Transmitters | Genetic Polymorphisms for catecholamine-O-methyltransferase (COMT) rs4680 | AG | 7 Participants |
| Low-Risk Group | Pharmacogenetic Variation on Central Nervous System Transmitters | Genetic Polymorphisms for catecholamine-O-methyltransferase (COMT) rs4680 | CC | 0 Participants |
| Low-Risk Group | Pharmacogenetic Variation on Central Nervous System Transmitters | Genetic Polymorphisms for catecholamine-O-methyltransferase (COMT) rs4680 | GG | 5 Participants |
| Low-Risk Group | Pharmacogenetic Variation on Central Nervous System Transmitters | Genetic Polymorphisms for catecholamine-O-methyltransferase (COMT) rs4680 | TC | 0 Participants |
| Low-Risk Group | Pharmacogenetic Variation on Central Nervous System Transmitters | Genetic Polymorphisms for catecholamine-O-methyltransferase (COMT) rs4680 | TG | 0 Participants |
| Low-Risk Group | Pharmacogenetic Variation on Central Nervous System Transmitters | Genetic Polymorphisms for catecholamine-O-methyltransferase (COMT) rs4680 | TT | 0 Participants |
| Low-Risk Group | Pharmacogenetic Variation on Central Nervous System Transmitters | Genetic Polymorphisms for dopamine receptor D (DRD3) rs6280 | AA | 0 Participants |
| Low-Risk Group | Pharmacogenetic Variation on Central Nervous System Transmitters | Genetic Polymorphisms for dopamine receptor D (DRD3) rs6280 | AG | 0 Participants |
| Low-Risk Group | Pharmacogenetic Variation on Central Nervous System Transmitters | Genetic Polymorphisms for dopamine receptor D (DRD3) rs6280 | CC | 6 Participants |
| Low-Risk Group | Pharmacogenetic Variation on Central Nervous System Transmitters | Genetic Polymorphisms for dopamine receptor D (DRD3) rs6280 | TC | 4 Participants |
| Low-Risk Group | Pharmacogenetic Variation on Central Nervous System Transmitters | Genetic Polymorphisms for dopamine receptor D (DRD3) rs6280 | TG | 0 Participants |
| Low-Risk Group | Pharmacogenetic Variation on Central Nervous System Transmitters | Genetic Polymorphisms for dopamine receptor D (DRD3) rs6280 | TT | 7 Participants |
Secondary
Rate of Distant Disease Progression
Distant failure was defined as the interval from end of RT to date of distant failure (or combined local + distant failure). Competing events were local failure or second malignancy. Patients without an event were censored at date of last contact. The 1-year cumulative incidence was estimated and reported with a 95% confidence interval.
Time frame: 1 year after completion of radiation therapy for last patient
Population: Eligible intermediate-risk patients who received focal radiation were included in this analysis. Of the 156 intermediate risk patients, 121 started radiation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low-Risk Group | Rate of Distant Disease Progression | 25.6 percentage of participants |
Secondary
Rate of Local Disease Progression
Local failure was defined as the interval from end of RT to date of local failure (or combined local + distant failure). Competing events were distant failure or second malignancy. Patients without an event were censored at date of last contact. The 1-year cumulative incidence was estimated and reported with a 95% confidence interval.
Time frame: 1 year after completion of radiation therapy for last patient
Population: Eligible intermediate-risk patients who received focal radiation were included in this analysis. Of the 156 intermediate risk patients, 121 started radiation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low-Risk Group | Rate of Local Disease Progression | 13.2 Percentage of participants |
Secondary
Topotecan Apparent Oral Clearance in Maintenance Chemotherapy
Topotecan plasma concentration-time data are collected on day 1 of maintenance cycle A1 after a single oral dose. Individual estimates of topotecan apparent oral clearance are obtained using post hoc analysis.
Time frame: Pre-dose, 0.25, 1.5 and 6 hours post-dose
Population: Eligible patients who received oral topotecan during maintenance therapy cycle A1 and had samples collected for PK analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Low-Risk Group | Topotecan Apparent Oral Clearance in Maintenance Chemotherapy | 41.4 L/h |
| Intermediate-Risk Group | Topotecan Apparent Oral Clearance in Maintenance Chemotherapy | 41.0 L/h |
| High-Risk Group | Topotecan Apparent Oral Clearance in Maintenance Chemotherapy | 44.6 L/h |
Secondary
Topotecan AUC0-24h in Consolidation Chemotherapy
Topotecan plasma concentration-time data are collected on day 1 of consolidation cycle 1 after a single IV dose. Individual estimates of topotecan AUC0-24h (area under concentration curve from time 0 to 24 hours post- dose) are obtained using post hoc analysis.
Time frame: Pre-infusion, 5 min., 1, 3, and 24 hours from end of infusion
Population: Eligible patients who received intravenous topotecan during consolidation cycle 1 and had PK samples collected were included in this analysis. Per protocol, low- and intermediate-risk patients did not receive topotecan during consolidation unless they experienced disease progression during induction. One such intermediate-risk patient was included.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Low-Risk Group | Topotecan AUC0-24h in Consolidation Chemotherapy | 117 µg·h/L |
| Intermediate-Risk Group | Topotecan AUC0-24h in Consolidation Chemotherapy | 116 µg·h/L |
Secondary
Topotecan AUC0-24h in Maintenance Chemotherapy
Topotecan plasma concentration-time data are collected on day 1 of maintenance cycle A1 after a single oral dose. Individual estimates of topotecan AUC0-24h (area under concentration curve from time 0 to 24 hours post- dose) are obtained using post hoc analysis.
Time frame: Pre-dose, 0.25, 1.5, 6, and 24 hours post-dose
Population: Eligible patients who received oral topotecan during maintenance therapy cycle A1 and had samples collected for PK analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Low-Risk Group | Topotecan AUC0-24h in Maintenance Chemotherapy | 10.90 µg·h/L |
| Intermediate-Risk Group | Topotecan AUC0-24h in Maintenance Chemotherapy | 11.60 µg·h/L |
| High-Risk Group | Topotecan AUC0-24h in Maintenance Chemotherapy | 10.33 µg·h/L |
Secondary
Topotecan Clearance in Consolidation Chemotherapy
Topotecan plasma concentration-time data are collected on day 1 of consolidation cycle 1 after a single IV dose. Individual estimates of topotecan clearance are obtained using post hoc analysis.
Time frame: Pre-infusion, 5 min., 1, and 3 hours from end of infusion
Population: Eligible patients who received intravenous topotecan during consolidation cycle 1 and had PK samples collected were included in this analysis. Per protocol, low- and intermediate-risk patients did not receive topotecan during consolidation unless they experienced disease progression during induction. One such intermediate-risk patient was included.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Low-Risk Group | Topotecan Clearance in Consolidation Chemotherapy | 30.3 L/h/m^2 |
| Intermediate-Risk Group | Topotecan Clearance in Consolidation Chemotherapy | 26.40 L/h/m^2 |