Treatment of Patients With Newly Diagnosed Medulloblastoma, Supratentorial Primitive Neuroectodermal Tumor, or Atypical Teratoid Rhabdoid Tumor

• Progression-Free Survival (PFS) in ERBB2-Negative Tumors Compared to ERBB2-Positive Tumors [ Time Frame: 2 years after tumor cell analysis in 122 participants ]
  The relationship between ERBB2 protein expression in tumors and progression-free survival was assessed in 122 participants with a diagnosis of medulloblastoma and with ERBB2 protein assessments. If the ERBB2 value was greater than zero, the ERBB2 was defined as positive for the participant. If the ERBB2 value was zero, the ERBB2 was defined as negative. Progression-free survival was calculated from the date of diagnosis to the date of disease progression/relapse, the date of death, or the date of last contact. The log-rank test was used to compare the PFS distributions of ERBB2 groups.
  
  
• Progression-Free Survival (PFS) Compared Between ERBB2 Assessment and Risk Group. [ Time Frame: 2 years after tumor cell analysis in 122 participants ]
  122 participants with a diagnosis of medulloblastoma were grouped by ERBB2 positive/negative assessment and risk group into 4 groups. Progression-free survival was calculated from the date of diagnosis to the date of disease progression/relapse, the date of death, or the date of last contact. The log-rank test was used to compare the PFS distributions of ERBB2 groups.
  
  
• Frequency of Mutations Associated With SHH and WNT Tumors [ Time Frame: within 3.5 years following completion of accrual ]

  To estimate the frequency of mutations associated with SHH and WNT tumors via targeted sequencing.

  This outcome was initially expected to be completed by September 2014. Technologic advancements have improved sequencing on formalin fixed paraffin embedded material using smaller quantities of nucleic acids. However, given that this technology is new, we had to thoroughly evaluate it on samples with abundant material first so as not to use up precious patient samples that are available in small quantities. The project has been delayed since extra time and care has gone into evaluating this technology to ensure that the data yield is accurate. We are now proceeding with a methodology that meets our quality controls.

  
  

• Reading Decoding Composite Scores in the Intervention and Standard of Care Groups [ Time Frame: Measurements will be made at time of randomization, at 3 months from initiation of treatment, and yearly thereafter for 10 years ]
  To compare the effects of a computer-based training system specifically targeting language, reading, and learning skills (Fast ForWord, Scientific Learning Corporation) with the current standard of care on reading decoding skills as measured by individual academic testing.
  
  
• Number of Average Risk Patients Whose Treatment Failure Included the Posterior Fossa [ Time Frame: Annually for 6 years post irradiation ]
  To monitor for treatment failure in the posterior fossa of patients whose tumor bed receives a reduced volume of radiation.
  
  
• Mean RT Dose to Specified Target Tissue Volume by Rate and Pattern of Failure, e.g. Local Failure, Distant Failure, Etc. [ Time Frame: Once all patients have been followed for 2 years ]
  To correlate radiation dosimetry of target and normal tissues with rate and patterns of failure and longitudinal measures of audiometric, endocrine and cognitive effects.
  
  

SECONDARY OBJECTIVES:

• To compare the effects of a computer-based training system specifically targeting language, reading, and learning skills (Fast ForWord, Scientific Learning Corporation) with the current standard of care on reading decoding skills as measured by individual academic testing.
• To monitor for treatment failure in the posterior fossa of patients whose tumor bed receives a reduced volume of radiation.
• To correlate radiation dosimetry of target and normal tissues with rate and patterns of failure and longitudinal measures of audiometric, endocrine and cognitive effects.

EXPLORATORY OBJECTIVES:

• To estimate the change in neuropsychological performance from the neuropsychology assessment battery (intellect, academic achievement and cognitive ability) and examine the relationship of these changes to risk group, age at diagnosis, and parent measures.
• To evaluate the differences between neurotoxicity in the average-risk patient group with that in the high-risk group through qMRI, and fMRI.
• To develop or refine novel models relating impact of medulloblastoma therapy on neurocognitive performance to quantitative and functional neuroimaging measures.

OUTLINE: This is a multicenter study. Patients are stratified according to disease risk (high-risk disease vs average-risk disease).

Patients in both strata undergo peripheral blood stem cell or bone marrow harvest.

• Stratum 1 (high-risk group):

  • Radiotherapy: Patients undergo craniospinal radiotherapy once daily 5 days a week for 6 weeks.
  • High-dose chemotherapy and autologous stem cell transplantation (SCT): Six weeks after the completion of radiotherapy, patients receive high-dose chemotherapy comprising vincristine IV followed by cisplatin IV over 6 hours on day -4 and cyclophosphamide IV over 1 hour on days -3 and -2. Patients undergo autologous SCT on day 0. Patients receive filgrastim (G-CSF) subcutaneously beginning on day 1 and continuing until blood counts recover. Patients receive vincristine IV on day 6. High-dose chemotherapy and autologous SCT repeat every 4 weeks for 3 additional courses in the absence of unacceptable toxicity.

• Stratum 2 (average-risk group):

  • Radiotherapy: Patients undergo craniospinal radiotherapy as in stratum 1, but at a lower dose.
  • High-dose chemotherapy and autologous SCT: Patients receive high-dose chemotherapy, autologous SCT, G-CSF, and post-transplantation vincristine as in stratum 1.

Some patients undergo a neuropsychology assessment at baseline, before chemotherapy, and then annually for 5 years.

After completion of study therapy, patients are followed every 3 months until month 30 (2.5 years) after diagnosis and then every 6 months until month 72 (6 years) after diagnosis.