Participants will be assigned to treatment strata based first on molecular subgroup assignment (WnT, SHH, or non-WnT non- SHH) and then by clinical risk stratification (extent of resection, M stage, histologic subtype, and cytogenetic features). all patients will be treated with risk-adapted radiation therapy and adjuvant chemotherapy. Patients assigned to Stratum W1 (WnT, M0, GTR/nTR, classic histology, and monosomy 6) will receive reduced dose radiation therapy (15Gy CSi/51Gy Boost). Patients assigned to Stratum W2, S1, n1 or n2 (all M0, GTR/nTR) will receive standard dose radiation therapy (23.4Gy CSi/54Gy Boost). Patients assigned to Stratum W3, S2, or n3 (all M+ and/or partially resected and/or MYC/MYCn amplified) will receive high dose radiation therapy (36-39.6Gy CSi/54Gy Boost). Radiation therapy will be followed by 4 cycles of adjuvant conventional chemotherapy with cyclophosphamide, cisplatin and vincristine for all patients. Patients assigned to Stratum n2 or n3 (non-WnT non-SHH with high risk factors) will receive 3 additional cycles of pemetrexed and gemcitabine chemotherapy intermixed into the conventional adjuvant chemotherapy cycles. Patients with SHH subtype (Stratum S1 or S2) will receive 12 months additional maintenance therapy with vismodegib after completing adjuvant conventional chemotherapy.
all participants will be assigned to a radiation and chemotherapy treatment plan.
This site is not participating in the exercise, computerized memory-training, nor sleep program interventions.
additional studies involving research imaging include studying the effect of cancer treatment on the developing brain. Tumor tissue will analyzed for other molecular markers that may help understand medulloblastoma. Standard of care endocrine, pulmonary, and cardiac testing will be studied to further understand the effects of the cancer treatment in pediatric patients.
1. Medulloblastoma or medulloblastoma variants including posterior fossa PNET as documented by an institutional pathologist.
2. Age greater than or equal to 3 years and less than 22 years of age at the time of diagnosis.
3. No previous radiotherapy, chemotherapy or other brain tumor directed therapy other than corticosteroid therapy and surgery.
4. Patients must begin treatment as outlined in the protocol within 36 days of definitive surgery (day of surgery is day 0; definitive surgery includes second surgeries to resect residual tumor).
5. Adequate performance status: children < 10-Lansky Score >= 30; children >= 10-Karnofsky >= 30 (except for posterior fossa syndrome).
6. Females of child-bearing potential cannot be pregnant or breast-feeding. Female participants > 10 years of age or post-menarche must have a negative serum or urine pregnancy test prior to enrollment.
7. Biological parent(s) of participant (child) enrolling on SJMB12. These parents will be assigned to cohort P. The exclusion criteria below do not apply to this cohort.
This site will not be participating in the exercise intervention portion of the study, therefore the inclusion criteria for exercise intervention is not applicable.
This site will not be participating in the neuroocognitive remediation intervention portion of the study, therefore the inclusion criteria for neurocognitive intervention is not applicable.
ELIGIBILITY FOR STRATUM S PATIENTS TO START MAINTENANCE CHEMOTHERAPY
To be assessed after adjuvant therapy, prior to start of maintenance
1. Participants must be Stratum S (SHH)
2. Must be able to swallow pills
3. BSA must be >0.67 and <2.5 m2
4. Male and female participants of reproductive potential must agree to effective contraception during and after study treatment.
5. ANC >1000/mm3 (after G-CSF discontinued)
6. Platelets >50,000/mm3 (without support)
7. Hgb >8 g/dL (with or without transfusion support)
8. Serum creatinine <= 1.5 mg/dL
9. Total bilirubin <= 1.5X the institutional ULN
10. SGPT (ALT) <= 2.5X the institutional ULN
11. SGOT (AST) <= 2.5X the institutional ULN
12. Alkaline Phosphatase <= 1.5X the institutional ULN
13. Serum albumin >= 2.5 g/dL