Medulloblastoma Treatment Guidelines

Initial Management and Diagnosis

The National Comprehensive Cancer Network recommends maximal safe surgical resection followed by risk-stratified craniospinal irradiation with concurrent and maintenance chemotherapy for medulloblastoma treatment, with the specific radiation dose and chemotherapy regimen determined by molecular subtype, extent of resection, and metastatic status 1, 2
Surgical resection should aim for gross total resection (GTR) while minimizing neurologic deficits, with goals including maximal cytoreduction, relief of hydrocephalus, reduction of tumor-associated mass effect, and obtaining adequate tissue for both histologic and molecular classification 3, 1
Obtain adequate tissue for molecular genetic characterization at initial surgery, including assessment for WNT activation, SHH activation with TP53 status, and Group 3/4 classification, which is critical for risk stratification 3, 2
Refer patients to fertility preservation counseling before initiating chemotherapy, given the young age at diagnosis 2

WNT-activated medulloblastoma has an excellent prognosis with long-term survival rates >90%, and is most common in children aged 7-14 years 2
SHH-activated medulloblastoma with TP53-wild-type has an intermediate prognosis, while TP53-mutant and/or MYCN amplification has a very poor prognosis, worse than TP53 mutation alone 2
Group 3 medulloblastoma has a poor prognosis with 5-year survival rates 20-30%, while Group 4 has a better prognosis with survival rates 75-90% 2

Average-risk patients should receive 23.4 Gy craniospinal irradiation (CSI) with involved field boost to 54 Gy, plus adjuvant/maintenance systemic therapy, including weekly vincristine during radiotherapy, followed by maintenance chemotherapy using either COG or St. Jude protocol 5, 4
High-risk patients should receive high-dose CSI 36 Gy with involved field boost to 54-55.8 Gy, plus adjuvant/maintenance systemic therapy, including St. Jude protocol or ACNS0332 protocol for maintenance 5, 4
Very high-risk patients with MYC amplification should receive high-dose CSI 36 Gy with involved field boost to 54-55.8 Gy, and carboplatin prior to each radiation fraction as a radiosensitizer, which improved event-free survival by 19% in high-risk Group 3 medulloblastoma 4, 3

Radiation therapy should not be recommended for patients <3 years of age, though radiation-avoiding strategies may be used for patients >3 years at the treating physician's discretion 5

Monitor for vincristine-associated neuropathy and cisplatin-associated ototoxicity throughout treatment, as these are the most common dose-limiting toxicities requiring intervention 5

Recurrent/progressive medulloblastoma after first-line therapy occurs in approximately one-third of patients and carries survival rates <10% 5
For recurrence after 3-5 years, rebiopsy the tumor to distinguish between recurrent medulloblastoma and secondary malignancy, and to identify actionable molecular findings 3
Treatment options for recurrent disease include targeted therapy based on molecular alterations, reirradiation if feasible, reresection for single, focal posterior fossa recurrence, and palliative/best supportive care for poor performance status 1, 3

Use MRI with gadolinium contrast for surveillance, including spine MRI, which is superior to other modalities for detecting leptomeningeal dissemination 2
FDG-PET/CT can be useful for evaluating metastatic disease and prognosis, particularly when MRI findings are equivocal, and increased FDG uptake correlates negatively with survival 2

Adults with medulloblastoma should be referred to specialized centers or "centers of excellence" with expertise in diagnosis and treatment at the time of new diagnosis or recurrence, as treatment at academic centers and high-volume facilities is associated with longer survival rates and more frequent access to optimal multimodality therapy 6
Routinely conduct DNA methylation testing for diagnosis and molecular subgrouping in adult patients 6