Medulloblastoma Treatment Guidelines
Treatment of medulloblastoma requires maximal safe surgical resection followed by risk-stratified craniospinal irradiation with concurrent and maintenance chemotherapy, with the specific radiation dose and chemotherapy regimen determined by molecular subtype, extent of resection, and metastatic status. 1
Initial Management and Diagnosis
Surgical resection should aim for gross total resection (GTR) while minimizing neurologic deficits. 1 The goals include maximal cytoreduction, relief of hydrocephalus, reduction of tumor-associated mass effect, and obtaining adequate tissue for both histologic and molecular classification. 1 Resection with ≤1.5 cm² residual disease is acceptable in some settings. 1
Obtain adequate tissue for molecular genetic characterization at initial surgery—this is critical for risk stratification. 1 Molecular subtyping should include assessment for WNT activation, SHH activation with TP53 status, and Group 3/4 classification. 1 For patients with resectable residual disease after initial surgery, consider second-look surgery. 1
Refer patients to fertility preservation counseling before initiating chemotherapy, given the young age at diagnosis. 1
Risk Stratification Based on Molecular Subtype
WNT-Activated Medulloblastoma (Low Risk)
- Excellent prognosis with long-term survival rates >90% 1
- Most common in children aged 7-14 years 1
- Frequently displays intratumoral hemorrhage on imaging 1
SHH-Activated Medulloblastoma
- TP53-wild-type: Intermediate prognosis 1
- TP53-mutant and/or MYCN amplification: Very poor prognosis, worse than TP53 mutation alone 1
- Represents 10-20% of medulloblastomas 1
Group 3 and 4 (Non-WNT/Non-SHH) Medulloblastoma
- Group 3: Poor prognosis with 5-year survival rates 20-30% 1
- Group 4: Better prognosis with survival rates 75-90% 1
- Each represents 25-35% of medulloblastomas 1
Risk-Stratified Treatment Approach
Average Risk (All Criteria Must Be Met)
- M0 disease (no metastases)
- Classic histology
- GTR or near-total resection (NTR)
Treatment: 23.4 Gy craniospinal irradiation (CSI) with involved field boost to 54 Gy, plus adjuvant/maintenance systemic therapy 1
Chemotherapy regimen: Weekly vincristine during radiotherapy, followed by maintenance chemotherapy using either COG protocol (cisplatin/lomustine/vincristine alternating with cisplatin/cyclophosphamide/vincristine) or St. Jude protocol (vincristine/cisplatin/cyclophosphamide). 1 These protocols are not interchangeable. 1
High Risk (Group 3 and 4)
- M+ disease (metastatic) OR
- Subtotal resection (STR) OR
- Large cell/anaplastic histology
Treatment: High-dose CSI 36 Gy with involved field boost to 54-55.8 Gy, plus adjuvant/maintenance systemic therapy 1
Chemotherapy regimen: Use St. Jude protocol or ACNS0332 protocol (6 cycles of cisplatin, cyclophosphamide, and vincristine) for maintenance. 1
Very High Risk
- MYC amplification
Treatment: High-dose CSI 36 Gy with involved field boost to 54-55.8 Gy 1
Critical addition for Group 3 tumors with MYC amplification: Add carboplatin prior to each radiation fraction as a radiosensitizer—this improved event-free survival by 19% in high-risk Group 3 medulloblastoma. 1
Chemotherapy regimen: Same maintenance options as high-risk disease. 1
Radiation Therapy Timing and Considerations
Initiate radiation therapy 3.1-5 weeks after surgery—this timing is associated with optimal outcomes. 2 Starting RT ≤3 weeks after surgery is associated with decreased 5-year survival (72.5% vs. 80.5%), while delays beyond 5 weeks but within 90 days do not adversely impact survival. 2
Radiation is not recommended for patients <3 years of age, though radiation-avoiding strategies may be used for patients >3 years at the treating physician's discretion. 1 This guideline applies to children receiving radiation-inclusive treatment strategies. 1
Toxicity Monitoring
Monitor for vincristine-associated neuropathy and cisplatin-associated ototoxicity throughout treatment. 1 These are the most common dose-limiting toxicities requiring intervention.
Recurrent or Progressive Disease
Recurrent/progressive medulloblastoma after first-line therapy occurs in approximately one-third of patients and carries survival rates <10%. 1
For recurrence after 3-5 years, rebiopsy the tumor to distinguish between recurrent medulloblastoma and secondary malignancy (such as diffuse high-grade glioma). 1 Biopsy may also identify actionable molecular findings. 1
Treatment options for recurrent disease:
- Targeted therapy based on molecular alterations: Dabrafenib/trametinib or vemurafenib for BRAF V600E-mutated tumors; larotrectinib or entrectinib for TRK fusion-positive tumors; nivolumab or pembrolizumab for hypermutant tumors; lorlatinib or alectinib for ALK rearrangement-positive tumors 1
- Reirradiation if feasible 1
- For single, focal posterior fossa recurrence: Consider reresection, which may confer overall survival benefit 1
- For poor performance status: Palliative/best supportive care with oral etoposide, bevacizumab, or nitrosoureas (lomustine or carmustine) 1
Surveillance and Follow-Up
Use MRI with gadolinium contrast for surveillance—spine MRI is superior to other modalities for detecting leptomeningeal dissemination. 1 Obtain sagittal T2-weighted images and postcontrast sagittal and axial T1-weighted images of the entire spine. 1
FDG-PET/CT can be useful for evaluating metastatic disease and prognosis, particularly when MRI findings are equivocal. 1 Increased FDG uptake correlates negatively with survival. 1
Special Considerations for Adult Patients
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. 1 Treatment at academic centers and high-volume facilities is associated with longer survival rates and more frequent access to optimal multimodality therapy. 1
Routinely conduct DNA methylation testing for diagnosis and molecular subgrouping in adult patients. 1