Adjuvant Treatment for Pediatric Medulloblastoma
Following surgery and radiation therapy, pediatric medulloblastoma requires risk-stratified maintenance chemotherapy, with all patients receiving multi-agent chemotherapy regimens that differ based on risk category—average-risk patients receive reduced-dose craniospinal irradiation (23.4 Gy) with maintenance chemotherapy, while high-risk and very high-risk patients receive high-dose craniospinal irradiation (36 Gy) with intensified chemotherapy protocols. 1, 2
Risk Stratification Framework
Risk classification determines the entire adjuvant treatment approach and must be established before initiating therapy: 1, 2
Average-risk criteria (all must be met): 1, 2
- M0 disease (no metastatic spread)
- Classic histology (not large cell/anaplastic)
- Gross total resection (GTR) or near-total resection (NTR)
High-risk criteria (any one present): 1, 2
- M+ disease (metastatic dissemination)
- Subtotal resection (STR)
- Large cell/anaplastic histology
- Groups 3 and 4 molecular subtypes
- MYC amplification (particularly Group 3 tumors)
Adjuvant Treatment by Risk Category
Average-Risk Patients
Radiation therapy: 23.4 Gy craniospinal irradiation with involved field boost to 54 Gy 1, 2, 3
Concurrent chemotherapy during radiation: Weekly vincristine (1.4 mg/m², maximum 2 mg) administered throughout the 6-week radiation period 2, 4, 5
Maintenance chemotherapy options (choose one protocol—these are NOT interchangeable): 1, 2, 5
- St. Jude Protocol: Vincristine, cisplatin, and cyclophosphamide in cycles 2, 5
- COG Protocol: Lomustine (CCNU), cisplatin, and vincristine 4
The St. Jude protocol demonstrated 79% 5-year progression-free survival in 330 average-risk patients, validating the reduced-dose radiation approach when combined with chemotherapy. 5, 3 The COG protocol using lomustine showed similar efficacy with 86% 3-year progression-free survival. 3
High-Risk Patients
Radiation therapy: High-dose craniospinal irradiation 36 Gy with involved field boost to 54-55.8 Gy 1, 2
Concurrent chemotherapy during radiation: Weekly vincristine throughout radiation 1, 2
Maintenance chemotherapy: St. Jude protocol or ACNS0332 protocol with intensified multi-agent regimens 2
Very High-Risk Patients (MYC Amplification)
Radiation therapy: High-dose craniospinal irradiation 36 Gy with involved field boost to 54-55.8 Gy 1, 2
Radiosensitization: Carboplatin administered prior to each radiation fraction 1, 2
This approach is specifically indicated for Group 3 tumors with MYC amplification, where a randomized phase III trial demonstrated 19% improvement in event-free survival with carboplatin radiosensitization. 1, 2
Maintenance chemotherapy: Intensified multi-agent protocols 2
Critical Timing Considerations
Radiation initiation: Begin within one month postoperatively 5
Age restrictions: Radiation is not recommended for patients <3 years of age; radiation-avoiding strategies with chemotherapy alone may be considered for patients >3 years at physician discretion 1, 2, 5
Essential Toxicity Monitoring
Monitor closely throughout treatment for: 2, 4
- Vincristine-associated peripheral neuropathy: Most common dose-limiting toxicity requiring dose modification or treatment interruption 2, 4
- Cisplatin-associated ototoxicity: Requires baseline and serial audiologic evaluation; may necessitate hearing aids in long-term survivors 4, 6
- Myelosuppression: More frequent with cyclophosphamide-based regimens (45.5% grade I, 24.5% grade II), requiring 5-7 day treatment interruptions 4, 7
- Electrolyte abnormalities: More common with CCNU-based protocols 4
Critical Pitfalls to Avoid
Do not mix protocols: The St. Jude and COG maintenance regimens use different drug combinations and schedules—switching mid-treatment compromises outcomes and complicates toxicity management. 1, 5
Do not reduce craniospinal irradiation below 23.4 Gy for average-risk patients: One randomized trial found increased relapse risk with further dose reduction below this threshold. 1, 5
Do not delay radiation therapy: Treatment interruptions during radiation, particularly from chemotherapy-induced myelosuppression, correlate with poorer outcomes. 7
Do not cap vincristine at 1 mg: The protocol specifies 1.4 mg/m² with a 2 mg maximum dose. 5
Long-Term Sequelae
Survivors face significant late effects requiring ongoing surveillance: 7, 6, 8
- Neurocognitive impairment: 48-62% of survivors experience 8-21% reduction in IQ compared to siblings 7
- Endocrinopathies: Approximately 20% require exogenous hormone replacement 6
- Hearing loss: Up to 13% require hearing aids from cisplatin ototoxicity 6
These outcomes underscore the importance of risk-stratified therapy to minimize radiation exposure in average-risk patients while maintaining disease control. 3, 8