Treatment of Medulloblastoma with Chemotherapy and Radiation Therapy
Treatment of medulloblastoma requires a risk-stratified approach with maximal safe surgical resection followed by craniospinal irradiation (CSI) and adjuvant chemotherapy to optimize survival outcomes while minimizing toxicity. 1
Initial Surgical Management
- Maximal safe surgical resection is the first step in treatment
- Goal: Gross total resection (GTR) or near-total resection (NTR) with <1.5 cm² residual disease 1
- Post-operative MRI should be performed within 24-72 hours to assess residual disease 1
- CSF sampling via lumbar puncture should be performed for staging (after spine imaging, delayed 2-3 weeks post-surgery) 1
Risk Stratification
Risk stratification is critical for determining appropriate radiation and chemotherapy regimens:
Average Risk
- M0 disease (no metastasis)
- Classic histology
- GTR or NTR 1
High Risk
- M+ disease (metastatic)
- Subtotal resection (STR)
- Large cell/anaplastic histology 1
Very High Risk
- MYC amplification 1
Radiation Therapy Approach
Average Risk Patients
- CSI dose: 23.4 Gy with boost to posterior fossa/tumor bed to 54 Gy 1
- This reduced-dose CSI approach with adjuvant chemotherapy has shown 79-86% progression-free survival at 5 years 2
High Risk Patients
- Higher dose CSI: 36 Gy with boost to posterior fossa/tumor bed to 54-55.8 Gy 1
- For Group 3 tumors: Consider adding carboplatin during radiation as a radiosensitizer 1
Technical Considerations
- Proton beam therapy is strongly recommended over conventional radiotherapy when available, particularly for pediatric patients 1
- Benefits include reduced radiation to normal tissues while maintaining equivalent tumor control 1
- Special caution for patients <3 years of age, where radiation-sparing approaches are preferred 1, 3
Chemotherapy Regimens
During Radiation
- Concurrent vincristine during radiotherapy acts as a radiosensitizer 2
- For Group 3 high-risk tumors: Carboplatin during radiation improves event-free survival by approximately 19% 1
Adjuvant/Maintenance Chemotherapy
- Post-radiation cisplatin-based chemotherapy regimens have shown 86% 5-year survival in pediatric patients 1
- Common regimens include:
- Cisplatin, lomustine (CCNU), and vincristine (Packer protocol) 4
- Alternating courses of cisplatin/etoposide and cyclophosphamide/vincristine (POG protocol) 4
- High-dose cyclophosphamide, cisplatin, and vincristine with stem cell rescue has shown promising early results (2-year PFS of 93.6% for average-risk patients) 5
Recurrent Disease Management
- Maximal safe resection should be attempted for recurrent tumors 1
- Chemotherapy options include:
Special Considerations
Age-Related Concerns
- Young age at diagnosis (<7 years) is a significant risk factor for neurocognitive impairment 3
- For children <3 years, radiation-sparing approaches are recommended 1
- Female patients should receive fertility preservation counseling due to risk of menstrual disorders and infertility 1, 6
Long-Term Monitoring
- Brain MRI every 3 months for first 2 years
- Biannual brain MRI for next 3 years
- Annual brain MRI thereafter 1
- Monitor for late effects including neurocognitive deficits, endocrine dysfunction, and secondary malignancies 3
Common Pitfalls and Caveats
- Pseudoprogression on imaging 4-8 weeks after radiation may mimic tumor progression and should be re-evaluated after 4 weeks 1
- Hematologic toxicity is common during chemotherapy, particularly with cisplatin-based regimens 4
- Ovarian protection should be considered for female patients 6
- Rebiopsy is recommended for late recurrences (>3-5 years) to rule out secondary malignancies 1
By following this risk-stratified approach combining surgery, radiation therapy, and chemotherapy, survival rates for medulloblastoma have improved significantly, with current protocols achieving 75-90% survival rates depending on risk factors 1.