When should craniospinal irradiation be initiated after a gross‑total resection of medulloblastoma in a pediatric patient?

Timing of Craniospinal Irradiation After Gross-Total Resection of Medulloblastoma

Craniospinal irradiation should be initiated within 28–30 days after gross-total resection of medulloblastoma in pediatric patients, with an absolute maximum of 42 days, to optimize survival outcomes. 1, 2

Evidence-Based Timing Recommendations

Optimal Window: 3–4 Weeks Post-Surgery

• Radiation therapy should begin 3–4 weeks (21–28 days) after surgical resection to allow adequate wound healing while avoiding treatment delays that compromise disease control. 3, 2
• The 2025 NCCN Guidelines for Pediatric CNS Cancers emphasize that most pediatric trials require CSI to begin within 30 days of tumor resection, based on evidence that delays worsen outcomes in children. 1
• A large National Cancer Database analysis of 1,338 pediatric medulloblastoma patients demonstrated that initiating radiation ≤3 weeks post-surgery was associated with decreased 5-year overall survival (72.5%) compared to starting at 3.1–4 weeks (80.5%), 4.1–5 weeks (79.4%), or >5 weeks (77.8%). 3

Maximum Acceptable Delay: 42 Days

• The upcoming EORTC and Alliance trials for adult medulloblastoma allow a maximum of 42 days from resection to radiation initiation, establishing this as the upper limit for treatment delay. 1
• Delays beyond 28 days are associated with significantly worse outcomes: patients starting radiation >45 days post-surgery had only 68% posterior fossa control at 5 years versus 89% for those treated ≤45 days (p=0.01). 4

Risk-Stratified Radiation Doses

Average-Risk Patients

• 23.4 Gy craniospinal irradiation with posterior fossa boost to 54 Gy, initiated within 28–30 days post-resection. 1, 5
• Average-risk criteria: M0 disease, classic histology, and gross-total or near-total resection with residual tumor <1.5 cm². 1, 5

High-Risk Patients

• 36 Gy craniospinal irradiation with primary site boost to 54–55.8 Gy, initiated within 28–30 days post-resection. 1, 5
• High-risk criteria: M+ disease, subtotal resection with residual >1.5 cm², or large cell/anaplastic histology. 1, 5

Very High-Risk Patients (MYC Amplification)

• 36 Gy craniospinal irradiation with boost to 54–55.8 Gy, with concurrent carboplatin before each fraction for Group 3 tumors specifically. 1, 5

Pre-Radiation Requirements

Imaging Timeline

• Obtain contrast-enhanced brain MRI within 24–72 hours after surgery to define the tumor bed and confirm extent of resection. 5
• Delay spinal MRI for 2–3 weeks post-surgery to avoid false-positive findings from surgical blood products that could incorrectly upstage the patient. 1, 5
• Complete disease staging with craniospinal MRI and CSF cytology is mandatory before radiation planning. 1

Molecular Testing

• Obtain adequate tissue for molecular genetic characterization (WNT, SHH, Group 3, Group 4 subtypes) during initial surgery, as molecular findings are critical for risk stratification and treatment planning. 1

Supporting Evidence for Early Initiation

Pediatric Data

• A 30-year single-institution review demonstrated that radiation treatment duration ≤45 days yielded 76% freedom from relapse at 5 years versus 43% for >45 days (p=0.004). 4
• A Chinese cohort study found that patients receiving radiation within 25 days had 74.1% 3-year disease-free survival versus 46.0% for later initiation (p=0.03). 6
• A German series confirmed that early initiation of postoperative radiation therapy within 28 days was associated with improved outcome on multivariate analysis. 2

Adult Considerations

• Although evidence is less robust in adults, the NOA-07 pilot trial for adult medulloblastoma had a median time from resection to radiochemotherapy of 53 days, suggesting slightly more flexibility in adults. 1
• However, increasing awareness about avoiding delays remains critical even in adult populations, as delays likely compromise outcomes across all age groups. 1

Adjuvant Chemotherapy Timing

• Chemotherapy should begin 6 weeks after completing radiation therapy, not before radiation, to allow bone marrow recovery while avoiding excessive delay of systemic therapy. 5, 7
• Either the Children's Oncology Group (COG) protocol or St. Jude protocol may be used, but these protocols are not interchangeable and must be followed as complete regimens. 1, 7

Critical Pitfalls to Avoid

• Do not delay radiation beyond 30 days without compelling medical justification, as each week of delay increases recurrence risk. 4, 2, 6
• Do not perform spinal MRI immediately post-surgery, as blood products will create false-positive enhancement that may lead to inappropriate treatment intensification. 5
• Do not initiate radiation before adequate wound healing (typically 3 weeks minimum), as the National Cancer Database analysis showed worse outcomes with radiation ≤3 weeks post-surgery. 3
• Do not omit molecular testing, as Group 3 tumors with high-risk features require concurrent carboplatin radiosensitization that improves event-free survival by 19%. 1, 5
• Do not exceed 90 days from surgery to radiation completion without documented progression, as this represents the outer boundary of acceptable delay. 3