What is the recommended radiation therapy protocol according to RTOG (Radiation Therapy Oncology Group) guidelines for pediatric patients with central nervous system tumors, such as medulloblastoma, requiring craniospinal radiation?

RTOG Guidelines for Craniospinal Radiation

For pediatric patients with medulloblastoma requiring craniospinal irradiation, the standard protocol consists of 23.4 Gy to the craniospinal axis for average-risk patients or 36 Gy for high-risk patients, followed by a posterior fossa boost to 55.8 Gy, combined with adjuvant chemotherapy. 1

Risk Stratification Framework

Risk stratification determines the craniospinal radiation dose:

Average-Risk Criteria (All Must Be Met)

• M0 disease (no metastatic dissemination) 1
• Classic histology (not large cell/anaplastic) 1
• Gross total resection (GTR) or near-total resection (NTR) with residual tumor <1.5 cm² 1

High-Risk Criteria (Any One Present)

• M+ disease (CSF or spinal dissemination) 1
• Subtotal resection (STR) or residual tumor >1.5 cm² 1
• Large cell or anaplastic histology 1
• Supratentorial PNET 1

Very High-Risk Criteria

• MYC amplification (particularly in Group 3 tumors) 1

Radiation Dose Schema

Average-Risk Patients

• Craniospinal irradiation: 23.4 Gy 1
• Posterior fossa boost: Total 36 Gy (additional 12.6 Gy) 1
• Primary site boost: Total 55.8 Gy (additional 32.4 Gy to tumor bed) 1

The reduced craniospinal dose of 23.4 Gy has gained widespread acceptance for average-risk patients when combined with chemotherapy, as it lessens neurocognitive side effects while maintaining disease control 1. However, one randomized trial found an increased relapse risk with dose reduction, making chemotherapy integration essential 1.

High-Risk and Very High-Risk Patients

• Craniospinal irradiation: 36 Gy 1
• Primary site boost: Total 54-55.8 Gy 1
• For Group 3 tumors with MYC amplification: Add carboplatin prior to each radiation fraction 1

Technical Radiation Planning Details

Primary Site Target Volume Definition

• Planning target volume (PTV): Postoperative tumor bed plus 2 cm anatomically confined margin, then expanded with 0.3-0.5 cm geometric margin 2
• Contrast-enhanced brain MRI should be performed within 24-72 hours after surgery to define the tumor bed 1
• Spinal MRI should be delayed 2-3 weeks post-surgery to avoid false-positive findings from blood products 1

Fractionation

• Standard fractionation: 2 Gy per fraction for all components 3
• Radiation must begin within 28 days of definitive surgery 2

Integration with Chemotherapy

Timing Sequence

• Radiation therapy first: Initiate within 28 days post-surgery 2
• Chemotherapy second: Begin 6 weeks after completing radiation 1, 2

Chemotherapy Regimens (Choose One Protocol)

• COG protocol: Vincristine weekly during radiation, followed by maintenance with cisplatin/lomustine/vincristine alternating with cisplatin/cyclophosphamide/vincristine 1
• St. Jude protocol: Similar radiation-concurrent vincristine, followed by vincristine/cisplatin/cyclophosphamide maintenance 1

Critical caveat: These protocols are not interchangeable - commit to one protocol and follow it completely 1

Evidence Quality and Nuances

The 23.4 Gy craniospinal dose for average-risk patients is supported by multiple prospective trials showing 5-year event-free survival of 83% 2 and overall survival of 86% 1. A multi-institution prospective trial (n=86) demonstrated that conformal posterior fossa irradiation after 23.4 Gy craniospinal irradiation resulted in only 4.9% posterior fossa failure rate at 5 years 2.

However, there is conflicting evidence: Some studies suggest even lower doses (18 Gy craniospinal) may be feasible with intensive chemotherapy, showing 5-year relapse-free survival of 71% 4, 5. Conversely, retrospective data indicate that low-dose craniospinal irradiation may increase relapse risk without adequate chemotherapy 1.

Proton Beam Therapy Considerations

Proton beam therapy is strongly recommended for medulloblastoma when available (JASTRO/JSPHO Level B evidence) 1. Proton therapy achieves equivalent survival outcomes to conventional photon therapy while significantly reducing doses to normal tissues, particularly the cochleae, temporal lobes, and hypothalamus 1. This translates to reduced risk of secondary malignancies and improved neurocognitive outcomes 1.

Critical Pitfalls to Avoid

• Do not reduce craniospinal dose below 23.4 Gy for average-risk patients without intensive chemotherapy - one randomized trial showed increased relapse risk with dose reduction alone 1
• Do not perform spinal MRI immediately post-surgery - wait 2-3 weeks to avoid false-positive findings from surgical blood products 1
• Do not omit CSF sampling - lumbar puncture after spine imaging is mandatory for staging due to propensity for CSF seeding 1
• Do not use conventional posterior fossa irradiation - conformal techniques reduce the posterior fossa volume receiving high doses by approximately 13%, significantly reducing toxicity to temporal lobes and cochleae 2
• Do not delay radiation beyond 28 days post-surgery - early initiation is associated with improved outcomes 2

Pattern of Failure Data

Isolated spinal relapse does not increase with reduced-dose (23.4 Gy) craniospinal irradiation when combined with chemotherapy 6. The majority of failures occur in the posterior fossa despite adequate boost doses, emphasizing the importance of complete surgical resection 7. Posterior fossa failures can occur even with doses exceeding 56 Gy, suggesting that surgical extent of resection is more critical than radiation dose escalation beyond standard levels 7.