What is the recommended adjuvant chemotherapy protocol for a 4-year-old standard risk patient with medulloblastoma?

Adjuvant Protocol for 4-Year-Old Standard Risk Medulloblastoma

For a 4-year-old with standard-risk medulloblastoma, administer 23.4 Gy craniospinal irradiation with involved field boost to 54 Gy plus weekly vincristine during radiation, followed by maintenance chemotherapy using either the St. Jude protocol (vincristine, cisplatin, cyclophosphamide) or COG protocol (lomustine, vincristine, cisplatin). 1, 2, 3

Risk Stratification Confirmation

Before initiating treatment, confirm the patient meets all standard-risk criteria: 1, 2

• M0 disease (no metastatic dissemination on spine MRI and CSF cytology)
• Classic histology (not large cell/anaplastic)
• Gross total resection (GTR) or near-total resection (NTR) (≤1.5 cm² residual disease)
• Molecular subtype that is not WNT-activated, SHH-activated with TP53 mutation, or Group 3 with MYC amplification

Radiation Therapy Component

Deliver reduced-dose craniospinal irradiation of 23.4 Gy to the craniospinal axis, followed by an involved field boost to 54 Gy to the primary tumor site. 1, 2, 3

• This reduced-dose approach has demonstrated 5-year progression-free survival of 79-86% when combined with adjuvant chemotherapy 4, 5
• Radiation should begin within one month postoperatively 3
• Administer weekly vincristine (1.4 mg/m² with 2 mg maximum, not capped at 1 mg) concurrently during the 6-week radiation period 1, 2, 3

Maintenance Chemotherapy Options

You must choose one of the following protocols—they are not interchangeable and should not be mixed: 1, 2, 3

St. Jude Protocol (Preferred by NCCN)

Administer vincristine, cisplatin, and cyclophosphamide in cycles following radiation completion. 1, 2, 3

• This three-drug combination was validated in 330 average-risk patients with comparable outcomes to other prospective studies 3
• Monitor closely for vincristine-associated peripheral neuropathy and cisplatin-associated ototoxicity as dose-limiting toxicities 2, 3

COG Protocol (Alternative)

Administer lomustine (CCNU), vincristine, and cisplatin during and after radiation therapy. 1, 5

• This regimen demonstrated 5-year progression-free survival of 79% in the Children's Cancer Group study 5
• Cisplatin dose modifications were required in >50% of patients before treatment completion 5

Critical Monitoring Requirements

Throughout treatment, monitor for: 2, 3, 5

• Vincristine-associated peripheral neuropathy (most common dose-limiting toxicity requiring intervention)
• Cisplatin-associated ototoxicity (hearing loss within speech frequencies occurs in approximately 15% of patients)
• Hematopoietic toxicity (most predominant side effect requiring dose adjustments) 4
• Nephrotoxicity from cisplatin (though grade III/IV toxicity is uncommon) 4

Common Pitfalls to Avoid

Do not use low-dose CSI below 23.4 Gy, as this compromises outcomes even with chemotherapy. 2, 3

Do not delay radiation therapy beyond one month postoperatively, as timing is critical for disease control. 3

Do not switch between St. Jude and COG protocols mid-treatment, as the maintenance regimens differ significantly in drug combinations, dosing schedules, and toxicity profiles. 1, 2, 3

Do not cap vincristine at 1 mg—the protocol specifies 1.4 mg/m² with a 2 mg maximum dose. 3

Fertility Preservation

Refer the patient to fertility preservation counseling before initiating chemotherapy, given the young age at diagnosis and gonadotoxic effects of alkylating agents (cyclophosphamide, lomustine) and cisplatin. 2

Expected Outcomes

With this treatment approach, expect: 4, 6, 5

• 5-year event-free survival: 79-86%
• 5-year overall survival: 83-90%
• Sites of relapse include local tumor site alone (10-15%), local plus disseminated disease (40-45%), and non-primary sites (15-20%)
• Brainstem involvement does not adversely affect outcome in standard-risk patients 6, 5