SFOP M4

Background

Prospective French (SFOP) protocol. 253 children with medulloblastoma/PNET treated 1992–1997. Evaluated role of pre-irradiation chemotherapy (carboplatin + procarbazine + vincristine, alternating with etoposide + cisplatin) followed by CSI RT and maintenance chemotherapy. Explored whether upfront chemotherapy could spare RT volume or dose in younger patients.

Interventions and follow up

Arm A: Neoadjuvant chemotherapy (4 cycles: carboplatin/procarbazine/vincristine alternating with etoposide/cisplatin) → CSI RT 25–36 Gy + posterior fossa/tumor bed boost to 54–55 Gy → maintenance vincristine/CCNU/cisplati
Primary endpoint: EFS, OS, response to neoadjuvant chemotherapy
mFollow up: 5.0 year

Results

Response to neoadjuvant chemo: ORR 59% (CR+PR)
5-yr EFS (M0): 75% (standard risk) vs 44% (high risk, M+)
5-yr OS: 72% (M0) vs 55% (M+)
Desmoplastic histology response: Superior response to neoadjuvant chemotherapy

Adverse events

Main adverse events: Neoadjuvant chemotherapy: myelosuppression (grade ≥3 neutropenia 82%), cisplatin ototoxicity (grade ≥2 in 35%), nephrotoxicity. RT-related: neurocognitive decline, endocrine deficiency. Treatment-related mortality 3%.

Conclusions

Pre-irradiation chemotherapy achieved high response rates and feasible delivery in medulloblastoma but did not clearly improve outcomes over RT alone in historical comparisons. The sequential approach demonstrated the chemosensitivity of medulloblastoma, particularly desmoplastic subtype.

Key Limitations

Key Limitations: No randomized comparison arm — historical control comparisons limit conclusions. Heterogeneous patient population (standard and high risk combined). Pre-molecular era classification. Treatment-related mortality from intensive neoadjuvant chemotherapy is a significant concern.

Clinical Context

The SFOP M4 protocol contributed to understanding the role of neoadjuvant chemotherapy in medulloblastoma. In current practice, upfront chemotherapy is used primarily in infants to delay or avoid CSI, not routinely in older children. The protocol informed subsequent trials including SFOP BBSFOP for infants.

References

References: Grill J et al, Neuro Oncol 2013 (SFOP results)