MB-15: PILOT STUDY OF REDUCED-DOSE CRANIOSPINAL IRRADIATION (CSI) WITH CONCURRENT CARBOPLATIN AND VINCRISTINE IN HIGH RISK MEDULLOBLASTOMA AND PRIMITIVE NEURO-ECTODERMAL TUMORS (PNETs)

OBJECTIVE: Examine the tolerability and efficacy of reduced-dose CSI (23.4 Gy) with concurrent carboplatin/vincristine for metastatic medulloblastoma and PNET. BACKGROUND: Children's Oncology Group study 99701 demonstrated the feasibility of adding daily carboplatin to radiation (36Gy CSI) for non-anaplastic metastatic medulloblastoma with 5 year overall survival of 83%. High dose CSI has been associated with significant late effects. Our pilot study used reduced-dose CSI (23.4 Gy) with concurrent carboplatin/vincristine. METHODS: Eligible patients were ages 3 - 25 with metastatic medulloblastoma or PNET. Anaplastic histology was excluded. Accrual goal was 10 patients. Therapy consisted of concurrent carboplatin/vincristine, and 23.4 Gy CSI and local boost, followed by adjuvant chemotherapy. RESULTS: Eight subjects were accrued over 7 years. The study was closed early due to slow accrual. Median follow-up is 7.5 years (range 1.5 - 9 years). Seven of 8 are alive, 6 without relapse, the 1 relapse occurred 2 years after diagnosis, but was salvaged. The 1 death was multi-system organ failure with no evidence of disease. During chemoradiation, all patients had grade 3/4 hematologic toxicity and 3 patients had grade 3/4 non-hematologic toxicity. Late effects of therapy included endocrine dysfunction in 6, hearing loss in 6 and cataracts in 2. IQ testing 2 years after diagnosis was done in 6 patients and ranged from 80 to 127. CONCLUSION: Our pilot study of reduced-dose of CSI with concurrent carboplatin/vincristine shows good tolerability and favorable outcomes. Late effects may be reduced compared to higher dose CSI.