P16METASTATIC MEDULLOBLASTOMA - UK RESULTS WITH INDUCTION AND HIGH DOSE CHEMOTHERAPY WITH HYPERFRACTIONATED ACCELERATED RADIOTHERAPY (THE MILAN STRATEGY)

INTRODUCTION: Historically, the 5-year overall survival (OS) for metastatic medulloblastoma (MMB) is less than 40%. The Milan Strategy of post-operative induction chemotherapy (IC) followed by hyperfractionated accelerated radiotherapy (HART) and response directed myeloablative high dose chemotherapy (HDC) or maintenance chemotherapy was reported in a study of 33 patients with MMB to improve 3-year OS to 77% (95% CI 61, 93) and 5-year OS to 73% (59, 87). We report the outcomes of patients treated using this strategy in UK centres. METHOD: Questionnaires were sent to all 20 UK paediatric oncology centres to collect retrospective data on treatment delivered, toxicity and survival with the Milan strategy. RESULTS: Between February 2009 and October 2011, 34 patients with MMB in 14 centres fulfilled the entry criteria of the original study. The median age at presentation was 7 years (range 3-15). Median interval from surgery to HART was 109 versus 85 days in the Milan series. The incidence of grade 3 haematological toxicities with IC and HDC was 83-100%. 16/16 patients who achieved CR by the end of therapy remain alive and in remission but only 3/18 with lesser responses are still alive (p < 0.0001). With follow up of 30-60 months, we estimate 3-year OS of 55% (95% Cl 38, 71). This result is outside the 95% CI of the Milan results and encompasses the historical result of 40%. We did not observe major late neurotoxicity. CONCLUSION: We did not replicate the improved results reported by the Milan group. The reasons could include differences in patient sub-groups and protocol compliance.