2003 Background: To assess the efficacy of treatment of medulloblastoma (MB) in adults (> 18 years). Methods: Ninety-five MB patients (pts) were enrolled a prospective phase II trial conducted between 1/1989 and 2/2009; 30 low-risk (LR) pts (T1, T2, T3a, M0, without postoperative residual disease) underwent radiotherapy (36 Gy) to the craniospinal axis, supplemented by a local tumor dose (18.8 Gy; total, 54.8 Gy), and 65 high-risk (HR) pts (T3b–T4, or postoperative residual tumor) received 2 cycles of “up-front chemotherapy” (cisplatin 25 mg/m2/daily for 4 days, etoposide 40 mg/m2/daily for 4 days, and cyclophosphamide 1,000 mg/m2 on day 4; every 4 weeks) before the same radiation therapy, followed by maintenance chemotherapy if M1, M2 or M3 disease was present. Results: Progression-free survival at 5 and 10 years (PFS-5 y and PFS-10 y) were 78% (62-93) and 46% (23-70) in LR vs. 50% (37- 62) and 36% (23-49) in HR (p = 0.009 and p = 0.03, respectively) patients. Survival at 5 and 10 years (OS-5 y and OS-10 y) was 92% (81-100) and 65% (43-7) in LR vs. 58% (46-71) and 45% (31-8) in HR (p = 0.002 and p = 0.02, respectively). Five-year and 10-year PFS was 68% (50-85) and 54% (34-74) in M0 pts vs. 35% (18-51) and 19% (2-35) in M1-2-3 pts (p = 0.007 and p = 0.006). OS- at 5 years and 10 years were 71% (54-88) and 62% (43-81) in M0 vs. 47% (29- 65) and 29% (11-47) in M1-2-3 pts (p = 0.09 and p = 0.04); residual disease had no significant impact on 10-year PFS or 10-year OS. There were no deaths from toxicity, which was mainly hematological and successfully managed with dose reductions and supportive care. Conclusions: Since the incidence of MB in adults is extremely rare, data appearing in literature on this condition have been reported in small retrospective series. The findings made in the present prospective study on a large series of patients, the first of its type to appear in literature, clearly indicate the standard of care in MB in adults, and should constitute a benchmark for further studies. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb, OncoMethylome Sciences, Roche, Schering-Plough GlaxoSmithKline, Merck Sharp & Dohme, Pfizer, Roche, Schering-Plough