Outcome for patients with metastatic (M2–3) medulloblastoma treated with SIOP/UKCCSG PNET-3 chemotherapy

Abstract

The aim of this study was to determine the outcome for patients with Chang stage M2–3 medulloblastoma (MB) treated with surgery and pre-radiotherapy (RT) chemotherapy (CT). Between 1992 and 2000, 68 patients aged 2.8–16.4 years (median 7.8 years) with M2–3 MB were treated with CT comprising vincristine, etoposide, carboplatin and cyclophosphamide. For 61 patients, CT was followed by craniospinal RT 35 Gy/21 fractions with a posterior fossa (PF) boost, 20 Gy/12 fractions. Twenty-four (35%) irradiated patients received a metastatic boost (mean dose to metastases 47.4 Gy, range 40.0–55.1 Gy). With 7.2-years of median follow-up, overall survival (OS) rates at 3 and 5 years were 50.0% (95% Confidence Interval (CI): 38.1–61.9%) and 43.9% (95% CI: 32.0–55.7%), respectively, event-free survival (EFS) rates at 3 and 5 years were 39.7% (95% CI: 28.1–51.3%) and 34.7% (95% CI: 23.2–46.2%), respectively. Univariate analysis did not demonstrate an impact of age, gender, M stage, extent of resection, RT duration or metastatic boost. For patients commencing RT within 110 days of surgery, EFS was significantly ( P = 0.04) worse than for those who commenced RT later than this. Response to pre-RT CT was assessable from institutional reports for 44 (65%) patients, and 17 (39%) had a complete response (CR), 15 (34%) a partial response (PR), 4 (9%) stable disease (SD) and 8 (18%) progression. Although CT improved outcome for M0-1 patients in the primitive neuroectodermal tumour (PNET-3) randomised study, and resulted in a high response rate in this study, there has been no apparent improvement in outcome for M2–3 patients when compared with earlier multi-institutional series. Newer approaches such as more intensive CT and RT need to be explored.