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Results of a Randomized Study of Preradiation Chemotherapy Versus Radiotherapy Alone for Nonmetastatic Medulloblastoma: The International Society of Paediatric Oncology/United Kingdom Children’s Cancer Study Group PNET-3 Study

Roger E. Taylor, Clifford C. Bailey, Kath Robinson, Claire L. Weston, David Ellison, James Ironside, Helen Lucraft, Richard Gilbertson, Diana M. Tait, David A. Walker, Barry L. Pizer, John Imeson, Linda S. Lashford

From the Cookridge Hospital and the Research School of Medicine, Leeds; University of Leicester, Leicester; Newcastle General Hospital, Newcastle Upon Tyne; University of Edinburgh, Western General Hospital, Edinburgh; Royal Marsden Hospital, Sutton; Queen’s Medical Centre, Nottingham; Alder Hey Children’s Hospital, Liverpool; Cancer Research UK, London, United Kingdom; and St. Jude Children’s Research Hosital, Memphis, TN.

Address reprint requests to R.E. Taylor, MD, Cookridge Hospital, Leeds, West Yorkshire, LS16 6QB, United Kingdom; email: Roger.Taylor{at}Leedsth.nhs.uk.

Purpose: To determine whether preradiotherapy (RT) chemotherapy would improve outcome for Chang stage M0–1 medulloblastoma when compared with RT alone. Chemotherapy comprised vincristine 1.5 mg/m² weekly for 10 weeks and four cycles of etoposide 100 mg/m² daily for 3 days, and carboplatin 500 mg/m² daily for 2 days alternating with cyclophosphamide 1.5 g/m².

Patients and Methods: Patients aged 3 to 16 years inclusive were randomly assigned to receive 35 Gy craniospinal RT with a 20 Gy posterior fossa boost, or chemotherapy followed by RT.

Results: Of 217 patients randomly assigned to treatment, 179 were eligible for analysis (chemotherapy + RT, 90 patients; RT alone, 89 patients). Median age was 7.67 years, and median follow-up was 5.40 years. Overall survival (OS) at 3 and 5 years was 79.5% and 70.7%, respectively. Event-free survival (EFS) at 3 and 5 years was 71.6% and 67.0%, respectively. EFS was significantly better for chemotherapy and RT (P = .0366), with EFS of 78.5% at 3 years and 74.2% at 5 years compared with 64.8% at 3 years and 59.8% at 5 years for RT alone. There was no statistically significant difference in 3-year and 5-year OS between the two arms (P = .0928). Multivariate analysis identified use of chemotherapy (P = .0248) and time to complete RT (P = .0100) as having significant effect on EFS.

Conclusion: This is the first large multicenter randomized study to demonstrate improved EFS for chemotherapy compared with RT alone. It is anticipated that this regimen could reduce ototoxicity and nephrotoxicity compared with cisplatin-containing schedules. The importance of avoiding interruptions to RT has been confirmed.

The UKCCSG is supported by Cancer Research UK. This study was supported by the following UKCCSG Brain Tumour Committee members: C. Bailey, M. Brada, C. Chandler, P. Chumas, C. D’Souza, D. Ellison, M. English, H.R. Gattamaneni, P. Griffiths, R. Grundy, J. Ironside, T. Jaspan, C. Kennedy, L. Lashford, S. Lowis, H. Lucraft, A. Michalski, A. Pearson, S. Picton, B. Pizer, J. Punt, K. Robson, F. Saran, H. Spoudeas, R.E. Taylor, and D. Walker.

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