title: 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.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Cookridge Hospital, Leeds, West Yorkshire, LS16 6QB, United Kingdom. Roger.Taylor@Leedsth.nhs.uk
authors.forename: Roger E
authors.initials: RE
authors.lastname: Taylor
authors.forename: Clifford C
authors.initials: CC
authors.lastname: Bailey
authors.forename: Kath
authors.initials: K
authors.lastname: Robinson
authors.forename: Claire L
authors.initials: CL
authors.lastname: Weston
authors.forename: David
authors.initials: D
authors.lastname: Ellison
authors.forename: James
authors.initials: J
authors.lastname: Ironside
authors.forename: Helen
authors.initials: H
authors.lastname: Lucraft
authors.forename: Richard
authors.initials: R
authors.lastname: Gilbertson
authors.forename: Diana M
authors.initials: DM
authors.lastname: Tait
authors.forename: David A
authors.initials: DA
authors.lastname: Walker
authors.forename: Barry L
authors.initials: BL
authors.lastname: Pizer
authors.forename: John
authors.initials: J
authors.lastname: Imeson
authors.forename: Linda S
authors.initials: LS
authors.lastname: Lashford
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002528:Cerebellar Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy* / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008527:Medulloblastoma / Q000188:drug therapy* / Q000532:radiotherapy* / Q000601:surgery; D020360:Neoadjuvant Therapy; D011879:Radiotherapy Dosage; D018714:Radiotherapy, Adjuvant; D016019:Survival Analysis; D016896:Treatment Outcome; D006113:United Kingdom; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D014750:Vincristine; D005047:Etoposide; D003520:Cyclophosphamide; D016190:Carboplatin