title: 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.
authors.affiliation: Cookridge Hospital, Leeds, West Yorkshire LS16 6QB, UK. 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: Kathryn J
authors.initials: KJ
authors.lastname: Robinson
authors.forename: Claire L
authors.initials: CL
authors.lastname: Weston
authors.forename: David A
authors.initials: DA
authors.lastname: Walker
authors.forename: David
authors.initials: D
authors.lastname: Ellison
authors.forename: James
authors.initials: J
authors.lastname: Ironside
authors.forename: Barry L
authors.initials: BL
authors.lastname: Pizer
authors.forename: Linda S
authors.initials: LS
authors.lastname: Lashford
mesh_terms: D000293:Adolescent; D000704:Analysis of Variance; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002528:Cerebellar Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy / Q000601:surgery; D002648:Child; D002675:Child, Preschool; D002985:Clinical Protocols; D003131:Combined Modality Therapy; D016001:Confidence Intervals; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D008297:Male; D008527:Medulloblastoma / Q000188:drug therapy* / Q000532:radiotherapy / Q000601:surgery; D009362:Neoplasm Metastasis / Q000628:therapy; D009364:Neoplasm Recurrence, Local / Q000209:etiology; D010349:Patient Compliance; D016896:Treatment Outcome