title: Hyperfractionated Accelerated Radiotherapy (HART) with maintenance chemotherapy for metastatic (M1-3) Medulloblastoma--a safety/feasibility study.
abstract: OBJECTIVE
  To evaluate feasibility and toxicity of Hyperfractionated Accelerated Radiotherapy (HART) 1.24Gy b.i.d. followed by chemotherapy for M1-3 Medulloblastoma (MB). The aim of HART was to use hyperfractionation to improve therapeutic ratio combined with acceleration to minimise tumour cell repopulation during radiotherapy (RT).
  
  
  METHODS
  Between February 2002 and May 2008, 34 eligible patients (22 male, 12 female) aged 3-15years (median 7) with metastatic MB (M1-9; M2-3, M3-22) received HART with a craniospinal radiotherapy (CSRT) dose of 39.68Gy followed by 22.32Gy boost to the whole posterior fossa and 9.92Gy metastatic boosts. The 8th and subsequent patients received vincristine (VCR) 1.5mg/m(2) weekly×8 doses over 8weeks starting during the 1st week of RT. Maintenance chemotherapy comprised 8 six-weekly cycles of VCR 1.5mg/m(2) weekly×3, CCNU 75mg/m(2) and cisplatin 70mg/m(2).
  
  
  RESULTS
  Median duration of HART was 34days (range 31-38). Grade 3-4 toxicities included mucositis (8), nausea (10), anaemia (5), thrombocytopaenia (2), leucopaenia (24). With 4.5-year median follow-up, 3-year EFS and OS were 59% and 71%, respectively. Of 10 relapses, 1 was outside the central nervous system (CNS), 1 posterior fossa alone and 8 leptomeningeal with 3 also associated with posterior fossa.
  
  
  CONCLUSIONS
  HART with or without VCR was well tolerated and may have a place in the multi-modality management of high-risk MB.
authors.affiliation: Swansea University, UK. Electronic address: Roger.Taylor@Wales.nhs.uk.
authors.forename: Roger E
authors.initials: RE
authors.lastname: Taylor
authors.affiliation: Cancer Research UK Clinical Trials Unit, University of Birmingham, UK.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Howman
authors.affiliation: Cancer Research UK Clinical Trials Unit, University of Birmingham, UK.
authors.forename: Keith
authors.initials: K
authors.lastname: Wheatley
authors.affiliation: Cancer Research UK Clinical Trials Unit, University of Birmingham, UK.
authors.forename: Elena E
authors.initials: EE
authors.lastname: Brogden
authors.affiliation: Cancer Research UK Clinical Trials Unit, University of Birmingham, UK.
authors.forename: Bridget
authors.initials: B
authors.lastname: Large
authors.affiliation: Cancer Research UK Clinical Trials Unit, University of Birmingham, UK.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Gibson
authors.affiliation: Nottingham University, UK.
authors.forename: Keith
authors.initials: K
authors.lastname: Robson
authors.affiliation: Newcastle University, UK.
authors.forename: Dipayan
authors.initials: D
authors.lastname: Mitra
authors.affiliation: Royal Marsden Hospital, London, UK.
authors.forename: Frank
authors.initials: F
authors.lastname: Saran
authors.affiliation: Great Ormond Street Hospital, London, UK.
authors.forename: Antony
authors.initials: A
authors.lastname: Michalski
authors.affiliation: Liverpool University, UK.
authors.forename: Barry L
authors.initials: BL
authors.lastname: Pizer
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002528:Cerebellar Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D059248:Chemoradiotherapy; D017024:Chemotherapy, Adjuvant; D002648:Child; D002675:Child, Preschool; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D019583:Dose Fractionation, Radiation; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007223:Infant; D008130:Lomustine / Q000008:administration & dosage / Q000009:adverse effects; D060046:Maintenance Chemotherapy; D008297:Male; D008527:Medulloblastoma / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000532:radiotherapy; D011879:Radiotherapy Dosage; D015996:Survival Rate; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D014750:Vincristine; D008130:Lomustine; D002945:Cisplatin
keywords: Chemotherapy; HART; Medulloblastoma; Metastatic