Hyperfractionated Accelerated Radiotherapy (HART) with maintenance chemotherapy for metastatic (M1-3) Medulloblastoma--a safety/feasibility study

Radiother Oncol. 2014 Apr;111(1):41-6. doi: 10.1016/j.radonc.2014.01.022. Epub 2014 Mar 11.

Abstract

Background and purpose: 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).

Materials and 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.

Conclusion: HART with or without VCR was well tolerated and may have a place in the multi-modality management of high-risk MB.

Keywords: Chemotherapy; HART; Medulloblastoma; Metastatic.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Cerebellar Neoplasms / drug therapy*
  • Cerebellar Neoplasms / pathology
  • Cerebellar Neoplasms / radiotherapy*
  • Chemoradiotherapy
  • Chemotherapy, Adjuvant
  • Child
  • Child, Preschool
  • Cisplatin / administration & dosage
  • Cisplatin / adverse effects
  • Dose Fractionation, Radiation
  • Feasibility Studies
  • Female
  • Humans
  • Infant
  • Lomustine / administration & dosage
  • Lomustine / adverse effects
  • Maintenance Chemotherapy
  • Male
  • Medulloblastoma / drug therapy*
  • Medulloblastoma / pathology
  • Medulloblastoma / radiotherapy*
  • Neoplasm Metastasis
  • Neoplasm Recurrence, Local / drug therapy
  • Neoplasm Recurrence, Local / radiotherapy
  • Radiotherapy Dosage
  • Survival Rate
  • Vincristine / administration & dosage
  • Vincristine / adverse effects

Substances

  • Vincristine
  • Lomustine
  • Cisplatin