Treatment of young children with localized medulloblastoma by chemotherapy alone: results of the prospective, multicenter trial HIT 2000 confirming the prognostic impact of histology

Neuro Oncol. 2011 Jun;13(6):669-79. doi: 10.1093/neuonc/nor025.

Abstract

This study was designed to confirm the previously observed favorable survival rates and prognostic factors in young children with nonmetastatic medulloblastoma (MB) treated with postoperative chemotherapy alone. Patients who received a diagnosis during the period January 2001 through December 2005 and who were aged <4 years received 3 cycles of postoperative systemic multiagent chemotherapy and intraventricular methotrexate. In cases of complete remission, treatment was terminated after 2 additional cycles of chemotherapy. Otherwise, secondary surgery, radiotherapy, and consolidation chemotherapy were recommended. At a median follow-up of 4.5 years, the 5-year event-free survival (EFS) and overall survival (OS) rates (± standard error) for 45 patients (median age, 2.5 years) were 57% ± 8% and 80% ± 6%, respectively. Nineteen patients with desmoplastic/nodular MB variants had better 5-year EFS and OS rates (90% ± 7% and 100% ± 0%, respectively) than did 23 patients with classic MB (30% ± 11% and 68% ± 10%, respectively; P < .001 for EFS; P = .008 for OS). Five-year EFS and OS rates for 3 children with anaplastic MB were 33% ± 27%. Desmoplastic/nodular histology was an independent prognostic factor for EFS. Twenty-nine of 30 patients without postoperative residual tumor remained in continuous complete remission. Our results confirm that histology of MB variants is a strong prognostic factor in this age group. Sustained tumor control can be achieved by this chemotherapy regimen in young children with desmoplastic/nodular MB variants. For children with non-desmoplastic/nonnodular MB variants, for which predominantly local relapses lead to less favorable survival rates, local radiotherapy has been introduced after chemotherapy since 2006.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carboplatin / administration & dosage
  • Cerebellar Neoplasms / pathology*
  • Cerebellar Neoplasms / therapy*
  • Child, Preschool
  • Combined Modality Therapy
  • Cyclophosphamide / administration & dosage
  • Etoposide / administration & dosage
  • Female
  • Follow-Up Studies
  • Humans
  • Infant
  • Leucovorin / administration & dosage
  • Magnetic Resonance Imaging
  • Male
  • Medulloblastoma / pathology*
  • Medulloblastoma / therapy*
  • Methotrexate / administration & dosage
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Recurrence, Local / therapy
  • Prognosis
  • Prospective Studies
  • Radiotherapy
  • Remission Induction
  • Survival Rate
  • Vincristine / administration & dosage

Substances

  • Vincristine
  • Etoposide
  • Cyclophosphamide
  • Carboplatin
  • Leucovorin
  • Methotrexate