Risk-adapted craniospinal radiotherapy followed by high-dose chemotherapy and stem-cell rescue in children with newly diagnosed medulloblastoma (St Jude Medulloblastoma-96): long-term results from a prospective, multicentre trial

Lancet Oncol. 2006 Oct;7(10):813-20. doi: 10.1016/S1470-2045(06)70867-1.


Background: Current treatment for medulloblastoma, which includes postoperative radiotherapy and 1 year of chemotherapy, does not cure many children with high-risk disease. We aimed to investigate the effectiveness of risk-adapted radiotherapy followed by a shortened period of dose-intense chemotherapy in children with medulloblastoma.

Methods: After resection, patients were classified as having average-risk medulloblastoma (< or = 1.5 cm2 residual tumour and no metastatic disease) or high-risk medulloblastoma (> 1.5 cm2 residual disease or metastatic disease localised to neuraxis) medulloblastoma. All patients received risk-adapted craniospinal radiotherapy (23.4 Gy for average-risk disease and 36.0-39.6 Gy for high-risk disease) followed by four cycles of cyclophosphamide-based, dose-intensive chemotherapy. Patients were assessed regularly for disease status and treatment side-effects. The primary endpoint was 5-year event-free survival; we also measured overall survival. This study is registered with ClinicalTrials.gov, number NCT00003211.

Findings: Of 134 children with medulloblastoma who underwent treatment (86 average-risk, 48 high-risk), 119 (89%) completed the planned protocol. No treatment-related deaths occurred. 5-year overall survival was 85% (95% CI 75-94) in patients in the average-risk group and 70% (54-84) in those in the high-risk group (p=0.04); 5-year event-free survival was 83% (73-93) and 70% (55-85), respectively (p=0.046). For the 116 patients whose histology was reviewed centrally, histological subtype correlated with 5-year event-free survival (p=0.04): 84% (74-95) for classic histology, 77% (49-100) for desmoplastic tumours, and 57% (33-80) for large-cell anaplastic tumours.

Interpretation: Risk-adapted radiotherapy followed by a shortened schedule of dose-intensive chemotherapy can be used to improve the outcome of patients with high-risk medulloblastoma.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antineoplastic Agents, Alkylating / therapeutic use
  • Cerebellar Neoplasms / mortality
  • Cerebellar Neoplasms / pathology
  • Cerebellar Neoplasms / therapy*
  • Child
  • Child, Preschool
  • Combined Modality Therapy
  • Cranial Irradiation / methods*
  • Cyclophosphamide / therapeutic use*
  • Disease Progression
  • Dose-Response Relationship, Drug
  • Female
  • Follow-Up Studies
  • Hematopoietic Stem Cell Transplantation / methods*
  • Humans
  • Male
  • Medulloblastoma / mortality
  • Medulloblastoma / pathology
  • Medulloblastoma / therapy*
  • Prospective Studies
  • Risk Factors
  • Survival Analysis
  • Survival Rate
  • Transplantation, Autologous
  • Treatment Outcome


  • Antineoplastic Agents, Alkylating
  • Cyclophosphamide

Associated data

  • ClinicalTrials.gov/NCT00003211