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

Amar Gajjar, Murali Chintagumpala, David Ashley, Stewart Kellie, Larry E. Kun, Thomas E. Merchant, Shaio Woo, Greg Wheeler, Valerie Ahern, Matthew J. Krasin, Maryam Fouladi, Alberto Broniscer, Robert Krance, Gregory A. Hale, Clinton F. Stewart, Robert Dauser, Robert A. Sanford, Christine Fuller, Ching Lau, James M. BoyettDana Wallace, Richard J. Gilbertson

Research output: Contribution to journalArticlepeer-review

612 Scopus citations

Abstract

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 (≤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.

Original languageEnglish (US)
Pages (from-to)813-820
Number of pages8
JournalLancet Oncology
Volume7
Issue number10
DOIs
StatePublished - Oct 2006

ASJC Scopus subject areas

  • Oncology

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