TY - JOUR
T1 - Risk-adapted craniospinal radiotherapy followed by high-dose chemotherapy and stem-cell rescue in children with newly diagnosed medulloblastoma (St Jude Medulloblastoma-96)
T2 - long-term results from a prospective, multicentre trial
AU - Gajjar, Amar
AU - Chintagumpala, Murali
AU - Ashley, David
AU - Kellie, Stewart
AU - Kun, Larry E.
AU - Merchant, Thomas E.
AU - Woo, Shaio
AU - Wheeler, Greg
AU - Ahern, Valerie
AU - Krasin, Matthew J.
AU - Fouladi, Maryam
AU - Broniscer, Alberto
AU - Krance, Robert
AU - Hale, Gregory A.
AU - Stewart, Clinton F.
AU - Dauser, Robert
AU - Sanford, Robert A.
AU - Fuller, Christine
AU - Lau, Ching
AU - Boyett, James M.
AU - Wallace, Dana
AU - Gilbertson, Richard J.
N1 - Funding Information:
This work was supported by a Cancer Center (CORE) Support Grant (CA 21765) from the National Institutes of Health, Musicians against Childhood Cancer (MACC), the Noyes Foundation, and the American Lebanese Syrian Associated Charities (ALSAC).
PY - 2006/10
Y1 - 2006/10
N2 - 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.
AB - 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.
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U2 - 10.1016/S1470-2045(06)70867-1
DO - 10.1016/S1470-2045(06)70867-1
M3 - Article
C2 - 17012043
AN - SCOPUS:33749044182
SN - 1470-2045
VL - 7
SP - 813
EP - 820
JO - Lancet Oncology
JF - Lancet Oncology
IS - 10
ER -