title: 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.
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 (< 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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Oncology, St Jude Children's Research Hospital, Memphis, TN 38105, USA. amar.gajjar@stjude.org
authors.forename: Amar
authors.initials: A
authors.lastname: Gajjar
authors.forename: Murali
authors.initials: M
authors.lastname: Chintagumpala
authors.forename: David
authors.initials: D
authors.lastname: Ashley
authors.forename: Stewart
authors.initials: S
authors.lastname: Kellie
authors.forename: Larry E
authors.initials: LE
authors.lastname: Kun
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Merchant
authors.forename: Shaio
authors.initials: S
authors.lastname: Woo
authors.forename: Greg
authors.initials: G
authors.lastname: Wheeler
authors.forename: Valerie
authors.initials: V
authors.lastname: Ahern
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Krasin
authors.forename: Maryam
authors.initials: M
authors.lastname: Fouladi
authors.forename: Alberto
authors.initials: A
authors.lastname: Broniscer
authors.forename: Robert
authors.initials: R
authors.lastname: Krance
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Hale
authors.forename: Clinton F
authors.initials: CF
authors.lastname: Stewart
authors.forename: Robert
authors.initials: R
authors.lastname: Dauser
authors.forename: Robert A
authors.initials: RA
authors.lastname: Sanford
authors.forename: Christine
authors.initials: C
authors.lastname: Fuller
authors.forename: Ching
authors.initials: C
authors.lastname: Lau
authors.forename: James M
authors.initials: JM
authors.lastname: Boyett
authors.forename: Dana
authors.initials: D
authors.lastname: Wallace
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Gilbertson
mesh_terms: D000293:Adolescent; D000328:Adult; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D002528:Cerebellar Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D016371:Cranial Irradiation / Q000379:methods*; D003520:Cyclophosphamide / Q000627:therapeutic use*; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D008297:Male; D008527:Medulloblastoma / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D011446:Prospective Studies; D012307:Risk Factors; D016019:Survival Analysis; D015996:Survival Rate; D014182:Transplantation, Autologous; D016896:Treatment Outcome
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003520:Cyclophosphamide