title: Chemotherapy dose-intensity and survival for childhood medulloblastoma.
abstract: OBJECTIVE
  To determine the relationship between prescribed dose-intensity of chemotherapy and survival in childhood medulloblastoma.
  
  
  METHODS
  A total of 55 trials from 1970-2009 were identified, 30 were eligible for analysis, with individual treatment regimes with 5-year (or more) outcome figures. Relationships of outcome to dose-intensity were analysed using weighted regression.
  
  
  RESULTS
  Overall, 2,434 patients were identified, 1,010 were classified as 'standard'- and 671 as 'high'-risk patients, with 5-year overall survivals (OS) of 67.2% (95% Confidence Interval=60.5%-73.6%) and 47.6% (95% Confidence Interval=39.5%-55.7%), respectively. A protective effect for chemotherapy versus craniospinal radiotherapy alone (5-year OS of 58.2% versus 51.6%) was found. Individually, vincristine, cisplatin, lomustine (CCNU) and cyclophosphamide appear to confer the most beneficial effect, particularly for high-risk patients. Positive relationships between OS and dose-intensity were found, except for lomustine, with cyclophosphamide offering the greatest protection.
  
  
  CONCLUSIONS
  Consideration of chemotherapy dose-intensity may further optimise treatment, particularly in the context of risk stratification.
authors.affiliation: Department of Paediatrics, Wythenshaw Hospital, Manchester, UK. rosssmith100@hotmail.com
authors.forename: R L
authors.initials: RL
authors.lastname: Smith
authors.forename: X
authors.initials: X
authors.lastname: Shi
authors.forename: E J
authors.initials: EJ
authors.lastname: Estlin
mesh_terms: D000293:Adolescent; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002528:Cerebellar Neoplasms / Q000188:drug therapy* / Q000401:mortality* / Q000532:radiotherapy; D002648:Child; D002675:Child, Preschool; D002945:Cisplatin / Q000008:administration & dosage; D017326:Clinical Trials, Phase III as Topic; D003520:Cyclophosphamide / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008130:Lomustine / Q000008:administration & dosage; D008297:Male; D008527:Medulloblastoma / Q000188:drug therapy* / Q000401:mortality* / Q000532:radiotherapy; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D000970:Antineoplastic Agents; D014750:Vincristine; D008130:Lomustine; D003520:Cyclophosphamide; D002945:Cisplatin