title: An international strategy to determine the role of high dose therapy in recurrent Wilms' tumour.
abstract: OBJECTIVE
  To review event-free (EFS) and overall survival (OS) from publications describing outcome for children with relapsed Wilms' tumour. Comparisons are made between those receiving myeloablative high dose chemotherapy with autologous stem-cell rescue (HDT) and those not (NoHDT).
  
  
  METHODS
  Relevant information was extracted from individual patient or summary data and 3-year EFS and OS rates established. These rates were combined in a weighted manner to derive hazard ratios (HRs).
  
  
  RESULTS
  Nineteen publications were identified (5 HDT, 6 NoHDT, 8 both). Pooling all studies suggested an advantage to HDT with a hazard ratio (HR) for EFS of 0.87 (95% confidence interval (CI) 0.67-1.12) and 0.94 (0.71-1.24) for OS. A stratified analysis confined to studies that provided individual patient data on both HDT and NoHDT gave HRs of 0.83 (0.56-1.24) and 0.92 (0.59-1.41). Further, analyses of risk groups, defined by treatment and/or histology prior to first relapse, suggested a HR for EFS of 0.90 (95% CI 0.62-1.31) for those of high and 0.50 (CI 0.31-0.82) for the very high risk patients.
  
  
  CONCLUSIONS
  The evidence suggests, although there are many caveats since the information summarised here is not from randomised trials, a great deal of uncertainty concerning the role of HDT in patients following relapse after treatment for their Wilms' tumour. For each risk group we propose a randomised trial comparing a standard with a more intensive therapy with specific choice of regimen tailored to the risk group (and co-operative groups) concerned. A synthesis of updated evidence from studies in this overview together with any emerging studies and future trial information will form the basis for future evidence-based clinical decision-making.
authors.affiliation: Division of Clinical Trials and Epidemiological Sciences, National Cancer Centre, Singapore. ha.tam.cam@nccs.com.sg
authors.forename: Tam C
authors.initials: TC
authors.lastname: Ha
authors.forename: Filippo
authors.initials: F
authors.lastname: Spreafico
authors.forename: Norbert
authors.initials: N
authors.lastname: Graf
authors.forename: Sandro
authors.initials: S
authors.lastname: Dallorso
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Dome
authors.forename: Marcio
authors.initials: M
authors.lastname: Malogolowkin
authors.forename: Rhoikos
authors.initials: R
authors.lastname: Furtwängler
authors.forename: Juliet P
authors.initials: JP
authors.lastname: Hale
authors.forename: Veronica
authors.initials: V
authors.lastname: Moroz
authors.forename: David
authors.initials: D
authors.lastname: Machin
authors.forename: Kathy
authors.initials: K
authors.lastname: Pritchard-Jones
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D018572:Disease-Free Survival; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000401:mortality; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000401:mortality; D014182:Transplantation, Autologous; D009396:Wilms Tumor / Q000188:drug therapy* / Q000401:mortality
chemical_list: D000970:Antineoplastic Agents