CNS-directed therapy for childhood @entity981 : XXXX Collaborative Group overview of 43 randomized trials.

@entity1 @entity1499 @entity981 @entity204
PURPOSE: A collaborative meta-analysis was performed to clarify the relative effects on relapse and survival of different types of therapies directed at the CNS in childhood @entity981 . MATERIALS AND METHODS: Data were sought for each individual @entity1 in all trials started in or before 1993 that included unconfounded randomized comparisons of such treatments. Log-rank survival analyses were performed for each trial, and overall results for groups of trials addressing similar questions were obtained from the totals of the observed minus expected number of events and their variances. RESULTS: Radiotherapy and long-term intrathecal therapy gave similar outcomes, with no significant difference in event-free survival despite random assignment of treatment to 2,848 @entity1 , 1,001 of whom suffered relapse or @entity204 . Intravenous @entity1499 reduced non-CNS rather than CNS relapses, and hence, the addition of intravenous @entity1499 to a treatment regimen including radiotherapy or long-term intrathecal therapy improved event-free survival, with a 17% reduction in the event rate (95% confidence interval, 6% to 27%; P =.003). The event-free survival at 10 years in these trials was 61.9% without intravenous @entity1499 and 68.1% with intravenous @entity1499 . There was no significant difference in survival (14% @entity204 rate reduction; P =.09). There were insufficient randomly assigned @entity1 to adequately address other questions, such as effect of different doses. No evidence was found of differences, between trials or between subgroups of different types of @entity1 , in the relative effects of treatment. CONCLUSION: Radiotherapy can be replaced by long-term intrathecal therapy. Intravenous @entity1499 gives some additional benefit by reducing non-CNS relapses.
