Therapeutic interventions for childhood cancer: An umbrella review of randomized evidence

Crit Rev Oncol Hematol. 2021 Aug;164:103414. doi: 10.1016/j.critrevonc.2021.103414. Epub 2021 Jul 6.


Treatment advancements in pediatric cancer have improved prognosis, but the strength of supporting evidence has not been thoroughly evaluated. To critically appraise it, we performed an umbrella review of meta-analyses of randomized controlled trials examining the efficacy and safety of therapeutic interventions for pediatric malignancies. Fourteen publications (68 meta-analyses, 31,496 participants) were eligible. Acute lymphoblastic leukemia (ALL) was investigated at most. Substantial heterogeneity was detected in 10 associations, with limited indications for small-study effects and excess-significance bias. The most concrete evidence pertained to the use of methotrexate and vincristine-prednisone pulses for ALL, improving event-free survival. Evidence regarding other cancers was relatively weak. Conclusively, we found few small meta-analyses focusing mainly on ALL. Randomized evidence stemming from adult populations still seems to serve as valuable indirect evidence backup. More randomized evidence and individual patient data meta-analyses are needed to increase certainty and precision in the care of pediatric cancer patients.

Keywords: Childhood cancer; Leukemia; Randomized controlled trials; Survival; Therapeutic interventions; Umbrella review.

Publication types

  • Review

MeSH terms

  • Adult
  • Child
  • Humans
  • Neoplasms* / drug therapy
  • Randomized Controlled Trials as Topic