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

Georgios Lavasidis, Georgios Markozannes, Orestis A. Panagiotou, Nikolaos A. Trikalinos, Eleni Th Petridou, Kirsten Voorhies, Evangelia E. Ntzani

Research output: Contribution to journalReview articlepeer-review

3 Scopus citations


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.

Original languageEnglish
Article number103414
JournalCritical Reviews in Oncology/Hematology
StatePublished - Aug 2021


  • Childhood cancer
  • Leukemia
  • Randomized controlled trials
  • Survival
  • Therapeutic interventions
  • Umbrella review


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