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

doi:10.1016/j.critrevonc.2021.103414

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.

Authors

Georgios Lavasidis¹, Georgios Markozannes², Orestis A Panagiotou³, Nikolaos A Trikalinos⁴, Eleni Th Petridou⁵, Kirsten Voorhies⁶, Evangelia E Ntzani⁷

Affiliations

¹ Evidence-based Medicine Unit, Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, University Campus, 45110, Ioannina, Greece; Department of Pediatrics, Klinikum Stadt Soest, Senator-Schwartz-Ring 8, 59494, Soest, Germany; Department of Ophthalmology, Marienhospital Osnabrück, Bischofsstraße 1, 49074, Osnabrück, Germany. Electronic address: lavasidis@outlook.com.gr.
² Evidence-based Medicine Unit, Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, University Campus, 45110, Ioannina, Greece. Electronic address: georgemarkozannes@gmail.com.
³ Department of Health Services, Policy & Practice, Brown University School of Public Health, 121 South Main St., Providence, RI, 02912, USA. Electronic address: orestis_panagiotou@brown.edu.
⁴ Division of Oncology, Department of Medicine, Washington University in St. Louis, 1 Brookings Dr, St. Louis, MO, 63130, USA. Electronic address: ntrikalinos@wustl.edu.
⁵ Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, Mikras Asias 75, 11527, Athens, Greece. Electronic address: epetrid@med.uoa.gr.
⁶ Department of Biostatistics, Brown University School of Public Health, 121 South Main St., Providence, RI, 02912, USA; Department of Population Medicine, Harvard Pilgrim Health Care Institute and Harvard Medical School, 401 Park Drive, Suite 401 East, Boston, MA, 02215, USA. Electronic address: kirsten_voorhies@alumni.brown.edu.
⁷ Evidence-based Medicine Unit, Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, University Campus, 45110, Ioannina, Greece; Department of Health Services, Policy & Practice, Brown University School of Public Health, 121 South Main St., Providence, RI, 02912, USA; Institute of Biosciences, University Research Center of loannina, University of Ioannina, 45110, Ioannina, Greece. Electronic address: entzani@uoi.gr.

PMID: 34242770
DOI: 10.1016/j.critrevonc.2021.103414

Abstract

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