TY - JOUR
T1 - Therapeutic interventions for childhood cancer
T2 - An umbrella review of randomized evidence
AU - Lavasidis, Georgios
AU - Markozannes, Georgios
AU - Panagiotou, Orestis A.
AU - Trikalinos, Nikolaos A.
AU - Petridou, Eleni Th
AU - Voorhies, Kirsten
AU - Ntzani, Evangelia E.
N1 - Publisher Copyright:
© 2021 Elsevier B.V.
PY - 2021/8
Y1 - 2021/8
N2 - 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.
AB - 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.
KW - Childhood cancer
KW - Leukemia
KW - Randomized controlled trials
KW - Survival
KW - Therapeutic interventions
KW - Umbrella review
UR - http://www.scopus.com/inward/record.url?scp=85110568777&partnerID=8YFLogxK
U2 - 10.1016/j.critrevonc.2021.103414
DO - 10.1016/j.critrevonc.2021.103414
M3 - Review article
C2 - 34242770
AN - SCOPUS:85110568777
SN - 1040-8428
VL - 164
JO - Critical Reviews in Oncology/Hematology
JF - Critical Reviews in Oncology/Hematology
M1 - 103414
ER -