• Bella S Ehrlich, Michael J McNeil, Linh T D Pham, Yichen Chen, Jocelyn Rivera, Carlos Acuna, Liz Sniderman, Firas M Sakaan, Alejandra Mendez Aceituno, Cesar A Villegas, Lisa M Force, Nancy S Bolous, Parima P Wiphatphumiprates, Jeremy S Slone, Angela K Carrillo, Srinithya R Gillipelli, Caitlyn Duffy, Anita V Arias, Meenakshi Devidas, Carlos Rodriguez-Galindo, Sheena Mukkada, and Asya Agulnik.
• Department of Global Pediatric Medicine, St Jude Children's Research Hospital, Memphis, TN, USA; Warren Alpert Medical School, Brown University, Providence, RI, USA.
• Lancet Oncol. 2023 Sep 1; 24 (9): 967977967-977.

BackgroundApproximately 90% of children with cancer live in low-income and middle-income countries (LMICs), where 5-year survival is lower than 20%. Treatment-related mortality in high-income countries is approximately 3-5%; however, in LMICs, treatment-related mortality has been reported in up to 45% of children with cancer. This study aimed to systematically explore the burden of treatment-related mortality in children with cancer in LMICs and to explore the association between country income level and treatment-related mortality.MethodsFor this systematic review and meta-analysis we identified articles published between Jan 1, 2010, and June 22, 2021, describing treatment-related mortality in paediatric patients (aged 0-21 years) with cancer in LMICs. We searched PubMed, Trip, Web of Science, Embase, and the WHO Global Metric Index databases. The search was limited to full-text articles and excluded case reports (<10 patients) and haematopoietic stem-cell transplantation recipients. Two reviewers independently screened studies for eligibility, extracted data from included publications, and evaluated data quality. Random and mixed-effects models were used to estimate treatment-related mortality burden and trends. The Cochran-Q statistic was used to assess heterogeneity between studies. This study is registered on PROSPERO (CRD42021264849).FindingsOf 13 269 identified abstracts, 501 studies representing 68 351 paediatric patients with cancer were included. The treatment-related mortality estimate was 6·82% (95% CI 5·99-7·64), accounting for 30·9% of overall mortality (4437 of 14 358 deaths). Treatment-related mortality was inversely related to country income. Treatment-related mortality was 14·19% (95% CI 9·65-18·73) in low-income countries, 9·21% (7·93-10·49) in lower-middle-income countries, and 4·47% (3·42-5·53) in upper-middle-income countries (Cochran-Q 42·39, p<0·0001). In upper-middle-income countries, the incidence of treatment-related mortality decreased over time (slope -0·002, p=0·0028); however, outcomes remained unchanged in low-income (p=0·21) and lower-middle-income countries (p=0·16).InterpretationApproximately one in 15 children receiving cancer treatment in LMICs die from treatment-related complications. Although treatment-related mortality has decreased in upper-middle-income countries over time, it remains unchanged in LMICs. There is an urgent need for targeted supportive care interventions to reduce global disparities in childhood cancer survival.FundingAmerican Lebanese Syrian Associated Charities and National Cancer Institute.Copyright © 2023 Elsevier Ltd. All rights reserved.

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