Late Effects in Childhood Cancer Survivors: A Global Call to Action Based on the PENTEC Initiative

Survival rates for children and young adults with cancer have significantly improved over recent decades, particularly in high-income countries (HICs), with five-year survival rates exceeding 80%.As a result, the burden of treatment-related late effects has emerged as a major global health challenge.These late sequelae may be progressive, irreversible and life-altering, with profound physical, psychosocial and economic consequences.Despite its association with many of these J o u r n a l P r e -p r o o f sequelae, radiotherapy remains a critical component of pediatric cancer care necessitating pediatricspecific evidence to guide safer practice and mitigate short-and long-term toxicity.The Pediatric Normal Tissue Effects in the Clinic (PENTEC) initiative was established to address this need by systematically evaluating dose-volume-risk relationships for normal tissues in children receiving radiotherapy, as impacted by developmental stage and other cancer therapies.PENTEC has produced organ-specific evidence and consensus-based guidelines that are now widely integrated into treatment planning in HICs.However, significant gaps remain including underrepresentation of survivorship endpoints in clinical trials and a paucity of evidence from low-and middle-income countries (LMIC) where survival rates are lower and survivorship infrastructure is less established.This report serves as a statement on the achievements and limitations of the PENTEC initiative, and highlights unique challenges specific to pediatric oncology faced by LMIC across infrastructure, workforce, health systems and sociocultural domains.Finally, it outlines priorities for global collaboration, education, advocacy and LMIC-led research.Broad dissemination and contextappropriate adaptation of PENTEC guidelines offer a cost-effective opportunity to reduce late morbidity and promote more equitable global survivorship outcomes.