Global to local burdens, inequalities, and achievable frontiers of child and adolescent malignant neoplasm of bone and articular cartilage across 953 countries and sublocations, 1980-2040, with deep learning-based forecasts.

Background: Malignant neoplasm of bone and articular cartilage (MNBAC), a major cause of cancer-related mortality, disproportionately impacts children and adolescents. However, comprehensive and future-oriented studies are still lacking. Methods: We systematically analyzed global-to-subnational MNBAC burdens, inequalities, and ideal achievable frontiers among those under 20 years old across 953 locations from 1980 to 2021. An advanced attention-based deep-learning pipeline was created for precise forecasting. Results: From 1990 to 2021, the global prevalence and incidence rate of MNBAC among those aged <20 years increased by 14.7 % and 14.3 %, respectively, leading to 139,154 prevalent cases by 2021. This disproportionately affected males and increased progressively with age, peaking in adolescents aged 15-19 years. Despite a slight global decline in MNBAC mortality, notable increases were observed in low-middle SDI region. 87.3 % of countries and 93.8 % of subnational locations experiencing increased mortality were situated in low to middle SDI regions, exemplified by Tokelau (377.8 %) and Indonesia's West Papua (148.6 %). Concurrently, the global YLD/YLL ratio for those <20 years increased, reflecting the ongoing transition from fatal to non-fatal burdens. This shift mainly impacted socio-economically advantaged settings, as 61 % of the top 100 countries were categorized as high and high-middle SDI. However, substantial gaps remain globally, with at least 94.1 % of countries and 81.4 % of subnational locations failing to meet achievable frontiers by 2021. Forecasts to 2040 anticipate further increases in incidence and stagnation in mortality, alongside widening disparities. Approximately 60.0 % of 672 subnational locations are forecasted to exhibit rising prevalence, with 41.2 % in the UK. By 2040, 30.0 % of the top 100 high-prevalence subnational locations will likely be in Sub-Saharan Africa, including 56 % in the UK. Mortality rates are forecasted to remain highest in low SDI region, especially in Eastern Sub-Saharan Africa, accounting for 47.7 % in Kenya alone. Conclusion: The MNBAC burden remains high, especially among adolescents, with anticipated increases in lower-income areas, necessitating targeted healthcare policies and increased investment. The Translational Potential of this Article: This study highlights the growing global burden of MNBAC and the urgent need for age-specific prevention, early detection, and equitable access to healthcare. Enhancing cancer registries, expanding financial protection, and integrating MNBAC management into national cancer control strategies could help reduce disparities and improve outcomes for affected children and adolescents.