Global, regional and national burdens of pediatric brain and CNS cancers (0-14 years), 1990-2021: Trend analysis and projections from GBD 2021

Global, regional and national burdens of pediatric brain and CNS cancers (0-14 years), 1990-2021: Trend analysis and projections from GBD 2021 | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 1 April 2025 V1 Latest version Share on Global, regional and national burdens of pediatric brain and CNS cancers (0-14 years), 1990-2021: Trend analysis and projections from GBD 2021 Authors : Dong Tang 0000-0001-6691-0355 , Zheng Huang , Shifu Li , Qian Zhang , Wengui Tao , Xiaobo Tian , Nibu Zhenmei , and Fenghua Chen [email protected] Authors Info & Affiliations https://doi.org/10.22541/au.174351802.29783414/v1 384 views 147 downloads Contents Abstract Supplementary Material Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Background Pediatric brain and central nervous system (CNS) cancers are the second most common childhood malignancy, yet global burden trends and disparities remain understudied. Methods Using Global Burden of Disease (GBD) 1990–2021 data, we analyzed incidence, mortality, prevalence, and disability-adjusted life years (DALYs) in children aged 0–14 years across 204 countries. Joinpoint regression identified temporal inflection points, decomposition analysis quantified DALY drivers (population growth, aging, epidemiology), and Bayesian Age-Period-Cohort models projected burdens to 2036. Results Global incidence declined by 0.54% annually (1990–2021), with similar reductions in DALYs (-1.49%/year) and mortality (-1.46%/year). High-SDI regions achieved burden reductions through early diagnosis and advanced therapies, while low-SDI regions (e.g., sub-Saharan Africa) experienced rising burdens due to healthcare resource limitations. Decomposition analysis revealed epidemiological improvements drove DALY declines in high-SDI areas, whereas population growth increased burdens in low-SDI settings. Projections indicate persistent global declines by 2036, but regional disparities may widen without targeted interventions. Conclusion Strengthening diagnostic capacity and equitable access to therapies in low-resource settings is critical to reducing global disparities. This study provides evidence to guide policy reforms for pediatric CNS cancer control. Global, regional and national burdens of pediatric brain and CNS cancers (0-14 years), 1990-2021: Trend analysis and projections from GBD 2021 Dong Tang 1,2,3 ; Zheng Huang 1,2,3 ; Shifu Li 1,2,3 ; Qian Zhang 1,2,3 ; Wengui Tao 1,2,3 ; Xiaobo Tian 1,2,3 ; Nibu Zhenmei 4 ; Fenghua Chen 1,2,3* 1. Department of Neurosurgery, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, China. 2. Cerebrovascular Diseases Research Center, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, China. 3. National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, China. 4. Department of Thoracic Surgery, People’s Hospital of Tibet Autonomous Region, Lhasa, China. * Corresponding Author: Fenghua Chen Xiang Ya Hospital Department of Neurosurgery, Central South University Changsha 410008, Hunan, People’s Republic of China Telephone: +86 0731-89753038 Email: [email protected] Keywords: brain and central nervous system cancers, Disease burden, GBD, Bayesian Projections, Joinpoint regression, Decomposition analysis Declarations Ethics approval and consent to participate The Institutional Review Board of the Xiangya Hospital of Central South University determined that approval for this research was not necessary, as it uses publicly available data. This study conforms to the Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER) for cross-sectional studies. Consent for publication Not applicable. Data availability All data used from the GHDx platform (https://vizhub.healthdata.org/gbd-results/). Conflict of Interest The authors have no conflicts to disclose. Funding Not applicable. Author contributions Conceptualization: Dong Tang; Zheng Huang; Shifu Li; Qian Zhang; Fenghua Chen Methodology: Dong Tang; Zheng Huang; Shifu Li; Wengui Tao; Fenghua Chen Formal analysis and investigation: Dong Tang; Qian Zhang; Xiaobo Tian; Nibu Zhenmei; Writing - original draft preparation: Dong Tang; Fenghua Chen Writing - review and editing: Dong Tang; Zheng Huang; Fenghua Chen All authors have read and agreed to the published version of the manuscript. Acknowledgments Thank you to all members of the GBD Database Collaboration Group. Abstract Background Pediatric brain and central nervous system (CNS) cancers are the second most common childhood malignancy, yet global burden trends and disparities remain understudied. Methods Using Global Burden of Disease (GBD) 1990–2021 data, we analyzed incidence, mortality, prevalence, and disability-adjusted life years (DALYs) in children aged 0–14 years across 204 countries. Joinpoint regression identified temporal inflection points, decomposition analysis quantified DALY drivers (population growth, aging, epidemiology), and Bayesian Age-Period-Cohort models projected burdens to 2036. Results Global incidence declined by 0.54% annually (1990–2021), with similar reductions in DALYs (-1.49%/year) and mortality (-1.46%/year). High-SDI regions achieved burden reductions through early diagnosis and advanced therapies, while low-SDI regions (e.g., sub-Saharan Africa) experienced rising burdens due to healthcare resource limitations. Decomposition analysis revealed epidemiological improvements drove DALY declines in high-SDI areas, whereas population growth increased burdens in low-SDI settings. Projections indicate persistent global declines by 2036, but regional disparities may widen without targeted interventions. Conclusion Strengthening diagnostic capacity and equitable access to therapies in low-resource settings is critical to reducing global disparities. This study provides evidence to guide policy reforms for pediatric CNS cancer control. Keywords: Brain and other CNS system cancers, Disease burden, GBD, Children, Joinpoint regression, Bayesian Projections Introduction Brain and other central nervous system (CNS) cancers, collectively known as CNS cancers, represent the second most prevalent type of cancer in children, following leukemia, and account for 20%-25% of all pediatric cancers 1,2 . The incidence of CNS cancers peaks in early childhood (<5 years) and again after the age of 15, with no significant gender-based differences in occurrence 3 . These cancers include a variety of pathological subtypes, among which highly malignant tumors such as medulloblastoma, diffuse intrinsic pontine glioma (DIPG), and glioblastoma are particularly notable due to their extremely high mortality rates and poor prognoses 4 . These aggressive tumors pose a significant threat to children’s health, not only because of their relatively short survival times but also due to the severe long-term side effects of treatment and the functional impairments suffered by survivors. Medulloblastoma is one of the most common and aggressive CNS tumors in children, with a 5-year survival rate ranging from 50% to 70%, depending on factors such as molecular subtype, age at diagnosis, and the presence of metastasis 5 . DIPG has an especially poor prognosis, with a median survival time of only 9-12 months and a 5-year survival rate of less than 1% 6 . Although glioblastoma is relatively rare in pediatric populations, it also carries a dismal prognosis, with a 5-year survival rate typically below 20% 7 . In addition to their high mortality rates, treatments for these tumors profoundly impact the quality of life, leading to neurocognitive deficits, endocrine disorders, and mental health issues 8 . Despite considerable advances in neurosurgical techniques and therapeutic approaches, these tumors remain major contributors to both mortality and long-term disability among children 9 . As such, a comprehensive understanding of the epidemiological trends and resulting national and societal burden of pediatric CNS cancers is essential for the development of effective public health policies and strategies for resource allocation. Disparities in the incidence and mortality of CNS cancers across different regions and countries highlight the critical role of socioeconomic factors and the distribution of healthcare resources. In low- and middle-income countries, the mortality rate for pediatric CNS cancers is significantly higher than in high-income countries, primarily due to limited access to diagnostic tools and treatment resources 10 . For example, the Global Burden of Disease (GBD) study reports a 5-year survival rate for pediatric CNS cancers of less than 30% in sub-Saharan Africa, compared to over 75% in North America and Western Europe 11 . This disparity underscores the importance of healthcare infrastructure and early diagnosis, emphasizing the urgent need to improve both the diagnosis and treatment of pediatric CNS cancers globally. This study employs several analytical methods to comprehensively assess the global burden of pediatric CNS cancers. Joinpoint Regression Analysis is utilized to explore incidence, prevalence, mortality, and Disability-Adjusted Life Years (DALYs) trends. This method identifies inflection points in trends, offering a precise understanding of potential shifts and the underlying factors driving changes in disease burden, which can help guide policy interventions. Additionally, a decomposition analysis method is applied to dissect changes in disease burden into components such as shifts in population age structure, population growth, and epidemiological trend shifts, thereby elucidating the relative contributions of various factors at both global and regional levels 12 . Frontier Analysis is used to compare the diagnostic and treatment performance across different countries and regions. Furthermore, to account for the dynamic nature of disease burden, the Bayesian Age-Period-Cohort (BAPC) model is employed to project future trends in incidence, prevalence, mortality, and DALYs from 2022 to 2036. This predictive model provides quantitative projections for future disease burden trends at both the global and national levels, aiding policymakers in formulating targeted prevention and treatment strategies 13 . These analyses will help identify high-risk regions and populations, optimize global resource allocation, and offer empirical evidence to inform future policy decisions. Through these comprehensive approaches, this study aims to provide a detailed understanding of the disease burden of pediatric CNS cancers across various regions and countries, uncovering future trends and offering robust data to support the advancement of neurosurgical techniques, improvement of patient outcomes, and the development of effective public health policies. Methods Overview This study analyzed data from the Global Burden of Disease (GBD) 2021 database, accessed via the Global Health Data Exchange query tool (http://ghdx.healthdata.org/gbd-results-tool) 14 . Central nervous system (CNS) cancers are classified as Level 3 (B.1.22) in the GBD 2019 cause hierarchy under neoplasms (B.1, Level 2) and non-communicable diseases (B, Level 1). These cancers correspond to ICD-10 codes C70–C72.9, which include malignancies of the meninges (C70), brain (C71), spinal cord, cranial nerves, or other parts of the CNS (C72). We focused on pediatric populations, analyzing data for children aged mortality (cases and rates), incidence (cases and rates), prevalence (cases and rates), and Disability-Adjusted Life Years (DALYs) along with age-standardized rates. This comprehensive approach provided a detailed understanding of the burden of CNS cancers in these age groups. Estimation Framework The GBD 2019 framework employed established methodologies to estimate health metrics, as detailed in prior studies 15,16 . Prevalence and incidence rates per 100,000 population were calculated by dividing the total and new case numbers by the population size. DALYs were determined by summing years of life lost (YLLs) due to premature mortality and years lived with disability (YLDs), offering a composite measure of disease burden. This framework allows for precise quantification of both chronic and recent disease impacts. Socio-demographic Index (SDI) The Socio-demographic Index (SDI) integrates metrics of development—per capita income, mean years of education, and fertility rates—into a single score ranging from 0 to 1. Higher SDI values indicate more advanced development. Globally, 204 countries and regions are categorized into five SDI quintiles based on their scores: low, low-middle, middle, high-middle, and high, facilitating stratified analyses of disease burden across different levels of socio-economic progress. Statistical Analysis This study assessed global, regional, and national trends from 1990 to 2021, focusing on age-standardized incidence, prevalence, mortality, and DALYs. Uncertainty was expressed using 95% confidence intervals. Joinpoint regression 17 analysis was employed to identify significant temporal changes by fitting linear segments to log-transformed data, with segments joined at statistically significant points. Models with zero joinpoints represented consistent trends. Age-specific rates and average annual percentage changes (AAPCs) were calculated to examine trends at multiple levels. Smoothing spline models were applied to investigate the association between CNS cancer burden metrics and SDI across 21 regions. Decomposition analysis was applied to disentangle the contributions of population aging, population growth, and changes in age-specific rates to trends in CNS cancer burden from 1990 to 2019. This method clarifies whether demographic factors or shifts in disease risk and healthcare delivery primarily drive changes in disease burden. The results can guide interventions targeting modifiable factors, such as reducing risk exposures or improving treatment accessibility 18 . Frontier analysis was employed to evaluate unrealized health improvements in CNS cancer outcomes relative to a country’s development level. This method constructs a nonlinear efficiency frontier that reflects the minimum expected disease burden (e.g., age-standardized DALYs) for a given Socio-demographic Index (SDI) score. Countries with burdens exceeding the frontier indicate opportunities for health system optimization. This analysis helps identify regions where targeted interventions—such as improved access to care or early diagnosis—could bridge the gap and reduce the disease burden 19 . Lastly, The Bayesian Age-Period-Cohort (BAPC) model integrates age, calendar period, and cohort factors to analyze disease trends and project future burdens. Using data from 1992 to 2021 as a training set, the model predicted CNS cancer burdens from 2022 to 2030. The Bayesian framework allows for uncertainty estimation and the inclusion of prior knowledge, enhancing the reliability of projections. These forecasts can inform resource allocation and policy planning to mitigate future disease impacts 20 . Software and Tools All statistical analyses and visualizations were conducted using R Studio (version 4.3.1) and the Joinpoint Regression Program (version 4.9.0.0). Key R packages included BAPC (version 0.0.36) for projections, INLA (version 23.6.29) for advanced modeling, and ggplot2 (version 3.5.1) for data visualization. Statistical significance was defined as p < 0.05. Results Global Trends Globally, the incidence of central nervous system (CNS) cancers in children aged 0-14 years demonstrated a general downward trend from 1990 to 2021 (AAPC: -0.54, 95% CI: -0.64, -0.43), with statistical significance indicated by the p-value for AAPC. Joinpoint regression analysis revealed three significant inflection points in the trend: 1996, 2005, and 2019. Although the overall trend was declining, there was a notable increase in incidence from 2005 to 2019 (APC: 0.45, 95% CI: 0.38, 0.51). The incidence increased during the 1990-1999 period (AAPC: 0.29, 95% CI: 0.18, 0.40), with statistical significance, and continued to rise through the subsequent decade (2000-2009) (AAPC: 0.29, 95% CI: -0.15, 0.73). Despite the significant turning point observed in 2019, the incidence remained elevated thereafter (AAPC: 0.23, 95% CI: 0.06, 0.41). Concerning disability-adjusted life years (DALYs), Joinpoint regression identified three intersection points, all reflecting a significant downward trend (AAPC: -1.49, 95% CI: -1.68, -1.30). Similarly, mortality showed a consistent and significant decline (AAPC: -1.46, 95% CI: -1.65, -1.27). Detailed data are provided in Figure 1, Table 1, and Supplementary Material Table 1. Global Trends by Sex The incidence of CNS cancers declined in both boys and girls, with a more pronounced decrease in boys (AAPC: -0.70, 95% CI: -0.84, -0.56), while the decline in girls was comparatively smaller (AAPC: -0.34, 95% CI: -0.51, -0.17). However, the incidence and total number of cases in boys remained higher than in girls. By 2021, the incidence in boys had decreased to 1.66 per 100,000 (95% UI: 1.15, 2.23) from 1990, while the total number of cases increased to 84,535.85 (95% UI: 59,148.21, 112,519.86). Similarly, the incidence and case numbers in girls surpassed 1990 levels, with an increase in incidence (AAPC: 0.35, 95% CI: 0.22, 0.48), although this trend did not reach statistical significance. Both boys and girls exhibited a decline in DALYs and mortality, with an APCC of -1.71 (95% CI: -1.88, -1.55) for DALYs and -1.28 (95% CI: -1.40, -1.15) for mortality. Detailed data are available in Supplementary Material Table 1. Global Trends by Age Group Between 1990 and 2021, the incidence of CNS cancers in the 10-14 age group showed a slight increase, from 1.36 per 100,000 (95% UI: 1.1, 1.59) in 1990 to 1.49 per 100,000 (95% UI: 1.27, 1.8) in 2019. Conversely, a downward trend was observed in other age groups. Prevalence decreased only in the 2-4 age group (APCC: -0.91, 95% CI: -1.24, -0.58). By 2021, the 5-9 age group had the highest number of cases, with 53,660 (95% UI: 44,497, 64,793). Regarding DALYs, all age groups exhibited a downward trend, with the most pronounced decrease in the 2-4 age group (APCC: -2.62, 95% CI: -2.62, -2.21), followed by the the 2-4 age group also showed the most significant decline (APCC: -2.42, 95% CI: -2.62, -2.21). Detailed data can be found in Supplementary Material Table 1. Global Trends by SDI and Correlation From 1990 to 2021, the incidence of CNS cancers in children aged 0-14 years declined across regions with high SDI, upper-middle SDI, and middle SDI. However, these trends were not statistically significant in high SDI and upper-middle SDI regions. In contrast, the incidence in low SDI regions showed a significant increase (APCC: 0.36, 95% CI: 0.26, 0.45). Regarding prevalence, all SDI regions exhibited an upward trend, with the most pronounced increase in high SDI regions (APCC: 0.95, 95% CI: 0.57, 1.34), followed by low SDI regions (APCC: 0.89, 95% CI: 0.83, 0.96). In terms of DALYs, all SDI regions exhibited a downward trend, with the most significant decrease in high SDI regions (APCC: -2.37, 95% CI: -2.61, -2.13), followed by middle SDI regions (APCC: -1.84, 95% CI: -2.03, -1.64). Similarly, mortality showed the most significant decline in high SDI regions (APCC: -2.34, 95% CI: -2.58, -2.10). Detailed data can be found in Supplementary Material Table 1. Regional Trends From 1990 to 2021, significant regional differences were observed in the incidence of CNS cancers in the 0-14 age group. Central Europe exhibited the most notable decrease (APCC: -1.01, 95% CI: -1.47, -0.55), while the High-income Asia Pacific region experienced the most significant increase (AAPC: 1.11, 95% CI: 0.59, 1.62). By 2021, the High-income Asia Pacific region had the highest prevalence, at 24.12 per 100,000 (95% UI: 19.93, 28.15), while Central Sub-Saharan Africa had the lowest prevalence at 1.03 per 100,000 (95% UI: 0.69, 1.48). North Africa and the Middle East showed the fastest increase in prevalence (APCC: 1.66, 95% CI: —), while regions such as Australasia, Central Europe, and Central Sub-Saharan Africa experienced declining trends, though not statistically significant. Central Asia had the highest DALYs rate, with 146.78 per 100,000 (95% UI: 122.03, 176.68), and this trend was increasing (APCC: 0.48, 95% CI: 0.17, 0.80). Most regions showed a decrease in DALYs, with the most notable decline in East Asia (APCC: -2.89, 95% CI: -3.21, -2.58), followed by Central Europe (APCC: -2.26, 95% CI: -2.67, -1.85). East Asia also exhibited the most prominent decrease in mortality (APCC: -2.84, 95% CI: -3.16, -2.52), followed by Central Europe (APCC: -2.25, 95% CI: -2.67, -1.83). Southern Sub-Saharan Africa demonstrated the most significant increase in mortality (APCC: 1.00, 95% CI: 0.40, 1.60), with statistical significance. Detailed results are shown in Supplementary Material Table 2. Figure 2A illustrates the smoothed incidence curves of CNS cancers across 21 regions, with a correlation of R = 0.71 and p < 0.001, showing that incidence was lowest at an SDI of 0.3 and increased as SDI increased. High-income Asia Pacific exhibited a significant growth trend. Figure 2B presents the trends in DALYs rates across the 21 regions, with the smoothed spline model suggesting that DALYs rates generally increase with SDI before eventually declining, yielding R = 0.33, p < 0.001. South Asia, Western Sub-Saharan Africa, Southeast Asia, and Central Sub-Saharan Africa remained stable, while other regions showed a rise and subsequent decline, with East Asia exhibiting the most pronounced decrease. Figure 2C shows the smoothed prevalence curves for the 21 regions, with R = 0.78 and p < 0.001, indicating that prevalence generally increases with SDI. Most regions exhibited an upward trend, while South Asia, Southeast Asia, Southern Sub-Saharan Africa, and Western Sub-Saharan Africa remained stable. East Asia showed the most significant increase. National Trends Between 1990 and 2021, Tokelau experienced the most significant increase in the incidence of CNS cancers in children aged 0-14 years, with an Average Annual Percent Change (AAPC) of 8.55 (95% CI: 7.51, 9.59), while Luxembourg demonstrated the most notable decline (AAPC: -2.10, 95% CI: -2.44, -1.77). Monaco had the highest incidence rate, at 8.07 cases per 100,000 (95% UI: 5.1, 11.67), while Gambia had the lowest at 0.15 cases per 100,000 (95% UI: 0.07, 0.23). In 2021, the countries with the highest number of incident cases were China, India, and the United States. Qatar had the highest prevalence in 2021 (9.87 per 100,000, 95% UI: 5.78, 16.14), whereas Gambia had the lowest (0.5 per 100,000, 95% UI: 0.24, 0.76). Tokelau, Niue, the Cook Islands, Bolivia, and Turkmenistan showed the most significant increases in prevalence. Mali had the lowest DALYs rate (14.62, 95% UI: 5.07, 23.45), followed by Palau (15.93, 95% UI: 11, 22.07), while Bolivia had the highest DALYs rate (137.92, 95% UI: 93.7, 181.67), with a higher AAPC of 5.63 (95% CI: 3.47, 7.83), followed by Palestine and Armenia. The countries showing the most prominent increase in DALYs were Tokelau, Niue, Bolivia, Cuba, and Turkmenistan, while Luxembourg, Romania, and Czechia showed the most significant decline. The Cook Islands had the lowest global mortality rate, at 0.1 deaths per 100,000 (95% UI: 0.06, 0.17), while Tajikistan had the highest, at 2.77 deaths per 100,000 (95% UI: 1.88, 4.17). Luxembourg, Slovakia, and Romania showed notable declines in mortality rates between 1990 and 2021. Detailed results are presented in Figure 3 and Supplementary Materials 3. Figure 4A presents the incidence rates across 204 countries, demonstrating a clear upward trend in incidence with increasing SDI. Monaco, San Marino, and Norway exhibited markedly higher incidence rates. Figure 4B shows DALYs rates, indicating a gradual upward trend as SDI increases, though eight countries (Tajikistan, Tokelau, Azerbaijan, Albania, Turkmenistan, Uzbekistan, Niue, and Suriname) exhibited significantly higher DALYs rates than expected. Figure 4C illustrates prevalence across 204 countries, with prevalence increasing with SDI. Monaco, Norway, and San Marino again exhibited rates above the smoothed curve. Figure 4D shows mortality rates, with a stable decline as SDI increases, though countries such as Brunei, Greenland, and Taiwan reported higher-than-expected mortality rates. Nine countries—Tajikistan, Tokelau, Azerbaijan, Albania, Turkmenistan, Uzbekistan, Niue, Monaco, and Suriname—showed DALY rates significantly higher than the smoothed curve. Decomposition Analysis of Change in DALYs The decomposition analysis of global and SDI-region-specific changes in DALYs is presented in Figure 5 and Supplementary Materials 4. Globally, the change in DALYs was attributed to population growth (-57.94%), population aging (5.21%), and epidemiological changes (152.72%). The contribution of population aging varied by SDI region, with negative contributions in low and middle-low SDI regions (-0.58% and -14.1%, respectively). In high SDI regions, epidemiological changes had the largest positive impact (85.58%). The impact of demographics and epidemiology on DALYs varied considerably by country and region, as detailed in the Supplementary Materials. Frontier Analysis Based on Age-Standardized DALYs Frontier analysis for 204 countries is shown in Figure 6, with black labels representing countries with the most significant effective differences, such as Norway, Czechia, the United Kingdom, Togo, Gambia, Guinea-Bissau, Australia, San Marino, Greenland, Iceland, France, the United States, and Canada. Blue labels denote countries with low SDI (0.85) and significant developmental differences, such as the United States, Canada, Germany, and the Netherlands. Burden of Disease Projections Projections for global trends indicate a decline in Age-Standardized Incidence Rate (ASIR), Age-Standardized Mortality Rate (ASMR), Age-Standardized Prevalence Rate (ASPR), and Age-Standardized Disability-Adjusted Life Year Rate (ASDR) by 2036. It is estimated that by 2036, there will be approximately 18,396 (95% UI: 12,919-23,871) incident cases, 9,163 (95% UI: 5,423-21,960) deaths, 81,363 (95% UI: 54,693-108,032) prevalent cases, and 751,454 (95% UI: 6,558-11,768) DALYs. Projections suggest that regions such as Western Sub-Saharan Africa, Eastern Sub-Saharan Africa, and Southern Sub-Saharan Africa will experience increases in incidence and DALYs, while mortality rates will rise in these regions, as well as in Oceania. Increases in prevalence are also expected in Southern Sub-Saharan Africa, Western Sub-Saharan Africa, Eastern Sub-Saharan Africa, North Africa, and the Middle East. Further details can be found in Supplementary Table 4. Discussion To the best of our knowledge, this is the first study to comprehensively present trends in the incidence, DALY rates, prevalence, and mortality rates of brain and other CNS cancers among children aged 0–14 years across 204 countries, globally, regionally, and nationally, from 1990 to 2021. Our findings reveal significant global increases in the incidence, DALYs, and mortality rates of CNS cancers over the study period, while prevalence showed an overall decline. Notably, 2019 appeared to mark a pivotal turning point, characterized by a pronounced downward trend across all four measures. Moreover, projections based on Bayesian Age-Period-Cohort (BAPC) analysis indicate a global decline in incidence, DALYs, prevalence, and mortality rates from 2022 to 2036. This improvement could be attributed to advancements in global health policies, as many nations have intensified efforts to promote early screening, diagnosis, and treatment of pediatric cancers in recent years. For instance, research in Lancet Oncology highlights enhanced policy support for childhood cancer, such as the widespread adoption of genetic testing and imaging technologies in numerous countries post-2015 21 . The WHO’s global immunization initiatives have also significantly reduced the incidence of virus-associated tumors 22 . Advances in surgery, radiotherapy, and chemotherapy, particularly precision medicine and molecular-targeted therapies, have played pivotal roles in reducing prevalence (fewer long-term burdened survivors), DALYs, and mortality rates 23 . Additionally, improved environmental and lifestyle factors, such as decreased exposure to radiation and chemical pollution, have contributed to this decline. Policies limiting pesticide use and improving air quality, particularly in developed countries, may have reduced the risk of childhood brain tumors. Studies indicate a positive correlation between air pollution and pediatric brain tumors, suggesting that pollution control may lower associated risks 24 . Although economic slowdowns were observed in multiple countries around 2019, investments in public health and advancements in medical technology accelerated, potentially driving the short-term reduction in tumor burden. While the COVID-19 pandemic posed challenges to healthcare resource allocation, it also fostered innovations such as telemedicine and system integration, which may have long-term benefits for managing pediatric cancers. Research suggests that post-pandemic medical innovations have enhanced precision management for childhood cancer 25 . The Socio-Demographic Index (SDI), a composite measure of a population’s development, has steadily improved in most countries, strongly correlating with disease burden metrics. As SDI increased, incidence and prevalence trends rose in most of the 21 global regions, while mortality and DALY rates initially increased before declining. This pattern likely reflects improved diagnostic capabilities and resource allocation, leading to higher detection rates but also lower mortality and DALY rates due to advancements in early diagnosis, effective treatments, and supportive care 26,27 . In high-SDI regions, such as High-Income North America, Western Europe, and Eastern Europe, significant declines in DALY and mortality rates were observed. Similarly, in upper-middle SDI regions such as East Asia and Central Europe, the downward trends were notable, likely due to rapid economic development and innovations in surgical techniques, radiotherapy precision, and targeted therapies that substantially reduced fatality and long-term burdens 28 . Conversely, low-SDI regions, such as Southern Sub-Saharan Africa, showed increasing mortality trends, which could be attributed to fragile healthcare systems, high treatment costs, and low diagnostic rates leading to delayed interventions. Additionally, the rising proportion of advanced maternal age, associated with elevated tumor risks, further exacerbates the burden in these areas 29 . Many low- and middle-SDI countries lack robust disease monitoring systems, resulting in underdiagnosed and unreported cases, particularly in regions like South Asia, Southeast Asia, and Sub-Saharan Africa. Some countries continue to face high mortality and DALY rates, including Tokelau, Niue, Bolivia, Cuba, and Turkmenistan, which also exhibit elevated ASDR and ASMR trends. For instance, Brazil shows a notable increase in mortality and DALY rates, underscoring the need for enhanced preventive and therapeutic strategies for CNS cancers. From 1990 to 2021, further analysis decomposed the changes in DALYs due to CNS cancers into population growth, aging, and epidemiological shifts. Globally, DALY reductions were primarily driven by epidemiological changes, which accounted for a 152.72% reduction in the global CNS cancer burden. High-, upper-middle-, and middle-SDI regions contributed the most to this decrease, with epidemiological improvements responsible for 85.58%, 79.63%, and 95.24% of DALY reductions, respectively. However, in low- and lower-middle-SDI regions, population growth emerged as the dominant factor, offsetting DALY reductions and accounting for a 156.27% and 109.07% increase in DALY burdens, respectively. Meanwhile, the impact of population aging on global CNS cancer DALYs remained relatively modest. To optimize DALY reductions relative to national development, we conducted a frontier analysis using age-standardized DALY rates and SDI data from 1990 to 2021. The efficiency gap, defined as the difference between observed DALYs and achievable DALYs, provided insights into national performance. Countries with low SDI scores (<0.45), such as Somalia, Timor-Leste, Papua New Guinea, Yemen, and Laos, exhibited minimal efficiency gaps, demonstrating successful outcomes despite resource limitations. These findings highlight the potential for sustainable health improvements through optimized resource utilization and international support. In contrast, countries with significant efficiency gaps spanned all SDI strata, reflecting diverse disease burden and resource allocation patterns. High-SDI countries (SDI Netherlands, showed high DALY rates, underscoring deficiencies in chronic disease management and health equity. Future strategies should focus on public health education, lifestyle interventions, and narrowing health disparities. Our study has several limitations. First, the GBD study relies on publicly available health data from various countries and regions, which may be incomplete or inaccurate, particularly in low- and middle-income countries. These regions often lack robust registration systems, medical infrastructure, and data collection mechanisms, introducing potential bias into burden estimates. Second, CNS cancers encompass diverse subtypes. Advances in diagnostic technology may result in evolving classifications and subtype identification, potentially affecting the interpretation of our findings. Third, burden estimates typically focus on short-term metrics such as mortality and DALYs. However, long-term consequences of treatment, including neurocognitive impairment, endocrine disorders, and mental health issues, profoundly impact patients’ quality of life. Future research should incorporate these long-term outcomes to better capture their contribution to the overall disease burden. By addressing these limitations, our findings aim to inform policy development, optimize resource allocation, and guide efforts to reduce the burden of pediatric CNS cancers globally. Conclusion This study provides a comprehensive assessment of the global, regional, and national burden of pediatric brain and other CNS cancers from 1990 to 2021. The findings highlight significant global improvements in disease burden, particularly in high- and high-middle SDI regions, driven by advancements in early detection, treatment, and healthcare infrastructure. However, low-SDI regions continue to face rising mortality and DALYs, underscoring the need for enhanced healthcare resources and early diagnostic capabilities. The analysis also identifies the critical role of epidemiological factors in shaping disease trends, with population growth in low-SDI regions dampening overall gains. 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Keywords brain tumors epidemiology pediatric oncology quality of life Authors Affiliations Dong Tang 0000-0001-6691-0355 Xiangya Hospital Central South University Department of Neurosurgery View all articles by this author Zheng Huang Xiangya Hospital Central South University Department of Neurosurgery View all articles by this author Shifu Li Xiangya Hospital Central South University Department of Neurosurgery View all articles by this author Qian Zhang Xiangya Hospital Central South University Department of Neurosurgery View all articles by this author Wengui Tao Xiangya Hospital Central South University Department of Neurosurgery View all articles by this author Xiaobo Tian Xiangya Hospital Central South University Department of Neurosurgery View all articles by this author Nibu Zhenmei Tibet Autonomous Region People's Hospital View all articles by this author Fenghua Chen [email protected] Xiangya Hospital Central South University Department of Neurosurgery View all articles by this author Metrics & Citations Metrics Article Usage 384 views 147 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Dong Tang, Zheng Huang, Shifu Li, et al. Global, regional and national burdens of pediatric brain and CNS cancers (0-14 years), 1990-2021: Trend analysis and projections from GBD 2021. Authorea . 01 April 2025. DOI: https://doi.org/10.22541/au.174351802.29783414/v1 If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download. For more information or tips please see 'Downloading to a citation manager' in the Help menu . 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