Results

Global Burden of Brain and CNS Tumors

In 1990, an estimated 38816.64 (95% UI: 30302.58–48085.63) new cases of brain and CNS tumors occurred among children and adolescents worldwide. In contrast, the estimated new cases in 2021 were 40,534.53 (33,345.94–49,609.04). From 1990 to 2021, the age‐standardized incidence rate (ASIR) declined from 1.72 (1.34–2.13) to 1.54 (1.27–1.88) per 100,000, indicating a moderate global reduction in incidence. Over the same period, the age‐standardized death rate (ASDR) fell from 1.14 (0.86–1.43) to 0.76 (0.61–0.93), while the age‐standardized DALY rate (ASDALYR) decreased from 462.05 (344.49–586.83) to 308.37 (244.28–381.13) (Figure 1 and Table S1). These consistent declines suggest notable global progress in pediatric CNS tumor control.

Figure 1: Global and regional age‐standardized rates (per 100,000) for CNS tumors. ASDALYR, age‐standardized DALY rate; ASDR, age‐standardized death rate; ASIR, age‐standardized incidence rate; CNS, central nervous system; DALY, disability‐adjusted life year; SDI, socio‐demographic index.

To explore age‐specific patterns, all cases were divided into four age groups (0–4, 5–9, 10–14, and 15–19 years). Between 1990 and 2021, the ASIR in the 0–4‐year group declined from 2.47 (1.81–3.25) to 1.77 (1.36–2.25), and in the 5–9‐year group from 1.79 (1.39–2.22) to 1.68 (1.36–2.03). In contrast, mild increases were observed among adolescents aged 10–19 years (Table S2). The ASDR decreased by nearly 47% in the 0–4‐year group and by over 30% in the 5–9‐year group, but showed smaller declines in older age groups (Table S3). Similarly, the ASDALYR dropped by roughly 47% and 30% in the two youngest groups, whereas reductions were less than 15 per 100,000 in adolescents (Table S4).

Burden of Brain and CNS Tumors in Five SDI Quantiles and 21 GBD Regions

Across five SDI regions, the middle‐SDI regions consistently had the largest number of incident cases from 1990 to 2021. However, the ASIR displayed a positive gradient with development level—in 2021, high‐SDI regions recorded the highest ASIR (2.64 [2.49–3.80]), which was about 3.5 times higher than in low‐SDI regions (0.75 [0.52–0.96]) (Figure 1 and Table S1). Among age groups, the 0–4‐year group carried the heaviest burden, while the 15–19‐year group consistently showed the lowest ASIR. For instance, ASIRs ranged from 1.24 (0.80–1.69) to 2.90 (2.18–3.99) in the youngest group, compared with 0.41 (0.29–0.52) to 2.31 (2.13–2.47) in the oldest (Table S2).

Mortality patterns differed from incidence. In 2021, the high‐middle SDI regions reported the highest ASDR (0.93 [0.77–1.16]) (Figure 1 and Table S1). Over the past three decades, ASDRs among older children (> 10 years) increased slightly in low and low‐middle SDI regions, in contrast to declining trends observed elsewhere (Table S3). Overall, ASDALYRs declined by about 47% and 38% in high‐middle and middle SDI regions, respectively (Figure 1 and Table S1). Notably, DALYs remained most concentrated in the 5–9‐year group, while substantial reductions were observed among those aged 0–4 years (Table S4).

Across 21 GBD regions in 2021, ASIRs ranged widely—from 0.31 (0.21–0.43) to 3.09 (2.37–4.14)—with East Asia, High‐income Asia Pacific, and High‐income North America showing the highest rates. Central Europe showed one of the largest declines in ASIR from 1990 to 2021, whereas Central Asia exhibited a marked increase (Figure 1 and Table S1). Regarding mortality, Central Asia, Andean Latin America, North Africa, and the Middle East reported the highest ASDRs. These patterns should be interpreted with caution, as they may partly reflect variation in data completeness, case ascertainment, and health system capacity across regions. In contrast, East Asia and Central and Eastern Europe showed marked declines (Figure 1 and Table S1).

Patterns in ASDALYRs reflected these regional differences. The proportion of regions exceeding 400 DALYs declined from 52.4% in 1990% to 28.6% in 2021, indicating overall global improvement. However, Central Asia showed an increase of approximately 20%, whereas East Asia experienced a substantial reduction (52.7%) (Figure 1 and Table S1).

Across age groups, the burden of CNS tumors remained highest among younger children (< 10 years), particularly in the 5–9‐year group. For example, the median ASDR in this group was 0.89 (0.77–1.04), compared with less than 0.80 per 100,000 in the other three groups (Tables S2–S4).

National Burden of Brain and CNS Tumors

In 2021, the ASIR varied widely across countries. Among 204 countries and territories, 92 reported ≥ 50 new cases of CNS tumors (highest: China, India, and the United States), while 61 reported ≥ 50 deaths. From 1990 to 2021, the ASIR increased in 141 countries and territories, indicating a gradual global expansion of the disease burden. The number of high‐burden countries (ASIR > 3.00 per 100,000) rose from 27 in 1990 (peak: San Marino; Figure S1A) to 32 in 2021 (peak: Monaco, Norway, and San Marino; Figure 2A and Table S5).

Figure 2: Global distribution of age‐standardized rates (per 100000) of CNS tumors in 2021. (A) Age‐standardized incidence rate in 2021; (B) Age‐standardized death rate in 2021; (C) age‐standardized DALY rate in 2021. ASDALYR, age‐standardized DALY rate; ASDR, age‐standardized death rate; ASIR, age‐standardized incidence rate; CNS, central nervous system; DALY, disability‐adjusted life year.

Countries with large populations (> 50 million) contributed substantially to global incidence but tended to have moderate ASIRs. For instance, China's ASIR was 3.13 (95% UI: 2.39–4.21) in 2021, ranking 27th globally (Table S5). In 1990, 65 countries had an ASDR exceeding 1.00 per 100,000 (Figure S1B); by 2021, that number had decreased to 40 (Figure 2B). The highest ASDR in 2021 was observed in Tajikistan at 2.49 (95% UI: 1.73–3.69). Over the past 32 years, ASDRs increased in 78 countries, with the sharpest rises in Tokelau, Turkmenistan, and Niue, while the greatest reductions occurred in Greenland, Serbia, and China (Table S5).

The number of countries with an ASDALYR above 800 per 100,000 decreased from 11 in 1990 (Figure S1C) to five in 2021 (Figure 2C). The highest ASDALYRs in 2021 were found in Tajikistan, Tokelau, and Azerbaijan, whereas Serbia, Greenland, and China achieved one of the largest improvements, with China's ASDALYR decreasing by at least 53.19% (Table S5).

Global and Regional Trends in CNS Tumors Across Different Age Groups

Figure S2 and Table S6 summarize the temporal trends (net and local drifts) in incidence and mortality of CNS tumors across four age groups during 1992–2021. The APC analysis revealed heterogeneous patterns among SDI regions. Globally, the net drift of incidence was −0.13% per year (95% CI: −0.29% to 0.02%, p = 0.099), suggesting a mild but statistically nonsignificant decrease, with marked regional differences. Low and low‐middle SDI regions showed evident annual increases, while the middle and high‐middle SDI regions remained near stability (~0.10%). In local drift analysis, the steepest incidence decline occurred in the 0–4‐year group within low SDI regions (−0.76% [−0.98% to −0.53%] per year). Conversely, adolescents (15–19 years) showed a worrying global increase (0.48% [0.15% to 0.80%] per year), particularly in middle and high‐middle SDI regions (Figure S2A).

Mortality trends exhibited clearer improvement. The global net drift of mortality was −1.16% per year (95% CI: −1.35% to −0.98%, p < 0.0001). The decline was more pronounced in high‐middle SDI regions (−2.06% [−2.32% to −1.79%] per year). In contrast, low and low‐middle SDI regions showed small but concerning annual increases of 0.29% (0.11%–0.47%) and 0.21% (0.10%–0.33%), respectively.

For local drifts, the 0–4‐year group experienced the steepest mortality reduction globally (−1.86% [−2.14% to −1.59%] per year), corresponding to over 55% decrease in the last three decades. The high‐middle SDI region led this trend (−3.49% [−3.93% to −3.05%] per year). Alarmingly, the low SDI region was the only area showing a positive local drift in the 0–4‐year group, suggesting a continued deterioration of mortality burden in the world's least‐developed settings (Figure S2B).

Age, Period, and Birth Cohort Effects of Brain and CNS Tumors

The age, period, and birth cohort effects on incidence are presented in Figure 3 and Table S9. Overall, similar age‐related patterns were observed across SDI quintiles, with the highest incidence risk in the 0–4‐year group, followed by a steady decline with increasing age. Notably, low‐SDI countries showed consistently lower incidence risks across all age groups compared to other regions (Figure 3A). Globally, period effects demonstrated a downward trend from 1992 to 2006, followed by a renewed increase from 2007 to 2021. Comparable fluctuations appeared in low, middle, and high‐middle SDI regions, while low‐middle and high SDI regions showed continuous increases, signaling potential challenges ahead. Compared with the reference period (1992–1996), the 2017–2021 period recorded the highest relative risks (RRs) in low‐middle (1.21, 95% CI: 1.17–1.25) and low SDI regions (1.13, 95% CI: 1.07–1.19), indicating less favorable epidemiologic trends (Figure 3B).

Figure 3: Age, period, and birth cohort effects on incidence of CNS tumors by SDI quintiles. (A) The age effect is depicted through the longitudinal rates specific to age, which are adjusted for variations across different birth cohorts, taking into account the period‐specific deviations. (B) Period effects are shown through the relative risk of mortality of brain and CNS tumors during different periods, calculated as the ratio of the age‐specific rates from the period from 1992 to 1996 to 2017–2021, with the baseline period set as 1992–1996. (C) Birth cohort effects are demonstrated by the cohort relative risk of mortality and calculated as the ratio of age‐specific rates from 1972 to 1981 cohort to 2012–2021 cohort, with the reference cohort set at 1992–2001. The dots and shaded areas denote the incidence rates or rate ratios and their corresponding 95% CIs. CNS, central nervous system; SDI, socio‐demographic index.

Birth cohort effects showed an inverted U‐shaped pattern globally and in middle and high‐middle SDI regions, while low and low‐middle SDI regions demonstrated a continuous rise. The highest RR was observed in the low‐SDI region (1.12, 95% CI: 1.05–1.20) among cohorts born in 2012–2021. Compared with the reference cohort (1992–2001), RRs for individuals born in 1997–2006, 2002–2011, and 2007–2016 were higher in the high‐SDI region (Figure 3C). These findings highlight widening disparities in pediatric CNS tumor incidence across socioeconomic strata.

The age effects on mortality largely paralleled those on incidence but exhibited steeper gradients. Generally, low‐SDI regions maintained the lowest mortality risks across all age groups (Figure S3A). However, mortality rates in middle and high‐middle SDI regions were higher for younger children (0–9 years) than in other SDI categories, particularly within the 0–4‐year group, suggesting poorer survival outcomes in early childhood. Despite an overall global decline in mortality, period effects varied across SDI levels. Compared with the reference period (1992–1996), RRs of mortality showed a gradual increase after an initial drop in low and low‐middle SDI regions (Figure S3B).

Cohort effects revealed significant mortality improvements worldwide, especially in middle, high‐middle, and high SDI regions. However, the low‐SDI region showed a mild yet persistent upward trend in RR (Figure S3C). These results indicate that, while global mortality from pediatric CNS tumors has declined across multiple dimensions, certain low‐resource regions remain vulnerable and require targeted public health interventions.

Prediction of Global ASIR, and ASDR up to 2036

Using the BAPC model, we projected global trends of ASIR and ASDR for CNS tumors from 2022 to 2036 (Figure 4 and Table S7). The ASIR is expected to show a gradual reduction, reaching 1.13 (95% CI: 0.76–1.49) by 2036. In contrast, the decline in mortality is projected to be more pronounced, with the ASDR estimated at 0.48 (0.36–0.59)—representing a reduction of over one‐third compared to 2021. These projections suggest continued global improvement in pediatric CNS tumor outcomes, though progress may remain uneven across regions.

Figure 4: Projects the numbers and age‐standardized rates (per 100000) of CNS tumors from 2022 to 2036. CNS, central nervous system.