Abstract
We investigated the epidemiologic characteristics of childhood brain tumors (CBT) in Korea, and compared our findings with those from the United States.
We searched the Korea National Cancer Incidence Database of the Korea Central Cancer Registry (KCCR) from 2005 to 2014, which included all Korean patients with CBT aged 0 to 19 years at diagnosis. The age-standardized incidence rates (ASR) and the 5-year relative survival rate (RSR) were determined. The Central Brain Tumor Registry of the United States (CBTRUS) classification and definitions were applied to allow direct comparison with U.S. data.
A total of 6,027 CBTs were identified. The ASR of all CBTs was 5.08 per 100,000 population, which was significantly lower than that in the United States (5.57). However, the ASR of nonmalignant CBTs in Korea (2.48) was significantly higher than that in the United States (2.15). Embryonal tumors (ASR: 0.99 and 0.72 in the 0–4 and 5–9 year age groups, respectively) were the most common CBTs in these respective age groups. Germ cell tumors (0.78) and pituitary tumors (1.63) were the most common CBTs in the 10–14 and 15–19 year age groups, respectively. The 5-year RSR of CBTs was 84% and varied according to histology.
High incidences of nonmalignant and germ cell tumors are distinct CBT features in Korean children and adolescents.
To our knowledge, this is the first and largest population-based epidemiologic study of CBTs in Asia. Our findings support the notion that East Asian populations have a higher incidence of central nervous system germ cell tumors than other races.
Introduction
Primary brain and central nervous system (CNS) tumors are the most prevalent neoplasms in children and adolescents aged 0 to 19 years, including those that are nonmalignant (1–3). Following leukemia, brain and CNS tumors are the second leading cause of cancer-related deaths in this age group (1).
Previous studies in several countries and regions have reported that the incidence rates of primary brain and CNS tumors in children and adolescents, referred to as childhood brain tumors (CBT), ranged from 1.08 to 5.57 per 100,000 population (1, 4). This wide range may be attributed to the differences in demographic characteristics such as race, parental age, and environmental exposures including therapeutic or diagnostic ionizing radiation as well as air pollution (5–8). However, methodologic discordances (particularly the lack of both a unified classification system and a universal definition for CBTs) are major obstacles to comparing these epidemiologic studies (6). In addition, most existing studies have been conducted using the International Incidence of Childhood Cancer (ICCC) standard, although this classification does not categorize CNS germ cell tumors (GCT) and leukemias/lymphomas in the brain and CNS sites as CNS neoplasms (site group III; ref. 4). Furthermore, nonmalignant tumors with benign and borderline behavior, which cause significant morbidity in clinical practice, were often not included in published epidemiologic studies. Under this background, the Central Brain Tumor Registry of the United States (CBTRUS), the world's largest brain tumor registry, began publishing statistical reports that include nonmalignant tumors in 2004 (1, 9, 10).
The Korea Central Cancer Registry (KCCR) launched in 1980 as a nationwide hospital-based cancer registry by Korean Ministry of Health and Welfare, and was expanded into a nationwide population-based cancer registry in 1999. To date, the KCCR is the largest national population-based cancer registry in Asia. The main objective of this study was to investigate the incidence of CBTs (including nonmalignant tumors) and patient survival rates in the Korean pediatric population. Moreover, we compared the incidence of CBTs between Korea and the United States directly using the same classification criteria and definitions.
Materials and Methods
Data sources
The KCCR data represent over 97% of cancer incidences in Korea and have been compiled since 1999 (11, 12). The KCCR revised its criteria for cancer registration to include benign and borderline tumors of the brain and CNS in 2004, and began collecting nonmalignant brain and CNS tumor data in 2005.
Data collection
We investigated malignant and nonmalignant brain and CNS tumors diagnosed in children and adolescents aged 0 to 19 years between 2005 and 2014. We collected and analyzed the characteristics of CBTs including the most valid basis for diagnosis, anatomic site, and histologic type using the International Classification of Diseases for Oncology, third edition (ICD-O-3; ref. 13). Anatomic sites were classified as follows: brain (ICD-O-3: C71.0–C71.9); meninges (C70.0–C70.9); spinal cord, cranial nerves, and other parts of the CNS (C72.0–C72.9); pituitary and pineal glands (C75.1–C75.3); and olfactory tumors of the nasal cavity [C30.0 (9522–9523)]. These classifications and histologic groupings were based on those of the CBTRUS (14), which are broadly based on the World Health Organization categories for brain tumors. Because the classification of malignant and nonmalignant tumors also complied with CBTRUS criteria, gliomas with ICD-O-3 codes of 9431/1 and 9432/1, as well as pilocytic astrocytomas with ICD-O-3 codes of 9421/1, were classified as malignant tumors. We then directly compared the overall incidence rate of CBTs between Korea and the United States. For survival analysis, we restricted the data to patients with primary brain and CNS tumors newly diagnosed between 2005 and 2014. We excluded patients who could not be followed owing to mismatched personal identification numbers as well as those identified only by their death certificates. To ascertain patient vital status for survival analyses, the KCCR database was linked to mortality data from Statistics Korea. Passive follow-up was conducted until December 31, 2015.
Statistical analysis
Age-specific rates, age-standardized rates (ASR), and male-to-female incidence rate ratios with 95% confidence intervals (CI) were calculated. Rates are expressed per 100,000 persons. The ASRs were calculated on the basis of 5-year age groups (0–4, 5–9, 10–14, and 15–19 years) and were standardized to the Segi world standard population (15). However, we standardized to the U.S. population of the year 2000 to directly compare our overall incidences with those in the United States (Fig. 1), because the CBTRUS is the largest compilation of population-based cancer registry data regarding the incidence of brain and CNS tumors, and reports statistics related to primary brain and CNS regularly (14). The male-to-female rate ratios (M:F rate ratio) were calculated by dividing the age-adjusted incidence rates for males by those for females. Relative survival rates (RSR) were calculated as the ratios of the observed survival of the cancer patients to the expected survival of the general population, which was calculated using the standard life table provided by Statistics Korea (11). The complete survival rate approach was utilized to calculate the RSRs. Therefore, 5 full years of follow-up data were not available for all patients included in the survival analysis. We did not calculate age-adjusted RSRs because there is no standard patient population to which childhood cancer patients can be compared. RSRs were estimated by the Ederer II method. All statistical analyses were conducted using SAS (version 9.3).
Results
Between 2005 and 2014, 6,027 cases of CBTs were identified in the KCCR database. Two thirds of all CBTs (4,000 cases) were confirmed by histologic diagnosis; approximately 52% were malignant. The median age at diagnosis was 12.4 years. The average annual incidence was 603 cases per year and the overall ASR was 5.02 per 100,000 population (95% CI, 4.89–5.15). The overall male-to-female incidence rate ratio was 1.04:1 [ASR: 5.11 (95% CI, 4.93–5.30) vs. 4.92 (95% CI, 4.74–5.11) in males and females, respectively; Table 1]. The incidence rate for total CBTs tended to increase slightly over the years, but the trend was not statistically significant (average annual percentage change: 1.8%, P = 0.06). The number and percentage of nonmalignant tumors identified over the first 2 years of our study period (2005–2006; 224 cases per year; 41.3%, 447/1,082) were significantly lower than those identified over the next 8 years (2007–2014; 320 cases/year; 51.7%, 2,555/4,945; P < 0.0001; Supplementary Fig. S1).
. | . | Incidence rate . | . | . |
---|---|---|---|---|
Histological groupa . | 10-year total (%) . | ASRb (95% CI) . | Median age (y) . | Sex ratio: Male/female . |
Tumors of neuroepithelial tissue | 2,539 (42.1) | 2.27 (2.18–2.36) | 10.0 | 1.07 |
Pilocytic astrocytoma | 423 (7.0) | 0.37 (0.33–0.41) | 10.9 | 0.81c |
Diffuse astrocytoma | 150 (2.5) | 0.13 (0.11–0.15) | 10.9 | 1.27 |
Anaplastic astrocytoma | 84 (1.4) | 0.07 (0.05–0.08) | 14.0 | 1.41 |
Unique astrocytoma variants | 93 (1.5) | 0.07 (0.06–0.09) | 12.6 | 0.85 |
Glioblastoma | 163 (2.7) | 0.13 (0.11–0.15) | 13.4 | 1.12 |
Oligodendroglioma | 39 (0.6) | 0.03 (0.02–0.04) | 14.4 | 1.36 |
Anaplastic oligodendroglioma | 13 (0.2) | 0.01 (0.00–0.01) | 16.7 | 1.12 |
Oligoastrocytic tumors | 8 (0.1) | 0.01 (0.00–0.01) | 13.6 | 0.99 |
Ependymal tumors | 207 (3.4) | 0.20 (0.17–0.23) | 8.3 | 1.18 |
Glioma malignant, NOS | 299 (5.0) | 0.27 (0.24–0.30) | 9.0 | 0.94 |
Choroid plexus tumors | 72 (1.2) | 0.08 (0.06–0.10) | 3.1 | 1.42 |
Other neuroepithelial tumors | 6 (0.1) | 0.01 (0.00–0.01) | 7.5 | 0.41 |
Neuronal and mixed neuronal-glial tumors | 327 (5.4) | 0.26 (0.23–0.29) | 12.5 | 1.01 |
Tumors of the pineal region | 35 (0.6) | 0.03 (0.02–0.04) | 9.0 | 1.68 |
Embryonal tumors | 620 (10.3) | 0.61 (0.56–0.66) | 7.0 | 1.19c |
Medulloblastoma | 362 (6.0) | 0.34 (0.30–0.38) | 8.1 | 1.59c |
Primitive neuroectodermal tumor | 134 (2.2) | 0.13 (0.11–0.15) | 7.4 | 0.86 |
Atypical teratoid/rhabdoid tumor | 76 (1.3) | 0.09 (0.07–0.11) | 1.4 | 0.93 |
Other embryonal tumors | 48 (0.8) | 0.05 (0.04–0.07) | 4.3 | 0.65 |
Tumors of cranial and spinal nerves | 324 (5.4) | 0.25 (0.22–0.28) | 14.3 | 1.07 |
Nerve sheath tumors | 324 (5.4) | 0.25 (0.22–0.28) | 14.3 | 1.07 |
Tumors of the meninges | 292 (4.8) | 0.23 (0.20–0.25) | 15.1 | 0.82 |
Meningioma | 166 (2.8) | 0.13 (0.11–0.15) | 15.1 | 0.70c |
Mesenchymal tumors | 55 (0.9) | 0.05 (0.04–0.06) | 12.0 | 1.11 |
Primary melanocytic lesions | 5 (0.1) | 0.00 (0.00–0.01) | 13.2 | 1.30 |
Other neoplasms related to the meninges | 66 (1.1) | 0.05 (0.04–0.06) | 16.6 | 0.92 |
Lymphomas and hemopoietic neoplasms | 74 (1.2) | 0.06 (0.05–0.08) | 11.2 | 1.75c |
Lymphoma | 29 (0.5) | 0.02 (0.01–0.03) | 13.2 | 1.74 |
Other hemopoietic neoplasms | 45 (0.7) | 0.04 (0.03–0.05) | 11.1 | 1.76 |
Germ cell tumors and cysts | 641 (10.6) | 0.49 (0.45–0.53) | 13.1 | 2.40c |
Germ cell tumors, cysts and heterotopias | 641 (10.6) | 0.49 (0.45–0.53) | 13.1 | 2.40c |
Germinoma | 403 (6.7) | 0.29 (0.26–0.32) | 14.3 | 2.41c |
Mixed germ cell tumor | 100 (1.7) | 0.08 (0.06–0.09) | 12.4 | 2.12c |
Yolk sac tumor/choriocarcinoma | 30 (0.5) | 0.02 (0.02–0.03) | 10.8 | 3.69c |
Teratoma | 72 (1.2) | 0.07 (0.05–0.09) | 7.0 | 2.94c |
Others | 36 (0.6) | 0.03 (0.02–0.04) | 13.4 | 1.56 |
Tumors of the sellar region | 1,031 (17.1) | 0.76 (0.72–0.81) | 16.1 | 0.55c |
Tumors of pituitary | 742 (12.3) | 0.52 (0.48–0.55) | 16.9 | 0.39c |
Craniopharyngioma | 289 (4.8) | 0.25 (0.22–0.28) | 10.4 | 1.01 |
Unclassified tumors | 1,126 (18.7) | 0.96 (0.90–1.02) | 11.8 | 1.10 |
Hemangioma | 248 (4.1) | 0.21 (0.18–0.23) | 13.0 | 1.40c |
Neoplasm, unspecified | 869 (14.4) | 0.74 (0.69–0.79) | 11.6 | 1.03 |
All others | 9 (0.1) | 0.01 (0.00–0.02) | 1.5 | 1.01 |
Total | 6,027 (100.0) | 5.02 (4.89–5.15) | 12.4 | 1.04 |
. | . | Incidence rate . | . | . |
---|---|---|---|---|
Histological groupa . | 10-year total (%) . | ASRb (95% CI) . | Median age (y) . | Sex ratio: Male/female . |
Tumors of neuroepithelial tissue | 2,539 (42.1) | 2.27 (2.18–2.36) | 10.0 | 1.07 |
Pilocytic astrocytoma | 423 (7.0) | 0.37 (0.33–0.41) | 10.9 | 0.81c |
Diffuse astrocytoma | 150 (2.5) | 0.13 (0.11–0.15) | 10.9 | 1.27 |
Anaplastic astrocytoma | 84 (1.4) | 0.07 (0.05–0.08) | 14.0 | 1.41 |
Unique astrocytoma variants | 93 (1.5) | 0.07 (0.06–0.09) | 12.6 | 0.85 |
Glioblastoma | 163 (2.7) | 0.13 (0.11–0.15) | 13.4 | 1.12 |
Oligodendroglioma | 39 (0.6) | 0.03 (0.02–0.04) | 14.4 | 1.36 |
Anaplastic oligodendroglioma | 13 (0.2) | 0.01 (0.00–0.01) | 16.7 | 1.12 |
Oligoastrocytic tumors | 8 (0.1) | 0.01 (0.00–0.01) | 13.6 | 0.99 |
Ependymal tumors | 207 (3.4) | 0.20 (0.17–0.23) | 8.3 | 1.18 |
Glioma malignant, NOS | 299 (5.0) | 0.27 (0.24–0.30) | 9.0 | 0.94 |
Choroid plexus tumors | 72 (1.2) | 0.08 (0.06–0.10) | 3.1 | 1.42 |
Other neuroepithelial tumors | 6 (0.1) | 0.01 (0.00–0.01) | 7.5 | 0.41 |
Neuronal and mixed neuronal-glial tumors | 327 (5.4) | 0.26 (0.23–0.29) | 12.5 | 1.01 |
Tumors of the pineal region | 35 (0.6) | 0.03 (0.02–0.04) | 9.0 | 1.68 |
Embryonal tumors | 620 (10.3) | 0.61 (0.56–0.66) | 7.0 | 1.19c |
Medulloblastoma | 362 (6.0) | 0.34 (0.30–0.38) | 8.1 | 1.59c |
Primitive neuroectodermal tumor | 134 (2.2) | 0.13 (0.11–0.15) | 7.4 | 0.86 |
Atypical teratoid/rhabdoid tumor | 76 (1.3) | 0.09 (0.07–0.11) | 1.4 | 0.93 |
Other embryonal tumors | 48 (0.8) | 0.05 (0.04–0.07) | 4.3 | 0.65 |
Tumors of cranial and spinal nerves | 324 (5.4) | 0.25 (0.22–0.28) | 14.3 | 1.07 |
Nerve sheath tumors | 324 (5.4) | 0.25 (0.22–0.28) | 14.3 | 1.07 |
Tumors of the meninges | 292 (4.8) | 0.23 (0.20–0.25) | 15.1 | 0.82 |
Meningioma | 166 (2.8) | 0.13 (0.11–0.15) | 15.1 | 0.70c |
Mesenchymal tumors | 55 (0.9) | 0.05 (0.04–0.06) | 12.0 | 1.11 |
Primary melanocytic lesions | 5 (0.1) | 0.00 (0.00–0.01) | 13.2 | 1.30 |
Other neoplasms related to the meninges | 66 (1.1) | 0.05 (0.04–0.06) | 16.6 | 0.92 |
Lymphomas and hemopoietic neoplasms | 74 (1.2) | 0.06 (0.05–0.08) | 11.2 | 1.75c |
Lymphoma | 29 (0.5) | 0.02 (0.01–0.03) | 13.2 | 1.74 |
Other hemopoietic neoplasms | 45 (0.7) | 0.04 (0.03–0.05) | 11.1 | 1.76 |
Germ cell tumors and cysts | 641 (10.6) | 0.49 (0.45–0.53) | 13.1 | 2.40c |
Germ cell tumors, cysts and heterotopias | 641 (10.6) | 0.49 (0.45–0.53) | 13.1 | 2.40c |
Germinoma | 403 (6.7) | 0.29 (0.26–0.32) | 14.3 | 2.41c |
Mixed germ cell tumor | 100 (1.7) | 0.08 (0.06–0.09) | 12.4 | 2.12c |
Yolk sac tumor/choriocarcinoma | 30 (0.5) | 0.02 (0.02–0.03) | 10.8 | 3.69c |
Teratoma | 72 (1.2) | 0.07 (0.05–0.09) | 7.0 | 2.94c |
Others | 36 (0.6) | 0.03 (0.02–0.04) | 13.4 | 1.56 |
Tumors of the sellar region | 1,031 (17.1) | 0.76 (0.72–0.81) | 16.1 | 0.55c |
Tumors of pituitary | 742 (12.3) | 0.52 (0.48–0.55) | 16.9 | 0.39c |
Craniopharyngioma | 289 (4.8) | 0.25 (0.22–0.28) | 10.4 | 1.01 |
Unclassified tumors | 1,126 (18.7) | 0.96 (0.90–1.02) | 11.8 | 1.10 |
Hemangioma | 248 (4.1) | 0.21 (0.18–0.23) | 13.0 | 1.40c |
Neoplasm, unspecified | 869 (14.4) | 0.74 (0.69–0.79) | 11.6 | 1.03 |
All others | 9 (0.1) | 0.01 (0.00–0.02) | 1.5 | 1.01 |
Total | 6,027 (100.0) | 5.02 (4.89–5.15) | 12.4 | 1.04 |
Abbreviation: NOS, not otherwise specified.
aHistologic grouping was performed on the basis of the classification of the CBTRUS 2008–2012 report (1).
bASR was adjusted using the world standard population.
cIndicates a statistically significant difference between sexes.
Comparison of CBT incidences in the KCCR versus CBTRUS
When analyzing the incidence rate using the U.S. population instead of the world standard population for direct comparison with CBTRUS, the ASR of all CBTs in Korea remained low [ASR: 5.08 (95% CI, 4.96–5.21); (Fig. 1A)]. The incidence rate of malignant CBTs in Korea [ASR: 2.61 (95% CI, 2.51–2.70)] was significantly lower than that in the United States [ASR: 3.42 (95% CI, 3.37–3.48)]. In contrast, the incidence rate of nonmalignant CBTs in Korea [ASR: 2.48 (95% CI, 2.39–2.57)] was significantly higher than that in the United States [ASR: 2.15 (95% CI, 2.11–2.20); (Fig. 1A)].
When analyzed according to age group, children aged 15 to 19 years had the highest CBT incidence rate both in Korea and the United States, followed by children aged 0 to 4 years, 5 to 9 years, and 10 to 14 years, respectively (Fig. 1B). The incidence rate of CBTs in children aged 10 to 19 years showed little difference between the two countries; however, the incidence rate of CBTs in children aged 0 to 9 years, especially in those in the 0–4 year age group, was significantly lower in Korea than in the United States [ASR: 4.53 (95% CI, 4.25–4.80) vs. 5.93 (95% CI, 5.78–6.08) in Korean vs. U.S. children aged 0–4 years, respectively; (Fig. 1B)].
The two most frequent histologic diagnoses in children aged 0 to 4 years were embryonal tumors (ASR: 0.99 in Korea and 1.24 in the United States) and pilocytic astrocytomas (ASRs: 0.41 in Korea and 1.03 in the United States); the absolute ASR values in the two countries differed. Pituitary tumors (ASRs: 1.63 in Korea and 1.66 in the United States), which were the most frequent CBTs in children aged 15 to 19 years, showed very similar incidence rates in both countries. Notably, the incidence rates of GCTs were significantly different between the two countries; these tumors were prevalent in Korean children aged 5 to 19 years, with the highest incidence in those 10 to 14 years of age (Table 2). The incidence rate of GCTs in Korean children aged 10 to 14 years [ASR: 0.78 (95% CI, 0.69–0.88)] was approximately 2.8-fold higher than that of U.S. children of the same age group [ASR: 0.28 (95% CI, 0.25–0.32)].
. | Most common histology . | Second most common histology . | Third most common histology . | |||
---|---|---|---|---|---|---|
Age group (years) . | Histology . | Rate (95% CI) . | Histology . | Rate (95% CI) . | Histology . | Rate (95% CI) . |
Korea, KCCR 2005–2014 | ||||||
0–4 | Embryonal tumors | 0.99 (0.87–1.12) | Pilocytic astrocytoma | 0.41 (0.33–0.49) | Ependymal tumors | 0.36 (0.28–0.43) |
5–9 | Embryonal tumors | 0.72 (0.62–0.82) | Germ cell tumors | 0.41 (0.34–0.49) | Glioma malignant, NOS | 0.39 (0.32–0.47) |
10–14 | Germ cell tumors | 0.78 (0.69–0.88) | Embryonal tumors | 0.42 (0.35–0.49) | Tumors of the pituitary/Pilocytic astrocytomac | 0.40 (0.33–0.46) |
15–19 | Tumors of the pituitary | 1.63 (1.49–1.77) | Germ cell tumors | 0.66 (0.57–0.75) | Nerve sheath tumors | 0.43 (0.36–0.50) |
0–19d | Embryonal tumors | 0.57 (0.53–0.62) | Tumors of the pituitary | 0.57 (0.53–0.61) | Pilocytic astrocytoma | 0.37 (0.33–0.40) |
US, CBTRUS 2008–2012 [1] | ||||||
0–4 | Embryonal tumors | 1.24 (1.17–1.31) | Pilocytic astrocytoma | 1.03 (0.96–1.09) | Glioma malignant, NOS | 0.93 (0.87–0.99) |
5–9 | Pilocytic astrocytoma | 1.01 (0.95–1.07) | Glioma malignant, NOS | 0.88 (0.82–0.94) | Embryonal tumors | 0.72 (0.67–0.77) |
10–14 | Pilocytic astrocytoma | 0.86 (0.81–0.92) | Glioma malignant, NOS | 0.51 (0.47–0.56) | Tumors of the pituitary | 0.49 (0.45–0.53) |
15–19 | Tumors of the pituitary | 1.66 (1.58–1.73) | Pilocytic astrocytoma | 0.60 (0.55–0.65) | Neuronal and mixed neuronal glial tumors | 0.48 (0.44–0.53) |
0–19d | Pilocytic astrocytoma | 0.87 (0.84–0.90) | Glioma malignant, NOS | 0.66 (0.63–0.68) | Embryonal tumors | 0.64 (0.62–0.67) |
(API only) | Pilocytic astrocytoma | 0.77 (0.66–0.89) | Tumors of the pituitary | 0.75 (0.65–0.88) | Embryonal tumors | 0.63 (0.53–0.74) |
. | Most common histology . | Second most common histology . | Third most common histology . | |||
---|---|---|---|---|---|---|
Age group (years) . | Histology . | Rate (95% CI) . | Histology . | Rate (95% CI) . | Histology . | Rate (95% CI) . |
Korea, KCCR 2005–2014 | ||||||
0–4 | Embryonal tumors | 0.99 (0.87–1.12) | Pilocytic astrocytoma | 0.41 (0.33–0.49) | Ependymal tumors | 0.36 (0.28–0.43) |
5–9 | Embryonal tumors | 0.72 (0.62–0.82) | Germ cell tumors | 0.41 (0.34–0.49) | Glioma malignant, NOS | 0.39 (0.32–0.47) |
10–14 | Germ cell tumors | 0.78 (0.69–0.88) | Embryonal tumors | 0.42 (0.35–0.49) | Tumors of the pituitary/Pilocytic astrocytomac | 0.40 (0.33–0.46) |
15–19 | Tumors of the pituitary | 1.63 (1.49–1.77) | Germ cell tumors | 0.66 (0.57–0.75) | Nerve sheath tumors | 0.43 (0.36–0.50) |
0–19d | Embryonal tumors | 0.57 (0.53–0.62) | Tumors of the pituitary | 0.57 (0.53–0.61) | Pilocytic astrocytoma | 0.37 (0.33–0.40) |
US, CBTRUS 2008–2012 [1] | ||||||
0–4 | Embryonal tumors | 1.24 (1.17–1.31) | Pilocytic astrocytoma | 1.03 (0.96–1.09) | Glioma malignant, NOS | 0.93 (0.87–0.99) |
5–9 | Pilocytic astrocytoma | 1.01 (0.95–1.07) | Glioma malignant, NOS | 0.88 (0.82–0.94) | Embryonal tumors | 0.72 (0.67–0.77) |
10–14 | Pilocytic astrocytoma | 0.86 (0.81–0.92) | Glioma malignant, NOS | 0.51 (0.47–0.56) | Tumors of the pituitary | 0.49 (0.45–0.53) |
15–19 | Tumors of the pituitary | 1.66 (1.58–1.73) | Pilocytic astrocytoma | 0.60 (0.55–0.65) | Neuronal and mixed neuronal glial tumors | 0.48 (0.44–0.53) |
0–19d | Pilocytic astrocytoma | 0.87 (0.84–0.90) | Glioma malignant, NOS | 0.66 (0.63–0.68) | Embryonal tumors | 0.64 (0.62–0.67) |
(API only) | Pilocytic astrocytoma | 0.77 (0.66–0.89) | Tumors of the pituitary | 0.75 (0.65–0.88) | Embryonal tumors | 0.63 (0.53–0.74) |
Abbreviation: NOS, not otherwise specified.
aHistologic group of unspecified neoplasm was excluded from this table. The incidence rate of unspecified neoplasm was 0.73, 0.74, 0.73, and 0.77 per 100,000 population in the 0–4, 5–9, 10–14, and 15–19 year old groups, respectively.
bRate indicated the age-specific rate.
cThese two childhood brain tumors showed same age-standardized rates with same number of cases (n = 129).
dFor analyses of 0–19 year-old patients, the age-standardized rate, adjusted using the 2000 U.S. standard population, was used.
We then compared the incidence of CBTs between Koreans and Asian/Pacific Islanders (API) using data from KCCR and CBTRUS, respectively. The ASR of API CBT patients was 6.03 (95% CI, 5.71–6.36), significantly higher than that of Korean patients (5.08; 95% CI, 4.96–5.21). In particular, the ASR of patients with CBT with tumors of neuroepithelial tissue and CNS nerves, including pilocytic astrocytoma, diffuse astrocytoma, and malignant glioma, was significantly higher in APIs. In contrast, the incidence of GCT was higher in Koreans [ASR: 0.52 (95% CI, 0.48–0.56)] than in APIs [ASR: 0.43 (95% CI, 0.34–0.52)]; however, statistical significance was not achieved in this analysis (Supplementary Table S1).
Distribution of CBTs by histology and site
Among all CBTs (n = 6,027; ASR, 5.02), neuroepithelial tumors were the most prevalent histologic group, accounting for 42% (ASR: 2.17), followed by tumors of the pituitary sellar region (17%; ASR: 0.76), GCTs and cysts (11%; ASR: 0.49), tumors of the cranial and spinal nerves (5%; ASR: 0.25), tumors of the meninges (5%; ASR: 0.23), and lymphomas and hemopoietic neoplasms (1%; ASR: 0.06; Table 1; Fig. 2A). Among malignant CBTs (n = 3,025; ASR: 2.62), neuroepithelial tumors were the most prevalent histologic group (69%; ASR: 1.88), followed by GCTs and cysts (19%; ASR: 0.43), lymphomas and hemopoietic neoplasms (2%; ASR: 0.05), tumors of the meninges (2%; ASR: 0.05), and tumors of the cranial and spinal nerves (0.1%; ASR: <0.01). Tumors of the pituitary sellar region accounted for less than 0.1% of malignant tumors, but comprised the most frequently reported histologic group (25%) among nonmalignant tumors. The proportion of unclassified tumors was 19% among all CBTs, and 8% among malignant CBTs (Fig. 2B).
When investigating incident rates according to histologic diagnoses, embryonal tumors (ASR: 0.61) exhibited the highest incidence rate, followed by pituitary tumors (ASR: 0.52) and GCTs (ASR: 0.49). Gliomas accounted for approximately 31% of all CBTs (ASR: 1.55) and approximately 47% of malignant CBTs (ASR: 1.23). GCTs (M:F ratio, 2.4:1), medulloblastomas (M:F ratio, 1.6:1), and hemangiomas (M:F ratio, 1.4:1) occurred more frequently in males, while pituitary tumors (M:F ratio, 0.4:1), pilocytic astrocytomas (M:F ratio, 0.8:1), and meningiomas (M:F ratio, 0.7:1) occurred more frequently in females (Table 1). The incidence rate of unspecified tumors was 0.74 per 100,000 population. Among malignant neuroepithelial tumors, which accounted for almost three quarters of malignant CBTs (69%; ASR: 1.88), embryonal tumors (20%) were the most frequently reported, followed by pilocytic astrocytomas (14%), malignant gliomas (10%), and ependymal tumor (6%; Fig. 2B). The remaining incidences and histologic distributions, as well as other specific age- and sex-related characteristics, are described in Table 1.
The pituitary and craniopharyngeal duct was the most frequently reported site of CBTs (19%). The cerebrum (including the frontal, temporal, parietal, and occipital areas), cerebellum, and brain stem tumors accounted for 17%, 12%, and 7% of all CBT locations, respectively (Fig. 2C). Pituitary and craniopharyngeal duct tumors, as well as meningeal tumors, were more likely to be nonmalignant (malignant:nonmalignant ratio, <0.5:1), while tumors in the cerebellum, brain stem, and pineal gland were more likely to be malignant (malignant:nonmalignant ratio, >2:1; Fig. 2C).
Survival outcomes by histologic diagnosis
For survival analysis, 5,794 of 6,027 CBT cases (96%) were included; the remaining 4% were excluded owing to incomplete registration of identification data. The 5-year RSR of all CBTs, including both malignant and nonmalignant tumors, was 84%. However, the 5-year RSRs ranged from 17% to 100% according to histologic diagnosis (Table 3). Among malignant neuroepithelial tumors, the 5-year RSR of pilocytic astrocytoma was the highest at 97%, whereas glioblastoma was the lowest at 17% (Fig. 3A). Among embryonal tumors, the 5-year RSR of medulloblastoma was the highest at 69%, that of primitive neuroectodermal tumor (PNET) was 51%, and that of atypical teratoid/rhabdoid tumor (AT/RT) was the lowest at 28% (Fig. 3B). Among GCTs, the 5-year RSR was favorable at 91% (95% CI, 88.0–93.2), although 88% of these tumors (507/572) exhibited malignant behavior. The 5-year RSR of germinomas was the highest at 98%, that of teratomas was 83%, that of mixed type tumors was 74%, and that of yolk sac tumors or choriocarcinomas was 71% (Table 3). For teratomas, the 5-year RSRs differed according to behavior; the values were 77% and 89% in malignant and nonmalignant GCTs, respectively (Fig. 3C).
. | . | Relative survival rate (%) . | ||
---|---|---|---|---|
Histologic groupb . | Cases . | 1-year (95% CI) . | 2-year (95% CI) . | 5-year (95% CI) . |
All cancers | 5,794 | 92.0 (91.2–92.6) | 86.9 (86.0–87.8) | 83.7 (82.7–84.7) |
Tumors of neuroepithelial tissue | 2,476 | 86.3 (84.9–87.6) | 76.5 | 70.4 (68.5–72.2) |
Pilocytic astrocytoma | 405 | 97.8 (95.8–98.9) | 97.3 (95.1–98.5) | 97.1 (94.8–98.4) |
Diffuse astrocytoma | 145 | 89.0 (82.7–93.1) | 78.3 (70.6–84.3) | 72.8 (64.5–79.5) |
Anaplastic astrocytoma | 82 | 70.8 (59.6–79.4) | 41.0 | 30.1 (20.3–40.4) |
Unique astrocytoma variants | 93 | 93.6 (86.2–97.1) | 88.9 (80.3–93.9) | 89.0 (80.4–94.0) |
Glioblastoma | 160 | 65.6 (57.7–72.4) | 29.4 (22.5–36.7) | 16.7 (11.1–23.3) |
Oligodendroglioma | 38 | 92.1 (77.5–97.4) | 92.1 (77.5–97.4) | 92.2 (77.6–97.5) |
Anaplastic oligodendroglioma | 12 | 100.0 | 72.8 (37.1–90.3) | 60.7 (25.1–83.5) |
Oligoastrocytic tumors | 8 | 100.0 | 62.5 (22.9–86.1) | 48.6 (13.8–77.0) |
Ependymal tumors | 204 | 93.6 (89.3–96.3) | 88.5 (83.2–92.2) | 75.5 (68.3–81.4) |
Glioma malignant, NOS | 289 | 70.6 (64.9–75.5) | 55.4 (49.4–61.0) | 50.5 (44.4–56.3) |
Choroid plexus tumors | 71 | 90.3 (80.5–95.3) | 88.8 (78.7–94.3) | 88.8 (78.7–94.4) |
Other neuroepithelial tumors | 6 | 100.0 | 83.4 (27.3–97.5) | 83.4 (27.3–97.5) |
Neuronal and mixed neuronal-glial tumors | 323 | 98.5 (96.3–99.4) | 97.8 (95.5–99.0) | 96.7 (93.7–98.2) |
Tumors of the pineal region | 33 | 87.9 (70.9–95.3) | 75.6 (57.0–87.0) | 75.6 (57.1–87.1) |
Embryonal tumors | 607 | 81.4 (78.1–84.3) | 70.3 (66.4–73.8) | 60.0 (55.8–64.0) |
Medulloblastoma | 359 | 88.6 (84.8–91.5) | 78.8 (74.1–82.7) | 68.7 (63.3–73.4) |
PNET | 129 | 77.6 (69.3–83.8) | 64.6 (55.6–72.3) | 50.5 (40.9–59.4) |
AT/RT | 73 | 50.8 (38.8–61.5) | 31.9 (21.5–42.8) | 28.1 (17.9–39.2) |
Other embryonal | 46 | 84.8 (70.8–92.5) | 80.4 (65.6–89.3) | 68.6 (52.7–80.2) |
Tumors of cranial and spinal nerves | 304 | 99.0 (97.0–99.7) | 98.7 (96.5–99.5) | 98.8 (96.6–99.6) |
Nerve sheath tumors | 304 | 99.0 (97.0–99.7) | 98.7 (96.5–99.5) | 98.8 (96.6–99.6) |
Tumors of the meninges | 270 | 94.1 (90.5–96.4) | 92.5 (88.6–95.1) | 90.1 (85.6–93.3) |
Meningioma | 149 | 95.3 (90.4–97.8) | 95.3 (90.4–97.8) | 93.5 (87.7–96.7) |
Mesenchymal tumors | 53 | 94.4 (83.5–98.2) | 88.5 (76.0–94.7) | 83.4 (69.2–91.5) |
Primary melanocytic lesions | 4 | 50.0 (5.8–84.5) | 25.0 (0.9–66.6) | |
Other neoplasms related to the meninges | 64 | 93.8 (84.2–97.6) | 93.8 (84.2–97.7) | 93.9 (84.3–97.7) |
Lymphomas and hemopoietic neoplasms | 73 | 93.2 (84.3–97.1) | 91.7 (82.4–96.2) | 91.8 (82.5–96.3) |
Lymphoma | 29 | 82.8 (63.4–92.5) | 79.1 (59.2–90.1) | 79.2 (59.3–90.1) |
Other hemopoietic neoplasms | 44 | 100.0 | 100.0 | 100.0 |
Germ cell tumors and cysts | 572 | 95.3 (93.2–96.8) | 93.9 (91.6–95.6) | 91.4 (88.7–93.5) |
Germ cell tumors, cysts, and heterotopias | 572 | 95.3 (93.2–96.8) | 93.9 (91.6–95.6) | 91.4 (88.7–93.5) |
Germinoma | 362 | 98.1 (96.0–99.1) | 97.8 (95.7–98.9) | 97.6 (95.3–98.8) |
Mixed germ cell tumor | 85 | 87.1 (77.9–92.6) | 81.1 (71.0–88.0) | 74.3 (63.2–82.5) |
YST/Choriocarcinoma | 28 | 85.7 (66.3–94.4) | 81.8 (61.7–92.0) | 71.2 (47.7–85.5) |
Teratoma | 61 | 91.9 (81.5–96.6) | 90.3 (79.5–95.6) | 82.6 (69.8–90.4) |
Others | 36 | 100.0 | 100.0 | 100.0 |
Tumors of sellar region | 1,018 | 99.0 (98.2–99.5) | 98.4 (97.4–99.1) | 97.8 (96.6–98.6) |
Tumors of pituitary | 735 | 99.7 (98.9–100.0) | 99.8 (99.0–100.0) | 99.7 (98.8–100.0) |
Craniopharyngioma | 283 | 97.2 (94.4–98.6) | 95.0 (91.7–97.0) | 93.3 (89.5–95.8) |
Unclassified tumors | 1,081 | 93.9 (92.3–95.2) | 91.4 (89.6–93.0) | 90.5 (88.6–92.2) |
Hemangioma | 245 | 99.2 (96.8–99.8) | 98.8 (96.2–99.6) | 98.9 (96.3–99.7) |
Others | 836 | 92.4 (90.4–94.0) | 89.3 (87.0–91.2) | 88.2 (85.7–90.2) |
Neoplasm, unspecified | 827 | 92.4 (90.4–94.0) | 89.3 (87.0–91.2) | 88.2 (85.7–90.2) |
All others | 9 | 89.0 (43.3–98.5) | 89.0 (43.4–98.5) | 89.0 (43.4–98.5) |
. | . | Relative survival rate (%) . | ||
---|---|---|---|---|
Histologic groupb . | Cases . | 1-year (95% CI) . | 2-year (95% CI) . | 5-year (95% CI) . |
All cancers | 5,794 | 92.0 (91.2–92.6) | 86.9 (86.0–87.8) | 83.7 (82.7–84.7) |
Tumors of neuroepithelial tissue | 2,476 | 86.3 (84.9–87.6) | 76.5 | 70.4 (68.5–72.2) |
Pilocytic astrocytoma | 405 | 97.8 (95.8–98.9) | 97.3 (95.1–98.5) | 97.1 (94.8–98.4) |
Diffuse astrocytoma | 145 | 89.0 (82.7–93.1) | 78.3 (70.6–84.3) | 72.8 (64.5–79.5) |
Anaplastic astrocytoma | 82 | 70.8 (59.6–79.4) | 41.0 | 30.1 (20.3–40.4) |
Unique astrocytoma variants | 93 | 93.6 (86.2–97.1) | 88.9 (80.3–93.9) | 89.0 (80.4–94.0) |
Glioblastoma | 160 | 65.6 (57.7–72.4) | 29.4 (22.5–36.7) | 16.7 (11.1–23.3) |
Oligodendroglioma | 38 | 92.1 (77.5–97.4) | 92.1 (77.5–97.4) | 92.2 (77.6–97.5) |
Anaplastic oligodendroglioma | 12 | 100.0 | 72.8 (37.1–90.3) | 60.7 (25.1–83.5) |
Oligoastrocytic tumors | 8 | 100.0 | 62.5 (22.9–86.1) | 48.6 (13.8–77.0) |
Ependymal tumors | 204 | 93.6 (89.3–96.3) | 88.5 (83.2–92.2) | 75.5 (68.3–81.4) |
Glioma malignant, NOS | 289 | 70.6 (64.9–75.5) | 55.4 (49.4–61.0) | 50.5 (44.4–56.3) |
Choroid plexus tumors | 71 | 90.3 (80.5–95.3) | 88.8 (78.7–94.3) | 88.8 (78.7–94.4) |
Other neuroepithelial tumors | 6 | 100.0 | 83.4 (27.3–97.5) | 83.4 (27.3–97.5) |
Neuronal and mixed neuronal-glial tumors | 323 | 98.5 (96.3–99.4) | 97.8 (95.5–99.0) | 96.7 (93.7–98.2) |
Tumors of the pineal region | 33 | 87.9 (70.9–95.3) | 75.6 (57.0–87.0) | 75.6 (57.1–87.1) |
Embryonal tumors | 607 | 81.4 (78.1–84.3) | 70.3 (66.4–73.8) | 60.0 (55.8–64.0) |
Medulloblastoma | 359 | 88.6 (84.8–91.5) | 78.8 (74.1–82.7) | 68.7 (63.3–73.4) |
PNET | 129 | 77.6 (69.3–83.8) | 64.6 (55.6–72.3) | 50.5 (40.9–59.4) |
AT/RT | 73 | 50.8 (38.8–61.5) | 31.9 (21.5–42.8) | 28.1 (17.9–39.2) |
Other embryonal | 46 | 84.8 (70.8–92.5) | 80.4 (65.6–89.3) | 68.6 (52.7–80.2) |
Tumors of cranial and spinal nerves | 304 | 99.0 (97.0–99.7) | 98.7 (96.5–99.5) | 98.8 (96.6–99.6) |
Nerve sheath tumors | 304 | 99.0 (97.0–99.7) | 98.7 (96.5–99.5) | 98.8 (96.6–99.6) |
Tumors of the meninges | 270 | 94.1 (90.5–96.4) | 92.5 (88.6–95.1) | 90.1 (85.6–93.3) |
Meningioma | 149 | 95.3 (90.4–97.8) | 95.3 (90.4–97.8) | 93.5 (87.7–96.7) |
Mesenchymal tumors | 53 | 94.4 (83.5–98.2) | 88.5 (76.0–94.7) | 83.4 (69.2–91.5) |
Primary melanocytic lesions | 4 | 50.0 (5.8–84.5) | 25.0 (0.9–66.6) | |
Other neoplasms related to the meninges | 64 | 93.8 (84.2–97.6) | 93.8 (84.2–97.7) | 93.9 (84.3–97.7) |
Lymphomas and hemopoietic neoplasms | 73 | 93.2 (84.3–97.1) | 91.7 (82.4–96.2) | 91.8 (82.5–96.3) |
Lymphoma | 29 | 82.8 (63.4–92.5) | 79.1 (59.2–90.1) | 79.2 (59.3–90.1) |
Other hemopoietic neoplasms | 44 | 100.0 | 100.0 | 100.0 |
Germ cell tumors and cysts | 572 | 95.3 (93.2–96.8) | 93.9 (91.6–95.6) | 91.4 (88.7–93.5) |
Germ cell tumors, cysts, and heterotopias | 572 | 95.3 (93.2–96.8) | 93.9 (91.6–95.6) | 91.4 (88.7–93.5) |
Germinoma | 362 | 98.1 (96.0–99.1) | 97.8 (95.7–98.9) | 97.6 (95.3–98.8) |
Mixed germ cell tumor | 85 | 87.1 (77.9–92.6) | 81.1 (71.0–88.0) | 74.3 (63.2–82.5) |
YST/Choriocarcinoma | 28 | 85.7 (66.3–94.4) | 81.8 (61.7–92.0) | 71.2 (47.7–85.5) |
Teratoma | 61 | 91.9 (81.5–96.6) | 90.3 (79.5–95.6) | 82.6 (69.8–90.4) |
Others | 36 | 100.0 | 100.0 | 100.0 |
Tumors of sellar region | 1,018 | 99.0 (98.2–99.5) | 98.4 (97.4–99.1) | 97.8 (96.6–98.6) |
Tumors of pituitary | 735 | 99.7 (98.9–100.0) | 99.8 (99.0–100.0) | 99.7 (98.8–100.0) |
Craniopharyngioma | 283 | 97.2 (94.4–98.6) | 95.0 (91.7–97.0) | 93.3 (89.5–95.8) |
Unclassified tumors | 1,081 | 93.9 (92.3–95.2) | 91.4 (89.6–93.0) | 90.5 (88.6–92.2) |
Hemangioma | 245 | 99.2 (96.8–99.8) | 98.8 (96.2–99.6) | 98.9 (96.3–99.7) |
Others | 836 | 92.4 (90.4–94.0) | 89.3 (87.0–91.2) | 88.2 (85.7–90.2) |
Neoplasm, unspecified | 827 | 92.4 (90.4–94.0) | 89.3 (87.0–91.2) | 88.2 (85.7–90.2) |
All others | 9 | 89.0 (43.3–98.5) | 89.0 (43.4–98.5) | 89.0 (43.4–98.5) |
Abbreviation: YST, yolk sac tumor.
aThe complete survival rate approach was utilized to calculate the relative survival rates. Therefore, 5 full years of follow-up data were not available for all patients included in the survival analysis.
bHistologic grouping was performed on the basis of the classification of the CBTRUS 2008–2012 report (1).
Discussion
To our knowledge, ours is the first nationwide, population-based epidemiologic study of CBTs in Asia. High incidences of nonmalignant CBTs and CNS germ cell tumors were observed in the Korean pediatric population. In particular, the incidence of CNS GCTs in Korean children and adolescents aged 0 to 19 years was twice as high as in the corresponding U.S. population. Survival rates were comparable with those in the United States.
The overall incidence of CBTs in Korea was lower than in the United States upon comparison of our data with that from the CBTRUS 2008–2012, whereas the incidence of nonmalignant tumors was higher. Our calculated incidence rate of CBTs in Korea (ASR: 5.02) is the second highest among children and adolescents aged 0 to 19 years reported so far (3, 4, 6, 16, 17). Aside from differences in diagnostic procedures and registry completeness, the high incidence may be attributable to the inclusion of nonmalignant lesions and intracranial and intraspinal GCTs in this study (18). When considering only the CBTs of the ICCC Site Group III, the incidence rate decreased to 2.19 per 100,000 population, which ranked 33 out of 40 selected countries [each with >500 registered cases listed in the International Agency for Research on Cancer (median ASR: 2.78; range: 1.08–4.91); ref. 4]. Because CBTs can be malignant and have poor prognoses regardless of their histologic behavior, it is important to consistently include nonmalignant tumors in CBT surveillance studies (19–21). Moreover, the inclusion of nonmalignant tumors in registries may better expose the differences in overall CBT incidences across countries or regions (20); nonmalignant tumors accounted for 48% of all CBTs in this study and 39% of the those in the CBTRUS.
The high incidence of CNS germ cell tumor in Korean children and adolescents is one of the key findings of our study. The association between CNS GCTs and race is controversial; previous studies have shown high incidences of CNS GCTs in East Asian populations including Korea, Japan, and Taiwan (22–25). However, a recent large-scale study that compared data from the U.S. Surveillance, Epidemiology, and End Results (SEER) program to that from the Japan Cancer Surveillance Research Group found that the incidences of malignant CNS GCTs in Japan and the United States are not significantly different (26). Meanwhile, a recent study found that the incidence rate of CNS GCTs (ASR: 0.18) in Korea is similar to that of the Asians/Pacific Islanders in the United States (ASR: 0.19) across all age groups (23). Our results also support the notion that East Asian populations have a higher incidence of CNS GCTs than other races (26). Moreover, according to the latest CBTRUS report, the incidence rate of CNS GCTs among 0–19 year-old APIs (ASR: 0.47), which is similar to that of our study (ASR: 0.52; Supplementary Table S1), was higher than that in Caucasian Americans (ASR: 0.23) and African Americans (ASR: 0.13; ref. 27). Additional studies are required to demonstrate the association between race and the development of CNS GCTs, including genetic origin.
Survival outcomes varied widely according to histologic diagnosis, although our data were consistent with those of previous studies (1, 6, 10, 17). The 5-year RSR for malignant CBT was 70%, which is equal to 70% revealed when analyzing the U.S. SEER 1995–2012 data and slightly higher than 67% per the German Childhood Cancer Registry (GCCR) 1990–1999 data and 61% per the European Automated Childhood Cancer Information System 1988–1997 data (6, 16, 17). Among embryonal tumors (one of the most prevalent CBTs in children), the 5-year RSRs for medulloblastoma, PNET, and AT/RT were 79%, 51%, and 28%, respectively, which were comparable with the GCCR 1991–2010 data (medulloblastoma, 69%; PNET 38%; and AT/RT, 32%) and the US SEER 2006–2010 data (medulloblastoma, 71%; PNET 40%; and AT/RT, 28%; refs. 6, 28). For malignant GCTs, the 5-year RSR was favorable (91%), and was slightly higher than in previous studies (81% and 85% in the 0–14 year age group according to the SEER and GCCR databases, respectively; refs. 1, 29). However, due to differences in the time periods and distributions of diagnosis represented across these studies, direct comparisons require careful interpretation. In addition, as CBTs have varying prognoses depending on the histologic type, further studies for long-term survival are needed (30).
The relatively high proportion of radiologically diagnosed but histologically unconfirmed cases (34%, 2,027/6,027) and of unspecified neoplasms (14%, 869/6,027) are limitations in this study. The proportion of radiologic diagnoses is somewhat higher than those in previous studies (12%–29%), which may influence the histologic distribution of CBTs (1, 17, 31). However, approximately 65% of the radiologically confirmed cases were tumors of the sellar region (25%, 510/2,027) or were unclassified (40%, 815/2,027); such tumors tended to show nonmalignant behavior. All tumors of the sellar region (except for a single malignant pituitary tumor) and 76% of unclassified neoplasms exhibited nonmalignant behavior. Therefore, the effect of these limitations on the distribution of malignant CBT appears to be relatively small. In addition, the first 2 years of our study period (2005 and 2006) may have been subject to reporting bias, as relatively small numbers of nonmalignant tumors were collected during this time. However, as our main objective was not to analyze yearly trends, we do not anticipate that this bias significant impacted study outcomes.
This study also has several strengths. First, our CBT incidence and survival data were based on a strictly controlled nationwide registry. Second, we directly compared the CBTRUS and KCCR data using identical classification criteria and definitions, and revealed novel differences in epidemiologic characteristics, including the high incidence of nonmalignant tumors among young Koreans. Third, we reaffirmed the high incidence of CNS GCTs in Korean children and adolescents.
In conclusion, our study represents the largest epidemiologic survey of CBTs in Asia. The high incidences of nonmalignant tumors and GCTs are unique features of primary brain and CNS tumors in Korean children and adolescents aged 0 to 19 years.
Disclosure of Potential Conflicts of Interest
No potential conflicts of interest were disclosed.
Authors' Contributions
Conception and design: J.-M. Kang, S.-H. Shin, K.-W. Jung, H.J. Park
Development of methodology: K.-W. Jung, H.J. Park
Acquisition of data (provided animals, acquired and managed patients, provided facilities, etc.): J. Ha, B.K. Park, K.-W. Jung
Analysis and interpretation of data (e.g., statistical analysis, biostatistics, computational analysis): J.-M. Kang, J. Ha, E.K. Hong, K.-W. Jung, H.J. Park
Writing, review, and/or revision of the manuscript: J.-M. Kang, J. Ha, H.Y. Ju, S.-H. Shin, Y.-J. Won, K.-W. Jung, H.J. Park
Administrative, technical, or material support (i.e., reporting or organizing data, constructing databases): J. Ha, B.K. Park, H.J. Park
Study supervision: J.-M. Kang, B.K. Park, H.J. Park
Acknowledgments
This work was supported by a research grant of the National Cancer Center (NCC-1610200), Republic of Korea. We are grateful to John Lee Villano (University of Kentucky, Lexington, KY, USA) for critiquing our manuscript.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.