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Purpose Primary malignant brain and other central nervous system tumors are rare cancers that have shown rising mortality rates in recent years. To elucidate potential factors involved in this rising death rate, we examined mortality trends for primary malignant BT in the United States stratified by histopathology groupings, age, race, and sex. Methods Mortality rates for demographic factors within primary malignant BT were generated using the National Center for Health Statistics' National Vital Statistics Systems data from 2004 to 2018. Additionally, histopathology-specific incidence-based mortality rates were calculated using the National Cancer Institute’s Surveillance, Epidemiology, and End-Results (SEER) 18 data from 2004 to 2018. Joinpoint modeling was used to estimate mortality trends and annual percent changes with corresponding 95% confidence intervals. Results Overall, there was a very small increase in mortality from 2004 to 2018. Individuals > 65 years saw a small increase in mortality, while changes in individuals of other ages were non-significant. Asian/Pacific Islander or American Indian/Alaskan Native had the largest increase in mortality. Among histopathology groupings, there was a small mortality increase in adults ages > 65 years with glioblastoma, while the mortality rate of other malignant gliomas declined in the same age group. CNS lymphoma mortality rates in patients ages 15–39 and 40–64 years declined significantly while rising significantly in the > 65 age group. In pediatric patients, embryonal tumor mortality had a non-significant increase between 2004 and 2007 but declined significantly between 2007 and 2018. Conclusion Examining age, race, sex, and histopathology-specific mortality trends at the population level can provide important information for clinicians, researchers, and aid in public health planning.

Background: Little is known regarding factors associated with calcitriol and a relative measure of calcitriol, the calcitriol-24,25-dihydroxyvitamin D3-calcifediol proportion ratio (C24CPR). Methods: Using a cross-sectional study design, healthy young adults of African and European descent, matched (1:1) on age (±5 years) provided a blood sample in non-summer months (N = 376). Vitamin D metabolites were measured in plasma with HPLC/MS-MS. West African genetic ancestry proportion (WGA) was estimated using STRUCTURE modeling of genetic ancestry-informative markers. Multivariable regression models were used to estimate the association of WGA and vitamin D–pathway gene variants with calcitriol and C24CPR, controlling for days from summer solstice, age, sex, blood pressure, body mass index, dietary vitamin D intake, oral contraceptive/medroxyprogesterone acetate use, smoking, tanning bed use, and time of day. Results: Calcitriol and C24CPR were not highly correlated (rho = 0.14), although both were significantly, positively, and monotonically associated with WGA (Ptrend 0.025 and Conclusions: Both absolute and relative measures of calcitriol were significantly higher among African Americans. Otherwise, these biomarkers appear to be genetically distinct. Impact: C24CPR may be better suited to personalized medicine, due to a higher proportion of population variability explained by genetic variation and a less skewed distribution.

Background A newly developed brain molecular marker (BMM) data item was implemented by US cancer registries for individuals diagnosed with brain tumors in 2018—including IDH and 1p/19q-co-deletion statuses for adult-type diffuse gliomas. We thus investigated the testing/reporting completeness of BMM in the United States. Methods Cases of histopathologically confirmed glioblastoma, astrocytoma, and oligodendroglioma diagnosed in 2018 were identified in the National Cancer Database. Adjusted odds ratios (ORadj) and 95% confidence intervals (CI) of BMM testing/reporting were evaluated for association with the selected patient, treatment, and facility-level characteristics using multivariable logistic regression. As a secondary analysis, predictors of MGMT promoter methylation testing/reporting among IDH-wildtype glioblastoma individuals were assessed. Key limitations of the BMM data item were that it did not include any details regarding testing technique or assay type and could not distinguish between a lack of testing and a lack of cancer registry reporting of testing results. Results Among 8306 histopathologically diagnosed adult-type diffuse gliomas nationally, overall BMM testing/reporting completeness was 81.1%. Compared to biopsy-only cases, odds of testing/reporting increased for subtotal (ORadj= 1.38 [95% CI: 1.20–1.59], P < .001) and gross total resection (ORadj=1.50 [95% CI: 1.31–1.72], P < .001). Furthermore, the odds were lowest at community centers (hospitals (67.3%; ORadj=0.35 [95% CI: 0.26–0.46], P < .001) and highest at academic/NCI-designated comprehensive cancer centers (85.4%; referent). By geographical location, BMM testing/reporting completeness ranged from a high of 86.8% at New England (referent) to a low of 76.0 % in the West South Central region (ORadj=0.57 [95% CI: 0.42–0.78]; P < .001). Extent of resection, Commission-on-Cancer facility type, and facility location were additionally significant predictors of MGMT testing/reporting among IDH-wildtype glioblastoma cases. Conclusions Initial BMM testing/reporting completeness for individuals with adult-type diffuse gliomas in the United States was promising, although patterns varied by hospital attributes and extent of resection.

The Central Brain Tumor Registry of the United States (CBTRUS), in collaboration with the Centers for Disease Control and Prevention and the National Cancer Institute, is the largest population-based registry focused exclusively on primary brain and other central nervous system (CNS) tumors in the United States (US) and represents the entire US population. This report contains the most up-to-date population-based data on primary brain tumors available and supersedes all previous reports in terms of completeness and accuracy. All rates are age-adjusted using the 2000 US standard population and presented per 100,000 population. The average annual age-adjusted incidence rate (AAAIR) of all malignant and non-malignant brain and other CNS tumors was 24.71 per 100,000 population (malignant AAAIR=7.02 and non-malignant AAAIR=17.69). This overall rate was higher in females compared to males (27.62 versus 21.60 per 100,000) and non-Hispanic persons compared to Hispanic persons (25.09 versus 22.95 per 100,000). The most commonly occurring malignant brain and other CNS histopathology was glioblastoma (14.2% of all tumors and 50.1% of all malignant tumors), and the most common non-malignant histopathology was meningioma (39.7% of all tumors and 55.4% of all non-malignant tumors). Glioblastoma was more common in males, and meningiomas were more common in females. In children and adolescents (ages 0-19 years), the incidence rate of all primary brain and other CNS tumors was 6.20 per 100,000 population. An estimated 93,470 new cases of malignant and non-malignant brain and other CNS tumors are expected to be diagnosed in the US population in 2022 (26,670 malignant and 66,806 non-malignant). There were 84,264 deaths attributed to malignant brain and other CNS tumors between 2015 and 2019. This represents an average annual mortality rate of 4.41 per 100,000 population and an average of 16,853 deaths per year. The five-year relative survival rate following diagnosis of a malignant brain and other CNS tumor was 35.7%, while for non-malignant brain and other CNS tumors the five-year relative survival rate was 91.8%.

The CBTRUS Statistical Report: Pediatric Brain Tumor Foundation Childhood and Adolescent Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2014–2018 comprehensively describes the current population-based incidence of primary malignant and non-malignant brain and other CNS tumors in children and adolescents ages 0–19 years, collected and reported by central cancer registries covering approximately 100% of the United States population. Overall, brain and other CNS tumors are the most common solid tumor, the most common cancer, and the most common cause of cancer death in children and adolescents ages 0–19 years. This report aims to serve as a useful resource for researchers, clinicians, patients, and families.

Background There are limited data available on incidence and survival of patients with choroid plexus tumors (CPT). This study provides the most current epidemiological analysis of choroid plexus tumors from 2004 to 2017 in the United States. Methods Data on 2013 patients with CPT were acquired from the Central Brain Tumor Registry of the United States in collaboration with the Centers for Disease Control and Prevention (CDC) and the National Cancer Institute, from 2004 to 2017. CPT cases were classified by the following pathological subtypes: choroid plexus papilloma (CPP), atypical choroid plexus papilloma (aCPP), and choroid plexus carcinoma (CPC). Frequencies and age-adjusted incidence rates (AAIR) per 100 000 and rate ratios per 100 000 (IRR) were reported for age, sex, race, and ethnicity for each pathological subtype with 95% confidence intervals (95% CI). Using CDC’s National Program of Cancer Registries survival database, survival curves and hazard ratios (HRs) evaluated overall survival from 2001 to 2016. Results CPP had the highest overall incidence (AAIR: 0.034, 95% CI: 0.033–0.036), followed by CPC (AAIR: 0.008, 95% CI: 0.008–0.009) and aCPP (AAIR: 0.005, 95% CI: 0.005–0.006). Incidence was highest among children less than one year old among all subtypes (CPP AAIR: 0.278; aCPP AAIR: 0.140; CPC AAIR: 0.195), reducing as patients aged. Overall survival was worse among patients with CPC, being five times more likely to die compared to patients with CPP (HR: 5.23, 95% CI: 4.05–7.54, P Conclusions This analysis is the most current and comprehensive study in the US on the incidence and survival for CPT. Population based statistics provide critical information in understanding disease characteristics, which impact patient care and prognosis.

Supplemental Table 3. Pairwise D’ and r2 Linkage Disequilibrium Values between Single Nucleotide Polymorphisms and Spearman's Correlation with West African Genetic Ancestry Proportion, African American (N=188) matched with European American (N=188) participants, Central Pennsylvania*

Supplemental Table 2. Allele Frequencies and Hardy-Weinberg Equilibrium (HWE) among African American (AA) and European American (EA) Participants (Central Pennsylvania) compared with 1000 Genomes African (AFR) and European (EUR) Populations

Background:Little is known regarding factors associated with calcitriol and a relative measure of calcitriol, the calcitriol-24,25-dihydroxyvitamin D3-calcifediol proportion ratio (C24CPR).Methods:Using a cross-sectional study design, healthy young adults of African and European descent, matched (1:1) on age (±5 years) provided a blood sample in non-summer months (N = 376). Vitamin D metabolites were measured in plasma with HPLC/MS-MS. West African genetic ancestry proportion (WGA) was estimated using STRUCTURE modeling of genetic ancestry-informative markers. Multivariable regression models were used to estimate the association of WGA and vitamin D–pathway gene variants with calcitriol and C24CPR, controlling for days from summer solstice, age, sex, blood pressure, body mass index, dietary vitamin D intake, oral contraceptive/medroxyprogesterone acetate use, smoking, tanning bed use, and time of day.Results:Calcitriol and C24CPR were not highly correlated (rho = 0.14), although both were significantly, positively, and monotonically associated with WGA (Ptrend 0.025 and R2 = 0.121 and 0.310, respectively). Variants in genes with associated with calcitriol (CALB1, CYP27B1, GC, and PPARGC1A) differed from those associated with C24CPR (CYP3A43, FGF23, KL, and VDR).Conclusions:Both absolute and relative measures of calcitriol were significantly higher among African Americans. Otherwise, these biomarkers appear to be genetically distinct.Impact:C24CPR may be better suited to personalized medicine, due to a higher proportion of population variability explained by genetic variation and a less skewed distribution.

Supplemental Table 4. Calcitriol-24,25-dihydroxyvitamin D3-calcifediol proportion ratio (C24CPR) and calcitriol (1,25(OH)2D3) adjusted least squares mean by demographic and environmental factors.

Supplemental Table 1. Distribution of Vitamin D Biomarkers By Race/Ethnicity, Sex and Oral Contraceptive Use.

Supplemental Figures 1a through 1d. Log linear plots of Plasma Calcitriol (1,25(OH)2D3) and plasma Calcitriol-24,25-Dihydroxyvitamin D3-Calcifediol Proportion ratio (C24CPR) in Relation to the Skin Melanin Index (SMI) and West African Genetic Ancestry Proportion (WGA) among healthy African American a European American participants.

Background Selected molecular biomarkers were incorporated into the US cancer registry reporting for patients with brain tumors beginning in 2018. We investigated the completeness and validity of these variables and described the epidemiology of molecularly defined brain tumor types. Methods Brain tumor patients with histopathologically confirmed diagnosis in 2018 were identified within the Central Brain Tumor Registry of the United States and NCI’s Surveillance, Epidemiology, and End Results Incidence databases. The brain molecular markers (BMM) site-specific data item was assessed for coding completeness and validity. 1p/19q status, MGMT promoter methylation, WHO grade data items, and new ICD-O-3 codes were additionally evaluated. These data were used to profile the characteristics and age-adjusted incidence rates per 100 000 population of molecularly defined brain tumors with 95% confidence intervals (95% CI). Results BMM completeness across the applicable tumor types was 75%-92% and demonstrated favorable coding validity. IDH-wildtype glioblastomas’ incidence rate was 1.74 (95% CI: 1.69-1.78), as compared to 0.14 for WHO grade 2 (95% CI: 0.12-0.15), 0.15 for grade 3 (95% CI: 0.14-0.16), and 0.07 for grade 4 (95% CI: 0.06-0.08) IDH-mutant astrocytomas. Irrespective of WHO grade, IDH mutation prevalence was highest in adolescent and young adult patients, and IDH-mutant astrocytomas were more frequently MGMT promoter methylated. Among pediatric-type tumors, the incidence rate was 0.06 for H3K27M-mutant diffuse midline gliomas (95% CI: 0.05-0.07), 0.03 for SHH-activated/TP53-wildtype medulloblastomas (95% CI: 0.02-0.03), and Conclusions Our findings illustrate the success of developing a dedicated, integrated diagnosis variable, which provides critical molecular information about brain tumors related to accurate diagnosis.

Supplementary Table 7: S-PrediXcan statistics at each brain tissue for the 31 identified gene associations.

Supplementary Table 6: Genes and their TWAS P-values for association with (a) GBM glioma (b) non-GBM glioma. s.d., standard deviation. Detailed are the S-MultiXcan P-value for association between gene expression and GBM/non-GBM risk and the corresponding Z-scores quantifying this relationship (e.g. a positive score indicates increased gene expression increases risk of GBM or non-GBM glioma). N and Nindep indicate the total number of single-tissue results used for S-MultiXcan analysis and the number of independent components after singular value decomposition, respectively. "p_i_best" and "t_i_best" correspond to the best single-tissue P-value and tissue model respectively, accordingly "p_i_worst" and "t_i_worset" correspond to the worst. "eigen_max" and "eigen_min" correspond to the maximum and minimum eigenvalue in the covariance matrix respectively, with "eigen_min_kept" corresponding to the minimum eigenvalue that survived thresholding.

Figures S1–S11, Tables S1–S6, Supplementary Materials and Methods, Supplementary Notes, and Supplementary References

Genome-wide association studies (GWAS) have so far identified 25 loci associated with glioma risk, with most showing specificity for either glioblastoma (GBM) or non-GBM tumors. The majority of these GWAS susceptibility variants reside in noncoding regions and the causal genes underlying the associations are largely unknown. Here we performed a transcriptome-wide association study to search for novel risk loci and candidate causal genes at known GWAS loci using Genotype-Tissue Expression Project (GTEx) data to predict cis-predicted gene expression in relation to GBM and non-GBM risk in conjunction with GWAS summary statistics on 12,488 glioma cases (6,183 GBM and 5,820 non-GBM) and 18,169 controls. Imposing a Bonferroni-corrected significance level of P < 5.69 × 10−6, we identified 31 genes, including GALNT6 at 12q13.33, as a candidate novel risk locus for GBM (mean Z = 4.43; P = 5.68 × 10−6). GALNT6 resides at least 55 Mb away from any previously identified glioma risk variant, while all other 30 significantly associated genes were located within 1 Mb of known GWAS-identified loci and were not significant after conditioning on the known GWAS-identified variants. These data identify a novel locus (GALNT6 at 12q13.33) and 30 genes at 12 known glioma risk loci associated with glioma risk, providing further insights into glioma tumorigenesis.Significance:This study identifies new genes associated with glioma risk, increasing understanding of how these tumors develop.

Aggregation of genome-wide common risk variants, such as polygenic risk score (PRS), can measure genetic susceptibility to cancer. A better understanding of how common germline variants associate with somatic alterations and clinical features could facilitate personalized cancer prevention and early detection. We constructed PRSs from 14 genome-wide association studies (median n = 64,905) for 12 cancer types by multiple methods and calibrated them using the UK Biobank resources (n = 335,048). Meta-analyses across cancer types in The Cancer Genome Atlas (n = 7,965) revealed that higher PRS values were associated with earlier cancer onset and lower burden of somatic alterations, including total mutations, chromosome/arm somatic copy-number alterations (SCNA), and focal SCNAs. This contrasts with rare germline pathogenic variants (e.g., BRCA1/2 variants), showing heterogeneous associations with somatic alterations. Our results suggest that common germline cancer risk variants allow early tumor development before the accumulation of many somatic alterations characteristic of later stages of carcinogenesis.Significance:Meta-analyses across cancers show that common germline risk variants affect not only cancer predisposition but the age of cancer onset and burden of somatic alterations, including total mutations and copy-number alterations.

Supplementary Figure 1: Quantile-Quantile Plots of -log10 (P-value) associations. (a) TWAS for GBM glioma; (b) TWAS for GBM glioma (lower 90% of associations); (c) TWAS for non-GBM glioma; (d) TWAS for non-GBM glioma (lower 90% of associations); (e) GWAS meta-analysis for GBM glioma; (f) GWAS meta-analysis for GBM glioma (lower 90% of associations); (g) GWAS meta-analysis for non-GBM glioma; (h) GWAS meta-analysis for non-GBM glioma (lower 90% of associations). Supplementary Figure 2: Manhattan Plots of SNP genomic co-ordinates against GWAS meta-analysis -log10 (P-value). (a) GBM glioma; (b) Non-GBM glioma. The red line represents the Bonferroni-corrected threshold of P{less than or equal to}5Ã-10-8. Supplementary Figure 3: Dendograms to display gene module clustering in brain tissues. Clustering was performed using the WGCNA (11) package for each tissue. (a) Amygdala; (b) Anterior cingulate cortex (BA24); (c) Caudate (basal ganglia); (d) Cerebellar Hemisphere; (e) Cerebellum; (f) Cortex; (g) Frontal Cortex (BA9); (h) Hippocampus; (i) Hypothalamus; (j) Nucleus accumbens (basal ganglia); (k) Putamen (basal ganglia); (l) Spinal cord (cervical c-1); (m) Substantia nigra. Supplementary Figure 4: Heatmaps illustrating gene module correlations in brain tissues. Darker colours indicate stronger associations. (a) Amygdala; (b) Anterior cingulate cortex (BA24); (c) Caudate (basal ganglia); (d) Cerebellar Hemisphere; (e) Cerebellum; (f) Cortex; (g) Frontal Cortex (BA9); (h) Hippocampus; (i) Hypothalamus; (j) Nucleus accumbens (basal ganglia); (k) Putamen (basal ganglia); (l) Spinal cord (cervical c-1); (m) Substantia nigra. Supplementary Figure 5: Module clustering of brain tissues with amygdala. Modules were created by clustering according to the amygdala tissue using WGCNA (11). These modules were applied to each tissue in turn and the Z statistic is a quantitative measure of module preservation. (a) Amygdala (reference); (b) Anterior cingulate cortex (BA24); (c) Caudate (basal ganglia); (d) Cerebellar Hemisphere; (e) Cerebellum; (f) Cortex; (g) Frontal Cortex (BA9); (h) Hippocampus; (i) Hypothalamus; (j) Nucleus accumbens (basal ganglia); (k) Putamen (basal ganglia); (l) Spinal cord (cervical c-1); (m) Substantia nigra. Supplementary Figure 6: TWAS power plots. Simulation analysis based on 12,488 glioma cases (6,183 GBM, 5,820 non-GBM) and 18,169 controls. Gene expression was generated from the distribution of gene expression levels from the respective brain tissue. Statistical power was calculated at P 0.4, case and control MAF > 0.01, PHWE in controls > 1x10-8. For the meta-analysis we considered all SNPs meeting the above criteria in all eight studies as well as having heterogeneity I2 < 75 in GBM/non-GBM glioma. a For the UCSF/Mayo study an imputation threshold of > 0.8 was applied. Supplementary Table 2: Prediction models trained on GTEx v7 data and covariance files obtained from http://predictdb.org/. Genes were retained if nested cross-validated correlation between predicted and actual levels > 0.10 (R2>1%) and P-value of the correlation test < 0.05. Supplementary Table 3: Previously reported glioma risk SNPs. Supplementary Table 4: Brain tissue, soft power threshold and number of independent genes. Soft power thresholds were chosen at the 90% threshold unless otherwise indicated. + For Cerebellar Hemisphere and Cerebellum, the 90% threshold was not achieved and 80% was imposed. For this reason such tissues were excluded from median calculations for soft power and number of independent genes. Supplementary Table 8: S-PrediXcan results for 31 genes in 922 whole-blood samples from the Depression Genes and Networks (DGN) study. Supplementary Table 9: Annotation of identified genes by presence within COSMIC cancer gene census and overlap with tumour copy number changes. *Cosmic cancer gene census annotation for CDKN2A was used.

Supplementary Table 5: Table of module color with module size and associated Z-statistics. Modules were created by clustering according to the Amygdala tissue using WGCNA11. These modules of gene number "moduleSize" were applied to each tissue in turn and the Z-statistic ("Zsummary.pres") is a quantitive measure of module preservation relative to Amygdala. (a) Anterior cingulate cortex (BA24); (b) Caudate (basal ganglia); (c) Cerebellar Hemisphere; (d) Cerebellum; (e) Cortex; (f) Frontal Cortex (BA9); (g) Hippocampus; (h) Hypothalamus; (i) Nucleus accumbens (basal ganglia); (j) Putamen (basal ganglia); (k) Spinal cord (cervical c-1); (l) Substantia nigra.

Background Pineoblastoma (PB) is a rare malignant brain tumor originating in the pineal gland. Here, we provide a comprehensive epidemiological analysis of PB in the United States from 2000 to 2017. Methods Data on 1133 patients with PB were acquired from the Central Brain Tumor Registry of the United States, in collaboration with the Centers for Disease Control and Prevention and the National Cancer Institute, from 2000 to 2017. Age-adjusted incidence rates (AAIRs) per 100 000 and incidence rate ratios (IRRs) were reported for age, sex, race, and ethnicity. Using the National Program of Cancer Registries survival database, median survival and hazard ratios (HRs) were evaluated for overall survival from 2001 to 2016. Results Incidence was highest in ages 0–4 years (AAIR: 0.049, 95% CI: 0.042–0.056), decreasing as age increased. Incidence was higher among patients who are Black compared to patients who are White (IRR: 1.71, 95% CI: 1.48–1.98, P < .001), and was impacted by age at diagnosis, with Black-to-White incidence highest in children ages 5–9 years (IRR: 3.43, 95% CI: 2.36–4.94, P < .001). Overall survival was lower for males (HR: 1.39, 95% CI: 1.07–1.79, P = .013). All age groups, excluding those over 40, had improved survival compared to ages 0–4 years. Those who received surgical intervention had better survival compared to those who did not receive surgical treatment. Conclusion PB incidence is highest among children and patients who are Black, and there may be a potential interaction between these factors. Survival is worse among males, young children, and elderly adults, and those who received no surgery. Comprehensive, population-based statistics provide critical information on PB characteristics that could be useful in impacting patient care and prognosis.

Background The Central Brain Tumor Registry of the United States (CBTRUS) contains information on all primary brain and other central nervous system (CNS) tumors diagnosed in the United States (US). Here we summarize the 2021 CBTRUS annual statistical report for clinicians. Methods Incidence survival data are obtained from the Centers for Disease Control’s National Program of Cancer Registries (NPCR) and National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) program. Survival data are obtained from NPCR. Mortality data are obtained from the National Vital Statistics System. Incidence and mortality rates are age-adjusted using the 2000 US population and presented per 100,000 population. Results An annual average of 86,355 cases of primary malignant and nonmalignant CNS tumors were diagnosed over the period 2014–2018, corresponding to an average annual age-adjusted incidence rate of 24.25. The most commonly occurring malignant tumor was glioblastoma (14.3%), and the most common predominately nonmalignant tumor was meningioma (39%). Over the 2014–2018 period, there were 16,606 annual average deaths due to malignant primary CNS tumors, corresponding to an average annual age-adjusted mortality rate of 4.43. In this report we detail key incidence, survival, and mortality statistics for major primary CNS tumor histologies, highlighting relevant differences by age, sex, and race. Conclusions This summary describes the most up to date population-based incidence of primary malignant and nonmalignant brain and other CNS tumors in the US, and mortality and survival for primary malignant tumors and aims to serve as a useful resource for clinicians.

Medicaid eligibility expansion, though not directly applicable to children, has been associated with improved access to care in children with cancer, but associations with overall survival are unknown. Data for children ages 0 to 14 years diagnosed with cancer from 2011 to 2018 were queried from central cancer registries data covering cancer diagnoses from 40 states as part of the Centers for Disease Control and Prevention’s National Program of Cancer Registries. Difference-in-differences analyses were used to compare changes in 2-year survival from 2011-2013 to 2015-2018 in Medicaid expansion relative to nonexpansion states. In adjusted analyses, there was a 1.50 percentage point (95% confidence interval = 0.37 to 2.64) increase in 2-year overall survival after 2014 in expansion relative to nonexpansion states, particularly for those living in the lowest county income quartile (difference-in-differences = 5.12 percentage point, 95% confidence interval = 2.59 to 7.65). Medicaid expansion may improve cancer outcomes for children with cancer.

The Central Brain Tumor Registry of the United States (CBTRUS), in collaboration with the Centers for Disease Control and Prevention (CDC) and National Cancer Institute (NCI), is the largest population-based cancer registry focused exclusively on primary brain and other central nervous system (CNS) tumors in the United States (US) and represents the entire US population. This report contains the most up-to-date population-based data on primary brain tumors available and supersedes all previous reports in terms of completeness and accuracy and is the first CBTRUS Report to provide the distribution of molecular markers for selected brain and CNS tumor histologies. All rates are age-adjusted using the 2000 US standard population and presented per 100,000 population. The average annual age-adjusted incidence rate (AAAIR) of all malignant and non-malignant brain and other CNS tumors was 24.25 (Malignant AAAIR=7.06, Non-malignant AAAIR=17.18). This overall rate was higher in females compared to males (26.95 versus 21.35) and non-Hispanics compared to Hispanics (24.68 versus 22.12). The most commonly occurring malignant brain and other CNS tumor was glioblastoma (14.3% of all tumors and 49.1% of malignant tumors), and the most common non-malignant tumor was meningioma (39.0% of all tumors and 54.5% of non-malignant tumors). Glioblastoma was more common in males, and meningioma was more common in females. In children and adolescents (age 0–19 years), the incidence rate of all primary brain and other CNS tumors was 6.21. An estimated 88,190 new cases of malignant and non-malignant brain and other CNS tumors are expected to be diagnosed in the US population in 2021 (25,690 malignant and 62,500 non-malignant). There were 83,029 deaths attributed to malignant brain and other CNS tumors between 2014 and 2018. This represents an average annual mortality rate of 4.43 per 100,000 and an average of 16,606 deaths per year. The five-year relative survival rate following diagnosis of a malignant brain and other CNS tumor was 35.6%, for a non-malignant brain and other CNS tumors the five-year relative survival rate was 91.8%.

The complex polygenic nature of lung cancer is not fully characterized. Our study seeks to identify novel phenotypes associated with lung cancer using cross-trait linkage disequilibrium score regression (LDSR). We measured pairwise genetic correlation (rg) and SNP heritability (h2) between 347 traits and lung cancer risk using genome-wide association study summary statistics from the UKBB and OncoArray consortium. Further, we conducted analysis after removing genomic regions previously associated with smoking behaviors to mitigate potential confounding effects. We found significant negative genetic correlations between lung cancer risk and dietary behaviors, fitness metrics, educational attainment, and other psychosocial traits. Alcohol taken with meals (rg = − 0.41, h2 = 0.10, p = 1.33 × 10–16), increased fluid intelligence scores (rg = − 0.25, h2 = 0.22, p = 4.54 × 10–8), and the age at which full time education was completed (rg = − 0.45, h2 = 0.11, p = 1.24 × 10–20) demonstrated negative genetic correlation with lung cancer susceptibility. The body mass index was positively correlated with lung cancer risk (rg = 0.20, h2 = 0.25, p = 2.61 × 10–9). This analysis reveals shared genetic architecture between several traits and lung cancer predisposition. Future work should test for causal relationships and investigate common underlying genetic mechanisms across these genetically correlated traits.

Brain and other central nervous system (CNS) tumors are among the most fatal cancers and account for substantial morbidity and mortality in the United States. Population-based data from the Central Brain Tumor Registry of the United States (a combined data set of the National Program of Cancer Registries [NPCR] and Surveillance, Epidemiology, and End Results [SEER] registries), NPCR, National Vital Statistics System and SEER program were analyzed to assess the contemporary burden of malignant and nonmalignant brain and other CNS tumors (hereafter brain) by histology, anatomic site, age, sex, and race/ethnicity. Malignant brain tumor incidence rates declined by 0.8% annually from 2008 to 2017 for all ages combined but increased 0.5% to 0.7% per year among children and adolescents. Malignant brain tumor incidence is highest in males and non-Hispanic White individuals, whereas the rates for nonmalignant tumors are highest in females and non-Hispanic Black individuals. Five-year relative survival for all malignant brain tumors combined increased between 1975 to 1977 and 2009 to 2015 from 23% to 36%, with larger gains among younger age groups. Less improvement among older age groups largely reflects a higher burden of glioblastoma, for which there have been few major advances in prevention, early detection, and treatment the past 4 decades. Specifically, 5-year glioblastoma survival only increased from 4% to 7% during the same time period. In addition, important survival disparities by race/ethnicity remain for childhood tumors, with the largest Black-White disparities for diffuse astrocytomas (75% vs 86% for patients diagnosed during 2009-2015) and embryonal tumors (59% vs 67%). Increased resources for the collection and reporting of timely consistent data are critical for advancing research to elucidate the causes of sex, age, and racial/ethnic differences in brain tumor occurrence, especially for rarer subtypes and among understudied populations.

Background Gliomas are the most common type of malignant brain and other CNS tumors, accounting for 80.8% of malignant primary brain and CNS tumors. They cause significant morbidity and mortality. This study investigates the intersection between age and sex to better understand variation of incidence and survival for glioma in the United States. Methods Incidence data from 2000 to 2017 were obtained from CBTRUS, which obtains data from the NPCR and SEER, and survival data from the CDC’s NPCR. Age-adjusted incidence rate ratios (IRR) per 100 000 were generated to compare male-to-female incidence by age group. Cox proportional hazard models were performed by age group, generating hazard ratios to assess male-to-female survival differences. Results Overall, glioma incidence was higher in males. Male-to-female incidence was lowest in ages 0-9 years (IRR: 1.04, 95% CI: 1.01-1.07, P = .003), increasing with age, peaking at 50-59 years (IRR: 1.56, 95% CI: 1.53-1.59, P < .001). Females had worse survival for ages 0-9 (HR: 0.93, 95% CI: 0.87-0.99), though male survival was worse for all other age groups, with the difference highest in those 20-29 years (HR: 1.36, 95% CI: 1.28-1.44). Incidence and survival differences by age and sex also varied by histological subtype of glioma. Conclusions To better understand the variation in glioma incidence and survival, investigating the intersection of age and sex is key. The current work shows that the combined impact of these variables is dependent on glioma subtype. These results contribute to the growing understanding of sex and age differences that impact cancer incidence and survival.

Purpose Despite advances in cancer diagnosis and clinical care, survival for many primary brain and other central nervous system (CNS) tumors remain poor. This study performs a comprehensive survival analysis on these tumors. Methods Survival differences were determined utilizing the National Program of Cancer Registries Survival Analytic file for primary brain and CNS tumors. Overall survival and survival of the 5 most common histopathologies, within specific age groups, were determined. Overall survival was compared for three time periods: 2004–2007, 2008–2012, and 2013–2017. Survival differences were evaluated using Kaplan–Meier and multivariable Cox proportional hazards models. Models were adjusted for sex, race/ethnicity, and treatment. Malignant and non-malignant brain tumors were assessed separately. Results Among malignant brain and CNS tumor patients overall, there were notable differences in survival by time period among all age groups. Similar differences were noted in non-malignant brain and CNS tumor patients, except for adults (aged 40–64 years), where no survival changes were observed. Survival differences varied within specific histopathologies across age groups. There were improvements in survival in 2008–2012 and 2013–2017, when compared to 2004–2007, in children, AYA, and older adults with malignant tumors, and among older adults with non-malignant tumors. Conclusion Overall survival for malignant brain and other CNS tumors improved slightly in 2013–2017 for all age groups as compared to 2004–2007. Significant changes were observed for non-malignant brain and other CNS tumors among older adults. Information regarding survival over time can be utilized to identify population level effects of diagnostic and treatment improvements.

Background Global incidence for brain tumors varies substantially without explanation. Studies correlating radon exposure and incidence are inconclusive. Particulate pollution has been linked to increased tumor incidence. Particulates may disrupt the blood-brain barrier allowing intracranial exposure to oncogenic radon. We investigated the relationship between exposure to residential radon, particulate pollution, and brain tumor incidence in the United States (US). Methods County-level median radon testing results and annual air quality index values were obtained and divided into tertiles. Counties without both values were excluded. Four groups of counties were generated: high particulate/high radon (high/high), high/low, low/high, and low/low. Using incidence data from the Central Brain Tumor Registry of the US (provided by CDC’s National Program of Cancer Registries and NCI’s SEER), annual age-adjusted incidence rates (AAAIRs) by group were generated by behavior. Incidence rate ratios were calculated to examine for significant differences (α = .05). Poisson regression accounting for possible confounders was conducted. Results Counties with available data included 83% of the US population. High/high exposure was significantly associated with increased AAAIR of all non-malignant tumors (up to 26% higher, including most meningiomas) even after accounting for potential confounders. An increased AAAIR was noted for all malignant tumors (up to 10% higher), including glioblastoma, but was negated after accounting for demographic/socioeconomic differences. Conclusions We present the first report suggesting increased non-malignant brain tumor incidence in regions with high particulate and radon exposure. These findings provide insight into unexplained variation in tumor incidence. Future studies are needed to validate these findings in other populations.

Background Epidemiological studies of adult glioma have identified genetic syndromes and 25 heritable risk loci that modify individual risk for glioma, as well increased risk in association with exposure to ionizing radiation and decreased risk in association with allergies. In this analysis, we assess whether there is a shared genome-wide genetic architecture between glioma and atopic/autoimmune diseases. Methods Using summary statistics from a glioma genome-wide association studies (GWAS) meta-analysis, we identified significant enrichment for risk variants associated with gene expression changes in immune cell populations. We also estimated genetic correlations between glioma and autoimmune, atopic, and hematologic traits using linkage disequilibrium score regression (LDSC), which leverages genome-wide single-nucleotide polymorphism (SNP) associations and patterns of linkage disequilibrium. Results Nominally significant negative correlations were observed for glioblastoma (GB) and primary biliary cirrhosis (rg = −0.26, P = .0228), and for non-GB gliomas and celiac disease (rg = −0.32, P = .0109). Our analyses implicate dendritic cells (GB pHM = 0.0306 and non-GB pHM = 0.0186) in mediating both GB and non-GB genetic predisposition, with GB-specific associations identified in natural killer (NK) cells (pHM = 0.0201) and stem cells (pHM = 0.0265). Conclusions This analysis identifies putative new associations between glioma and autoimmune conditions with genomic architecture that is inversely correlated with that of glioma and that T cells, NK cells, and myeloid cells are involved in mediating glioma predisposition. This provides further evidence that increased activation of the acquired immune system may modify individual susceptibility to glioma.

Background Limited population-based data exist for the brainstem gliomas for children ages ≤19 years, which includes high-grade aggressively growing tumors such as diffuse intrinsic pontine glioma (DIPG). We examined the overall incidence and survival patterns in children with brainstem high-grade glioma (HGG) by age, sex, and race and ethnicity. Methods We used data from Central Brain Tumor Registry of the United States (CBTRUS), obtained through data use agreements with the Centers for Disease Control (CDC) and the National Cancer Institute (NCI) from 2000 to 2017, and survival data from the CDCs National Program of Cancer Registries (NPCR), from 2001 to 2016 for malignant brainstem HGG for ages ≤19 years (per WHO ICD-O-3 codes). HGG was determined by established histologic and/or imaging criteria. Age-adjusted incidence rates and survival data were used to assess differences overall and by age, sex race, and ethnicity. Results The incidence of brainstem HGG was higher among the female and Non-Hispanic population. Majority (69.8%) of these tumors were diagnosed radiographically. Incidence was higher in children aged 1-9 years compared to older children. Whites had a higher incidence compared to Blacks. However, the risk of death was higher among Blacks and Other race compared to Whites. There was no difference in survival by sex. Conclusions We report the most comprehensive incidence and survival data on these lethal brainstem HGGs. Incidence and survival among patients with brainstem HGGs differed significantly by race, ethnicity, age-groups, and grade.

The distribution of multiple primary cancers has been described previously using data from the Surveillance, Epidemiology, and End Results (SEER) Program. However, a complete picture regarding the distribution of multiple primary cancers in the United States is still lacking. The objective of the current study is to present a comprehensive description of multiple primary cancers in the United States.Invasive cancer cases (including in situ bladder cancers) diagnosed between 2001 and 2016 from 49 population-based state cancer registries in the United States were evaluated for this study. The sequence number central assigned to each tumor was used to determine whether a tumor was a first primary cancer or a subsequent multiple primary cancer. Tumors with a sequence number 00 or 01 were classified as the first primary cancer, while tumors with a sequence number 02 or above were classified as a multiple primary cancer. The percentage of multiple primary cancers was calculated by sex, age, race/ethnicity, cancer site, registry, and diagnosis year. In addition, the percentage of cancers diagnosed at a local stage among multiple primaries was compared with that among first primaries.Overall, about 19.0% of cases were reported as multiple primary cancers; the percentage was higher among non-Hispanic Whites and among older patients. Bladder, melanoma of the skin, and lung cancers had the highest percentage of cases reported as multiple primaries. The percentage of multiple primary cancers also varied by registry and has been increasing over time. Cancers reported as multiple primaries were more likely to be diagnosed at a local stage than those reported as first primaries.Cancers registered as multiple primaries are common in the United States, showing an increasing trend over time and wide variation by race/ethnicity, age, cancer type, and registry. The findings have some practical implications for cancer registries that collect data and for researchers conducting investigations using information on multiple primary cancers.

Background The Central Brain Tumor Registry of the United States (CBTRUS) uses a histology grouping model based on the World Health Organization (WHO) classifications to group records for clinically relevant statistical reporting. Newly identified genetic markers more accurately stratify patients than histology alone and were incorporated into the 2016 update to the WHO Classification. Methods CBTRUS and consulting neuropathologists reviewed and aligned histology groupings with the 2016 WHO update. “Obsolete” (terms not currently in use) histology nomenclature along with their International Classification of Disease, Oncology 3rd edition (ICD-O-3) codes were identified, some histologies were reclassified to 2016 WHO, and new codes found in 2016 WHO were incorporated. An evaluation of the frequency of histology codes affected in the realignment process, and incidence and survival pre- and post-realignment was conducted. Results After review, 67 codes were noted as obsolete, 51 codes were reclassified, and 12 new codes were incorporated. Histology groups most affected were mesenchymal tumors and neuronal/mixed neuronal-glial tumors. Reorganization resulted in 2588 (0.65%) cases with grouping reassignment or reporting change, indicating that the 2016 WHO Classification revision has impacted the collection and reporting of primary brain and other CNS tumors. Conclusion This work demonstrates the need to be responsive to changes in classification and coding in order to ensure the most up-to-date and accurate statistics for brain and CNS tumors. This will require collaboration from all stakeholders within the brain tumor community, so to have the ability to reconcile clinical practices and surveillance requirements.

Background Glioma incidence is 25% lower in Hispanics than White non-Hispanics. The US Hispanic population is diverse, and registry-based analyses may mask incidence differences associated with geographic/ancestral origins. Methods County-level glioma incidence data in Hispanics were retrieved from the Central Brain Tumor Registry of the United States. American Community Survey data were used to determine the county-level proportion of the Hispanic population of Mexican/Central American and Caribbean origins. Age-adjusted incidence rate ratios and incidence rate ratios (IRRs) quantified the glioma incidence differences across groups. State-level estimates of admixture in Hispanics were obtained from published 23andMe data. Results Compared to predominantly Caribbean-origin counties, predominantly Mexican/Central American-origin counties had lower age-adjusted risks of glioma (IRR = 0.83; P < 0.0001), glioblastoma (IRR = 0.86; P < 0.0001), diffuse/anaplastic astrocytoma (IRR = 0.78; P < 0.0001), oligodendroglioma (IRR = 0.82; P < 0.0001), ependymoma (IRR = 0.88; P = 0.012), and pilocytic astrocytoma (IRR = 0.76; P < 0.0001). Associations were consistent in children and adults and using more granular geographic regions. Despite having lower glioma incidence, Hispanic glioblastoma patients from predominantly Mexican/Central American-origin counties had poorer survival than Hispanics living in predominantly Caribbean-origin counties. Incidence and survival differences could be partially explained by state-level estimates of European admixture in Hispanics with European admixture associated with higher incidence and improved survival. Conclusions Glioma incidence and outcomes differ in association with the geographic origins of Hispanic communities, with counties of predominantly Mexican/Central American origin at significantly reduced risk and those of Caribbean origin at comparatively greater risk. Although typically classified as a single ethnic group, appreciating the cultural, socioeconomic, and genetic diversity of Hispanics can advance cancer disparities research.

Introduction: Ki-67 expression, a marker of tumor proliferation, is considered a prognostic factor in primary CNS lymphoma (PCNSL). Apparent diffusion coefficient (ADC) parameters have also been proposed as imaging biomarkers for tumor progression and proliferative activity in various malignancies. The aim of this study is to investigate the correlation between ADC parameters, Ki-67 expression, overall survival (OS) and progression free survival (PFS) in PCNSL. Materials and Methods: Patients diagnosed with PCNSL at MD Anderson Cancer Center between Mar 2000 and Jul 2016 and at Ben Taub Hospital between Jan 2012 and Dec 2016 were retrospectively studied. Co-registered ADC maps and post-contrast images underwent whole tumor segmentation. Normalized ADC parameters (nADC) were calculated as the ratio to normal white matter. Percentiles of nADC were calculated and were correlated with Ki-67 using Pearson’s correlation coefficient and clinical outcomes (OS and PFS) using Cox proportional hazards models. Results: Selection criteria yielded 90 patients, 23 patients living with HIV (PLWH) and 67 immunocompetent patients. Above median values for nADCmean, nADC15, nADC75 and nADC95 were associated with improved OS in all patients (p < 0.05). Above median values for nADCmin, nADCmean, nADC1, nADC5 and kurtosis were associated with improved PFS in all patients (p < 0.05). In patients with available Ki-67 expression data (n = 22), nADCmean, nADC15 and nADC75 inversely correlated with Ki-67 expression (p < 0.05). For PLWH, there was no correlation between ADC parameters and Ki-67 expression or clinical outcomes. Conclusions: ADC histogram analysis can predict tumor proliferation and survival in immunocompetent patients with PCNSL, but with limited utility in PLWH.

Ependymoma is the third most common brain tumor in children, with well-described molecular characterization but poorly understood underlying germline risk factors. To investigate whether genetic predisposition to longer telomere length influences ependymoma risk, we utilized case–control data from three studies: a population-based pediatric and adolescent ependymoma case–control sample from California (153 cases, 696 controls), a hospital-based pediatric posterior fossa type A (EPN-PF-A) ependymoma case–control study from Toronto’s Hospital for Sick Children and the Children’s Hospital of Philadelphia (83 cases, 332 controls), and a multicenter adult-onset ependymoma case–control dataset nested within the Glioma International Case-Control Consortium (GICC) (103 cases, 3287 controls). In the California case–control sample, a polygenic score for longer telomere length was significantly associated with increased risk of ependymoma diagnosed at ages 12–19 (P = 4.0 × 10−3), but not with ependymoma in children under 12 years of age (P = 0.94). Mendelian randomization supported this observation, identifying a significant association between genetic predisposition to longer telomere length and increased risk of adolescent-onset ependymoma (ORPRS = 1.67; 95% CI 1.18–2.37; P = 3.97 × 10−3) and adult-onset ependymoma (PMR-Egger = 0.042), but not with risk of ependymoma diagnosed before age 12 (OR = 1.12; 95% CI 0.94–1.34; P = 0.21), nor with EPN-PF-A (PMR-Egger = 0.59). These findings complement emerging literature suggesting that augmented telomere maintenance is important in ependymoma pathogenesis and progression, and that longer telomere length is a risk factor for diverse nervous system malignancies.

Background:Sex plays an important role in the incidence, prognosis, and mortality of cancers, but often is not considered in disease treatment.Methods:We quantified sex differences in cancer incidence using the United States Cancer Statistics (USCS) public use database and sex differences in cancer survival using Surveillance, Epidemiology, and End Results (SEER) public use data from 2001 to 2016. Age-adjusted male-to-female incidence rate ratios (IRR) with 95% confidence intervals (CI) were generated by primary cancer site, race, and age groups. In addition, age-adjusted hazard ratios with 95% CI by sex within site were generated.Results:In general, cancer incidence and overall survival were lower in males than females, with Kaposi sarcoma (IRR: 9.751; 95% CI, 9.287–10.242; P < 0.001) having highest male-to-female incidence, and thyroid cancers (HR, 1.774; 95% CI, 1.707–1.845) having largest male-to-female survival difference. Asian or Pacific Islanders had particularly high male-to-female incidence in larynx cancers (IRR: 8.199; 95% CI, 7.203–9.363; P < 0.001), relative to other races. Among primary brain tumors, germ cell tumors had the largest male-to-female incidence (IRR: 3.03; 95% CI, 2.798–3.284, P < 0.001).Conclusions:Overall, incidence and survival of cancer vary significantly by sex, with males generally having lower incidence and survival compared with females. Male-to-female incidence differences were also noted across race and age groups. These results provide strong evidence that the fundamental biology of sex differences affects cancers of all types.Impact:This study represents the most recent and comprehensive reporting of sex differences in cancer incidence and survival in the United States. Identifying disadvantaged groups is critical as it can provide useful information to improve cancer survival, as well as to better understand the etiology and pathogenesis of specific cancers.

BackgroundEpendymoma is a histologically defined central nervous system tumor most commonly occurring in childhood. Population-level incidence differences by race/ethnicity are observed, with individuals of European ancestry at highest risk. We aimed to determine whether extent of European genetic ancestry is associated with ependymoma risk in US populations.MethodsIn a multi-ethnic study of Californian children (327 cases, 1970 controls), we estimated the proportions of European, African, and Native American ancestry among recently admixed Hispanic and African American subjects and estimated European admixture among non-Hispanic white subjects using genome-wide data. We tested whether genome-wide ancestry differences were associated with ependymoma risk and performed admixture mapping to identify associations with local ancestry. We also evaluated race/ethnicity-stratified ependymoma incidence data from the Central Brain Tumor Registry of the United States (CBTRUS).ResultsCBTRUS data revealed that African American and Native American children have 33% and 36%, respectively, reduced incidence of ependymoma compared with non-Hispanic whites. In genetic analyses, a 20% increase in European ancestry was associated with a 1.31-fold higher odds of ependymoma among self-reported Hispanics and African Americans (95% CI: 1.08–1.59, Pmeta = 6.7 × 10−3). Additionally, eastern European ancestral substructure was associated with increased ependymoma risk in non-Hispanic whites (P = 0.030) and in Hispanics (P = 0.043). Admixture mapping revealed a peak at 20p13 associated with increased local European ancestry, and targeted fine-mapping identified a lead variant at rs6039499 near RSPO4 (odds ratio = 1.99; 95% CI: 1.45–2.73; P = 2.2 × 10−5) but which was not validated in an independent set of posterior fossa type A patients.ConclusionsInterethnic differences in ependymoma risk are recapitulated in the genomic ancestry of ependymoma patients, implicating regions to target in future association studies.

OBJECTIVESpinal schwannoma remains the third most common intradural spinal tumor following spinal meningioma and ependymoma. The available literature is generally limited to single-institution reports rather than epidemiological investigations. As of 1/1/2004, registration of all benign central nervous system tumors in the United States became mandatory after the Benign Brain Tumor Cancer Registries Amendment Act took action, which provided massive resources for United States population-based epidemiological studies. This article describes the epidemiology of spinal schwannoma in the United States from January 1, 2006, through December 31, 2014.METHODSIn this study, the authors utilized the Central Brain Tumor Registry of the United States, which corresponds to 100% of the American population. The Centers for Disease Control and Prevention’s National Program of Cancer Registries and the National Cancer Institute’s Surveillance Epidemiology and End Results program provide the resource for this data registry. The authors included diagnosis years 2006 to 2014. They used the codes per the International Coding of Diseases for Oncology, 3rd Edition: histology code 9560/0 and site codes C72.0 (spinal cord), C70.1 (spinal meninges), and C72.1 (cauda equina). Rates are per 100,000 persons and are age-adjusted to the 2000 United States standard population. The age-adjusted incidence rates and 95% confidence intervals are calculated by age, sex, race, and ethnicity.RESULTSThere were 6989 spinal schwannoma cases between the years 2006 and 2014. The yearly incidence eminently increased between 2010 and 2014. Total incidence rate was 0.24 (95% CI 0.23–0.24) per 100,000 persons. The peak adjusted incidence rate was seen in patients who ranged in age from 65 to 74 years. Spinal schwannomas were less common in females than they were in males (incidence rate ratio = 0.85; p < 0.001), and they were less common in blacks than they were in whites (IRR = 0.52; p < 0.001) and American Indians/Alaska Natives (IRR = 0.50; p < 0.001) compared to whites. There was no statistically significant difference in incidence rate between whites and Asian or Pacific Islanders (IRR = 0.92; p = 0.16).CONCLUSIONSThe authors’ study results demonstrated a steady increase in the incidence of spinal schwannomas between 2010 and 2014. Male sex and the age range 65–74 years were associated with higher incidence rates of spinal schwannomas, whereas black and American Indian/Alaska Native races were associated with lower incidence rates. The present study represents the most thorough assessment of spinal schwannoma epidemiology in the American population.

BACKGROUNDThe NIH Revitalization Act, implemented 29 years ago, set to improve the representation of women and minorities in clinical trials. In this study, we investigate progress made in all phase therapeutic clinical trials for neuro-epithelial CNS tumors stratified by demographic-specific age-adjusted disease incidence and mortality. Additionally, we identify workforce characteristics associated with clinical trials meeting established accrual benchmarks.METHODSRegistry study of published clinical trials for World Health Organization defined neuro-epithelial CNS tumors between January 2000 and December 2019. Study participants were obtained from PubMed and ClinicalTrials.gov. Population-based data originated from the CBTRUS for incidence analyses. SEER-18 Incidence-Based Mortality data was used for mortality analysis. Descriptive statistics, Fisher exact, and χ2 tests were used for data analysis.RESULTSAmong 662 published clinical trials representing 49,907 participants, 62.5% of study participants were men and 37.5% were women (PCONCLUSIONSFollowing the Revitalization Act, minorities and women remain underrepresented when compared with their demographic-specific incidence and mortality in therapeutic clinical trials for neuroepithelial tumors. This study provides a framework for clinical trial accrual efforts and offers guidance regarding workforce considerations associated with enrollment of vulnerable patients.Key PointsMinorities and women with brain tumor diagnosis remain significantly under-accrued for neuro-oncology clinical trials compared to Caucasians and men based on proportional disease burden and demographic-specific mortality.Importance of the StudyThe current state of clinical trial accrual in the U.S. for adult patients with gliomas across different demographic groups has not been comprehensively studied. This study aims to quantify clinical trial accrual by age-adjusted disease incidence and mortality for gender and race during a 20-year period following the NIH Revitalization Act, and to identify workforce characteristics associated with clinical trials meeting established race and gender accrual benchmarks. Minorities and women with brain tumor diagnosis remain significantly under-accrued for neuro-oncology clinical trials compared to Caucasians and men based on proportional disease burden and demographic-specific mortality. Despite the enactment of the NIH Revitalization Act to improve the representation of women and minorities in clinical trials nearly 30 years ago, this goal remains unmet in the field of neuro-oncology. Significant work is required to continue to implement and improve interventions to increase accrual of diverse patient populations.

Purpose of Review Brain and other central nervous system (CNS) tumors, while rare, cause significant morbidity and mortality across all ages. This article summarizes the current state of the knowledge on the epidemiology of brain and other CNS tumors. Recent Findings For childhood and adolescent brain and other CNS tumors, high birth weight, non-chromosomal structural birth defects and higher socioeconomic position were shown to be risk factors. For adults, increased leukocyte telomere length, proportion of European ancestry, higher socioeconomic position, and HLA haplotypes increase risk of malignant brain tumors, while immune factors decrease risk. Summary Although no risk factor accounting for a large proportion of brain and other CNS tumors has been discovered, the use of high throughput “omics” approaches and improved detection/measurement of environmental exposures will help us refine our current understanding of these factors and discover novel risk factors for this disease.

BACKGROUND Glioma incidence is 25% lower in U.S. Hispanics than in White non-Hispanics. The US Hispanic population is diverse and registry-based analyses may mask incidence differences associated with geographic/ancestral origins. METHODS County-level glioma incidence data in U.S. Hispanics were retrieved from the Central Brain Tumor Registry of the United States (CBTRUS), which includes data from the Centers for Disease Control’s National Program of Cancer Registries and the National Cancer Institute’s Surveillance, Epidemiology, and End Results program and covers ~100% of the U.S. population. American Community Survey (ACS) data were used to determine county-level proportion of the Hispanic population of Mexican/Central American origin, Caribbean origin (Puerto Rican, Cuban, Dominican), or other origin. Incidence rate ratios (IRRs) were generated to assess the association of glioma incidence in Hispanics with predominant origin group. RESULTS Compared to Hispanics living in predominantly Caribbean-origin counties, Hispanics in predominantly Mexican/Central American-origin counties were at lower age-adjusted risk of glioma (IRR=0.83; P< 0.0001), glioblastoma (IRR=0.86; P< 0.0001), diffuse and anaplastic astrocytoma (IRR=0.78; P< 0.0001), oligodendroglioma (IRR=0.82; P< 0.0001), ependymoma (IRR=0.88; P=0.0121), and pilocytic astrocytoma (IRR=0.76; P< 0.0001). Associations were consistent in children and adults, and when using more granular regions of origin. However, Central American origin was associated with modestly increased incidence of several lower-grade glioma histologies. Associations were only partially attenuated after adjusting for state-level estimated of European admixture in Hispanics using 23andMe data. CONCLUSIONS Glioma incidence in U.S. Hispanics differs significantly in association with the geographic origins of the Hispanic community, with those of Mexican/Central American origin at significantly reduced risk relative to those of Caribbean origin. U.S. Hispanics are culturally, socioeconomically, and genetically diverse. Although classified as a single ethnic group in most registry data, more granular analytic approaches could advance cancer epidemiology and disparities research.

Cancer surveillance is critical for monitoring the burden of cancer and the progress in cancer control. The accuracy of these data is important for decision makers and others who determine resource allocation for cancer prevention and research. In the United States, cancer registration is conducted according to uniform data standards, which are updated and maintained by the North American Association of Central Cancer Registries. Underlying cancer registration efforts is a firm commitment to ensure that data are accurate, complete, and reflective of current clinical practices. Cancer registries ultimately depend on medical records that are generated for individual patients by clinicians to record newly diagnosed cases. For the cancer registration of brain and other CNS tumors, the Central Brain Tumor Registry of the United States is the self-appointed guardian of these data. In 2017, the Central Brain Tumor Registry of the United States took the initiative to promote the inclusion of molecular markers found in the 2016 WHO Classification of Tumours of the Central Nervous System into information collected by cancer registries. The complexities of executing this latest objective are presented according to the cancer registry standard-setting organizations whose collection practices for CNS tumors are directly affected.