Atopy improves survival and decreases risk of brain metastasis in cutaneous melanoma.

Importance: Development of new therapies in melanoma has increased survival, and as a result more patients are living to develop brain metastasis (BrM). Identifying patients at increased risk of BrM is therefore of significant public health importance. Objective: To determine whether history of atopy is associated with improved survival or reduced incidence of BrM in cutaneous melanoma. Design: A retrospective cohort study conducted from June 2022 to March 2024. Setting: Population-based in states with Surveillance, Epidemiology and End Results (SEER) supported cancer registries. Participants: Individuals (≥65 years) diagnosed with cutaneous melanoma between January 1, 2008 and December 31, 2017 that are participants in traditional Medicare. Exposures: Individuals were compared that had history of atopy (allergic rhinitis, atopic dermatitis, asthma, and/or allergic/atopic conjunctivitis) diagnosed prior to melanoma diagnosis, ascertained using ICD-9 or ICD-10 codes in Medicare claims. Main Outcomes and Measures: Primary endpoints were diagnosis with a BrM or death during the follow-up period. Associations between atopy and endpoints were assessed using cox proportional hazards models to estimate hazard ratios (HR) and p-values. Results: A total of 29,956 cutaneous melanoma cases were identified (median age 76, 60% male and 97% non-Hispanic White). Overall, 7.1% developed BrM during follow up. Among the 35% that had history of atopy, the most common condition was atopic dermatitis (19%). After adjustment for demographic and prognostic factors, atopy was associated with a 16% decrease in death (HR=0.84 [95%CI:0.80-0.87], pFDR<0.001). Among those with non-metastatic disease at time of diagnosis, atopy conferred a 15% decrease in cumulative incidence BrM (HR=0.85 [95%CI: 0.76-0.94], pFDR=0.006), with a 25% decrease associated with atopic dermatitis (HR=0.75 [95%CI:0.65-0.86], pFDR<0.001). Among those with metastatic disease at diagnosis (any metastatic site), only those who received immune checkpoint inhibitors had a survival benefit associated with atopy (HR=0.31, [95%CI:0.15-0.64], p=0.001 vs HR=1.41, [95%CI:0.87-2.27], p=0.165). Conclusions and Relevance: Atopy, particularly atopic dermatitis, was significantly associated with improved survival and decreased incidence of BrM. The improved survival associated with these conditions in the context of immunotherapy suggests that these conditions in the elderly may identify those with more robust immune function that may be more responsive to treatment.

CBTRUS Statistical Report: American Brain Tumor Association & NCI Neuro-Oncology Branch Adolescent and Young Adult Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2016-2020.

Recent analyses have shown that, whereas cancer survival overall has been improving, it has not improved for adolescents and young adults ages 15-39 years (AYA). The clinical care of AYA with primary brain and other central nervous system (CNS) tumors (BT) is complicated by the fact that the histopathologies of such tumors in AYA differ from their histopathologies in either children (ages 0-14 years) or older adults (ages 40+ years). The present report, as an update to a 2016 publication from the Central Brain Tumor Registry of the United States and the American Brain Tumor Association, provides in-depth analyses of the epidemiology of primary BT in AYA in the United States and is the first to provide biomolecular marker-specific statistics and prevalence by histopathology for both primary malignant and non-malignant BT in AYA. Between 2016 and 2020, the annual average age-specific incidence rate (AASIR) of primary malignant and non-malignant BT in AYA was 12.00 per 100,000 population, an average of 12,848 newly diagnosed cases per year. During the same period, an average of 1,018 AYA deaths per year were caused by primary malignant BT, representing an annual average age-specific mortality rate of 0.96 per 100,000 population. When primary BT were categorized by histopathology, pituitary tumors were the most common (36.6%), with an AASIR of 4.34 per 100,000 population. Total incidence increased with age overall; when stratified by sex, the incidence was higher in females than males at all ages. Incidence rates for all primary BT combined and for non-malignant tumors only were highest for non-Hispanic American Indian/Alaska Native individuals, whereas malignant tumors were more frequent in non-Hispanic White individuals, compared with other racial/ethnic groups. On the basis of histopathology, the most common molecularly defined tumor was diffuse glioma (an AASIR of 1.51 per 100,000). Primary malignant BT are the second most common cause of cancer death in the AYA population. Incidence rates of primary BT overall, as well as specific histopathologies, vary significantly by age. Accordingly, an accurate statistical assessment of primary BT in the AYA population is vital for better understanding the impact of these tumors on the US population and to serve as a reference for afflicted individuals, for researchers investigating new therapies, and for clinicians treating these patients.

Sex differences in adverse events in Medicare individuals ≥ 66 years of age post glioblastoma treatment.

PURPOSE: Glioblastoma (GB) is the most common primary malignant brain tumor with the highest incidence occurring in older adults with a median age at diagnosis of 64 years old. While treatment often improves survival it brings toxicities and adverse events (AE). Here we identify sex differences in treatment patterns and AE in individuals ≥ 66 years at diagnosis with GB. METHODS: Using the SEER-Medicare dataset sex differences in adverse events were assessed using multivariable logistic regression performed to calculate the male/female odds ratio (M/F OR) and 95% confidence intervals [95% CI] of experiencing an AE adjusted for demographic variables and Elixhauser comorbidity score. RESULTS: Males with GB were more likely to receive standard of care (SOC; Surgery with concurrent radio-chemotherapy) [20%] compared to females [17%], whereas females were more likely to receive no treatment [26%] compared to males [21%]. Females with GB receiving SOC were more likely to develop gastrointestinal disorders (M/F OR = 0.76; 95% CI,0.64-0.91, p = 0.002) or blood and lymphatic system disorders (M/F OR = 0.79; 95% CI,0.66-0.95, p = 0.012). Males with GB receiving SOC were more likely to develop cardiac disorders (M/F OR = 1.21; 95% CI,1.02-1.44, p = 0.029) and renal disorders (M/F OR = 1.65; 95% CI,1.37-2.01, p < 0.001). CONCLUSIONS: Sex differences for individuals, 66 years and older, diagnosed with GB exist in treatment received and adverse events developed across different treatment modalities.

Childhood, adolescent, and adult primary brain and central nervous system tumor statistics for practicing healthcare providers in neuro-oncology, CBTRUS 2015-2019.

Background: 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 aggregation of histopathology-specific population-based data for primary brain and other central nervous system (CNS) in the US. CBTRUS publishes an annual statistical report which provides critical reference data for the broad neuro-oncology community. Here, we summarize the key findings from the 2022 CBTRUS annual statistical report for healthcare providers. Methods: Incidence data were obtained from the CDC's National Program of Cancer Registries (NPCR) and NCI's Surveillance, Epidemiology, and End Results Program for 52 central cancer registries (CCRs). Survival data were obtained from 42 NPCR CCRs. All rates are per 100 000 and age-adjusted using the 2000 US standard population. Overall median survival was estimated using Kaplan-Meier models. Survival data for selected molecularly defined histopathologies are from the National Cancer Database. Mortality data are from the National Vital Statistics System. Results: The average annual age-adjusted incidence rate of all primary brain and other CNS tumors was 24.25/100 000. Incidence was higher in females and non-Hispanics. The most commonly occurring malignant and predominately non-malignant tumors was glioblastoma (14% of all primary brain tumors) and meningioma (39% of all primary brain tumors), respectively. Mortality rates and overall median survival varied by age, sex, and histopathology. Conclusions: This summary describes the most up-to-date population-based incidence, mortality, and survival, of primary brain and other CNS tumors in the US and aims to serve as a concise resource for neuro-oncology providers.

The impact of COVID-19 on 2020 monthly incidence trends of primary brain and other CNS tumors.

BACKGROUND: To mitigate disease spread, restrictions implemented in the United States surrounding the COVID-19 pandemic created an environment that led to delays in cancer diagnosis. The data needed to accurately analyze the impact of the pandemic on brain and CNS tumor incidence has not been available until now. Utilizing incidence data from the Central Brain Tumor Registry of the United States (CBTRUS) we analyzed the impact of the COVID-19 pandemic on primary brain and other CNS tumor incidence for the first year of the pandemic. METHODS: Monthly age-adjusted incidence rates and incidence trends for 2019 and 2020 were determined for age at diagnosis, sex, race, ethnicity, diagnostic confirmation, behavior, tumor histopathology, and county-level urbanization. Monthly incidence rate ratios comparing 2020 and 2019 were evaluated for the same factors. RESULTS: Overall, there was a notable decrease in incidence rates in March-May 2020 when compared to 2019. These decreases were driven by nonmalignant tumors, with a 50% incidence decrease between March 2020 and 2019. Individuals who were Black had a larger incidence decrease in early 2020 than individuals who were White. Radiographically confirmed tumors saw larger incidence decreases than histologically confirmed tumors. There were no changes in monthly incidence of glioblastoma in 2020 compared to 2019. CONCLUSIONS: These data provide evidence that disruptions in medical care, such as governmental and health care mandates, in response to the COVID-19 pandemic resulted in an overall decreased incidence of primary brain tumors in early 2020.

Association of county-level socioeconomic status with meningioma incidence and outcomes.

BACKGROUND: Prior literature suggests that individual socioeconomic status (SES) may influence incidence, treatments, and survival of brain tumor cases. We aim to conduct the first national study to evaluate the association between US county-level SES and incidence, treatment, and survival in meningioma. METHODS: The Central Brain Tumor Registry of the United States analytic dataset, which combines data from CDC's National Program of Cancer Registries (NPCR) and National Cancer Institute's Surveillance, Epidemiology, and End Results Program, was used to identify meningioma cases from 2006 to 2019. SES quintiles were created using American Community Survey data. Logistic regression models were used to evaluate associations between SES and meningioma. Cox proportional hazard models were constructed to assess the effect of SES on survival using the NPCR analytic dataset. RESULTS: A total of 409 681 meningioma cases were identified. Meningioma incidence increased with higher county-level SES with Q5 (highest quintile) having a 12% higher incidence than Q1 (incidence rate ratios (IRR) = 1.12, 95%CI: 1.10-1.14; P < .0001). The Hispanic group was the only racial-ethnic group that had lower SES associated with increased meningioma incidence (Q5: age-adjusted incidence ratio (AAIR) = 9.02, 95%CI: 8.87-9.17 vs. Q1: AAIR = 9.33, 95%CI: 9.08-9.59; IRR = 0.97, 95%CI: 0.94-1.00; P = .0409). Increased likelihood of surgical treatment was associated with Asian or Pacific Islander non-Hispanic individuals (compared to White non-Hispanic (WNH)) (OR = 1.28, 95%CI: 1.23-1.33, P < .001) and males (OR = 1.31, 95%CI: 1.29-1.33, P < .001). Black non-Hispanic individuals (OR = 0.90, 95%CI: 0.88-0.92, P < .001) and those residing in metropolitan areas (OR = 0.96, 95%CI: 0.96-0.96, P < .001) were less likely to receive surgical treatment compared to WNH individuals. Overall median survival was 137 months, and survival was higher in higher SES counties (Q5 median survival = 142 months). CONCLUSIONS: Higher county-level SES was associated with increased meningioma incidence, surgical treatment, and overall survival. Racial-ethnic stratification identified potential disparities within the meningioma population. Further work is needed to understand the underpinnings of socioeconomic and racial disparities for meningioma patients.

Brain tumors in United States military veterans.

BACKGROUND: Comprehensive analysis of brain tumor incidence and survival in the Veteran population has been lacking. METHODS: Veteran data were obtained from the Veterans Health Administration (VHA) Medical Centers via VHA Corporate Data Warehouse. Brain tumor statistics on the overall US population were generated from the Central Brain Tumor Registry of the US data. Cases were individuals (≥18 years) with a primary brain tumor, diagnosed between 2004 and 2018. The average annual age-adjusted incidence rates (AAIR) and 95% confidence intervals were estimated per 100 000 population and Kaplan-Meier survival curves evaluated overall survival outcomes among Veterans. RESULTS: The Veteran population was primarily white (78%), male (93%), and between 60 and 64 years old (18%). Individuals with a primary brain tumor in the general US population were mainly female (59%) and between 18 and 49 years old (28%). The overall AAIR of primary brain tumors from 2004 to 2018 within the Veterans Affairs cancer registry was 11.6. Nonmalignant tumors were more common than malignant tumors (AAIR:7.19 vs 4.42). The most diagnosed tumors in Veterans were nonmalignant pituitary tumors (AAIR:2.96), nonmalignant meningioma (AAIR:2.62), and glioblastoma (AAIR:1.96). In the Veteran population, survival outcomes became worse with age and were lowest among individuals diagnosed with glioblastoma. CONCLUSIONS: Differences between Veteran and US populations can be broadly attributed to demographic composition differences of these groups. Prior to this, there have been no reports on national-level incidence rates and survival outcomes for Veterans. These data provide vital information that can drive efforts to understand disease burden and improve outcomes for individuals with primary brain tumors.

Capturing evolving definitions of 12 select rare CNS tumors: a timely report from CBTRUS and NCI-CONNECT.

PURPOSE: Incidence, prevalence, and survival are population-based statistics describing cancer burden. The National Cancer Institute's (NCI) Comprehensive Oncology Network Evaluating Rare CNS Tumors (NCI-CONNECT) specializes in tumor biology and outcomes for 12 rare CNS tumor types selected for their importance in adults, research interest, or potential for targeted treatment. The aim of this study was to update incidence, prevalence, and survival statistics for these tumors. METHODS: The Central Brain Tumor Registry of the United States (CBTRUS) database, a combined dataset of Centers for Disease Control and Prevention's (CDC) National Program of Cancer Registries (NPCR) and NCI's Surveillance, Epidemiology and End Results (SEER) data, was used to calculate average annual age-adjusted incidence rates (AAAIR) per 100,000 population overall and by sex, race-ethnicity, and age for diagnosis years 2008-2019. Incidence time trends were calculated for diagnosis years 2004-2019. NPCR data were used to calculate relative survival rates. Point prevalence on December 31, 2019 was estimated using annual age-specific incidence and survival. RESULTS: AAAIR was 1.47 per 100,000 for these tumors combined, with highest incidence in ependymomas (AAAIR = 0.41/100,000). Most tumor types were more common in males, adults (ages 40 + years) or children (ages < 15 years), and non-Hispanic White individuals. Ependymomas were the most prevalent tumor type (19,320 cases) followed by oligodendrogliomas (14,900 cases). Ependymomas had the highest five-year survival (90.6%) and primary CNS sarcomas the lowest (7.7%). CONCLUSIONS: These data provide means to measure the impact of clinical care and evaluate new therapies and the evolving histopathology definitions in rare CNS tumor types.

CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2016-2020.

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 CBTRUS 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 24.83 per 100,000 population (malignant AAAIR=6.94 and non-malignant AAAIR=17.88). This overall rate was higher in females compared to males (27.85 versus 21.62 per 100,000) and non-Hispanic persons compared to Hispanic persons (25.24 versus 22.61 per 100,000). Gliomas accounted for 26.3% of all tumors. The most commonly occurring malignant brain and other CNS histopathology was glioblastoma (14.2% of all tumors and 50.9% of all malignant tumors), and the most common predominantly non-malignant histopathology was meningioma (40.8% of all tumors and 56.2% of all non-malignant tumors). Glioblastomas were 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 6.13 per 100,000 population. There were 86,030 deaths attributed to malignant brain and other CNS tumors between 2016 and 2020. This represents an average annual mortality rate of 4.42 per 100,000 population and an average of 17,206 deaths per year. The five-year relative survival rate following diagnosis of a malignant brain and other CNS tumor was 35.7%, for a non-malignant brain and other CNS tumor the five-year relative survival rate was 91.8%.

Associations between urbanicity and spinal cord astrocytoma management and outcomes.

BACKGROUND: The management of spinal cord astrocytomas (SCAs) remains controversial and may include any combination of surgery, radiation, and chemotherapy. Factors such as urbanicity (metropolitan versus non-metropolitan residence) are shown to be associated with patterns of treatment and clinical outcomes in a variety of cancers, but the role urbanicity plays in SCA treatment remains unknown. METHODS: The Central Brain Tumor Registry of the United States (CBTRUS) analytic dataset, which combines data from CDC's National Program of Cancer Registries (NPCR) and NCI's Surveillance, Epidemiology, and End Results Programs, was used to identify individuals with SCAs between 2004 and 2019. Individuals' county of residence was classified as metropolitan or non-metropolitan. Multivariable logistic regression models were used to evaluate associations between urbanicity and SCA. Cox proportional hazard models were constructed to assess the effect of urbanicity on survival using the NPCR survival dataset (2004-2018). RESULTS: 1697 metropolitan and 268 non-metropolitan SCA cases were identified. The cohorts did not differ in age or gender composition. The populations had different racial/ethnic compositions, with a higher White non-Hispanic population in the non-metropolitan cohort (86 % vs 66 %, p < 0.001) and a greater Black non-Hispanic population in the metropolitan cohort (14 % vs 9.9 %, p < 0.001). There were no significant differences in likelihood of receiving comprehensive treatment (OR=0.99, 95 % CI [0.56, 1.65], p = >0.9), or survival (hazard ratio [HR]=0.92, p = 0.4) when non-metropolitan and metropolitan cases were compared. In the metropolitan cohort, there were statistically significant differences in SCA treatment patterns when stratified by race/ethnicity (p = 0.002). CONCLUSIONS: Urbanicity does not significantly impact SCA management or survival. Race/ethnicity may be associated with likelihood of receiving certain SCA treatments in metropolitan communities.

The joint impacts of sex and race/ethnicity on incidence of grade 1 versus grades 2-3 meningioma across the lifespan.

Background: Previous research has identified older age, African-American race, and female sex as meningioma risk factors, but there is limited information on their joint effects, or on how these demographic factors vary across strata of tumor grade. Methods: The Central Brain Tumor Registry of the United States (CBTRUS) is a population-based registry combining data from the CDC's National Program of Cancer Registries and NCI's Surveillance, Epidemiology and End Results Program which covers ~100% of the U.S. population and aggregates incidence data on all primary malignant and nonmalignant brain tumors. These data were used to explore the joint impacts of sex and race/ethnicity on average annual age-adjusted incidence rates of meningioma. We calculated meningioma incidence rate ratios (IRRs) by sex and race/ethnicity, across strata of age and tumor grade. Results: Compared to individuals who are non-Hispanic White, individuals who are non-Hispanic Black had significantly higher risk of grade 1 (IRR = 1.23; 95% CI: 1.21-1.24) and grade 2-3 meningioma (IRR = 1.42; 95% CI: 1.37-1.47). The female-to-male IRR peaked in the fifth decade of life across all racial/ethnic groups and tumor grades, but was 3.59 (95% CI: 3.51-3.67) for WHO grade 1 meningioma and 1.74 (95% CI: 1.63-1.87) for WHO grade 2-3 meningioma. Conclusions: This study reveals the joint effects of sex and race/ethnicity on meningioma incidence throughout the lifespan and across strata of tumor grade, highlighting incidence disparities among females and African-Americans that may inform future strategies for tumor interception.

Complete prevalence of primary malignant and nonmalignant brain tumors in comparison to other cancers in the United States.

BACKGROUND: Primary brain tumors (BTs) are rare, but cause morbidity and mortality disproportionately to their incidence. Prevalence estimates population-level cancer burdens at a specified time. This study estimates the prevalence of malignant and non-malignant BTs in comparison to other cancers. METHODS: Incidence data were obtained from the Central Brain Tumor Registry of the United States (2000-2019, varying), a combined data set including the Center for Disease Control and Prevention's National Program of Cancer Registries and National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program. Incidence of non-BT cancers were obtained from the United States Cancer Statistics (2001-2019). Incidence and survival estimates for all cancers were obtained from SEER (1975-2018). Complete prevalence as of December 31, 2019, was estimated using prevEst. Estimates were generated overall for non-BT cancers, by BT histopathology, age groups at prevalence (0-14, 15-39, 40-64, 65+ years), and sex. RESULTS: We estimated 1,323,121 individuals with a diagnosis of BTs at the date of prevalence. The majority of BT cases had non-malignant tumors (85.3%). Among all cancers, BTs were the most prevalent cancer type among those ages 15 to 39 years, second among those ages 0 to 14 years, and in the top five among those ages 40 to 64 years. The plurality of prevalent cases (43.5%) occurred among those ages 65+ years. Overall, females had a higher prevalence of BTs than males, with an overall female:male prevalence ratio of 1.68. CONCLUSIONS: BTs contribute significantly to the cancer burden in the United States, particularly among those younger than age 65 years. Understanding complete prevalence is crucial for monitoring cancer burden to inform clinical research and public policy.

CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2015-2019.

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%.

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.

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.