Quinn T. Ostrom

CBTRUS Statistical Report: Primary Brain and Central Nervous System Tumors Diagnosed in the United States in 2007–2011

The Central Brain Tumor Registry of the United States (CBTRUS), in collaboration with the Centers for Disease Control and Prevention and 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 23.41 (Malignant AAAIR = 7.08, non-Malignant AAAIR = 16.33). This rate was higher in females compared to males (25.84 versus 20.82), Whites compared to Blacks (23.50 versus 23.34), and non-Hispanics compared to Hispanics (23.84 versus 21.28). The most commonly occurring malignant brain and other CNS tumor was glioblastoma (14.6% of all tumors), and the most common non-malignant tumor was meningioma (37.6% of all 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 6.06. An estimated 86,010 new cases of malignant and non-malignant brain and other CNS tumors are expected to be diagnosed in the US in 2019 (25,510 malignant and 60,490 non-malignant). There were 79,718 deaths attributed to malignant brain and other CNS tumors between 2012 and 2016. This represents an average annual mortality rate of 4.42. The five-year relative survival rate following diagnosis of a malignant brain and other CNS tumor was 35.8%, and the five-year relative survival rate following diagnosis of a non-malignant brain and other CNS tumors was 91.5%.

Epidemiologic and Molecular Prognostic Review of Glioblastoma

Glioblastoma multiforme (GBM) is the most common and aggressive primary central nervous system malignancy with a median survival of 15 months. The average incidence rate of GBM is 3.19/100,000 population, and the median age of diagnosis is 64 years. Incidence is higher in men and individuals of white race and non-Hispanic ethnicity. Many genetic and environmental factors have been studied in GBM, but the majority are sporadic, and no risk factor accounting for a large proportion of GBMs has been identified. However, several favorable clinical prognostic factors are identified, including younger age at diagnosis, cerebellar location, high performance status, and maximal tumor resection. GBMs comprise of primary and secondary subtypes, which evolve through different genetic pathways, affect patients at different ages, and have differences in outcomes. We report the current epidemiology of GBM with new data from the Central Brain Tumor Registry of the United States 2006 to 2010 as well as demonstrate and discuss trends in incidence and survival. We also provide a concise review on molecular markers in GBM that have helped distinguish biologically similar subtypes of GBM and have prognostic and predictive value. Cancer Epidemiol Biomarkers Prev; 23(10); 1985–96. ©2014 AACR.

Alex's Lemonade Stand Foundation Infant and Childhood Primary Brain and Central Nervous System Tumors Diagnosed in the United States in 2007-2011

The CBTRUS Statistical Report: Alexs Lemonade Stand Foundation Infant and Childhood Primary Brain and Central Nervous System Tumors Diagnosed in the United States in 2007–2011 comprehensively describes the current population-based incidence of primary malignant and non-malignant brain and CNS tumors in children ages 0–14 years, collected and reported by central cancer registries covering approximately 99.8% of the United States population (for 2011 only, data were available for 50 out of 51 registries). Overall, brain and CNS tumors are the most common solid tumor, the most common cancer, and the most common cause of cancer death in infants and children 0–14 years. This report aims to serve as a useful resource for researchers, clinicians, patients, and families.

Epidemiology of gliomas.

Gliomas are the most common type of primary intracranial tumors. Some glioma subtypes cause significant mortality and morbidity that are disproportionate to their relatively rare incidence. A very small proportion of glioma cases can be attributed to inherited genetic disorders. Many potential risk factors for glioma have been studied to date, but few provide explanation for the number of brain tumors identified. The most significant of these factors includes increased risk due to exposure to ionizing radiation, and decreased risk with history of allergy or atopic disease. The potential effect of exposure to cellular phones has been studied extensively, but the results remain inconclusive. Recent genomic analyses, using the genome-wide association study (GWAS) design, have identified several inherited risk variants that are associated with increased glioma risk. The following chapter provides an overview of the current state of research in the epidemiology of intracranial glioma.

Current State of Our Knowledge on Brain Tumor Epidemiology

The overall incidence of brain tumors for benign and malignant tumors combined is 18.71 per 100,000 person-years; 11.52 per 100,000 person-years for benign tumors and 7.19 per 100,000 person-years for malignant tumors. Incidence, response to treatment, and survival after diagnosis vary greatly by age at diagnosis, histologic type of tumor, and degree of neurologic compromise. The only established environmental risk factor for brain tumors is ionizing radiation exposure. Exposure to radiofrequency electromagnetic fields via cell phone use has gained a lot of attention as a potential risk factor for brain tumor development. However, studies have been inconsistent and inconclusive due to systematic differences in study designs and difficulty of accurately measuring cell phone use. Recently studies of genetic risk factors for brain tumors have expanded to genome-wide association studies. In addition, genome-wide studies of somatic genetic changes in tumors show correlation with clinical outcomes.

Childhood Brain Tumor Epidemiology: A Brain Tumor Epidemiology Consortium Review

Childhood brain tumors are the most common pediatric solid tumor and include several histologic subtypes. Although progress has been made in improving survival rates for some subtypes, understanding of risk factors for childhood brain tumors remains limited to a few genetic syndromes and ionizing radiation to the head and neck. In this report, we review descriptive and analytical epidemiology childhood brain tumor studies from the past decade and highlight priority areas for future epidemiology investigations and methodological work that is needed to advance our understanding of childhood brain tumor causes. Specifically, we summarize the results of a review of studies published since 2004 that have analyzed incidence and survival in different international regions and that have examined potential genetic, immune system, developmental and birth characteristics, and environmental risk factors. Cancer Epidemiol Biomarkers Prev; 23(12); 2716–36. ©2014 AACR.

American Brain Tumor Association Adolescent and Young Adult Primary Brain and Central Nervous System Tumors Diagnosed in the United States in 2008-2012.

Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH USA Central Brain Tumor Registry of the United States, Hinsdale, IL USA Department of Pediatric Hematology-Oncology, Rainbow Babies and Children s Hospital, Cleveland, OH USA Division of Hematology, Oncology and BMT, Nationwide Children’s Hospital and The Ohio State University, Columbus, OH USA School of Public Health, University of Memphis, Memphis, TN USA Keck School of Medicine, University of Southern California, Los Angeles, CA USA Department of Pediatric Hematology and Oncology, Cleveland Clinic Children’s Hospital, Cleveland, OH USA Solon High School, Solon, OH USA

Trends in central nervous system tumor incidence relative to other common cancers in adults, adolescents, and children in the United States, 2000 to 2010.

Time trends in cancer incidence rates (IR) are important to measure the changing burden of cancer on a population over time. The overall IR of cancer in the United States is declining. Although central nervous system tumors (CNST) are rare, they contribute disproportionately to mortality and morbidity. In this analysis, the authors examined trends in the incidence of the most common cancers and CNST between 2000 and 2010.

Descriptive epidemiology of pituitary tumors in the United States, 2004-2009.

OBJECT Pituitary tumors are abnormal growths that develop in the pituitary gland. The Central Brain Tumor Registry of the United States (CBTRUS) contains the largest aggregation of population-based data on the incidence of primary CNS tumors in the US. These data were used to determine the incidence of tumors of the pituitary and associated trends between 2004 and 2009. METHODS Using incidence data from 49 population-based state cancer registries, 2004-2009, age-adjusted incidence rates per 100,000 population for pituitary tumors with ICD-O-3 (International Classification of Diseases for Oncology, Third Edition) histology codes 8040, 8140, 8146, 8246, 8260, 8270, 8271, 8272, 8280, 8281, 8290, 8300, 8310, 8323, 9492 (site C75.1 only), and 9582 were calculated overall and by patient sex, race, Hispanic ethnicity, and age at diagnosis. Corresponding annual percent change (APC) scores and 95% confidence intervals were also calculated using Joinpoint to characterize trends in incidence rates over time. Diagnostic confirmation by subregion of the US was also examined. The overall annual incidence rate increased from 2.52 (95% CI 2.46-2.58) in 2004 to 3.13 (95% CI 3.07-3.20) in 2009. Associated time trend yielded an APC of 4.25% (95% CI 2.91%-5.61%). When stratifying by patient sex, the annual incidence rate increased from 2.42 (95% CI 2.33-2.50) to 2.94 (95% CI 2.85-3.03) in men and 2.70 (95% CI 2.62-2.79) to 3.40 (95% CI 3.31-3.49) in women, with APCs of 4.35% (95% CI 3.21%-5.51%) and 4.34% (95% CI 2.23%-6.49%), respectively. When stratifying by race, the annual incidence rate increased from 2.31 (95% CI 2.25-2.37) to 2.81 (95% CI 2.74-2.88) in whites, 3.99 (95% CI 3.77-4.23) to 5.31 (95% CI 5.06-5.56) in blacks, 1.77 (95% CI 1.26-2.42) to 2.52 (95% CI 1.96-3.19) in American Indians or Alaska Natives, and 1.86 (95% CI 1.62-2.13) to 2.03 (95% CI 1.80-2.28) in Asians or Pacific Islanders, with APCs of 3.91% (95% CI 2.88%-4.95%), 5.25% (95% CI 3.19%-7.36%), 5.31% (95% CI -0.11% to 11.03%), and 2.40% (95% CI -3.20% to 8.31%), respectively. When stratifying by Hispanic ethnicity, the annual incidence rate increased from 2.46 (95% CI 2.40-2.52) to 3.03 (95% CI 2.97-3.10) in non-Hispanics and 3.12 (95% CI 2.91-3.34) to 4.01 (95% CI 3.80-4.24) in Hispanics, with APCs of 4.15% (95% CI 2.67%-5.65%) and 5.01% (95% CI 4.42%-5.60%), respectively. When stratifying by age at diagnosis, the incidence of pituitary tumor was highest for those 65-74 years old and lowest for those 15-24 years old, with corresponding overall age-adjusted incidence rates of 6.39 (95% CI 6.24-6.54) and 1.56 (95% CI 1.51-1.61), respectively. CONCLUSIONS In this large patient cohort, the incidence of pituitary tumors reported between 2004 and 2009 was found to increase. Possible explanations for this increase include changes in documentation, changes in the diagnosis and registration of these tumors, improved diagnostics, improved data collection, increased awareness of pituitary diseases among physicians and the public, longer life expectancies, and/or an actual increase in the incidence of these tumors in the US population.

Genome-wide association study of glioma subtypes identifies specific differences in genetic susceptibility to glioblastoma and non-glioblastoma tumors.

Genome-wide association studies (GWAS) have transformed our understanding of glioma susceptibility, but individual studies have had limited power to identify risk loci. We performed a meta-analysis of existing GWAS and two new GWAS, which totaled 12,496 cases and 18,190 controls. We identified five new loci for glioblastoma (GBM) at 1p31.3 (rs12752552; P = 2.04 × 10−9, odds ratio (OR) = 1.22), 11q14.1 (rs11233250; P = 9.95 × 10−10, OR = 1.24), 16p13.3 (rs2562152; P = 1.93 × 10−8, OR = 1.21), 16q12.1 (rs10852606; P = 1.29 × 10−11, OR = 1.18) and 22q13.1 (rs2235573; P = 1.76 × 10−10, OR = 1.15), as well as eight loci for non-GBM tumors at 1q32.1 (rs4252707; P = 3.34 × 10−9, OR = 1.19), 1q44 (rs12076373; P = 2.63 × 10−10, OR = 1.23), 2q33.3 (rs7572263; P = 2.18 × 10−10, OR = 1.20), 3p14.1 (rs11706832; P = 7.66 × 10−9, OR = 1.15), 10q24.33 (rs11598018; P = 3.39 × 10−8, OR = 1.14), 11q21 (rs7107785; P = 3.87 × 10−10, OR = 1.16), 14q12 (rs10131032; P = 5.07 × 10−11, OR = 1.33) and 16p13.3 (rs3751667; P = 2.61 × 10−9, OR = 1.18). These data substantiate that genetic susceptibility to GBM and non-GBM tumors are highly distinct, which likely reflects different etiology.