Carol Kruchko

Bio: Carol Kruchko is an academic researcher from Case Western Reserve University. The author has contributed to research in topics: Population & Medicine. The author has an hindex of 27, co-authored 84 publications receiving 10946 citations.

CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2007-2011.

Abstract: The Central Brain Tumor Registry of the United States (CBTRUS), in collaboration with the Centers for Disease Control (CDC) and National Cancer Institute (NCI), 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 (malignant and non-malignant) and supersedes all previous CBTRUS reports in terms of completeness and accuracy. All rates (incidence and mortality) 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 23.79 (Malignant AAAIR=7.08, non-Malignant AAAIR=16.71). This rate was higher in females compared to males (26.31 versus 21.09), Blacks compared to Whites (23.88 versus 23.83), and non-Hispanics compared to Hispanics (24.23 versus 21.48). The most commonly occurring malignant brain and other CNS tumor was glioblastoma (14.5% of all tumors), and the most common non-malignant tumor was meningioma (38.3% 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 6.14. An estimated 83,830 new cases of malignant and non-malignant brain and other CNS tumors are expected to be diagnosed in the US in 2020 (24,970 malignant and 58,860 non-malignant). There were 81,246 deaths attributed to malignant brain and other CNS tumors between 2013 and 2017. This represents an average annual mortality rate of 4.42. The 5-year relative survival rate following diagnosis of a malignant brain and other CNS tumor was 23.5% and for a non-malignant brain and other CNS tumor was 82.4%.

Brain tumor epidemiology: consensus from the Brain Tumor Epidemiology Consortium.

Abstract: Epidemiologists in the Brain Tumor Epidemiology Consortium (BTEC) have prioritized areas for further research. Although many risk factors have been examined over the past several decades, there are few consistent findings, possibly because of small sample sizes in individual studies and differences between studies in patients, tumor types, and methods of classification. Individual studies generally have lacked samples of sufficient size to examine interactions. A major priority based on available evidence and technologies includes expanding research in genetics and molecular epidemiology of brain tumors. BTEC has taken an active role in promoting understudied groups, such as pediatric brain tumors; the etiology of rare glioma subtypes, such as oligodendroglioma; and meningioma, which, although it is not uncommon, has only recently been registered systematically in the United States. There also is a pressing need for more researchers, especially junior investigators, to study brain tumor epidemiology. However, relatively poor funding for brain tumor research has made it difficult to encourage careers in this area. In this report, BTEC epidemiologists reviewed the group's consensus on the current state of scientific findings, and they present a consensus on research priorities to identify which important areas the science should move to address.

Alex's Lemonade stand foundation infant and childhood primary brain and central nervous system tumors diagnosed in the United States in 2007-2011

Abstract: The CBTRUS Statistical Report: Alex's 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.

Adult Glioma Incidence and Survival by Race or Ethnicity in the United States From 2000 to 2014.

Abstract: Importance Glioma is the most commonly occurring malignant brain tumor in the United States, and its incidence varies by age, sex, and race or ethnicity. Survival after brain tumor diagnosis has been shown to vary by these factors. Objective To quantify the differences in incidence and survival rates of glioma in adults by race or ethnicity. Design, Setting, and Participants This population-based study obtained incidence data from the Central Brain Tumor Registry of the United States and survival data from Surveillance, Epidemiology, and End Results registries, covering the period January 1, 2000, to December 31, 2014. Average annual age-adjusted incidence rates with 95% CIs were generated by glioma histologic groups, race, Hispanic ethnicity, sex, and age groups. One-year and 5-year relative survival rates were generated by glioma histologic groups, race, Hispanic ethnicity, and insurance status. The analysis included 244 808 patients with glioma diagnosed in adults aged 18 years or older. Data were collected from January 1, 2000, to December 31, 2014. Data analysis took place from December 11, 2017, to January 31, 2018. Results Overall, 244 808 patients with glioma were analyzed. Of these, 150 631 (61.5%) were glioblastomas, 46 002 (18.8%) were non-glioblastoma astrocytomas, 26 068 (10.7%) were oligodendroglial tumors, 8816 (3.6%) were ependymomas, and 13 291 (5.4%) were other glioma diagnoses in adults. The data set included 137 733 males (56.3%) and 107 075 (43.7%) females. There were 204 580 non-Hispanic whites (83.6%), 17 321 Hispanic whites (7.08%), 14 566 blacks (6.0%), 1070 American Indians or Alaska Natives (0.4%), and 5947 Asians or Pacific Islanders (2.4%). Incidences of glioblastoma, non-glioblastoma astrocytoma, and oligodendroglial tumors were higher among non-Hispanic whites than among Hispanic whites (30% lower overall), blacks (52% lower overall), American Indians or Alaska Natives (58% lower overall), or Asians or Pacific Islanders (52% lower overall). Most tumors were more common in males than in females across all race or ethnicity groups, with the great difference in glioblastoma where the incidence was 60% higher overall in males. Most tumors (193 329 [79.9%]) occurred in those aged 45 years or older, with differences in incidence by race or ethnicity appearing in all age groups. Survival after diagnosis of glioma of different subtypes was generally comparable among Hispanic whites, blacks, and Asians or Pacific Islanders but was lower among non-Hispanic whites for many tumor types, including glioblastoma, irrespective of treatment type. Conclusions and Relevance Incidence of glioma and 1-year and 5-year survival rates after diagnosis vary significantly by race or ethnicity, with non-Hispanic whites having higher incidence and lower survival rates compared with individuals of other racial or ethnic groups. These findings can inform future discovery of risk factors and reveal unaddressed health disparities.

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

Abstract: Brain and central nervous system (CNS) tumors found in adolescents and young adults (AYA) are a distinct group of tumors that pose challenges not only to treatment but also to reporting. Overall, cancer that occurs in this age group is biologically distinct from those that occur in both younger and older age groups1,2 posing significant challenges for clinicians. The most commonly diagnosed histologies in AYA vary from those in both children age (0-14 years), and older adults (40+ years).3,4 Prognosis and expected survival also varies between younger and older adults, with those who are diagnosed with brain and CNS tumors at younger ages having significantly longer survival. Despite this survival advantage, recent analyses have reported that while cancer survival has been improving overall, AYA have not experienced these same increases in survival and in some cases may have worse survival than those cancers diagnosed in persons over age 40 years.5 This report provides an in depth analyses of the epidemiology of brain and CNS tumors in adolescents and young adults in the United States (US), and is the first report to provide histology-specific statistics in this population for both malignant and non-malignant brain and other CNS tumors. In 2006, the National Institutes of Health, the National Cancer Institute (NCI) and the LiveStrong Young Adult Alliance conducted a Progress Review Group to investigate AYA Oncology entitled Research and care imperatives for adolescents and young adults with cancer: A Report of the Adolescent and Young Adult Oncology Progress Review Group. This group established the standard age range for the AYA group as 15-39 years. This is the age range used by the Surveillance Epidemiology and End Results (SEER) program of the NCI, as well as in the 2015 CBTRUS Statistical Report.3,6 Brain tumors and other CNS tumors are less common in AYA than in older adults, but they have a higher incidence than brain tumors in children (age 0-14 years).3 Non-malignant tumors are significantly more common in AYA than children (Average annual age adjusted incidence in age 15-39 years: 6.17 per 100,000; age 0-14 years: 0.79 per 100,000), while malignant tumors are slightly more common in those age 0-14 years (Average annual age adjusted incidence in 15-39 years old: 3.26 per 100,000; 0-14 years old: 3.73 per 100,000). While a rare cancer overall, brain and CNS tumors are among the most common cancers occurring in this age group (4.4% of all cancers in those age 15-39 years as compared to 32.4% in children age 0-14 years, and 2.2% of cancers in adults age 40+ years).3,4,7 Malignant brain and CNS tumors are the 11th most common cancer and the 3rd most common cause of cancer death7,8 in the AYA population. Incidence rates of brain tumors overall as well as specific histologies vary significantly by age. It is, therefore, important to provide an accurate statistical assessment of brain and other CNS tumors in the adolescent and young adult population to better understand their impact on the US population and to serve as a reference for afflicted individuals, for researchers investigating new therapies and for clinicians treating patients.

CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2007-2011.

Abstract: The Central Brain Tumor Registry of the United States (CBTRUS), in collaboration with the Centers for Disease Control (CDC) and National Cancer Institute (NCI), 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 (malignant and non-malignant) and supersedes all previous CBTRUS reports in terms of completeness and accuracy. All rates (incidence and mortality) 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 23.79 (Malignant AAAIR=7.08, non-Malignant AAAIR=16.71). This rate was higher in females compared to males (26.31 versus 21.09), Blacks compared to Whites (23.88 versus 23.83), and non-Hispanics compared to Hispanics (24.23 versus 21.48). The most commonly occurring malignant brain and other CNS tumor was glioblastoma (14.5% of all tumors), and the most common non-malignant tumor was meningioma (38.3% 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 6.14. An estimated 83,830 new cases of malignant and non-malignant brain and other CNS tumors are expected to be diagnosed in the US in 2020 (24,970 malignant and 58,860 non-malignant). There were 81,246 deaths attributed to malignant brain and other CNS tumors between 2013 and 2017. This represents an average annual mortality rate of 4.42. The 5-year relative survival rate following diagnosis of a malignant brain and other CNS tumor was 23.5% and for a non-malignant brain and other CNS tumor was 82.4%.

The Molecular Signatures Database Hallmark Gene Set Collection

Abstract: The Molecular Signatures Database (MSigDB) is one of the most widely used and comprehensive databases of gene sets for performing gene set enrichment analysis. Since its creation, MSigDB has grown beyond its roots in metabolic disease and cancer to include >10,000 gene sets. These better represent a wider range of biological processes and diseases, but the utility of the database is reduced by increased redundancy across, and heterogeneity within, gene sets. To address this challenge, here we use a combination of automated approaches and expert curation to develop a collection of “hallmark” gene sets as part of MSigDB. Each hallmark in this collection consists of a “refined” gene set, derived from multiple “founder” sets, that conveys a specific biological state or process and displays coherent expression. The hallmarks effectively summarize most of the relevant information of the original founder sets and, by reducing both variation and redundancy, provide more refined and concise inputs for gene set enrichment analysis.

The somatic genomic landscape of glioblastoma

Abstract: We describe the landscape of somatic genomic alterations based on multidimensional and comprehensive characterization of more than 500 glioblastoma tumors (GBMs). We identify several novel mutated genes as well as complex rearrangements of signature receptors, including EGFR and PDGFRA. TERT promoter mutations are shown to correlate with elevated mRNA expression, supporting a role in telomerase reactivation. Correlative analyses confirm that the survival advantage of the proneural subtype is conferred by the G-CIMP phenotype, and MGMT DNA methylation may be a predictive biomarker for treatment response only in classical subtype GBM. Integrative analysis of genomic and proteomic profiles challenges the notion of therapeutic inhibition of a pathway as an alternative to inhibition of the target itself. These data will facilitate the discovery of therapeutic and diagnostic target candidates, the validation of research and clinical observations and the generation of unanticipated hypotheses that can advance our molecular understanding of this lethal cancer.

Comprehensive, Integrative Genomic Analysis of Diffuse Lower-Grade Gliomas.

Abstract: BACKGROUND: Diffuse low-grade and intermediate-grade gliomas (which together make up the lower-grade gliomas, World Health Organization grades II and III) have highly variable clinical behavior that is not adequately predicted on the basis of histologic class. Some are indolent; others quickly progress to glioblastoma. The uncertainty is compounded by interobserver variability in histologic diagnosis. Mutations in IDH, TP53, and ATRX and codeletion of chromosome arms 1p and 19q (1p/19q codeletion) have been implicated as clinically relevant markers of lower-grade gliomas. METHODS: We performed genomewide analyses of 293 lower-grade gliomas from adults, incorporating exome sequence, DNA copy number, DNA methylation, messenger RNA expression, microRNA expression, and targeted protein expression. These data were integrated and tested for correlation with clinical outcomes. RESULTS: Unsupervised clustering of mutations and data from RNA, DNA-copy-number, and DNA-methylation platforms uncovered concordant classification of three robust, nonoverlapping, prognostically significant subtypes of lower-grade glioma that were captured more accurately by IDH, 1p/19q, and TP53 status than by histologic class. Patients who had lower-grade gliomas with an IDH mutation and 1p/19q codeletion had the most favorable clinical outcomes. Their gliomas harbored mutations in CIC, FUBP1, NOTCH1, and the TERT promoter. Nearly all lower-grade gliomas with IDH mutations and no 1p/19q codeletion had mutations in TP53 (94%) and ATRX inactivation (86%). The large majority of lower-grade gliomas without an IDH mutation had genomic aberrations and clinical behavior strikingly similar to those found in primary glioblastoma. CONCLUSIONS: The integration of genomewide data from multiple platforms delineated three molecular classes of lower-grade gliomas that were more concordant with IDH, 1p/19q, and TP53 status than with histologic class. Lower-grade gliomas with an IDH mutation either had 1p/19q codeletion or carried a TP53 mutation. Most lower-grade gliomas without an IDH mutation were molecularly and clinically similar to glioblastoma. (Funded by the National Institutes of Health.)