Barnholtz‐Sloan, Jill S.

Abstract 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.

Abstract INTRODUCTION The NIH Revitalization Act, implemented 29 years ago, set to improve the representation of women and minorities in clinical trials. In this study, we investigate the progress made in neuro-oncology in all phase therapeutic clinical trials for neuro-epithelial central nervous system tumors in comparison to their demographic-specific age-adjusted disease incidence and mortality. METHODS Registry study of all published clinical trials for World Health Organization (WHO) defined neuro-epithelial CNS tumors between January 2000 and December 2019. Study participants for trials were obtained from PubMed and ClinicalTrials.gov. Population-based data from the CBTRUS for incidence analyses. SEER-18 Incidence-Based Mortality data was used for mortality analysis. Descriptive statistics, Fisher exact, and c2 tests were used to analyze the data. RESULTS Among 662 published clinical trial articles representing 49, 907 accrued participants, 62.5% of study participants were men and 37.5% were women (P< 0.0001) representing a mortality specific over-accrual for men (P= 0.001) and under-accrual for women (P= 0.001). Whites, Asians, Blacks, and Hispanics represented 91.7%, 1.5%, 2.6%, and 1.7% of trial participants. Compared with their US cancer mortality, Blacks (47% of expected mortality, P=.008), Hispanics (17% of expected mortality, P< .001) and Asians (33% of expected mortality, P< .001) were underrepresented compared with Whites (114% of expected mortality, P< .001). CONCLUSIONS Nearly 30 years since the Revitalization Act, minorities and women are consistently underrepresented when compared with their demographic-specific incidence and mortality in therapeutic clinical trials for neuroepithelial tumors. This study provides a framework for investigating cancer clinical trial accrual and offers guidance regarding workforce factors associated with enrollment of vulnerable patients.

AbstractBackgroundWith increasing molecular analyses of meningiomas, there is a need to harmonize language used to capture clinical data across centers to ensure that molecular alterations are appropriately linked to clinical variables of interest. Here the International Consortium on Meningiomas presents a set of core and supplemental meningioma-specific common data elements (CDEs) to facilitate comparative and pooled analyses.MethodsThe generation of CDEs followed the 4-phase process similar to other National Institute of Neurological Disorders and Stroke (NINDS) CDE projects: discovery, internal validation, external validation, and distribution.ResultsThe CDEs were organized into patient- and tumor-level modules. In total, 17 core CDEs (10 patient level and 7 tumor level) as well as 14 supplemental CDEs (7 patient level and 7 tumor level) were defined and described. These CDEs are now made publicly available for dissemination and adoption.ConclusionsCDEs provide a framework for discussion in the neuro-oncology community that will facilitate data-sharing for collaborative research projects and aid in developing a common language for comparative and pooled analyses. The meningioma-specific CDEs presented here are intended to be dynamic parameters that evolve with time and The Consortium welcomes international feedback for further refinement and implementation of these CDEs.

Abstract BACKGROUND With increasing studies reporting on the molecular profiling of meningiomas, there is a need to harmonize language used to capture clinical data across centers to ensure that molecular alterations are appropriately linked to clinical variables of interest. Here the International Consortium on Meningiomas presents a final set of core and supplemental meningioma-specific Common Data Elements (CDEs) to facilitate comparative and pooled analyses. METHODS The generation of CDEs followed the four-phase process similar to other National Institute of Neurological Disorders and Stroke (NINDS) CDE projects: development/discovery based on data from published and ongoing meningioma trials, internal validation, external validation including presentation of our data form at the Society for Neuro-Oncology previously, and distribution. RESULTS We developed a set of CDEs organized into patient- and tumor-level modules. In total, the Consortium identified 16 core CDEs (9 patient-level and 7-tumour-level) e.g. age at index surgery, diagnosis of neurofibromatosis, prior chemotherapy or radiation, tumor location, extent of resection, recurrence, etc. An additional 15 supplemental CDEs were defined and described (8 patient-level and 7 tumour-level) e.g. race, cause of death, multiple tumors, tumor size, Simpson grade, second intervention, etc. These CDES are now made publicly available for dissemination and adoption. We also present a narrative review and analysis of recent and ongoing meningioma trials. CONCLUSIONS These CDEs provide a framework for discussion in the neuro-oncology community that will facilitating data sharing for collaborative research projects and aid in developing a common language for comparative and pooled analyses. The CDEs are intended to be dynamic parameters that evolve with time and The Consortium welcomes international feedback for further refinement and implementation of these CDEs.

Abstract Glioblastomas are the most common form of malignant primary brain tumor and an important cause of morbidity and mortality. In recent years there have been important advances in understanding the molecular pathogenesis and biology of these tumors, but this has not translated into significantly improved outcomes for patients. In this consensus review from the Society for Neuro-Oncology (SNO) and the European Association of Neuro-Oncology (EANO), the current management of isocitrate dehydrogenase wildtype (IDHwt) glioblastomas will be discussed. In addition, novel therapies such as targeted molecular therapies, agents targeting DNA damage response and metabolism, immunotherapies, and viral therapies will be reviewed, as well as the current challenges and future directions for research.

Abstract With increasing epidemiological and biological studies on meningiomas, standardized clinical data capture will be necessary to interpret results across studies and to translate them to clinical practice. To meet this need for consistent clinical data capture, the International Consortium on Meningioma, has developed a set of common data elements (CDEs), to be used across clinical and biological research. Building from terminology used in clinical practice and ongoing studies, we used a consensus-of-experts approach to arrive at a set of standardized and vetted data elements. Areas of focus include patient characteristics, patient history, radiological and intra-operative description, histological diagnosis and molecular testing, non-surgical interventions, and surveillance. These data elements are implemented in Research Electronic Data Capture (REDCap) forms. With REDCap implementation, components of the CDE set can be selected and instituted in a local REDCap instance for efficient study start-up. The scope of the current CDE set focuses on surgically treated meningioma. However, modular forms provide flexibility and to allow the scope to be expanded to include non-surgically treated meningioma. Dissemination plans are underway to introduce the CDEs to neuro-oncology researchers and clinicians through publication and presentations, where feedback will be solicited. Adoption of CDEs for research will improve consistency and interpretability across studies, expediting research in this frequently occurring tumor.

Abstract Background The etiological basis of glioma is poorly understood. We have used genetic markers in a Mendelian Randomisation (MR) framework to examine if lifestyle, cardiometabolic and inflammatory factors influence the risk of glioma. This methodology reduces bias from confounding and is not affected by reverse causation. Methods We identified genetic instruments for 37 potentially modifiable risk factors and evaluated their association with glioma risk using data from a genome-wide association study of 12,488 glioma patients and 18,169 controls. We used the estimated odds ratio of glioma associated with each of the genetically defined traits to infer evidence for a causal relationship with the following exposures: lifestyle and dietary factors (height, plasma IGF-1, blood carnitine, blood methionine, blood selenium, blood zinc, circulating adiponectin, circulating carotenoids, iron status, serum calcium, vitamin [A1, B12, B6, E and 25-hydroxyvitamin D], fatty acids levels [mono-unsaturated, omega-3 and omega-6] and circulating fetuin-A); cardiometabolic factors (birth weight, HDL cholesterol, LDL cholesterol, total cholesterol, total triglycerides, basal metabolic rate, body fat percentage, body mass index, fasting glucose, fasting proinsulin, HbA1C levels, diastolic and systolic blood pressure, waist circumference, waist-to-hip ratio) were included; inflammatory factors (C-reactive protein (CRP), plasma IL-6 sRa and serum IgE). Results After correction for the testing of multiple potential risk factors and excluding associations driven by one single nucleotide polymorphism (SNP) no significant association with glioma risk was observed (i.e. PCorrected > 0.05). Conclusions This study did not provide evidence supporting any of the 37 factors examined as having a significant influence on glioma risk.