Engagement Methods in Brain Tumor Genomic Research: Multimethod Comparative Study.

Background: Engaging patients, care partners, and others in research planning and conduct is increasingly valued. However, identifying the most effective ways to do so remains a challenge.

Objective: This study aimed to evaluate participation and participant experience using 3 engagement methods with the Low-Grade Glioma (LGG) Registry's Optimizing Engagement in Discovery of Molecular Evolution of Low-Grade Glioma (OPTIMUM) project, part of the National Cancer Institute's Participant Engagement and Cancer Genome Sequencing Network.

Tumor-initiating genetics and therapy drive divergent molecular evolution in IDH-mutant gliomas.

Astrocytomas and oligodendrogliomas are slow-growing and treatment-sensitive IDH-mutant gliomas diagnosed at ages 30-50. Local tumor regrowth and treatment resistance is inevitable resulting in 3-10 year astrocytoma and up to >20 years oligodendroglioma survival. We sought to identify genetic changes associated with tumor evolution in response to therapy through multi-timepoint whole-genome/whole-exome sequencing of 206 IDH-mutant glioma patient samples collected through the Glioma Longitudinal Analysis (GLASS) Consortium.

Distribution of copy number alterations and impact of chromosome arm call thresholds for meningioma.

Chromosome-arm copy number alterations (CNAs) are an important component of cancer molecular classifiers. CNAs are often translated into binary chromosome arm calls (arm gain/loss) using an arm call threshold before integration into classification schemes. However, substantial variability exists in thresholds used to define arm calls from CNA data.

Optimizing participant and community engagement in cancer genomic sequencing research.

Purpose: We describe strategies implemented across research centers of the Participant Engagement and Cancer Genome Sequencing (PE-CGS) Network to optimize engagement of participants and communities in cancer genomics research. We also present consensus definitions of engagement and engagement optimization, informed by our shared experiences in the Network.

Methods: Key informant interviews and a document review identified engagement and optimization strategies across PE-CGS research centers.

Years of life lost due to central nervous system tumor subtypes in the United States.

Background: Years of Life Lost (YLL) is a disease burden measure quantifying the number of years lost due to premature mortality for a given disease. The present study sought to assess YLL for primary brain and other central nervous system (CNS) tumor histopathologies in the United States.

Methods: Mortality, incidence, and life expectancy data for mortalities occurring in 2018 were obtained from the National Vital Statistics System and the National Program of Cancer Registries.

Glioma mutational signatures associated with haloalkane exposure are enriched in firefighters.

Background: Glioma is the most common malignant primary brain tumor and is associated with significant morbidity and mortality. Modifiable risk factors remain unidentified. New advances in exposure assessment, genomic analyses, and statistical techniques permit more accurate evaluation of glioma risk associated with exogenous occupational or environmental exposures.

Quality of life after surgery for lower grade gliomas.

Background: Few large studies have investigated quality of life (QOL) for adults diagnosed with lower grade glioma (LGG).

Methods: QOL was assessed for 320 adults with LGG (World Health Organization grade 2/3) enrolled in the International Low Grade Glioma Registry by using the Medical Outcomes Study 36-Item Short Form health survey. Data on symptoms were also collected.

A systematic review and individual participant data meta-analysis of gonadal steroid hormone receptors in meningioma.

Objective: The relationship between patient and meningioma characteristics and hormone receptors (HRs) of progesterone, estrogen, and androgen remains poorly defined despite literature suggesting that meningiomas are sensitive to gonadal steroid hormones. Therefore, the authors sought to collect and compare data on this topic by performing a systematic review and meta-analysis of reported studies of HR status in meningiomas.

Methods: A MEDLINE PubMed literature review conducted for articles published between January 1, 1951, and December 31, 2020, resulted in 634 unduplicated articles concerning meningiomas and HRs.

Priorities to Promote Participant Engagement in the Participant Engagement and Cancer Genome Sequencing (PE-CGS) Network.

Background: Engaging diverse populations in cancer genomics research is of critical importance and is a fundamental goal of the NCI Participant Engagement and Cancer Genome Sequencing (PE-CGS) Network. Established as part of the Cancer Moonshot, PE-CGS is a consortium of stakeholders including clinicians, scientists, genetic counselors, and representatives of potential study participants and their communities. Participant engagement is an ongoing, bidirectional, and mutually beneficial interaction between study participants and researchers.

Pleiotropic variation confers risk of meningioma and estrogen-mediated cancers.

Background: Risk of tumors of the breast, ovary, and meninges has been associated with hormonal factors and with one another. Genome-wide association studies (GWAS) identified a meningioma risk locus on 10p12 near previous GWAS hits for breast and ovarian cancers, raising the possibility of genetic pleiotropy.

Methods: We performed imputation-based fine-mapping in three case-control datasets of meningioma (927 cases, 790 controls), female breast cancer (28 108 cases, 22 209 controls), and ovarian cancer (25 509 cases, 40 941 controls).

A molecularly integrated grade for meningioma.

Background: Meningiomas are the most common primary intracranial tumor in adults. Clinical care is currently guided by the World Health Organization (WHO) grade assigned to meningiomas, a 3-tiered grading system based on histopathology features, as well as extent of surgical resection. Clinical behavior, however, often fails to conform to the WHO grade.

Disparities in patient engagement with video telemedicine among high-video-use providers during the COVID-19 pandemic.

Aims: Known racial, ethnic, age, and socioeconomic disparities in video telemedicine engagement may widen existing health inequities. We assessed if telemedicine disparities were alleviated among patients of high-video-use providers at a large cardiovascular practice.

Methods And Results: All telemedicine visits from 16 March to 31 October 2020 and patient demographics were collected from an administrative database.

Environmental and sex-specific molecular signatures of glioma causation.

Background: The relative importance of genetic and environmental risk factors in gliomagenesis remains uncertain.

Methods: Using whole-exome sequencing data from 1105 adult gliomas, we evaluate the relative contribution to cancer cell lineage proliferation and survival of single-nucleotide mutations in tumors by IDH mutation subtype and sex. We also quantify the contributions of COSMIC cancer mutational signatures to these tumors, identifying possible risk exposures.

Brain Tumor Discussions on Twitter (#BTSM): Social Network Analysis.

Background: The Brain Tumor Social Media (#BTSM) Twitter hashtag was founded in February 2012 as a disease-specific hashtag for patients with brain tumor.

Objective: To understand #BTSM's role as a patient support system, we describe user descriptors, growth, interaction, and content sharing.

Methods: We analyzed all tweets containing #BTSM from 2012 to 2018 using the Symplur Signals platform to obtain data and to describe Symplur-defined user categories, tweet content, and trends in use over time.

Social media partnerships with patient organizations for neuro-oncology patient recruitment.

Background: In neuro-oncology, traditional methods of enrolling the large numbers of participants required for studies of disease etiology and treatment response are costly, labor intensive, and may not include patients in regions without tumor registries.

Methods: In the Yale Acoustic Neuroma (AN) Study and International Low-Grade Glioma (LGG) Registry, we partnered with several brain tumor patient organizations to develop social media enrollment campaigns and use web-based data collection resources at the Yale University School of Public Health to test alternative methods to enroll neuro-oncology patients for epidemiologic study.

Results: In the AN study, we enrolled 1024 patients over 2 years.

Longitudinal molecular trajectories of diffuse glioma in adults.

The evolutionary processes that drive universal therapeutic resistance in adult patients with diffuse glioma remain unclear. Here we analysed temporally separated DNA-sequencing data and matched clinical annotation from 222 adult patients with glioma. By analysing mutations and copy numbers across the three major subtypes of diffuse glioma, we found that driver genes detected at the initial stage of disease were retained at recurrence, whereas there was little evidence of recurrence-specific gene alterations.

Lack of association between modifiable exposures and glioma risk: a Mendelian randomization analysis.

Background: The etiological basis of glioma is poorly understood. We have used genetic markers in a Mendelian randomization (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.

Publisher Correction: Mendelian randomisation study of the relationship between vitamin D and risk of glioma.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Glioma risk associated with extent of estimated European genetic ancestry in African Americans and Hispanics.

Glioma incidence is highest in non-Hispanic Whites, and to date, glioma genome-wide association studies (GWAS) to date have only included European ancestry (EA) populations. African Americans and Hispanics in the US have varying proportions of EA, African (AA) and Native American ancestries (NAA). It is unknown if identified GWAS loci or increased EA is associated with increased glioma risk.

Longer genotypically-estimated leukocyte telomere length is associated with increased meningioma risk.

Purpose: Telomere length-associated SNPs have been associated with incidence and survival rates for malignant brain tumors such as glioma. Here, we study the influence of genetically determined lymphocyte telomere length (LTL) by comparing telomerase associated SNPs between the most common non-malignant brain tumor, i.e.