Mobile phone use and brain tumour risk - COSMOS, a prospective cohort study.

BACKGROUND: Each new generation of mobile phone technology has triggered discussions about potential carcinogenicity from exposure to radiofrequency electromagnetic fields (RF-EMF). Available evidence has been insufficient to conclude about long-term and heavy mobile phone use, limited by differential recall and selection bias, or crude exposure assessment. The Cohort Study on Mobile Phones and Health (COSMOS) was specifically designed to overcome these shortcomings. METHODS: We recruited participants in Denmark, Finland, the Netherlands, Sweden, and the UK 2007-2012. The baseline questionnaire assessed lifetime history of mobile phone use. Participants were followed through population-based cancer registers to identify glioma, meningioma, and acoustic neuroma cases during follow-up. Non-differential exposure misclassification was reduced by adjusting estimates of mobile phone call-time through regression calibration methods based on self-reported data and objective operator-recorded information at baseline. Hazard ratios (HR) and 95% confidence intervals (CI) for glioma, meningioma, and acoustic neuroma in relation to lifetime history of mobile phone use were estimated with Cox regression models with attained age as the underlying time-scale, adjusted for country, sex, educational level, and marital status. RESULTS: 264,574 participants accrued 1,836,479 person-years. During a median follow-up of 7.12 years, 149 glioma, 89 meningioma, and 29 incident cases of acoustic neuroma were diagnosed. The adjusted HR per 100 regression-calibrated cumulative hours of mobile phone call-time was 1.00 (95 % CI 0.98-1.02) for glioma, 1.01 (95 % CI 0.96-1.06) for meningioma, and 1.02 (95 % CI 0.99-1.06) for acoustic neuroma. For glioma, the HR for ≥ 1908 regression-calibrated cumulative hours (90th percentile cut-point) was 1.07 (95 % CI 0.62-1.86). Over 15 years of mobile phone use was not associated with an increased tumour risk; for glioma the HR was 0.97 (95 % CI 0.62-1.52). CONCLUSIONS: Our findings suggest that the cumulative amount of mobile phone use is not associated with the risk of developing glioma, meningioma, or acoustic neuroma.

Palliative care for in-patient malignant glioma patients in Germany.

OBJECTIVE: Malignant gliomas impose a significant symptomatic burden on patients and their families. Current guidelines recommend palliative care for patients with advanced tumors within eight weeks of diagnosis, emphasizing early integration for malignant glioma cases. However, the utilization rate of palliative care for these patients in Germany remains unquantified. This study investigates the proportion of malignant glioma patients who either died in a hospital or were transferred to hospice care from 2019 to 2022, and the prevalence of in-patient specialized palliative care interventions. METHODS: In this cross-sectional, retrospective study, we analyzed data from the Institute for the Hospital Remuneration System (InEK GmbH, Siegburg, Germany), covering 2019 to 2022. We included patients with a primary or secondary diagnosis of C71 (malignant glioma) in our analysis. To refine our dataset, we identified cases with dual-coded primary and secondary diagnoses and excluded these to avoid duplication in our final tally. The data extraction process involved detailed scrutiny of hospital records to ascertain the frequency of hospital deaths, hospice transfers, and the provision of complex or specialized palliative care for patients with C71-coded diagnoses. Descriptive statistics and inferential analyses were employed to evaluate the trends and significance of the findings. RESULTS: From 2019 to 2022, of the 101,192 hospital cases involving malignant glioma patients, 6,129 (6% of all cases) resulted in in-hospital mortality, while 2,798 (2.8%) led to hospice transfers. Among these, 10,592 cases (10.5% of total) involved the administration of complex or specialized palliative medical care. This provision rate remained unchanged throughout the COVID-19 pandemic. Notably, significantly lower frequencies of complex or specialized palliative care implementation were observed in patients below 65 years (p < 0.0001) and in male patients (padjusted = 0.016). In cases of in-hospital mortality due to malignant gliomas, 2,479 out of 6,129 cases (40.4%) received specialized palliative care. CONCLUSION: Despite the poor prognosis and complex symptomatology associated with malignant gliomas, only a small proportion of affected patients received advanced palliative care. Specifically, only about 10% of hospitalized patients with malignant gliomas, and approximately 40% of those who succumb to the disease in hospital settings, were afforded complex or specialized palliative care. This discrepancy underscores an urgent need to expand palliative care access for this patient demographic. Additionally, it highlights the importance of further research to identify and address the barriers preventing wider implementation of palliative care in this context.

Stable glioma incidence and increased patient survival over the past two decades in Norway: a nationwide registry-based cohort study.

BACKGROUND: Surveillance of incidence and survival of central nervous system tumors is essential to monitor disease burden and epidemiological changes, and to allocate health care resources. Here, we describe glioma incidence and survival trends by histopathology group, age, and sex in the Norwegian population. MATERIAL AND METHODS: We included patients with a histologically verified glioma reported to the Cancer Registry of Norway from 2002 to 2021 (N = 7,048). Population size and expected mortality were obtained from Statistics Norway. Cases were followed from diagnosis until death, emigration, or 31 December 2022, whichever came first. We calculated age-standardized incidence rates (ASIR) per 100,000 person-years and age-standardized relative survival (RS).  Results: The ASIR for histologically verified gliomas was 7.4 (95% CI: 7.3-7.6) and was higher for males (8.8; 95% CI: 8.5-9.1) than females (6.1; 95% CI: 5.9-6.4). Overall incidence was stable over time. Glioblastoma was the most frequent tumor entity (ASIR = 4.2; 95% CI: 4.1-4.4). Overall, glioma patients had a 1-year RS of 63.6% (95% CI: 62.5-64.8%), and a 5-year RS of 32.8% (95% CI: 31.6-33.9%). Females had slightly better survival than males. For most entities, 1- and 5-year RS improved over time (5-year RS for all gliomas 29.0% (2006) and 33.1% (2021), p < 0.001). Across all tumor types, the RS declined with increasing age at diagnosis. INTERPRETATION: The incidence of gliomas has been stable while patient survival has increased over the past 20 years in Norway. As gliomas represent a heterogeneous group of primary CNS tumors, regular reporting from cancer registries at the histopathology group level is important to monitor disease burden and allocate health care resources in a population.

Incidence trends of adult glioma in Norway and its association with occupation and education: A registry-based cohort study.

BACKGROUND: Gliomas constitute 75 % of all malignant primary adult brain tumors. Being the most frequent histologic subtype, glioblastomas (GBMs) cause substantial morbidity and mortality worldwide and the Nordic countries have some of the highest incidence rates in the world. Therefore, we investigated the incidence of gliomas in Norway including time trends and associations with education and occupation. METHODS: We retrieved individual-level data from databases at Statistics Norway containing information on education and occupation and linked them to data on adult glioma patients diagnosed during 2004-21 from the Cancer Registry of Norway. Age-standardized incidence rates (ASIRs) (World Standard Population) were calculated and analyzed with regards to sex and morphology. Poisson regression was used to test for time-trends, and to analyze the associations between education, occupation and glioma incidence, adjusted for age, sex, and calendar year. Estimates were reported as incidence rate ratios (IRRs) with 95 % confidence intervals (CIs). RESULTS: The overall ASIR of gliomas (per 100,000 person-years) was 7.1 (95 % CI 6.9-7.3), with no specific time trend during the study period. The incidence increased with age. Compared to the other subtypes, GBMs were diagnosed at older ages. The risks of developing glioma overall and GBM were associated with occupation but not with educational level. The relative risk of glioma and GBM were respectively 1.17 (95 % CI 1.05-1.31) and 1.17 (95 % CI 1.02-1.35) among high-skilled white-collar workers compared to blue-collar workers. CONCLUSIONS: The overall and sex-specific ASIRs of gliomas and GBMs did not show any noticeable time trends. The higher risk of developing glioma overall and GBM in high-skilled white-collar workers compared to blue-collar workers calls for further investigations.

Protocol for investigating data quality and reporting outcomes of pediatric gliomas in population-based cancer registry research.

Cancer registry data on pediatric gliomas come with inherent limitations as inclusion criteria and registration practices of these tumors differ between registries due to specific guidelines that are lacking. These limitations can lead to biased estimates in incidence and survival outcomes. Here, we present a protocol to investigate data quality and comparability for retrospective population-based pediatric glioma studies. We describe steps for obtaining institutional permissions, dealing with data quality issues, regrouping tumors, and reporting tumors in a clinically relevant manner. For complete details on the use and execution of this protocol, please refer to Hoogendijk et al.1.

Risk of subsequent gliomas and meningiomas among 69,460 5-year survivors of childhood and adolescent cancer in Europe: the PanCareSurFup study.

BACKGROUND: Childhood cancer survivors are at risk of subsequent gliomas and meningiomas, but the risks beyond age 40 years are uncertain. We quantified these risks in the largest ever cohort. METHODS: Using data from 69,460 5-year childhood cancer survivors (diagnosed 1940-2008), across Europe, standardized incidence ratios (SIRs) and cumulative incidence were calculated. RESULTS: In total, 279 glioma and 761 meningioma were identified. CNS tumour (SIR: 16.2, 95% CI: 13.7, 19.2) and leukaemia (SIR: 11.2, 95% CI: 8.8, 14.2) survivors were at greatest risk of glioma. The SIR for CNS tumour survivors was still 4.3-fold after age 50 (95% CI: 1.9, 9.6), and for leukaemia survivors still 10.2-fold after age 40 (95% CI: 4.9, 21.4). Following cranial radiotherapy (CRT), the cumulative incidence of a glioma in CNS tumour survivors was 2.7%, 3.7% and 5.0% by ages 40, 50 and 60, respectively, whilst for leukaemia this was 1.2% and 1.7% by ages 40 and 50. The cumulative incidence of a meningioma after CRT in CNS tumour survivors doubled from 5.9% to 12.5% between ages 40 and 60, and in leukaemia survivors increased from 5.8% to 10.2% between ages 40 and 50. DISCUSSION: Clinicians following up survivors should be aware that the substantial risks of meningioma and glioma following CRT are sustained beyond age 40 and be vigilant for symptoms.

Epidemiology and survival of adult-type diffuse glioma in Belgium during the molecular era.

BACKGROUND: Survival data of diffuse adult-type glioma is mostly based on prospective clinical trials or small retrospective cohort studies. Real-world data with large patient cohorts is currently lacking. METHODS: Using the nationwide, population-based Belgian Cancer Registry, all known histological reports of patients diagnosed with an adult-type diffuse glioma in Belgium between 2017 and 2019 were reviewed. The ICD-O-3 morphology codes were matched with the histological diagnosis. The gathered data were transformed into the 2021 World Health Organization classification of CNS tumors using the IDH- and 1p/19q-mutation status. RESULTS: Between 2017 and 2019, 2233 diffuse adult-type gliomas were diagnosed in Belgium. Full molecular status was available in 67.1% of identified cases. The age-standardized incidence rate of diffuse adult-type glioma in Belgium was estimated at 8.55 per 100 000 person-years and 6.72 per 100 000 person-years for grade 4 lesions. Median overall survival time in IDH-wild-type glioblastoma was 9.3 months, significantly shorter compared to grade 4 IDH-mutant astrocytoma (median survival time: 25.9 months). The 3-year survival probability was 86.0% and 75.7% for grades 2 and 3 IDH-mutated astrocytoma. IDH-wild-type astrocytoma has a worse prognosis with a 3-year survival probability of 31.6% for grade 2 and 5.7% for grade 3 lesions. CONCLUSIONS: This registry-based study presents a large cohort of adult-type diffuse glioma with known molecular status and uses real-world survival data. It adds to the current literature which is mainly based on historical landmark trials and smaller retrospective cohort studies.

Association between viral infections and glioma risk: a two-sample bidirectional Mendelian randomization analysis.

BACKGROUND: Glioma is one of the leading types of brain tumor, but few etiologic factors of primary glioma have been identified. Previous observational research has shown an association between viral infection and glioma risk. In this study, we used Mendelian randomization (MR) analysis to explore the direction and magnitude of the causal relationship between viral infection and glioma. METHODS: We conducted a two-sample bidirectional MR analysis using genome-wide association study (GWAS) data. Summary statistics data of glioma were collected from the largest meta-analysis GWAS, involving 12,488 cases and 18,169 controls. Single-nucleotide polymorphisms (SNPs) associated with exposures were used as instrumental variables to estimate the causal relationship between glioma and twelve types of viral infections from corresponding GWAS data. In addition, sensitivity analyses were performed. RESULTS: After correcting for multiple tests and sensitivity analysis, we detected that genetically predicted herpes zoster (caused by Varicella zoster virus (VZV) infection) significantly decreased risk of low-grade glioma (LGG) development (OR = 0.85, 95% CI: 0.76-0.96, P = 0.01, FDR = 0.04). No causal effects of the other eleven viral infections on glioma and reverse causality were detected. CONCLUSIONS: This is one of the first and largest studies in this field. We show robust evidence supporting that genetically predicted herpes zoster caused by VZV infection reduces risk of LGG. The findings of our research advance understanding of the etiology of glioma.

Age and sex disparities in Latin-American adults with gliomas: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to identify if there are ethnic differences in the age and sex distribution of gliomas in the Latino adult population. METHODS: A systematic review and meta-analysis were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 recommendations. Databases used were MEDLINE, LILACS, Web of Science, and Scopus. Studies were included if they reported the age and/or sex distribution of gliomas in Latin adults, published in English or Spanish from January 1st, 1985, to December 1st, 2022. The quality of the studies was assessed using the Newcastle-Ottawa Quality Assessment Scale and the NIH Quality Assessment Tool. RESULTS: From 1096 articles, fifteen studies with information on 6,815 patients were selected for the systematic review, and thirteen were selected for the meta-analysis. The mean ages of diagnosis of glioma and glioblastoma were 50.9, 95\%\ CI [47.8-53.9] years and 53.33 years, 95 \% CI [51-55.6], respectively. The male-to-female incidence rate ratio of gliomas was 1.39. CONCLUSION: Our study found mean ages of glioma and glioblastoma were 6 and 10 years lower than those reported in the CBTRUS. Our study suggests disparities in the age and sex distribution of gliomas in Latin America compared to other regions. PROSPERO REGISTRATION NUMBER: CRD42021274423.

Histopathologic patterns of intracranial neoplasms at Lagos University Teaching Hospital, Nigeria. A ten-year hospital-based retrospective study.

Background: The most common intracranial neoplasm worldwide is meningioma, followed by gliomas, and then pituitary adenomas. There are geographical differences in the pattern of occurrence of intracranial neoplasms.The purpose of this study is to establish the pattern of occurrence of different histological types of intracranial neoplasms with their age and sex distributions in our environment - Lagos, Nigeria.The histological patterns, age, and gender distributions of all the intracranial neoplasms diagnosed within the study period at the Department of Anatomic and Molecular Pathology, LUTH, Lagos, Nigeria were noted and analysed with SPSS version 23. Result: There were 296 patients (165 females, 131 males; mean age of 37.0 years) diagnosed with an intracranial neoplasm within the study period. The most frequently diagnosed intracranial neoplasm was meningioma (105 cases; 35%, median age of 42 years, male to female ratio of 1:2.2), followed by pituitary adenoma (78 cases; 26%, median age of 47 years, male to female ratio of 1.3:1), and then gliomas (71 cases; 24%, median age of 28, male to female ratio of 1:1.39). Conclusion: The result of the study shows pituitary adenoma to be more common than gliomas, unlike what is seen in Caucasians where the reverse is the case.

Chinese Dietary Indices and Glioma: New Insights of a Case-Control Study in the Chinese Population.

Identifying modifiable factors in primary prevention strategies is a typical goal of glioma epidemiology. Among many glioma risk factors, diet was always considered as one. Most of the relevant studies thus far were concentrated on the West. It was crucial to investigate the connection between the Chinese diet and gliomas given the stark variations between western and eastern diets. A food frequency questionnaire including 114 items was used to investigate the food intake of the study subjects. The Chinese Dietary Quality Index (CDQI), the Chinese Dietary Balance Index (CDBI), the Dietary Antioxidant Index (DAI), the Dietary Inflammation Index (DII), and the Chinese Healthy Eating Index (CHEI) were calculated based on the data provided by the food frequency questionnaire to evaluate dietary quality, dietary balance, dietary antioxidants, dietary inflammation and adherence to the Chinese dietary guidelines in 506 glioma patients and 506 controls, respectively. After adjusting covariates, CHEI (OR = 0.90, 95% CI: 0.88-0.93) and DAI (OR = 0.61, 95% CI: 0.54-0.70) were correlated to a reduced glioma risk, and CDBI-based undernutrition (OR = 1.08, 95% CI: 1.06-1.12) and overnutrition (OR = 1.14, 95% CI: 1.09-1.20) and DII (OR = 2.20, 95% CI: 1.81-2.68) were correlated to an elevated glioma risk. Moreover, restrictive cubic spline analysis showed that there were significant nonlinear dose-response relationships between CHEI, CDBI, DAI, DII, and glioma. Therefore, adhering to the Chinese dietary guidelines was connected with a lower glioma risk, and undernutrition and overnutrition in the Chinese diet were associated with an increased risk of glioma.

Central nervous system tumours among users of vaginal oestradiol tablets: A nationwide population-based study.

BACKGROUND AND PURPOSE: It is currently unknown whether vaginal oestradiol is associated with development of meningioma and glioma. The aim of this study was to examine associations between cumulative use and treatment intensity of vaginally administered oestradiol tablets and incidence of meningioma and glioma in a nationwide, population-based study. METHODS: We conducted a nested case-control study within a nationwide cohort of Danish women followed from 2000 to 2018. The cohort consisted of 590,676 women aged 50-60 years at study start, without prior cancer diagnosis or use of systemic hormone therapy. Information on cumulative dose, duration, and intensity of vaginal oestradiol tablet use was assessed from filled prescriptions. Conditional logistic regression provided adjusted hazard ratios (HRs) for the association between vaginal oestradiol use and diagnosis of meningioma or glioma. RESULTS: We identified 1108 women with meningioma and 835 with glioma. Of these, 19.8% and 14.0% used vaginal oestradiol tablets, respectively. The HRs in those with ever-use of vaginal oestradiol tablets was 1.14 (95% confidence interval [CI] 0.97-1.34) for meningioma and 0.90 (95% CI 0.73-1.11) for glioma. The corresponding HRs for new users exclusively were 1.18 (95% CI 0.99-1.40) for meningioma and 0.89 (95% CI 0.71-1.13) for glioma. Intensity of vaginal oestradiol tablet use according to duration and user status yielded slightly elevated HRs for meningioma without an apparent dose-response pattern, while the HRs for glioma were generally below unity. Among new users, the HR with high intensity of current or recent vaginal oestradiol tablet use for 2+ years was 1.66 (95% CI 1.09-2.55) for meningioma and 0.77 (95% CI 0.41-1.44) for glioma. CONCLUSION: Use of vaginal oestradiol tablets was associated with a slightly increased incidence of meningioma but not of glioma. Owing to the observational nature of the study, residual bias cannot be ruled out.

Prevalence, risk factors and prognostic value of anxiety and depression in recurrent glioma patients.

Anxiety and depression are frequently noticed in glioma patients, while few studies report this issue in recurrent glioma patients. Hence, this study aimed to evaluate the prevalence of anxiety and depression, as well as their risk factors and prognostic value in recurrent glioma patients. Eighty recurrent glioma patients, 40 newly-diagnosed glioma patients, and 40 healthy controls were enrolled in this study. Then, the Hospital Anxiety and Depression Scale for anxiety (HADS-A) and for depression (HADS-D) were used to assess the anxiety and depression status of all subjects. The HADS-A score (8.6 ± 3.3 vs. 7.0 ± 2.9 vs. 4.3 ± 2.5), anxiety rate (58.8% vs. 32.5% vs. 10.0%), HADS-D score (7.9 ± 3.0 vs. 6.9 ± 3.1 vs. 4.0 ± 2.6), and depression rate (45.0% vs. 30.0% vs. 7.5%) were all highest in recurrent glioma patients, followed by newly-diagnosed glioma patients, and were lowest in healthy controls (all P < 0.001). Furthermore, female sex (vs. male sex) was independently correlated with anxiety (odds ratio (OR): 3.042, P = 0.029); meanwhile, higher World Health Organization (WHO) pathological grade was independently correlated with depression (OR: 2.573, P = 0.019) in recurrent glioma patients. Additionally, anxiety was correlated with shortened progression-free survival (PFS) (P = 0.028) and overall survival (OS) (P = 0.047), while depression only had a correlation trend with shortened PFS (without statistical significance) (P = 0.069) and was associated with shortened OS (P = 0.035) in recurrent glioma patients. The prevalence of anxiety and depression is high in recurrent glioma patients, which relates to gender, WHO pathological grade, and estimates worsen survival.

Mismatch Repair Deficiency and Lynch Syndrome Among Adult Patients With Glioma.

PURPOSE: The Lynch syndrome (LS)-glioma association is poorly documented. As for mismatch repair deficiency (MMRd) in glioma, a hallmark of LS-associated tumors, there are only limited data available. We determined MMRd and LS prevalence in a large series of unselected gliomas, and explored the associated characteristics. Both have major implications in terms of treatment, screening, and prevention. METHODS: Somatic next-generation sequencing was performed on 1,225 treatment-naive adult gliomas referred between 2017 and June 2022. For gliomas with ≥1 MMR pathogenic variant (PV), MMR immunohistochemistry (IHC) was done. Gliomas with ≥1 PV and protein expression loss were considered MMRd. Eligible patients had germline testing. To further explore MMRd specifically in glioblastomas, isocitrate dehydrogenase (IDH)-wild type (wt), we performed IHC, and complementary sequencing when indicated, in a series of tumors diagnosed over the 2007-2021 period. RESULTS: Nine gliomas were MMRd (9/1,225; 0.73%). Age at glioma diagnosis was <50 years for all but one case. Eight were glioblastomas, IDH-wt, and one was an astrocytoma, IDH-mutant. ATRX (n = 5) and TP53 (n = 8) PV were common. There was no TERT promoter PV or EGFR amplification. LS prevalence was 5/1,225 (0.41%). One 77-year-old patient was a known LS case. Four cases had a novel LS diagnosis, with germline PV in MSH2 (n = 3) and MLH1 (n = 1). One additional patient had PMS2-associated constitutional mismatch repair deficiency. Germline testing was negative in three MSH6-deficient tumors. In the second series of glioblastomas, IDH-wt, MMRd prevalence was 12.5% in the <40-year age group, 2.6% in the 40-49 year age group, and 1.6% the ≥50 year age group. CONCLUSION: Screening for MMRd and LS should be systematic in glioblastomas, IDH-wt, diagnosed under age 50 years.

Palliative care referral across the disease trajectory in high-grade glioma.

PURPOSE: Adults with high-grade glioma (HGG), WHO grade III or IV, have substantial palliative care needs. Our aim was to determine occurrence, timing, and factors associated with palliative care consultation (PCC) in HGG at one large academic institution. METHODS: HGG patients receiving care between 08/1/2011 and 01/23/2020 were identified retrospectively from a multi-center healthcare system cancer registry. Patients were stratified by any PCC (yes/no), and timing of initial PCC by disease phase: diagnosis (before radiation), during initial treatment (first-line chemotherapy/radiation), second-line treatment(s), or end-of-life (after last chemotherapy). RESULTS: Of 621 HGG patients, 134 (21.58%) received PCC with the vast majority occurring during hospital admission [111 (82.84%)]. Of the 134, 14 (10.45%) were referred during the diagnostic phase; 35 (26.12%) during initial treatment; 20 (14.93%) during second-line treatment; and 65 (48.51%) during end of life. In multivariable logistic regression, only higher Charlson Comorbidity Index was associated with greater odds of PCC [OR 1.3 (95% CI 1.2-1.4), p < 0.01]; but not age or histopathology. Patients who received PCC prior to end of life had longer survival from diagnosis than those referred during end of life [16.5 (8, 24) months vs. 11 (4, 17); p < 0.01]. CONCLUSION: A minority of HGG patients ever received PCC, which primarily occurred in the inpatient setting, and nearly half during the end-of-life phase. Thus, only about one in ten patients in the entire cohort potentially received the benefits of earlier PCC despite earlier referral having an association with longer survival. Further studies should elucidate barriers and facilitators to early PCC in HGG.

Epidemiology, biology, and management of venous thromboembolism in gliomas: An interdisciplinary review.

Patients with diffuse glioma are at high risk of developing venous thromboembolism (VTE) over the course of the disease, with up to 30% incidence in patients with glioblastoma (GBM) and a lower but nonnegligible risk in lower-grade gliomas. Recent and ongoing efforts to identify clinical and laboratory biomarkers of patients at increased risk offer promise, but to date, there is no proven role for prophylaxis outside of the perioperative period. Emerging data suggest a higher risk of VTE in patients with isocitrate dehydrogenase (IDH) wild-type glioma and the potential mechanistic role of IDH mutation in the suppression of production of the procoagulants tissue factor and podoplanin. According to published guidelines, therapeutic anticoagulation with low molecular weight heparin (LMWH) or alternatively, direct oral anticoagulants (DOACs) in patients without increased risk of gastrointestinal or genitourinary bleeding is recommended for VTE treatment. Due to the elevated risk of intracranial hemorrhage (ICH) in GBM, anticoagulation treatment remains challenging and at times fraught. There are conflicting data on the risk of ICH with LMWH in patients with glioma; small retrospective studies suggest DOACs may convey lower ICH risk than LMWH. Investigational anticoagulants that prevent thrombosis without impairing hemostasis, such as factor XI inhibitors, may carry a better therapeutic index and are expected to enter clinical trials for cancer-associated thrombosis.

Role of DNA methylation in the relationship between glioma risk factors and glioma incidence: a two-step Mendelian randomization study.

Genetic evidence suggests glioma risk is altered by leukocyte telomere length, allergic disease (asthma, hay fever or eczema), alcohol consumption, childhood obesity, low-density lipoprotein cholesterol (LDLc) and triglyceride levels. DNA methylation (DNAm) variation influences many of these glioma-related traits and is an established feature of glioma. Yet the causal relationship between DNAm variation with both glioma incidence and glioma risk factors is unknown. We applied a two-step Mendelian randomization (MR) approach and several sensitivity analyses (including colocalization and Steiger filtering) to assess the association of DNAm with glioma risk factors and glioma incidence. We used data from a recently published catalogue of germline genetic variants robustly associated with DNAm variation in blood (32,851 participants) and data from a genome-wide association study of glioma risk (12,488 cases and 18,169 controls, sub-divided into 6191 glioblastoma cases and 6305 non-glioblastoma cases). MR evidence indicated that DNAm at 3 CpG sites (cg01561092, cg05926943, cg01584448) in one genomic region (HEATR3) had a putative association with glioma and glioblastoma risk (False discovery rate [FDR] < 0.05). Steiger filtering provided evidence against reverse causation. Colocalization presented evidence against genetic confounding and suggested that differential DNAm at the 3 CpG sites and glioma were driven by the same genetic variant. MR provided little evidence to suggest that DNAm acts as a mediator on the causal pathway between risk factors previously examined and glioma onset. To our knowledge, this is the first study to use MR to appraise the causal link of DNAm with glioma risk factors and glioma onset. Subsequent analyses are required to improve the robustness of our results and rule out horizontal pleiotropy.

Glioblastoma and Other Primary Brain Malignancies in Adults: A Review.

Importance: Malignant primary brain tumors cause more than 15 000 deaths per year in the United States. The annual incidence of primary malignant brain tumors is approximately 7 per 100 000 individuals and increases with age. Five-year survival is approximately 36%. Observations: Approximately 49% of malignant brain tumors are glioblastomas, and 30% are diffusely infiltrating lower-grade gliomas. Other malignant brain tumors include primary central nervous system (CNS) lymphoma (7%) and malignant forms of ependymomas (3%) and meningiomas (2%). Symptoms of malignant brain tumors include headache (50%), seizures (20%-50%), neurocognitive impairment (30%-40%), and focal neurologic deficits (10%-40%). Magnetic resonance imaging before and after a gadolinium-based contrast agent is the preferred imaging modality for evaluating brain tumors. Diagnosis requires tumor biopsy with consideration of histopathological and molecular characteristics. Treatment varies by tumor type and often includes a combination of surgery, chemotherapy, and radiation. For patients with glioblastoma, the combination of temozolomide with radiotherapy improved survival when compared with radiotherapy alone (2-year survival, 27.2% vs 10.9%; 5-year survival, 9.8% vs 1.9%; hazard ratio [HR], 0.6 [95% CI, 0.5-0.7]; P < .001). In patients with anaplastic oligodendroglial tumors with 1p/19q codeletion, probable 20-year overall survival following radiotherapy without vs with the combination of procarbazine, lomustine, and vincristine was 13.6% vs 37.1% (80 patients; HR, 0.60 [95% CI, 0.35-1.03]; P = .06) in the EORTC 26951 trial and 14.9% vs 37% in the RTOG 9402 trial (125 patients; HR, 0.61 [95% CI, 0.40-0.94]; P = .02). Treatment of primary CNS lymphoma includes high-dose methotrexate-containing regimens, followed by consolidation therapy with myeloablative chemotherapy and autologous stem cell rescue, nonmyeloablative chemotherapy regimens, or whole brain radiation. Conclusions and Relevance: The incidence of primary malignant brain tumors is approximately 7 per 100 000 individuals, and approximately 49% of primary malignant brain tumors are glioblastomas. Most patients die from progressive disease. First-line therapy for glioblastoma is surgery followed by radiation and the alkylating chemotherapeutic agent temozolomide.

Clinical features and outcomes of pediatric intracranial gliomas: results from single center's 226 cases and corroborated with SEER database.

BACKGROUND: Pediatric gliomas are the most common central nervous system (CNS) tumors in children and adolescents and show different clinical and histopathological characteristics from the adult. The prognostic factors were poorly defined in pediatric intracranial gliomas. METHODS: We collected pediatric intracranial glioma cases in our institution between February 2011 and June 2022. The patient clinical data, tumor growth characteristics, treatments, and follow-up data were analyzed by Cox regression analysis to identify impact factors on the prognosis of pediatric intracranial glioma patients. To corroborate our data, an independent cohort of pediatric intracranial glioma from the Surveillance, Epidemiology, and End Results Program (SEER) database was analyzed. RESULTS: A total of 181 cases of pediatric low-grade glioma (PLGG) and 45 cases of pediatric high-grade glioma (PHGG) were included. In multivariate Cox regression analysis, tumor size > 59.5 mm (p = 0.006) and non-gross total resection (non-GTR; subtotal resection, STR, p = 0.042; biopsy, p = 0.012) were associated with decreased overall survival (OS) in PLGG patients. In PHGG patients, only chemotherapy (p = 0.023) was associated with OS while tumor size was marginally prognostic for OS (p = 0.051). Additional independent analysis of 2734 PLGG and 741 PHGG from the SEER database corroborated that larger tumor size was associated with decreased OS in LGG (p = 0.001) and HGG (p < 0.001) patients, separately. CONCLUSION: In this study, we found that tumor size was a significant prognostic factor for the OS of PLGG patients in our series. Besides the tumor size, the extent of resection also independently impacted the prognosis of PLGG patients. While in PHGG patients, only chemotherapy was associated with improved OS and tumor size was marginally prognostic.