Search

Background: The genetic causal association between the mitochondrial DNA copy number (mtDNA-CN) and the development of glioma and glioblastoma (GBM) remains unclear., Methods: The summary-level datasets for mtDNA-CN were obtained from participants in the UK Biobank and the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium. Additionally, summary statistics datasets related to glioma were collected from a comprehensive meta-analysis genome-wide association study, which included 12,488 cases and 18,169 controls. The main method employed was inverse variance weighting, supplemented by Bonferroni correction to account for multiple tests. Additionally, sensitivity analyses were performed to address potential pleiotropy and strengthen the reliability of the results., Results: In the primary analysis, no genetic causal association was found between mtDNA-CN and glioma (OR = 1.20, 95%CI = 0.94-1.52, P = 0.1394), nor with low-grade glioma (OR = 1.09, 95%CI = 0.79-1.51, P = 0.5588). However, a suggestive genetic relationship between mtDNA-CN and glioblastoma was observed (OR = 1.42, 95%CI = 1.02-1.96, P = 0.0347). These findings were replicated in the MR analysis. Comprehensive analyses, including heterogeneity and pleiotropy analyses, as well as reverse analysis, confirmed the robustness of these results., Conclusion: Our MR study did not find a genetic causal association between mtDNA-CN and the risk of glioma. A suggestive causal association between GBM and mtDNA-CN was detected., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

We present an updated analysis on the incidence of primary brain tumors in the Metropolitan Area of Genova, the capital of the northwestern Italian region Liguria.The number of cases and incidence rates for all malignant brain tumors, glioblastoma, malignant brain tumors other than glioblastoma, and brain tumors not otherwise specified were calculated for each of seven three-year and one-eighth four-year periods in which the quarter century 1993-2017 was divided. The rates were age-adjusted (AAR) using the 2013 European standard population, presented per 100,000 person-years and the average percentage change over the three-year period was calculated.The number of cases of all malignant brain tumors and glioblastoma was higher in males than in females in each three-year period and in the entire quarter century 1993-2017. During the latter, the average three-year percentage change in AARs for all brain tumors was minimal [0.6 (95% C.I. = -1.0/2.1) %] while for glioblastoma there was a change of 5.3 (95% C.I. = -0.4/11.3) %. The partially concurrent decline in the incidence rates of malignant brain tumors other than glioblastoma or not otherwise specified suggests that the observed increase in the incidence rate of glioblastoma during 1993-2017 may have been at least partially linked to the improvement during the same period in sensitivity and specificity of the diagnosis of glioblastoma, depleting the reservoirs of other malignant or unspecified brain tumors. Research into possibly increased environmental risk factors (e.g., population exposure to ionizing radiation) for glioblastoma in Genova remains warranted., (© 2024. The Author(s).)

Purpose: We present results of a retrospective population-based investigation of patterns of care and outcome of glioblastoma patients in Austria., Patients and Methods: In this nation-wide cooperative project, all Austrian glioblastoma patients newly diagnosed between 2014 and 2018 and registered in the ABTR-SANOnet database were included. Histological typing used criteria of the WHO classification of CNS tumors, 4th edition 2016. Patterns of care were assessed, and all patients were followed until the end of 2019., Results: 1,420 adult glioblastoma cases were identified. 813 (57.3%) patients were male and 607 (42.7%) female. Median age at diagnosis was 64 years (range: 18-88). Median overall survival (OS) was 11.6 months in the total cohort and 10.9 months in patients with proven IDH-wildtype. Median OS in the patient group ≤ 65 years receiving postoperative standard of care therapy was 16.1 months. In the patient group > 65 years with postoperative therapy, median OS was 11.2 months. Follow-up ≥ 5 years identified 13/264 (4.9%) long-term survivors. Brain tumor surgery frequently was assisted by 5-aminolevulinic acid (5-ALA) fluorescence (up to 55%). Postoperative treatment was initiated around one month after surgery (median: 31 days) following standardized protocols in 1,041/1,420 (73.3%) cases. In 830 patients (58.5%), concomitant radiochemotherapy was started according to the established standard of care. Treatment in case of progressive disease was considerably variable. 170/1,420 patients (12.0%) underwent a second surgical procedure, 467 (33.0%) received systemic treatment after progression, and 173 (12.2%) were re-irradiated., Conclusion: Our data illustrate and confirm nation-wide translation of effective standard of care to Austrian glioblastoma patients in the recent past. In the case of progressive disease, highly variable therapeutic approaches were used, most frequently accompanied by anti-angiogenic therapy. Long-term survival was observed in a minor proportion of mostly younger patients who typically had gross total tumor resection, a favorable postoperative ECOG score, and standard of care therapy., (© 2024. The Author(s).)

Background: The incidence of leptomeningeal metastases (LM) has been reported diversely. This study aimed to investigate the incidence, risk factors, and prognosis of LM in patients with isocitrate dehydrogenase (IDH)-wildtype glioblastoma., Methods: A total of 828 patients with IDH-wildtype glioblastoma were enrolled between 2005 and 2022. Baseline preoperative MRI including post-contrast fluid-attenuated inversion recovery (FLAIR) was used for LM diagnosis. Qualitative and quantitative features, including distance between tumor and subventricular zone (SVZ) and tumor volume by automatic segmentation of the lateral ventricles and tumor, were assessed. Logistic analysis of LM development was performed using clinical, molecular, and imaging data. Survival analysis was performed., Results: The incidence of LM was 11.4%. MGMTp unmethylation (odds ratio [OR] = 1.92, P = .014), shorter distance between tumor and SVZ (OR = 0.94, P = .010), and larger contrast-enhancing tumor volume (OR = 1.02, P < .001) were significantly associated with LM. The overall survival (OS) was significantly shorter in patients with LM than in those without (log-rank test; P < .001), with median OS of 12.2 and 18.5 months, respectively. The presence of LM remained an independent prognostic factor for OS in IDH-wildtype glioblastoma (hazard ratio = 1.42, P = .011), along with other clinical, molecular, imaging, and surgical prognostic factors., Conclusions: The incidence of LM is high in patients with IDH-wildtype glioblastoma, and aggressive molecular and imaging factors are correlated with LM development. The prognostic significance of LM based on post-contrast FLAIR imaging suggests the acknowledgment of post-contrast FLAIR as a reliable diagnostic tool for clinicians., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

As the prevalence of Type 2 Diabetes Mellitus (T2DM) and Glioblastoma (GBM) rises globally, the relationship between T2DM and GBM remains controversial. This study aims to investigate whether genetically predicted T2DM is causally associated with GBM. We performed bidirectional Mendelian randomization (MR) analysis using data from genome-wide studies on T2DM (N = 62,892) and GBM (N = 218,792) in European populations. The results of the inverse-variance weighted (IVW) approach served as the primary outcomes. We applied Cochran's Q test and MR-Egger regression for heterogeneity assessment. Leave-one-out analysis was used to evaluate whether any single SNP significantly influenced the observed effect. Our findings reveal a significant causal association between T2DM and an increased risk of GBM (OR [95% CI] 1.70 [1.09, 2.65], P = 0.019). Conversely, the reverse association between T2DM and GBM was insignificant (OR [95% CI] 1.00 [0.99, 1.01], P = 0.408) (P > 0.40). Furthermore, the results from Cochran's Q-test and funnel plots in the MR-Egger method indicated no evidence of pleiotropy between the SNPs and GBM. Additionally, we mapped causal SNPs to genes and identified 10 genes, including MACF1, C1orf185, PTGFRN, NOTCH2, ABCB10, GCKR, THADA, RBMS1, SPHKAP, and PPARG, located on chromosomes 1, 2, and 3. These genes are involved in key biological processes such as the BMP signaling pathway and various metabolic pathways relevant to both conditions. This study provides robust evidence of a significant causal relationship between T2DM and an increased risk of GBM. The identified SNP-mapped genes highlight potential biological mechanisms underlying this association., (© 2024. The Author(s).)

Objective: To investigate the incidence rate of primary brain tumors (PBTs) among Palestinian children over a 6-year interval. This study also aimed to identify the predominant histopathologic types identified in these children., Methods: This retrospective epidemiologic study focused on PBTs in children (<15 years) in Palestine. The data were collected from the registry system at Al-Makassed Hospital in Jerusalem, a prominent referral institution in Palestine and the largest center for PBTs in the region, over a 6 years period from 2018 to 2023., Results: The incidence rate of PBTs in children (<15 years) was 1.33 per 100,000 person-years, with a 5% mortality rate. Pilocytic astrocytoma was the most common type (24%), followed by medulloblastoma (15.2%) and glioblastoma (6.3%). About one half of the tumors in children were malignant. Headaches were the most common first sign or symptom. About 20% of brain tumors in children were situated within the ventricles, making it the most prevalent location of these tumors, followed by the cerebellum (15.19%) and frontal lobe (11.39%)., Conclusions: This is the first national study in Palestine investigating PBTs in children. The crude incidence rate of primary brain tumors among Palestinian children was lower than the incidence rate in many countries around the world. It is recommended that more research be done on the epidemiology and distribution of PBTs in children in Palestine., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Backgrounds: Primary brain tumors (PBTs) are uncommon, but they significantly increase the risk of disability and death. There is a deficiency of data concerning the epidemiology and anatomical distribution of PBTs among adults in Palestine., Methods: A retrospective descriptive study in which data were collected from the clinical reports of Palestinian patients diagnosed with PBTs at Al-Makassed Hospital during the period (2018-2023)., Results: In Palestinian adolescents and adults, the incidence rate of PBTs was 3.92 per 100,000 person-years. Glioblastoma (18.8%) was the most common type identified, and it was more common in males. Non-malignant tumors were more common than malignant tumors (2.41 vs. 1.52 per 100,000). The mortality rate from PBTs was 4.8%. The most common initial symptom was headaches, and it occurred more with non-malignant tumors (57.28% vs. 42.72%, p-value < 0.001). Cerebral meninges (26.3%) were the most common location for primary brain tumors (p-value < 0.001)., Conclusion: This is the first study of primary brain tumor epidemiology in Palestine. The overall incidence of PBTs in Palestinian adolescents and adults was 3.96 per 100,000, which was lower than the incidence rate of primary brain tumors worldwide. More studies on the epidemiology and distribution of PBTs in Palestine are recommended., (© 2024. The Author(s).)

Background: Although the COVID-19 pandemic has exerted potential impact on patients with glioblastomas (GBMs), it remains unclear whether the survival and its related risk factors of GBM patients would be altered or not during the period spanning from pre-COVID-19 to post-COVID-19 pandemic era. This study aimed to clarify the important issues above., Methods: Two observational cohorts were utilized, including the nationwide American cohort from the Surveillance, Epidemiology, and End-Results (SEER) and the Chinese glioblastoma cohort (CGC) at our institution during 2018-2020. Demographics, tumour features, treatment regimens and clinical outcomes were collected. Cox regression model, competing risk model, and subgroup and sensitivity analysis were used to dynamically estimate the survival and its relevant risk factors over different diagnosis years from the pre-COVID-19 (2018 and 2019) to post-COVID-19 (2020) pandemic. Causal mediation analysis was further adopted to explore the potential relationship between risk factors and mortality., Results: This study included 11321 GBM cases in SEER and 226 GBM patients in CGC, respectively. Instead of the diagnostic years of 2018-2020, the prognostic risk factors, such as advanced age, bilateral tumour and absence of comprehensive therapy (surgery combined with chemoradiotherapy), were identified to persistently affect GBM survival independently during the period from 2018 to 2020 in the SEER cohort (all P < 0.05). In CGC, lack of comprehensive therapy for GBM patients were restated as survival risk factors during the same timeframe. Causal mediation analysis showed that the effect of comprehensive therapy on all-cause mortality played a determinant role (direct effect value -0.227, 95% CI -0.248 to -0.207), which was partially mediated by age (9.11%) rather than tumour laterality., Conclusions: As the timeframe shifted from pre-COVID-19 to post-COVID-19 pandemic, survival of GBM patients remained stable, yet advanced age, bilateral tumours, and passive treatment continuingly impacted GBM survival. It is necessary to optimize the comprehensive treatment for GBM patients even in the post-pandemic era., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: Glioblastoma (GB) is the most common primary malignant brain tumor with the highest incidence occurring in older adults with a median age at diagnosis of 64 years old. While treatment often improves survival it brings toxicities and adverse events (AE). Here we identify sex differences in treatment patterns and AE in individuals ≥ 66 years at diagnosis with GB., Methods: Using the SEER-Medicare dataset sex differences in adverse events were assessed using multivariable logistic regression performed to calculate the male/female odds ratio (M/F OR) and 95% confidence intervals [95% CI] of experiencing an AE adjusted for demographic variables and Elixhauser comorbidity score., Results: Males with GB were more likely to receive standard of care (SOC; Surgery with concurrent radio-chemotherapy) [20%] compared to females [17%], whereas females were more likely to receive no treatment [26%] compared to males [21%]. Females with GB receiving SOC were more likely to develop gastrointestinal disorders (M/F OR = 0.76; 95% CI,0.64-0.91, p = 0.002) or blood and lymphatic system disorders (M/F OR = 0.79; 95% CI,0.66-0.95, p = 0.012). Males with GB receiving SOC were more likely to develop cardiac disorders (M/F OR = 1.21; 95% CI,1.02-1.44, p = 0.029) and renal disorders (M/F OR = 1.65; 95% CI,1.37-2.01, p < 0.001)., Conclusions: Sex differences for individuals, 66 years and older, diagnosed with GB exist in treatment received and adverse events developed across different treatment modalities., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Comprehensive analysis of brain tumor incidence and survival in the Veteran population has been lacking., Methods: Veteran data were obtained from the Veterans Health Administration (VHA) Medical Centers via VHA Corporate Data Warehouse. Brain tumor statistics on the overall US population were generated from the Central Brain Tumor Registry of the US data. Cases were individuals (≥18 years) with a primary brain tumor, diagnosed between 2004 and 2018. The average annual age-adjusted incidence rates (AAIR) and 95% confidence intervals were estimated per 100 000 population and Kaplan-Meier survival curves evaluated overall survival outcomes among Veterans., Results: The Veteran population was primarily white (78%), male (93%), and between 60 and 64 years old (18%). Individuals with a primary brain tumor in the general US population were mainly female (59%) and between 18 and 49 years old (28%). The overall AAIR of primary brain tumors from 2004 to 2018 within the Veterans Affairs cancer registry was 11.6. Nonmalignant tumors were more common than malignant tumors (AAIR:7.19 vs 4.42). The most diagnosed tumors in Veterans were nonmalignant pituitary tumors (AAIR:2.96), nonmalignant meningioma (AAIR:2.62), and glioblastoma (AAIR:1.96). In the Veteran population, survival outcomes became worse with age and were lowest among individuals diagnosed with glioblastoma., Conclusions: Differences between Veteran and US populations can be broadly attributed to demographic composition differences of these groups. Prior to this, there have been no reports on national-level incidence rates and survival outcomes for Veterans. These data provide vital information that can drive efforts to understand disease burden and improve outcomes for individuals with primary brain tumors., (Published by Oxford University Press on behalf of the Society for Neuro-Oncology 2023.)

Glioblastoma multiforme (GBM) is an aggressive variant of central nervous system gliomas that carries a dismal prognosis. Although GBM is the most frequently occurring and malignant type of glioma accounting for more than 60% of all brain tumors in adults, its overall incidence is rare, occurring at a rate of 3.21 per 100,000 persons. Little is known about the etiology of GBM, but one proposed theory is that GBM pathogenesis may be linked to a chronic inflammatory course initiated by traumatic injury to the brain. Limited case reports have suggested an association between GBMs and traumatic brain injury (TBI), but larger case-control and epidemiologic studies have been inconclusive. We present three service members (two active duty and one retired) who developed GBM near the original site of prior head trauma. Each service member's military occupation was in the special operations community and shared a common theme of TBI following head trauma/injury. The current research on the association between TBI and GBM is limited and conflicting, predominantly due to the low incidence of the disease in the general population. Evidence has indicated that TBI should be considered a chronic disease with long-term health impacts, including long-term disability, dementia, epilepsy, mental health conditions, and cardiovascular diseases. With the addition of our patients, as well as a recently published study proposing a molecular association between trauma and GBM, further research is needed to better understand the potential relationship., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2023. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

The reported risk factors for glioblastoma (GBM), i.e., ionizing radiation, Li-Fraumeni syndrome, Neurofibromatosis I, and Turcot syndrome, also increase the risk of other brain tumor types. Risk factors for human GBM are associated with different oncogenic mutation profiles. Pedigreed domestic dogs with a shorter nose and flatter face (brachycephalic dogs) display relatively high rates of glioma formation. The genetic profiles of canine gliomas are also idiosyncratic. The association of putatively different mutational patterns in humans and canines with GBM suggests that different oncogenic pathways can result in GBM formation. Strong epidemiological evidence for an association between exposure to chemical carcinogens and an increased risk for development of GBM is currently lacking. Ionizing radiation induces point mutations, frameshift mutations, double-strand breaks, and chromosomal insertions or deletions. Mutational profiles associated with chemical exposures overlap with the broad mutational patterns seen with ionizing radiation. Weak statistical associations between chemical exposures and GBM reported in epidemiology studies are biologically plausible. Molecular approaches comparing reproducible patterns seen in spontaneous GBM with analogous patterns found in GBMs resected from patients with known significant exposures to potentially carcinogenic chemicals can address difficulties presented by traditional exposure assessment., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: Epilepsy is a common comorbidity in patients with glioblastoma, however, clinical data on status epilepticus (SE) in these patients is sparse. We aimed to investigate the risk factors associated with the occurrence and adverse outcomes of SE in glioblastoma patients., Methods: We retrospectively analysed electronic medical records of patients with de-novo glioblastoma treated at our institution between 01/2006 and 01/2020 and collected data on patient, tumour, and SE characteristics., Results: In the final cohort, 292/520 (56.2 %) patients developed seizures, with 48 (9.4 % of the entire cohort and 16.4 % of patients with epilepsy, PWE) experiencing SE at some point during the course of their disease. SE was the first symptom of the tumour in 6 cases (1.2 %) and the first manifestation of epilepsy in 18 PWE (6.2 %). Most SE episodes occurred postoperatively (n = 37, 77.1 %). SE occurrence in PWE was associated with postoperative seizures and drug-resistant epilepsy. Adverse outcome (in-house mortality or admission to palliative care, 10/48 patients, 20.8 %), was independently associated with higher status epilepticus severity score (STESS) and Charlson Comorbidity Index (CCI), but not tumour progression. 32/48 SE patients (66.7 %) were successfully treated with first- and second-line agents, while escalation to third-line agents was successful in 6 (12.5 %) cases., Conclusion: Our data suggests a link between the occurrence of SE, postoperative seizures, and drug-resistant epilepsy. Despite the dismal oncological prognosis, SE was successfully treated in 79.2 % of the cases. Higher STESS and CCI were associated with adverse SE outcomes., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Outside of the work reported in this paper, H.M. Hamer has served on the scientific advisory boards of Arvelle, Bial, Corlieve, Eisai, GW, Novartis, Sandoz, UCB Pharma and Zogenix. He has been part of the speakers’ bureaus of or received unrestricted grants from Amgen, Ad-Tech, Alnylam, Bracco, Desitin, Eisai, GW, Nihon Kohden, Novartis, Pfizer, and UCB Pharma. The remaining authors have no conflicts of interest., (Copyright © 2023. Published by Elsevier Ltd.)

Objective: Racial and socioeconomic disparities in neuro-oncological care for patients with brain tumors remain underexplored. This study aimed to analyze county-level disparities in glioblastoma (GBM) care in the United States, focusing on access to surgery and the use of adjuvant temozolomide chemotherapy and radiation therapy., Methods: Using repeated cross-sectional data from the Surveillance, Epidemiology, and End Results 17 database; the Area Health Resources File; and the American Community Survey, from 2010 to 2019, the authors performed multivariate regression analyses to understand the associations between county-level racial and socioeconomic characteristics, as well as the rates of surgery performed, delays in surgery, and use of adjuvant chemotherapy and radiation therapy for newly diagnosed GBM., Results: In total, 29,609 GBM patients from 602 different US counties over a decade were included in this study. Counties with lower rates of surgery for GBM were associated with a higher percentage of Black residents (coefficient [CE] -0.001, 95% CI -0.002 to 0; p < 0.05) and being located in the Midwest (CE -0.132, 95% CI -0.195 to -0.069; p < 0.001) or West (CE -0.127, 95% CI -0.189 to -0.065; p < 0.001) relative to the Northeast. Counties with delayed surgical treatment were more likely to lack neurosurgeons (adjusted OR [aOR] 2.52, 95% CI 1.77-3.60; p < 0.001), have a higher percentage of Black residents (aOR 1.011, 95% CI 1.00-1.02; p < 0.05), and be located in the Midwest (aOR 3.042, 95% CI 1.12-8.24; p < 0.05) or West (aOR 3.175, 95% CI 1.12-8.97 p < 0.05). Counties with high rates of adjuvant radiation therapy were less likely to have higher percentages of Black residents (aOR 0.987, 95% CI 0.980-0.995; p < 0.01) and uninsured individuals (aOR 0.962, 95% CI 0.937-0.987; p < 0.01)., Conclusions: Counties without neurosurgeons and those with a higher percentage of Black patients have delays in surgical care and demonstrate lower overall rates of surgery and adjuvant therapy for GBM. This study underscores the need for targeted interventions and policies that address structural barriers in healthcare access, improve equitable distribution of the neurosurgery workforce, and ensure timely and comprehensive GBM care to all populations.

Background: Patients with a prior malignancy are at elevated risk of developing subsequent primary malignancies (SPMs). However, the risk of developing subsequent primary glioblastoma (SPGBM) in patients with a prior cancer history is poorly understood., Methods: We used the Surveillance, Epidemiology, and End Results (SEER) database and identified patients diagnosed with non-CNS malignancy between 2000 and 2018. We calculated a modified standardized incidence ratio (M-SIR), defined as the ratio of the incidence of SPGBM among patients with initial non-CNS malignancy to the incidence of GBM in the general population, stratified by sex latency, and initial tumor location., Results: Of the 5,326,172 patients diagnosed with a primary non-CNS malignancy, 3559 patients developed SPGBM (0.07%). Among patients with SPGBM, 2312 (65.0%) were men, compared to 2,706,933 (50.8%) men in the total primary non-CNS malignancy cohort. The median age at diagnosis of SPGBM was 65 years. The mean latency between a prior non-CNS malignancy and developing a SPGBM was 67.3 months (interquartile range [IQR] 27-100). Overall, patients with a primary non-CNS malignancy had a significantly elevated M-SIR (1.13, 95% CI 1.09-1.16), with a 13% increased incidence of SPGBM when compared to the incidence of developing GBM in the age-matched general population. When stratified by non-CNS tumor location, patients diagnosed with primary melanoma, lymphoma, prostate, breast, renal, or endocrine malignancies had a higher M-SIR (M-SIR ranges: 1.09-2.15). Patients with lung cancers (M-SIR 0.82, 95% CI 0.68-0.99), or stomach cancers (M-SIR 0.47, 95% CI 0.24-0.82) demonstrated a lower M-SIR., Conclusion: Patients with a history of prior non-CNS malignancy are at an overall increased risk of developing SPGBM relative to the incidence of developing GBM in the general population. However, the incidence of SPGBM after prior non-CNS malignancy varies by primary tumor location, with some non-CNS malignancies demonstrating either increased or decreased predisposition for SPGBM depending on tumor origin. These findings merit future investigation into whether these relationships represent treatment effects or a previously unknown shared predisposition for glioblastoma and non-CNS malignancy., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Glioblastoma (GBM) is the most common brain tumor in the United States, with an annual incidence rate of 3.21 per 100,000. It is the most aggressive type of diffuse glioma and has a median survival of months after treatment. This study aims to assess the accuracy of different novel deep learning models trained on a set of simple clinical, demographic, and surgical variables to assist in clinical practice, even in areas with constrained health care infrastructure., Methods: Our study included 37,095 patients with GBM from the SEER (Surveillance Epidemiology and End Results) database. All predictors were based on demographic, clinicopathologic, and treatment information of the cases. Our outcomes of interest were months of survival and vital status. Concordance index (C-index) and integrated Brier scores (IBS) were used to evaluate the performance of the models., Results: The patient characteristics and the statistical analyses were consistent with the epidemiologic literature. The models C-index and IBS ranged from 0.6743 to 0.6918 and from 0.0934 to 0.1034, respectively. Probabilistic matrix factorization (0.6918), multitask logistic regression (0.6916), and logistic hazard (0.6916) had the highest C-index scores. The models with the lowest IBS were the probabilistic matrix factorization (0.0934), multitask logistic regression (0.0935), and logistic hazard (0.0936). These models had an accuracy (1-IBS) of 90.66%; 90.65%, and 90.64%, respectively. The deep learning algorithms were deployed on an interactive Web-based tool for practical use available via https://glioblastoma-survanalysis.herokuapp.com/., Conclusions: Novel deep learning algorithms can better predict GBM prognosis than do baseline methods and can lead to more personalized patient care regardless of extensive electronic health record availability., (Copyright © 2023 Elsevier Inc. All rights reserved.)

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.

Background: No study has compared the risk of Alzheimer's disease (AD) in patients with brain tumors, gliomas, or glioblastomas with the risk in patients with other tumors., Objective: To determine whether, compared with other tumors, brain tumors, gliomas, and glioblastomas increase the risk of AD., Methods: This study identified a case group of 24,441 patients from the Surveillance, Epidemiology, and End Results (SEER) database who were diagnosed with only one primary tumor at age > 20 years in 1975-2019 and died from AD at age > 65 years as case group. The control group comprised 122,205 subjects from the SEER database who died from causes other than AD but otherwise had the same conditions as those in the case group., Results: There was a significantly lower prevalence of glioma (0.074% versus 0.14%, p = 0.007) and glioblastoma (0.0082% versus 0.074%, p = 0.001) in patients who died from AD than in those who died from other causes, while brain tumors were not significantly associated with AD death (p = 0.227). When adjusted for factors including age at death, sex, race, tumor behavior, radiation therapy and tumor-directed surgery, glioblastoma was related to a significantly lower AD risk than other tumors (odds ratio: 0.19, 95% CI: 0.05-0.77). Additionally, patients who were older, female, American Indian/Alaska Native, had a benign tumor, radiation therapy and tumor-directed surgery had a significantly higher risk of dying from AD., Conclusion: Gliomas and glioblastomas were associated with a significantly lower risk of death from AD than other tumors.

Background: Disparities in treatment and outcomes disproportionately affect minority ethnic and racial populations in many surgical fields. Although substantial research in racial disparities has focused on outcomes, little is known about how surgeon recommendations can be influenced by patient race. The aim of this study was to investigate racial and socioeconomic disparities in the surgical management of primary brain tumors., Methods: In this registry-based cohort study, we used data from the Surveillance, Epidemiology, and End Results (SEER) database (1975-2016) and the American College of Surgeons National Cancer Database (NCDB) in the USA for independent analysis. Adults (aged ≥20 years) with a new diagnosis of meningioma, glioblastoma, pituitary adenoma, vestibular schwannoma, astrocytoma, and oligodendroglioma, with information on tumour size and surgical recommendation were included in the analysis. The primary outcome of this study was the odds of a surgeon recommending against surgical resection at diagnosis of primary brain neoplasms. This outcome was determined using multivariable logistic regression with clinical, demographic, and socioeconomic factors., Findings: This study included US national data from the SEER (1975-2016) and NCDB (2004-17) databases of adults with a new diagnosis of meningioma (SEER n=63 674; NCDB n=222 673), glioblastoma (n=35 258; n=104 047), pituitary adenoma (n=27 506; n=87 772), vestibular schwannoma (n=11 525; n=30 745), astrocytoma (n=5402; n=10 631), and oligodendroglioma (n=3977; n=9187). Independent of clinical and demographic factors, including insurance status and rural-urban continuum code, Black patients had significantly higher odds of recommendation against surgical resection of meningioma (adjusted odds ratio 1·13, 95% CI 1·06-1·21, p<0·0001), glioblastoma (1·14, 1·01-1·28, p=0·038), pituitary adenoma (1·13, 1·05-1·22, p<0·0001), and vestibular schwannoma (1·48, 1·19-1·84, p<0·0001) when compared with White patients in the SEER dataset. Additionally, patients of unknown race had significantly higher odds of recommendation against surgical resection for pituitary adenoma (1·80, 1·41-2·30, p<0·0001) and vestibular schwannoma (1·49, 1·10-2·04, p=0·011). Performing a validation analysis using the NCDB dataset confirmed these significant results for Black patients with meningioma (1·18, 1·14-1·22, p<0·0001), glioblastoma (1·19, 1·12-1·28, p<0·0001), pituitary adenoma (1·21, 1·16-1·25, p<0·0001), and vestibular schwannoma (1·19, 1·04-1·35, p=0·0085), and indicated and indicated that the findings are independent of patient comorbidities. When further restricted to the most recent decade in SEER, these inequities held true for Black patients, except those with glioblastoma (meningioma [1·18, 1·08-1·28, p<0·0001], pituitary adenoma [1·20, 1·09-1·31, p<0·0001], and vestibular schwannoma [1·54, 1·16-2·04, p=0·0031])., Interpretation: Racial disparities in surgery recommendations in the USA exist for patients with primary brain tumours, independent of potential confounders including clinical, demographic, and select socioeconomic factors. Further studies are needed to understand drivers of this bias and enhance equality in surgical care., Funding: None., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background and Purpose: To determine the refined estimates of the surgical effects on the short- and long-term prognoses of oldest-old patients (aged ≥80 years) with glioblastomas., Materials and Methods: Using the Surveillance, Epidemiology, and End Results registry, we identified the oldest-old patients with glioblastomas between 2005 and 2016. Propensity score matching, Kaplan-Meier analysis, Cox regression analysis, and competing risk model were used to assess the curative efficacy of the surgical treatments. Stratification and interaction analysis were performed to explore the potential interaction effects. The conditional survival rates were calculated to explore the longitudinal change in the survival probability over time., Results: This study enrolled 3309 patients with a median overall survival of 3 months. The overall survival differed significantly among the different surgical groups. Considering the gross total resection as reference, subtotal resection presented adjusted subdistribution hazard ratio (95% confidence interval) of 1.197 (1.052-1.362; p < 0.001); biopsy/partial resection, 1.242 (1.083-1.424; p = 0.002); and no surgery, 1.309 (1.145-1.497; p < 0.006). Age ≥ 83 years, widowed/other status, tumor size 4-5 cm, and temporal tumors showed significant interaction effects. The adjusted subdistribution hazard ratio of radical resection was 0.729 (0.645-0.825; p < 0.001). Based on disease-specific survival, the 1-year survival rate was 18% and 26% for the non-radical and radical surgery groups, respectively. The 1-year conditional survival rates in the second year were 54% and 39% in the non-radical and radical surgery groups, respectively. The 3-year survival rates were 10% in both the groups., Conclusions: Radical surgery may have short-term benefits in the oldest-old patients with glioblastoma, with a significant increase in the 1-year survival rate. However, its contribution in the long-term outcome is limited due to decreased conditional survival rates from the second year after surgery. Prudent patient selection and improved postoperative management may be needed to promote the therapeutic efficacy of tumor resection synergistically., Competing Interests: Conflicts of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: As lifespans for persons living with HIV (PLWH) have improved over the last decade, there has been a simultaneous increase in non-AIDS-related cancer in that group. However, there is a paucity of data regarding the incidence of glioblastoma multiforme (GBM) in PLWH. Better understanding of the oncogenesis, natural history, and treatment outcomes of GBM in PLWH should lead to improved treatment strategies., Methods: We performed a comprehensive literature search of six electronic databases to identify eligible cases of GBM among PLWH. Kaplan-Meier estimates, Fisher's exact test, and logistic regression were used to interrogate the data. Epidemiologic data on global HIV prevalence was obtained from the 2016 UNAIDS incidence report, and CNS cancer incidence was obtained from the GDB 2016 Brain and Other CNS Cancer Collaborators., Results: There is an inverse relationship between the incidence of HIV and CNS cancer globally. Median overall survival (OS) from GBM diagnosis was 8 months. Estimates for survival at 1 and 2 years were 28 and 5%, respectively. There were no statistically significant predictors of OS in this setting. There was a significant difference (p < 0.01) in OS in PLWH and GBM when compared to TCGA age matched cohorts., Conclusion: The diagnosis of GBM in PLWH is severely underreported in the literature. Despite maximal treatment, OS in this patient population is significantly less than in HIV-negative people. There was a poor prognosis of GBM in PLWH, which is inconsistent with previous reports. Further investigation is required for PLWH and concomitant GBM. Analyses must consider if HAART is maintained in PLWH during GBM treatment., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Purpose: Venous thromboembolic events (VTEs) are a major complication in cancer patients, and therefore, also in brain cancer patients, anticoagulants are considered appropriate in the treatment of VTEs., Methods: Frequency, risk factors, and treatment of VTEs, as well as associated complications, were assessed in a population-based cohort of glioblastoma patients in the Canton of Zurich, Switzerland. Correlations between clinical data and survival were retrospectively analyzed using the log-rank test and Cox regression models., Results: Four hundred fourteen glioblastoma patients with isocitrate dehydrogenase wild-type status were identified. VTEs were documented in 65 patients (15.7%). Median time from tumor diagnosis to the occurrence of a VTE was 1.8 months, and 27 patients were diagnosed with VTEs postoperatively (within 35 days; 42.2%). History of a prior VTE was more common in patients who developed VTEs than in those who did not (p = 0.004). Bevacizumab treatment at any time during the disease course was not associated with occurrence of VTEs (p = 0.593). Most patients with VTEs (n = 61, 93.8%) were treated with therapeutic anticoagulation. Complications occurred in 14 patients (23.0%), mainly intracranial hemorrhages (n = 7, 11.5%). Overall survival did not differ between patients diagnosed with VTEs and those who had no VTE (p = 0.139). Tumor progression was the major cause of death (n = 283, 90.7%), and only three patients (1.0%) died in association with acute VTEs., Conclusions: Venous thromboembolic events occurred early in the disease course, suggesting that the implementation of primary venous thromboembolism prophylaxis during first-line chemoradiotherapy could be explored in a randomized setting., (© 2022 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Objective: Glioblastoma Multiforme (GBM), a devastating the most common primary malignant intracranial brain tumors. In India, the incidence of this malignancy is escalating, however, there are very few studies on this tumor entity from Indian population. The present study sought to investigate the prevalence and prognostic significance of Signal Transducer and Activator of Transcription 3 (STAT3) gene expression in GBM patients from Western India., Method: STAT3 gene expression using real-time PCR was detected in total 55 GBM patients. The impact of STAT3 aberrant expression on progression-free survival (PFS) and overall (OS) was analysed using univariate and multivariate survival analysis. The data were analysed using SPSS statistical software and p value ≤0.05 was considered as significant., Results: The aberrant STAT3 expression was found in 85% (47/55) of patients with -1.12 fold change down-regulation in 49% (23/47) and 3.36 fold change up-regulation was noted in 51% (24/47) of patients. In wild type IDH tumors (n=30), down regulation and up regulation of STAT3 was noted in 63% and 27% of patients, respectively, whereas, for IDH mutant GBM tumors (n=25), the incidence of low expression and high expression of STAT3 was noted in 16% and 68% of patients, respectively. Thus, we found that incidence of STAT3 down regulation was significantly high in patients with IDH wild type tumors, whereas, in IDH mutant GBM tumors, the incidence of up-regulated STAT3 was significantly high (P=0.021, χ2=12.81, r=+0.310). In Kaplan-Meier univariate survival analysis, a part from age (P=0.006), tumor location (P=0.025), and KPS score (P=0.002), co-detection of STAT3 up regulation and presence of IDH mutation (P=0.030) remained significant prognostic factors for PFS and OS. In multivariate survival analysis also, co-detection of STAT3 high expression and presence of IDH mutation remained independent prognosticators for PFS (HR=6.45, 95% CI=1.32-31.40, P=0.021) and OS (HR=8.69, 95% CI=1.66-45.51, P=0.010)., Conclusion: For GBM tumors, STAT3 up-regulation and presence of IDH mutations together predicts better survival. This reflects unique molecular etiology for GBM patients. Therefore, they would be useful in the future for targeted therapy and for clinicians they would be useful for better patient management. However, study on a larger sample size is required for validation., (© 2022. The Author(s).)

Purpose: Social determinants of health (SDoH)-socioeconomic and environmental factors-impact outcomes. The Area Deprivation Index (ADI), a composite of seventeen SDoH factors, has been correlated with poorer outcomes. We aimed to compare outcomes and treatment access for glioblastoma, a universally fatal malignant brain tumor, in patients more (ADI 34-100%) versus less disadvantaged (ADI 0-33%)., Methods: A 5-year retrospective study of Rhode Island Hospital and Mayo Clinic databases was conducted from 2012 to 2017 for patients ≥ 18 years with glioblastoma. Patient addresses were matched to ADI percentiles and grouped into more (top 66% ADI) and less disadvantaged. Adjusted multivariable regressions were used to compare outcomes between groups., Results: A total of 434 patients met inclusion; 92.9% were insured, 56.2% were more disadvantaged (n = 244), and the more disadvantaged cohort was younger on average (62 years). After adjustment, the more disadvantaged group had decreased odds of receiving gross total resection (adjusted odds ratio (aOR) 0.43, 95% CI [0.27-0.68]; p < 0.001). This cohort also had decreased odds of undergoing chemotherapy (aOR 0.51[0.26-0.98]), radiation (aOR 0.39[0.20-0.77]), chemoradiation (aOR 0.42[0.23-0.77]), tumor-treating fields (aOR 0.39[0.16-0.93]), and clinical trial participation (aOR 0.47[0.25-0.91]). No differences in length of survival or postoperative Karnofsky Performance Status Scale were observed., Conclusion: More disadvantaged glioblastoma patients had decreased odds of receiving gross total resection. They also exhibited decreased odds of receiving standard of care like chemoradiation as well as participating in a clinical trial, compared to the less disadvantaged group. More research is needed to identify modifiable SDoH barriers to post-operative treatment in disadvantaged patients with glioblastoma., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Survival of patients with glioblastoma (GBM) increased in the 2000s, most prominently after the addition of temozolomide to the standard-of-care treatment protocol. The reason for subsequent improvements in survival in the late 2000s and early 2010s was less clear, with explanations including the introduction of bevacizumab, better surgical methods, and advances in supportive care. It is uncertain whether the trend of improving population-level survival has continued., Materials and Methods: Data from the Surveillance, Epidemiology, and End Results (SEER) Program was analyzed comparing survival of adult GBM patients diagnosed in consecutive 3-year periods from 2000 to 2017. Kaplan-Meier survival analysis and Cox proportional hazards models were used., Results: A total of 38,352 patients diagnosed with GBM between 2000 and 2017 met inclusion criteria. Median survival and percent survival to 12 and 24 months all progressively increased between 2000 and 2011. There were no significant differences in survival comparing 2009-2011 with 2012-2014 or 2015-2017. During the 2015-2017 period, median survival was 11 months, with 12 and 24-month survival proportions of 45.7% (95% confidence interval, 44.5-47.0) and 19.0% (95% confidence interval, 18.6-21.2), respectively., Conclusions: After a period of progressive improvement in GBM survival between 2000 and 2011, survival plateaued. Subsequent advances since 2011 have not yet been translated to improved survival on the population-level as of 2017., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Biological sex impacts a wide array of molecular and cellular functions that impact organismal development and can influence disease trajectory in a variety of pathophysiological states. In nonreproductive cancers, epidemiological sex differences have been observed in a series of tumors, and recent work has identified previously unappreciated sex differences in molecular genetics and immune response. However, the extent of these sex differences in terms of drivers of tumor growth and therapeutic response is less clear. In glioblastoma (GBM), the most common primary malignant brain tumor, there is a male bias in incidence and outcome, and key genetic and epigenetic differences, as well as differences in immune response driven by immune-suppressive myeloid populations, have recently been revealed. GBM is a prototypic tumor in which cellular heterogeneity is driven by populations of therapeutically resistant cancer stem cells (CSCs) that underlie tumor growth and recurrence. There is emerging evidence that GBM CSCs may show a sex difference, with male tumor cells showing enhanced self-renewal, but how sex differences impact CSC function is not clear. In this mini-review, we focus on how sex hormones may impact CSCs in GBM and implications for other cancers with a pronounced CSC population. We also explore opportunities to leverage new models to better understand the contribution of sex hormones vs sex chromosomes to CSC function. With the rising interest in sex differences in cancer, there is an immediate need to understand the extent to which sex differences impact tumor growth, including effects on CSC function., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: For recurrent glioblastoma (GB) patients, several therapy options have been established over the last years such as more aggressive surgery, re-irradiation or chemotherapy. Age and the Karnofsky Performance Status Scale (KPSS) are used to make decisions for these patients as these are established as prognostic factors in the initial diagnosis of GB. This study's aim was to evaluate preoperative patient comorbidities by using the age-adjusted Charlson Comorbidity Index (ACCI) as a prognostic factor for recurrent GB patients., Methods: In this retrospective analysis we could include 123 patients with surgery for primary recurrence of GB from January 2007 until December 2016 (43 females, 80 males, mean age 57 years (range 21-80 years)). Preoperative age, sex, ACCI, KPSS and adjuvant treatment regimes were recorded for each patient. Extent of resection (EOR) was recorded as a complete/incomplete resection of the contrast-enhancing tumor part., Results: Median overall survival (OS) was 9.0 months (95% CI 7.1-10.9 months) after first re-resection. Preoperative KPSS > 80% (P < 0.001) and EOR (P = 0.013) were associated with significantly improved survival in univariate analysis. Including these factors in multivariate analysis, preoperative KPSS < 80 (HR 2.002 [95% CI: 1.246-3.216], P = 0.004) and EOR are the only significant prognostic factor (HR 1.611 [95% CI: 1.036-2.505], P = 0.034). ACCI was not shown as a prognostic factor in univariate and multivariate analyses., Conclusion: For patients with surgery for recurrent glioblastoma, the ACCI does not add further information about patient's prognosis besides the well-established KPSS and extent of resection., (© 2022. The Author(s).)

Objective: Glioblastomas multiforme (GBMs) are the most common primary CNS tumors. Epidemiologic studies have investigated the effect of demographics on patient survival, but the literature remains inconclusive., Methods: This study included all adult patients with intracranial GBMs reported in the surveillance epidemiology and end results (SEER)-9 population database (1975-2018). The sample consisted of 32,746 unique entries. We forecast the annual GBM incidence in the US population through the year 2060 using time series analysis with autoregressive moving averages. A survival analysis of the GBM-specific time to death was also performed. Multivariate Cox proportional hazards (PH) regression revealed frank violations of the PH assumption for multiple covariates. Parametric models best described the GBM population's survival pattern; the results were compared to the semi-parametric analysis and the published literature., Results: We predicted an increasing GBM incidence, which demonstrated that by the year 2060, over 1,800 cases will be reported annually in the SEER. All eight demographic variables were significant in the univariable analysis. The calendar year 2005 was the cutoff associated with an increased survival probability. A male survival benefit was eliminated in the year-adjusted Cox. Infratentorial tumors, nonmetropolitan areas, and White patient race were the factors erroneously associated with survival in the multivariate Cox analysis. Accelerated Failure Time (AFT) lognormal regression was the best model to describe the survival pattern in our patient population, identifying age >30 years old as a poor prognostic and patients >70 years old as having the worst survival. Annual income >USD 75,000 and supratentorial tumors had good prognostics, while surgical intervention provided the strongest survival benefit., Conclusions: Annual GBM incidence rates will continue to increase by almost 50% in the upcoming 30 years. Cox regression analysis should not be utilized for time-to-event predictions in GBM survival statistics. AFT lognormal distribution best describes the GBM-specific survival pattern, and as an inherent population characteristic, it should be implemented by researchers for future studies. Surgical intervention provides the strongest survival benefit, while patient age >70 years old is the worst prognostic. Based on our study, the demographics such as gender, race, and county type should not be considered as meaningful prognostics when designing future trials., (© 2022 S. Karger AG, Basel.)

Background: Prevalence and dynamics of certain morphological variants of neuroglial brain malignancies (ICD-10 C71) are unknown in the Russian Federation., Objective: To assess the incidence of neuroglial brain malignancies in 2000-2020 considering individual records of morphologically verified cases in the cancer registry of the Arkhangelsk region., Material and Methods: We analyzed overall and age-adjusted incidence of neuroglial brain malignancies in 2000-2020 considering morphological subtypes of tumor. Incidence of morphologically verified glioblastoma was assessed in detail taking into account gender, age and place of residence. Segmented regression analysis was used to assess the dynamics and significance of linear trends., Results: In total, there were 1699 brain malignancies for the period from 2000 to 2020. Morphological verification was obtained in 1289 (76%) patients including 467 (27%), 92 (5%) and 307 (18%) ones with glioblastoma, anaplastic G3 glioma and G2 glioma, respectively. Percentage of glioblastoma and anaplastic gliomas increased from 23.4% and 3.9% in 2000 to 55.3% and 9.2% in 2020, respectively. Age-adjusted incidence for the entire C71 group decreased from 5.2 to 3.2 cases per 100,000 after 2015 (annual decline 7.1%). However, incidence of glioblastoma monotonously increased from 1.0 to 2.1 per 100,000 (annual increment 6.2%). Incidence was similar in men and women. Age-adjusted incidence was 50-70% higher among rural population., Conclusion: Significant increase (>2 times) in the incidence of glioblastoma was found over the past twenty years. Probably, it is associated with improved diagnosis and registration of this disease. In-depth analysis of morbidity and survival of patients with rare neuroglial tumors is required.

Objective: To evaluate different hypofractionated radiotherapy (HRT) regimens for newly diagnosed elderly glioblastoma (GBM) patients., Methods: We performed a systematic review with network meta-analysis (NMA), including searches on CENTRAL, Medline, EMBASE, CINAHL, clinical trial databases and manual search. Only randomized clinical trials (RCTs) were included. Primary outcomes: overall survival (OS) and adverse events (AE). Secondary outcomes: progression-free-survival (PFS) and quality of life (QoL). We used the Cochrane Risk of Bias (RoB) table for assessing individual studies and CINeMA for evaluating the certainty of the final body of evidence., Results: Four RCTs (499 patients) were included. For OS, the estimates from NMA did not provide strong evidence of a difference between the HRTs: 40 Gray (Gy) versus 45 Gy (HR: 0.89; CI 95%: 0.42, 1.91); 34 Gy versus 45 Gy (HR: 0.85; CI 95% 0.43, 1.70); 25 Gy versus 45 Gy (HR: 0.81; CI 95% 0.32, 2.02); 34 Gy versus 40 Gy (HR: 0.95; CI 95% 0.57, 1.61); and 25 Gy versus 34 Gy (HR: 0.95; CI 95% 0.46, 1.97). We performed qualitative synthesis for AE and QoL due to data scarcity and clinical heterogeneity among studies. The four studies reported a similar QoL (assessed by different methods) between arms. One RCT reported grade ≥ 3 AE, with no evidence of a difference between arms. PFS was reported in one study (25 Gy versus 40 Gy), with no evidence of a difference between arms., Conclusion: This review found no evidence of a difference between the evaluated HRTs for efficacy and safety., Competing Interests: The authors have declared that no competing interests exist.

Background: Glioblastoma (GBM) is a malignant human brain tumor that has an extremely poor prognosis. Classic mutations such as IDH (isocitrate dehydrogenase) mutations, EGFR (epidermal growth factor receptor) alternations, and MGMT (O6-methylguanine-methyltransferase) promoter hypermethylation have been used to stratify patients and provide prognostic significance. Epigenetic perturbations have been demonstrated in glioblastoma tumorigenesis. Despite the genetic markers used in the management of glioblastoma patients, new biomarkers that could predict patient survival independent of known biomarkers remain to be identified., Methods: ATAC-seq (assay for transposase accessible chromatin followed by sequencing) and RNA-seq have been used to profile chromatin accessible regions using glioblastoma patient samples with short-survival versus long-survival. Cell viability, cell cycle, and Western blot analysis were used to characterize the cellular phenotypes and identify signaling pathways., Results: Analysis of chromatin accessibility by ATAC-seq coupled with RNA-seq methods identified the GSTM1 (glutathione S-transferase mu-1) gene, which featured higher chromatin accessibility in GBM tumors with short survival. GSTM1 was confirmed to be a significant prognostic marker to predict survival using a different GBM patient cohort. Knockdown of GSTM1 decreased cell viability, caused cell cycle arrest, and decreased the phosphorylation levels of the NF-kB (nuclear factor kappa B) p65 subunit and STAT3 (signal transducer and activator of transcription 3) (pSer727)., Conclusions: This report demonstrates the use of ATAC-seq coupled with RNA-seq to identify GSTM1 as a prognostic marker of GBM patient survival. Activation of phosphorylation levels of NF-kB p65 and STAT3 (pSer727) by GSTM1 is shown. Analysis of chromatin accessibility in patient samples could generate an independent biomarker that can be used to predict patient survival., (© 2021. The Author(s).)

Introduction: Glioblastoma is an aggressive cancer with a notoriously poor prognosis. Recent advances in treatment have increased overall survival, though this may be accompanied by an increased incidence of leptomeningeal disease (LMD). LMD carries a particularly severe prognosis and remains a late stage manifestation of glioblastoma without satisfactory treatment. The objective of this review is to survey the literature on treatment of LMD in glioblastoma and to more fully characterize the current therapeutic strategies., Methods: The authors performed a systematic review following PRISMA criteria on PubMed and OVID databases. Articles that included adult patients with LMD from glioblastoma were retrieved and reviewed., Results: LMD in glioblastoma patients is increasing in incidence, with reports of up to 21%. The overall survival without treatment is alarmingly brief, with patients surviving between 1.6-3.8 months. All studies showed that treatment does improve overall survival significantly, increasing to 11.7 months in one study. However, no one adjuvant or surgical therapy has been shown to improve survival in LMD significantly over another. Direct treatment methods include chemotherapy (standard, anti-angiogenic, intrathecal, immunotherapy), and radiation. Hydrocephalus is a complication in LMD that can be treated with ventriculoperitoneal shunt placement, however treating hydrocephalus and delivering intrathecal chemotherapy is a challenge., Conclusion: Though evidence remains lacking and there is no consensus, treatments show a trend towards improving survival and should be considered on a case-by-case basis. Further studies are necessary in the pursuit of a standard of care., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Meningiomas are the most common primary brain tumors, followed by glioblastomas. Nevertheless, no previous studies have been conducted to evaluate the epidemiology of meningiomas and glioblastomas in the southern region of Italy. Thus, the aim of our study was to evaluate incidence, temporal trend and survival rate of meningiomas and glioblastomas in the province of Catania during the study period. Moreover, a geoepidemiological analysis was performed in order to identify possible geographical and temporal clusters., Methods: All subjects with meningiomas and glioblastomas diagnosed from 2003 to 2016 in the province of Catania were collected, using the local cancer registry. Incidence rate (IR) was calculated by gender, age-groups and tumor behavior. Temporal changes in incidence trend were assessed using a Joinpoint regression analysis while survival analysis was performed using Kaplan-Meier method. Cluster analysis was performed using Kulldorff's spatial scan statistic., Results: In the province of Catania, a total of 1488 cases of meningiomas and 443 cases of glioblastomas were identified from 2003 to 2016, with an IR of 9.8/100,000 person-years (95%CI 9.3-10.3) and 2.9/100,000 person-years (95%CI 2.7-3.2), respectively. Meningiomas were more common among women (p-value<0.0001), while glioblastomas among men (p-value<0.0001). IR progressively increased over the ages, reaching a peak in the 75-84 and 65-74 years-old group in, respectively, meningiomas and glioblastomas. Mean survival was higher in subjects diagnosed with meningiomas as compared to those with glioblastomas (10.7 years and 15.8 months, respectively), with age as the strongest risk factor for death. Spatial and space-time cluster of high incidence of meningiomas was detected in a small community on the eastern flank of the Mt. Etna volcano., Conclusions: Epidemiology of meningioma and glioblastoma in the province of Catania is close to that reported worldwide. Spatial and space-time cluster of meningiomas were found in Pedara. Further studies on risks factor are necessary., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background/aim: Microsatellite instability tests and programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) in the immune checkpoint pathway are the tests that determine who will benefit from immune checkpoint inhibitor therapy. We aimed to show the expression of DNA mismatch repair proteins and PD-1/PD-L1 molecules that inhibit immune checkpoints, to explain the relationship between them, and to demonstrate their predictive role in recurrent and nonrecurrent glioblastoma., Materials and Methods: We analyzed 27 recurrent and 47 nonrecurrent cases at our archive. We performed immunohistochemical analysis to determine expressions of PD-1, PD-L1, and mismatch repair proteins in glioblastoma. We evaluated the relationship between these two group and compared the results with the clinicopathological features., Results: The mean age of diagnosis was significantly lower in recurrent glioblastoma patients. Median survival was longer in this group. We found that PD-L1 expression was reduced in recurrent cases. Additionally, recurrent cases had a significantly higher rate of microsatellite instability. Loss of PMS2 was high in both group but was substantially higher in recurrent cases., Conclusion: The presence of microsatellite instability and low PD-L1 levels, which are among the causes of treatment resistance in glioblastoma, were found to be compatible with the literature in our study, with higher rates in recurrent cases. In recurrent cases with higher mutations and where immunotherapy resistance is expected less, low PD-L1 levels thought that different combinations with other immune checkpoint inhibitors can be tried as predictive and prognostic marker in GBM patients., (This work is licensed under a Creative Commons Attribution 4.0 International License.)

Glioblastoma is an aggressive disease that is difficult to treat, in large part due to the high level of molecular heterogeneity that limits the utility of targeted therapies. As such, population studies have been essential in characterizing the factors that promote survival. In this review, we summarize the findings in these studies. Demographic trends, molecular markers (IDH mutation, MGMT promoter methylation, TERT promoter mutation, chromosome 1p19q codeletion, PTEN, and p53 among others), radiographic correlates (peritumoral edema, enhancement, cyst formation, necrosis, and invasion among others), nonsteroidal anti-inflammatory drug (NSAID) and statin use, and ketogenic diet have been assessed. Overall, studies have found that IDH mutation and MGMT promoter methylation are positive prognostic markers and TERT is a negative prognostic marker, although subgroup analysis has revealed differential responses. NSAID and statin use have also suggested improved survival reaching significance in some studies. Ketogenic diet has not yet been adequately assessed. Further studies to characterize the interplay of these and other genetic and environmental factors are warranted.

Access to healthcare in Mexico is available to its population via publicly and privately funded institutions. The public sector, administered by both the local and federal government under the jurisdiction of the Department of Health, provides healthcare to the majority of the country's population. Privately funded institutions vary in size and scope of practice, ranging from small clinics focused on family practice, to large tertiary hospitals with capacity for treating patients with complex conditions and performing clinical research. The evaluation and treatment of patients with cancer in Mexico is also available through both sectors. In the country's capital, Mexico City, patients with glioblastoma are primarily treated at the National Institute of Neurology and Neurosurgery and the National Institute of Oncology. Epidemiological data is incomplete due to the lack of a national cancer registry. In the case of neoplasms of the central nervous system, the available information suggests that gliomas represent 33% of all intracranial tumors. The treatment of patients in Mexico diagnosed with glioblastoma has not been standardized owing to the lack of resources in some communities and the expense of antineoplastic agents. Current options range from a biopsy only to maximal safe resection followed by adjuvant treatment with radiation and chemotherapy. Currently, basic science and clinical research is being conducted in academic institutions associated with universities and in private hospitals. Studies include the evaluation of tumor biology, neuroimaging biomarkers and new treatment options such as the use of chloroquine.

Background: Glioblastoma (GBM) is the most common primary brain tumor. Epidemiologic studies on GBM are rarely reported in the special age group of adolescents and young adults (AYA) in comparison to other age groups. We aim to present data on GBM in Jordan, with a focus on the AYA age, including the incidence, gender, location and outcome, as well as long term survival (LTS)., Methods: Data on GBM was requested from the Jordan Cancer Registry (JCR), and statistical analysis was performed. All data were retrospective and anonymized., Results: Eight hundred GBM cases were analyzed from 2000 to 2016 including 505 males (63.1 %). Males outnumbered females across are studied years (p-value <0.001). There were 49 pediatrics (0-14 years, 6.1 %), 125 AYA (15-39 years, 15.6 %), 358 adults (40-59 years, 44.8 %) and 268 elderly (60+ years, 33.5 %) cases. Supratentorial location predominated across all age groups (p-value <0.001). The preponderance of males and supratentorial tumors remained across the AYA age group in comparison to others. The median overall survival (OS) was 23.61 months. AYA age group had a better outcome in comparison to the adults/elderly age group (p-value< 0.001). LTS appear to be more common in the AYA age group (p-value 0.021)., Conclusions: This is the first comparative epidemiologic study of GBM in Jordan, focusing on the AYA age group. The AYA age group appears to be associated with a better outcome compared to older age groups, with more LTS compared to others., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Glioblastoma (GBM) is the most common type of brain cancer with poor survival outcomes and unsatisfactory response to current therapeutic strategies. Recent studies have demonstrated that ferroptosis-related genes (FRGs) are linked with the occurrence and development of GBM and may become promising biological indicators in GBM therapy., Methods: We systematically assessed the relationship between FRGs expression profiles and prognosis in glioma patients based on the Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) datasets to establish a risk score model according to the gene signature of multiple survival-associated DEGs. Further, the differences between the tumor microenvironment score, immune cell infiltration, immune checkpoint expression levels, and drug sensitivity in the high- and low-risk group are analyzed through a variety of algorithms in R software., Results: GBM patients were divided into two subgroups (high- and low-risk) according to the established risk score model. Patients in the high-risk group showed significantly reduced overall survival compared with those in the low-risk group. Also, we found that the high-risk group showed higher ImmuneScore and StromalScore, while different subgroups have significant differences in immune cell infiltration, immune checkpoint expression levels, and drug sensitivity. In summary, we developed and validated an FRGs risk model, which served as an independent prognostic indicator for GBM. Besides, the two subgroups divided by the model have significant differences, which provides novel insights for further studies as well as the personalized treatment of patients.

Glioblastoma is the most common primary malignant brain tumour. Despite advances in diagnostic and therapeutic treatments, it is still associated with poor outcome The purpose of this study of cases is to describe the epidemiological, clinical, therapeutic and evolutionary features of patients with glioblastoma admitted to the Department of Hematology-Oncology (DHO) in Marrakech in 2016 and 2017. We conducted a literature review of epidemiological, clinical, radiological, anatomopathological, therapeutic and evolutionary data from 40 patients. Glioblastoma accounted for 47.6% of treated intracranial tumours. The average age of patients was 52.4±12.3 years. Functional impotence and signs of intracranial hypertension were the main symptoms. Tumours mainly occurred in the parietal region (44%) and were large (57.5%). Aphasia was related to tumour size (p=0.042). Nine cases had glioblastomas-IDH1-wild and one case had glioblastoma-IDH1-mutant. On admission, patients had poor performance-status. This was due to a prolonged time between surgery and DHO admission (p= 0.034). Patients with sensory impairments were older (62.5±3 years) than those without sensory impairments (51.2±12 years) (p=0,045). In-patient women received chemoradiotherapy (1.5±1 month) earlier than men (2.3±1.2 months) (p=0.03). Survival was 13.6±5.3 months; it was unrelated to the time to surgery (p=0.076), the time to DHO (p=0.058), and the time to chemoradiotherapy (p=0.073). The epidemiological, clinical, radiological and evolutionary features of our sample were comparable to literature data. The molecular profiling was not systematically realized. Despite prolonged treatment times, no link to survival was detected., Competing Interests: Les auteurs ne déclarent aucun conflit d´intérêts., (Copyright: Moulay Yassine Belghali et al.)

Purpose: Patients with glioblastoma (GBM) or brain metastases (MET) and atrial fibrillation (AF) might be at an increased risk of intracranial hemorrhage (ICH) due to anticoagulation (AC). Our aim was to assess this risk., Methods: Our institution's database (from 2005 to 2017) was screened for patients with GBM or MET and AF with an indication for AC according to their CHA 2 DS 2 VASc stroke risk score (≥ 2). Required follow-up was at least 3 months. AC was either performed with heparins, phenprocoumon or non-Vitamin K antagonist oral anticoagulants. Applying the propensity score approach, patient cohorts (matched according to primary tumor, age, sex) were generated (GBM [or MET] with AF ± AC, GBM [or MET] without AF/AC, no GBM [or MET] but AF on AC). ICH was defined as clinical deterioration caused by new blood on imaging. A log rank test was performed to compare the risk for ICH between the three groups., Results: In total, 104 patients were identified of which 49 with GBM (37% on AC) and 37 with MET (46% on AC) were successfully matched. Median follow up was 8.6 and 7.2 months, respectively. ICH occurred in 10.2% of GBM + AF and 12.2% GBM-AF, whereas 8% of patients with AF on AC suffered ICH (p = 0.076). 13.5% of patients with MET + AF had ICHs, in the controls it was 16% for MET-AF and 8% for AF on AC (p = 0.11)., Conclusion: AC did not seem to influence the incidence of ICH in patients with glioblastoma or brain metastases within follow up of just under 9 months.

Background: Glioblastoma (GBM) is the most common and malignant gliomas of adults and recur, resulting in death, despite surgery, radiotherapy, and temozolomide-based chemotherapy. There are a few reports on immunotherapy for the mismatch repair (MMR)-deficient GBMs with high tumor mutational burden (TMB). However, the clinicopathological and genetic features of the MMR genes altered in GBMs have not been elucidated yet., Methods: The authors analyzed targeted next-generation sequencing (NGS) data from 282 (276 primary and 6 recurrent) glioblastomas to evaluate the mutational status of six DNA repair-related genes: MLH1, MSH2, MSH6, PMS2, POLE, and POLD1. Tumors harboring somatic or germline mutations in one or more of these six genes were classified as an MMR gene-altered GBM. The clinicopathologic and molecular characteristics of MMR gene-altered GBMs were compared to those of tumors without MMR gene alterations., Results: Sixty germline or somatic mutations were identified in 37 cases (35 primary and two recurrent) of GBM. The most frequently mutated genes were MSH6 and POLE. Single nucleotide variants were the most common, followed by frameshift deletions or insertions and approximately 60% of the mutations were germline mutations. Two patients who showed MSH2 (c.2038C > T) and MSH6 (c.1082G > A) mutations had familial colon cancer. The clinical findings were not different between the two groups. However, the presence of MGMT promoter methylation and high tumor mutation burden (TMB) values (> 20) were correlated with MMR gene alterations., Conclusion: Since MMR-related genes can be found even in primary glioblastoma and are correlated with high TMB and MGMT promoter methylation, MMR genes should be carefully analyzed in NGS study on glioblastomas.

Background: Cancer patients in general and glioblastoma patients, in particular, have an increased risk of developing complications from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and reaching a balance between the risk of exposure to infection and the clinical benefit of their treatment is ideal. The aggressive behavior of this group of tumors justifies the need for a multidisciplinary team to assist in clinical decisions during the current pandemic. Brazil is now ranked #2 in the number of cases and deaths from COVID-19 pandemic, and existing disparities in the treatment of neuro-oncology patients in Brazil will challenge the clinical and surgical decisions of this population, possibly affecting global survival., Objective: To search the literature about the management of glioblastomas during COVID-19 pandemic to guide surgical and clinical decisions in this population of patients in Brazil., Methods: We performed a systematic search on the PubMed electronic database targeting consensus statements concerning glioblastoma approaches during COVID-19 pandemic up to July 18, 2020., Results: When approaching glioblastoma during the COVID-19 pandemic, important parameters that help in the decision-making process are age, performance status, tumor molecular profile, and patient consent. Younger patients should follow the standard protocol after maximal safe resection, mainly those with MGMT methylated tumors. Aged and underperforming patients should be carefully evaluated, and probably a monotherapy scheme is to be considered. Centers are advised to engage in telemedicine and to elaborate means to reduce local infection., Conclusion: Approaching glioblastoma during the COVID-19 pandemic will be challenging worldwide, but particularly in Brazil, where a significant inequality of healthcare exists.

Objective: The clinical impact and optimal method of assessing nutritional status (NS) have not been rigorously examined in glioblastoma. We investigated the relationship between NS and postoperative survival (PS) in glioblastoma using 4 nutritional indices and identified which index best modeled PS., Methods: NS was retrospectively assessed for patients with glioblastoma undergoing surgery at our institution from 2007 to 2019 using the albumin level, albumin/globulin ratio (AGR), nutritional risk index (NRI), and prognostic nutritional index (PNI). Optimal cut points for each index were identified using maximally selected rank statistics and previously established criteria. The predictive value of each index on PS was determined using Cox proportional hazards models adjusted for prognostic variables. The best-performing model was identified using the Akaike Information Criterion., Results: Our analysis included 242 patients (64% male) with a mean age of 57.6 years, Karnofsky Performance Status of 77.6, 5-factor modified frailty index of 0.59, albumin level of 4.2 g/dL, AGR of 1.9, NRI of 105.6, and PNI of 47.4. Median PS after index and repeat surgery was 12.7 and 7.8 months, respectively. On multivariable analysis, low albumin level (hazard ratio [HR], 2.09; 95% confidence interval [CI], 1.52-2.89; P < 0.001), mild NRI (HR, 1.61; 95% CI, 1.04-2.49; P = 0.032), moderate/severe NRI (HR, 2.51; 95% CI, 1.64-3.85; P < 0.001), and low PNI (HR, 2.51; 95% CI, 1.78-3.53; P < 0.001), but not low AGR (HR, 1.17; 95% CI, 0.89-1.54; P = 0.270), predicted decreased PS. PNI had the lowest Akaike Information Criterion., Conclusions: NS predicts PS in glioblastoma. PNI may provide the best model for assessing NS. NS is an important modifiable aspect of brain tumor management that warrants increased attention., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: The incidence of glioblastoma increases significantly with age. With the growing and aging population, there is a lack of comprehensive analysis of recent glioblastoma incidence trend in the United States. This study aims to provide in-depth description of the patterns of incidence trends and to examine the age-period-cohort effects to the trends of glioblastoma specific to elderly patients., Methods: The incidence rates were age-adjusted and reported per 100,000 population. We calculated the annual percent change (APC) in incidence using the Joinpoint Regression Program and conducted an age-period-cohort analysis of elderly glioblastoma reported between 2000 and 2017 to the Surveillance Epidemiology and End Results (SEER) 18 registry database., Results: The overall incidence rate of elderly patients with glioblastoma was 13.16 per 100,000 (95% CI, 12.99-13.32) from 2000 to 2017. Non-Hispanic whites (20,406, 83.6%) made up the majority. The incidence rate of male was about 1.62 times that of female. The trend of incidence remained stable and there was a non-significant increasing tendency for all elderly patients (APC 0.3, 95% CI, - 0.1 to 0.7, p = 0.111). There was a significantly increasing incidence trend for non-Hispanic white (APC 0.6, 95% CI, 0.2 to 1.1, p = 0.013), supratentorial location (APC 0.7, 95% CI, 0.2 to 1.3, p = 0.016), tumor size < 4 cm (APC 2.5, 95% CI, 1.4 to 3.6, p < 0.001), and a significantly decreasing trend for overlapping/NOS location (APC -0.9, 95% CI, - 1.6 to - 0.2, p = 0.012), and unknown tumor size (APC -4.9, 95% CI, - 6.6 to - 3.3, p < 0.001). The age-period-cohort analysis showed the effect of age on incidence trends (p< 0.001, Wald test), while did not indicate the period and cohort effects of the incidence trends of glioblastoma (p = 0.063 and p =0.536, respectively, Wald test)., Conclusion: The overall incidence of glioblastoma in the elderly population remained stable between 2000 and 2017. Period and cohort effects were not evident in the trend of glioblastoma incidence. Future population-based studies exploring the difference in the trend of glioblastoma incidence by specific molecular subgroups are warranted to further our understanding of the etiology of glioblastoma.

Introduction: Glioblastoma (GBM) is an aggressive brain tumor associated with high degree of resistance to treatment. Given its heterogeneity, it is important to understand the molecular landscape of this tumor for the development of more effective therapies. Because of the different genetic profiles of patients with GBM, we sought to identify genetic variants in Lebanese patients with GBM (LEB-GBM) and compare our findings to those in the Cancer Genome Atlas (TCGA)., Methods: We performed whole exome sequencing (WES) to identify somatic variants in a cohort of 60 patient-derived GBM samples. We focused our analysis on 50 commonly mutated GBM candidate genes and compared mutation signatures between our population and publicly available GBM data from TCGA. We also cross-tabulated biological covariates to assess for associations with overall survival, time to recurrence and follow-up duration., Results: We included 60 patient-derived GBM samples from 37 males and 23 females, with age ranging from 3 to 80 years (mean and median age at diagnosis were 51 and 56, respectively). Recurrent tumor formation was present in 94.8% of patients (n = 55/58). After filtering, we identified 360 somatic variants from 60 GBM patient samples. After filtering, we identified 360 somatic variants from 60 GBM patient samples. Most frequently mutated genes in our samples included ATRX, PCDHX11, PTEN, TP53, NF1, EGFR, PIK3CA, and SCN9A. Mutations in NLRP5 were associated with decreased overall survival among the Lebanese GBM cohort (p = 0.002). Mutations in NLRP5 were associated with decreased overall survival among the Lebanese GBM cohort (p = 0.002). EGFR and NF1 mutations were associated with the frontal lobe and temporal lobe in our LEB-GBM cohort, respectively., Conclusions: Our WES analysis confirmed the similarity in mutation signature of the LEB-GBM population with TCGA cohorts. It showed that 1 out of the 50 commonly GBM candidate gene mutations is associated with decreased overall survival among the Lebanese cohort. This study also highlights the need for studies with larger sample sizes to inform clinicians for better prognostication and management of Lebanese patients with GBM., Competing Interests: The authors have declared that no competing interests exist.