bluuebunny/crossref_metadata_2025_split huggingface dataset:
DDDR-48. EZH2 INHIBITION AS A POTENTIAL THERAPEUTIC AVENUE IN THE TREATMENT OF MENINGIOMA
Authors: Casaos Joshua , Vitte Jeremie , Perryman Travis , Harary Maya , Shah Shilp , Na Brian , Everson Richard , Giovannini Marco 
Published: November 2024

Abstract

INTRODUCTION
High grade meningiomas provide challenges to treatment as these neoplasms are more likely to recur, exhibit invasion of brain parenchyma, and result in decreased long term survival. Recent works demonstrate the epigenetic modifier, EZH2, to be increased in higher grade meningiomas, and to correlate with poor survival. The selective targeting of EZH2 has shown promise in other malignancies with overexpression of or gain-of-function mutations in EZH2, leading to promising findings. Here we sought to investigate the effect of EZH2 inhibition on meningioma cell growth and viability, using a panel of in vitro models.

METHODS
Human immortalized meningioma cell lines, mouse meningioma cell lines and a panel of human primary cell cultures with varying baseline protein expression of NF2, SMARCB1, and EZH2, were selected for investigation. Cells were treated with several selective small molecule inhibitors of EZH2. Cell proliferation, cell cycle and cell death processes were assessed. RNAseq was used to assess transcriptional changes in response to EZH2 inhibition. Western blots were used to assess protein changes in response to EZH2 inhibition.

RESULTS
EZH2 inhibition significantly impairs meningioma cell proliferation, at varying IC50s, in all cell lines and primary cultures tested, utilizing a panel of EZH2 inhibitors. EZH2 inhibition resulted in significantly decreased colony formation in a high-grade cell line. Furthermore, EZH2 inhibition results in a reduction of Ki67+ cells, induction of cell cycle arrest, and apoptosis. Similar grouping of differential gene expression in immortalized cell lines and primary cell cultures is observed across cell lines and primary cell cultures, after EZH2 inhibition.

CONCLUSION
Our work demonstrates that EZH2 inhibition results in growth inhibition, cell cycle arrest, and cell death, across all cell lines, and cell cultures tested. Futhermore, modulation of protein levels of the EZH2 target H3K27 is observed upon treatment. RNA changes are broad and involve cell proliferative and migratory processes. This work provides the framework for further investigation of EZH2 inhibition in meningioma.
EPID-02. BLOOD-BASED CLASSIFICATION OF IDH-STATUS OF NON-ENHANCING GLIOMAS: A MACHINE LEARNING APPROACH
Authors: Hadad Sara , Warrier Gayathri , Mccoy Lucie , Hansen Helen , Chen Jiaying , Rice Terri , Wrensch Margaret , Taylor Jennie , Clarke Jennifer , Wiencke John , Molinaro Annette 
Published: November 2024

Abstract

BACKGROUND
Non-invasive determination of IDH mutational status in patients with glioma could offer significant therapeutic opportunities. While IDH wildtype (WT) tumors typically show enhancement on MRI, IDH mutant (MUT) tumors often lack this enhancement. However, relying solely on anatomic radiology may lead to misclassification, and currently, tissue acquisition is the primary method for assessing IDH-status in gliomas. These limitations hamper the development of neoadjuvant or intraoperative therapeutic strategies based on IDH-status; thus, more minimally invasive methods to determine IDH-status are needed. In this study, we assessed peripheral immune cell proportions, which vary by glioma subtype, from pre-surgery peripheral blood samples as an alternative method of classifying the IDH-status in gliomas without enhancement.

MATERIALS AND METHODS
We employed a highly accurate large language model (GPT-4-Turbo-128k) with over 99% accuracy to read radiology notes and exclude patients with enhancing gliomas. Then, we identified 12 immune cell subtypes from whole blood using deconvolution algorithms based on DNA methylation data. These immune cell subtypes, along with patient age, were integrated into a machine learning model (random forest) to predict IDH-status (WT vs. MUT), leveraging conditional Generative Adversarial Networks to generate synthetic data and mitigate bias in the datasets. Two independent datasets were included for training and validating the model.

RESULTS
The random forest model had an AUC of 0.90 and accurately identified IDH-status in 81% of a training set of 287 gliomas (65 WT and 222 MUT at varied time points after diagnosis). In an independent validation data set of 99 gliomas (6 WT and 93 MUT) from pre-surgery blood samples, the AUC was 0.93, and accurately predicted IDH-status in 92% of cases with a sensitivity of 93% and specificity of 83%.

CONCLUSIONS
We predicted the IDH-status of non-enhancing gliomas using patients’ age and immunomethylomic data from pre-surgical peripheral blood samples. This minimally invasive approach is a promising step toward reducing risk and enabling earlier therapies based on IDH-status.
EPID-03. BRAIN CANCER IN AFRICA: UNCOVERING THE HIDDEN EPIDEMIC THROUGH A SYSTEMATIC REVIEW
Authors: UWISHEMA Olivier 
Published: November 2024

Abstract

BACKGROUND
Cancer poses a significant public health threat globally, leading to substantial morbidity. While malignancies were previously thought to predominantly affect high-income countries, numerous studies indicate an increasing burden on resource-limited nations. Brain cancer, in particular, can be devastating due to treatment challenges and high mortality rates. Africa, with its resource-limited countries, must establish proper healthcare infrastructure to reduce cancer incidence and enhance patient survival. Additionally, the scarcity of data in this area in Africa presents a challenge to effective management. This study aims to explore the available evidence on the epidemiology and etiology of brain cancer in resource-limited African countries, highlighting the growing burden and advocating for further research.

MATERIALS AND METHODS
We conducted a systematic review by searching PubMed and Scopus using a predefined approach. Additionally, we utilized the Global Cancer Observatory and Global Burden of Disease databases. Studies reporting on brain cancer epidemiology, etiology, and impact in Africa were included, with the level of evidence assessed according to Centre for Evidence-Based Medicine guidelines.

RESULTS
Brain cancer presents a significant healthcare challenge in many African developing nations due to poor survival rates, inadequate funding and resources for reporting, identification, and treatment, as well as limited comprehensive research.

CONCLUSION
This study underscores the urgent need to address brain cancer as a major public health crisis in Africa. Improved treatment options and access to screening are essential to mitigate the disease burden. Thus, substantial and comprehensive research on brain cancer within Africa is crucial for effective management and reducing associated morbidity and mortality.
EPID-07. MAJOR CONGENITAL ANOMALIES AND RISK OF CHILDHOOD BRAIN TUMORS IN 9 STATES
Authors: Hoang Thanh , Schraw Jeremy , Taylor Michael , Plon Sharon , Lupo Philip , Scheurer Michael 
Published: November 2024

Abstract
Children with congenital anomalies have a higher risk of developing a childhood brain tumor (CBT), but it remains unclear if associations vary by cancer histology, which could inform our understanding of these associations. Thus, we characterized co-occurrences of major congenital anomalies with six CBTs. We leveraged a population-based registry linkage study of live births, congenital anomalies, and cancer from nine states. Dates of birth and last follow-up varied by state, ranging between January 1, 1990 to December 31, 2018, for a total of 22,599,099 live births. CBT classification was based on the International Classification of Childhood Cancer for children diagnosed up to age 18 years. Major congenital anomalies were classified based on the National Birth Defects Prevention Network Surveillance Guidelines. Children with any genetic anomalies were excluded. We used Cox regression to evaluate associations between major congenital anomalies and astrocytoma, medulloblastoma, ependymoma, atypical teratoid/rhabdoid tumor (ATRT), primitive neuroectodermal tumors (PNET), and mixed and unspecified gliomas (“mixed gliomas”), adjusting for sex, state, maternal education, maternal race/ethnicity, and maternal age. Sensitivity analyses were conducted stratifying by number of major anomalies (0, 1, 2+) and age at cancer diagnosis (&lt;1, 1-4, 5-9, 10+ years). There were 5,685 diagnosed with any CBT. Having any major congenital anomaly was significantly associated with astrocytoma, ATRT, medulloblastoma, mixed glioma, and PNET (aHR range: 1.79-5.78) but not ependymoma. When stratified by number of major anomalies, effect estimates were similar. Due to small numbers when stratified by age at cancer diagnosis, unadjusted analyses were conducted. Associations were strongest in children diagnosed with astrocytoma, ATRT, medulloblastoma, mixed glioma, or PNET before age 1 (HR range: 3.03-5.47) compared to other age groups (HR range: 1.25-3.07). Children with any major congenital anomaly have an increased risk of developing astrocytoma, ATRT, medulloblastoma, mixed glioma, or PNET, particularly by 1 year.
EPID-10. THE INCIDENCE OF PRIMARY BRAIN TUMORS IN JAPAN IN 2016-2019
Authors: Narita Yoshitaka , Ohno Makoto 
Published: November 2024

Abstract
The national cancer registries in Japan have started since 2016 and the actual number of cancer patients in including primary central nervous system (CNS) tumors in Japan was revealed. Average number of primary CNS tumors in 2016-2019 was 29,492 and the crude incidence rate per 100,000 people (CIR) was 23.30. Malignant and benign CNS tumors was 6,696 (22.7%) and 22,796 (77.3%) and each CIR was 5.29 and 18.00, respectively. Among 29,492 tumors, 10,537 (35.7%) meningioma, 5,217 (17.7%) pituitary adenoma, 4,537 (15.4%) neuroepithelial tumor, 2,730 (9.3%) neurinoma and 1,166 (4.0%) primary CNS lymphoma (PCNSL) were reported. Regarding to malignant brain tumors, 2,071 glioblastoma, 362 astrocytoma grade II, 390 anaplastic astrocytoma grade III, 138 pilocytic astrocytoma,182 oligodendroglioma grade II, 154 anaplastic oligodendroglioma grade III, 140 ependymal tumors, 128 embryonal tumors including 91 medulloblastoma, 211 germ cell tumor (GCT) were found. CIR of neuroepithelial tumor, glioblastoma, PCNSL, embryonal tumors and GCT were 3.64, 1.68, 0.93, 0.10 and 0.17, respectively. According to the Central Brain Tumor Registry of the United States (CBTRUS) (2016-2020), CIR in the US was 26.73, and age-adjusted incidence rates of primary CNS tumors per 100,000 population in the US based on the US population in 2000 (AIR) was 24.83 and AIR in Japan was 17.15. AIR of glioblastoma in the US and Japan was 3.27 and 1.05, AIR of PCNSL was 0.44 and 0.51, AIR of embryonal tumors was 0.21 and 0.16, AIR of GCTs was 0.08 and 0.27, and AIR of meningioma was 9.73 and 5.11, respectively. This report demonstrated that the incidence of neuroepithelial tumors and embryonal tumors in Japan was approximately half to one-third, whereas that of GCTs in Japan was approximately 3 times comparing to the US.
EPID-12. NEIGHBORHOOD SOCIOECONOMIC STATUS PREDICTS SURVIVAL IN GLIOBLASTOMA: A SINGLE CENTER COHORT STUDY
Authors: Sun Yifei , Estevez-Ordonez Dagoberto , Atchley Travis , Markert James , Nabors Burt 
Published: November 2024

Abstract

BACKGROUND
Glioblastoma (GBM) is the most common primary brain malignancy. Despite recent progress in treatments, prognosis for patients remain poor. Recent literature has suggested the association of GBM outcomes and socioeconomic status. However, there is limited evidence regarding the association of neighborhood-level socioeconomic status on GBM outcomes.

OBJECTIVE
To investigate the impact of neighborhood-level socioeconomic status on GBM outcomes.

METHODS
We retrospectively reviewed all adult GBM patients at a single institution from 2008 to 2023. Patient addresses underwent geospatial analysis and Area Deprivation Index (ADI) was extracted. Univariable and multivariable survival analyses were performed. A Cox proportional hazards model was used to assess the effect of ADI and other socioeconomic variables while controlling for a priori selected clinical variables with known relevance to survival.

RESULTS
In total, 1492 patients met inclusion criteria. The average age at diagnosis was 62±14.2 years with a median overall survival of 12.1 [Interquartile Range (IQR) 5-22] months. The median ADI was 66 (IQR 46-84). Patients with high socioeconomic deprivation (ADI&gt;75) were less likely to receive chemotherapy (92% vs 96%, p=.03), and had worse overall survival compared to patients with low socioeconomic deprivation (10 vs 13 months, p=.001). In the multivariable model, patients with high ADI had worse overall survival (hazard ratio [HR], 1.42; 95% confidence interval [CI], 1.16-1.73, p&lt;.001). To account for changes in WHO guidelines, we implemented the model on patients diagnosed between 2017-2023 and findings were consistent (HR 1.34, 95%CI 1.07-1.68, p=.011).

CONCLUSIONS
We present the largest study reporting the effect of neighborhood-level socioeconomic status on overall survival of GBM patients. Neighborhood-level socioeconomic status provides the most accurate capture of the patient-level socioeconomic determinants of health. Patients with higher ADI have worse overall survival after controlling for other socioeconomic and clinical variables. These results suggest significant association between neighborhood-level socioeconomic status and overall survival in GBM patients.
EPID-13. PREDICTORS OF HISTOPATHOLOGIC RESULTS OF BRAIN BIOPSY IN PATIENTS SUSPECTED OF SECONDARY CNS LYMPHOMA
Authors: Basit Khan A , Suki Dima , Goethe Eric , Fernandez Luis , Patel Rajan , Westin Jason , Chi T Linda , Weinberg Jeffrey 
Published: November 2024

Abstract
Patients suspected of secondary CNS lymphoma (SCNSL) often undergo brain biopsies. Recent studies doubt biopsy utility due to high SCNSL diagnosis rates. We sought to enumerate histopathologic biopsy results in suspected SCNSL patients to evaluate utility of biopsy. We furthermore assess clinical and radiographic factors based on ability to distinguishing SCNSL from non-SCNSL. 109 patients with non-CNS lymphoma who subsequently presented with brain lesions that underwent biopsy at MD Anderson Cancer Center were included. Histopathologic diagnoses were obtained. Pre-operative imaging was assessed for contemporary radiologic diagnoses by obtaining the leading differential reported at the time of the study. Subsequently, a staff neuroradiologist, blinded to biopsy outcomes and clinical considerations, provided a retrospective diagnosis. 61 patients had SCNSL whereas 48 did not. Non-SCNSL biopsy results included infection (n=16, 33%), glioma (n=12, 25%), nonspecific (n=12, 25%), and other metastases (n=3, 6%). Patients with non-indolent lymphoma (DLBCL, mantle cell, Burkitt’s, and lymphoblastic lymphoma) were more likely to have SCNSL on biopsy (p&lt;0.001, OR 12.55). Patients with SCNSL had shorter time interval since initial diagnosis (median 18.1mo vs. 63.2mo, p=0.008). Systemic progression of disease at biopsy was not associated with SCNSL (p=0.35). There was no difference in age, stage, LDH, Albumin, ECOG, IPI, anatomic location, or B-symptoms at times of diagnosis or neurosurgery. No patient had positive CSF cytology prior to biopsy. Neither retrospective nor contemporary radiographic diagnoses had sufficient accuracy to replace biopsy. A positive retrospective diagnosis trended towards association with SCNSL pathology (sensitivity=0.94, specificity=0.23, PPV=0.65, NPV=0.70, p=0.08). A positive contemporary diagnosis was associated with SCNSL pathology (sensitivity=0.67, specificity=0.73, PPV=0.76, NPV=0.64, p&lt;0.001). Similar biopsy proportions yielded SCNSL and non-SCNSL. Although some factors are associated with SCNSL, none can reliably distinguish patients. Given the divergent treatments for the reported pathologies, our study reiterates the necessity of biopsy in suspected SCNSL.
EPID-18. PATTERNS OF CARE AND CLINICAL OUTCOMES OF PATIENTS WITH GLIOBLASTOMA FROM 2005-2020: A REAL-WORLD ANALYSIS
Authors: Jayram Diya , Bellur Shreyas , Ozair Ahmad , Ahmad Shahzaib , Hodgson Lydia , Frias Numa , Podder Vivek , Ganiyani Mohammad Arfat , Ahluwalia Manmeet 
Published: November 2024

Abstract

BACKGROUND
Survival for glioblastoma (GBM) remains low, with disparities affecting outcomes. Standard of care (SoC) includes surgery and adjuvant chemoradiation. This study explores demographics, treatment patterns, and outcomes of GBM patients in the United States.

METHODS
A retrospective study was conducted on patients with GBM in the National Cancer Database for GBM patients between 2005-2020 according to ESMO Guidance for Reporting Oncology Real-World (GROW). Trends were analyzed with descriptive statistics and X2-test between time periods: 2005-08, 2009-12, 2013-16, and 2017-20. Predictors of SoC receipt were analyzed with multivariate logistic regression. Median overall survival (mOS) estimated using Kaplan-Meier and Cox regression models. Adjustment made using demographic, socioeconomic, and clinical factors. Outcomes reported as (Odds Ratio [OR]/Hazard Ratio [HR] 95% Confidence Interval) per STROBE guidelines.

RESULTS
Of 104,697 GBM patients, 42.5% were female. 91.2% White, 5.7% Black, and 2.0% were Asian. 5.3% were Hispanic. Median age was 65 years (IQR:57-73). Percentage of patients ≥65 years increased from 48.8% in 2005-08 to 54.0% in 2017-20. 56.5% of patients received SoC. SoC usage increased over time: 2009-12 (OR:1.26, 1.21-1.31, P&lt;0.001) vs 2013-16 (OR:1.36, 1.31-1.41, P&lt;0.001) vs 2017-20 (OR:1.51, 1.45-1.57 P&lt;0.001). Females (OR:0.91, 0.89-0.93 P&lt;0.001), Black (OR:0.81, 0.77-0.86 P&lt;0.001), and Hispanics (OR:0.92, 0.86-0.97, P=0.004) were less likely to receive SoC than males, White, and non-Hispanics. Privately insured were more likely to receive SoC than Medicare (OR:0.83, 0.80-0.87, P&lt;0.001), Medicaid (OR:0.68, 0.64-0.71, P&lt;0.001), and uninsured patients (OR:0.60, 0.55-0.64, P&lt;0.001). SoC recipients had mOS of 14.6 months (14.5-14.8) vs 4.8 (4.7-4.9) for non-recipients (P&lt;0.001). Compared to 2005-08, survival improved over time: 2017-20 (HR:0.83, 0.82-0.85, P&lt;0.001) vs 2013-16 (HR:0.88, 0.86-0.89, P&lt;0.001) vs 2009-12 (HR:0.93, 0.91-0.94, P&lt;0.001).

CONCLUSIONS
Receipt of SoC has risen with significant increase in survival. However, female, Black, and Hispanic patients were less likely to receive SoC. Targeted efforts are warranted to mitigate disparities.
EPID-20. PRIMARY INTRAMEDULLARY PILOMYXOID ASTROCYTOMA OF SPINAL CORD (PIPASC): A SYSTEMATIC REVIEW OF CASE REPORTS AND CASE SERIES OF TWO DECADES
Authors: Qadri Haseeb Mehmood , Bashir Asif 
Published: November 2024

Abstract

BACKGROUND
Pilomyxoid Astrocytoma (PMA), new variant of pilocytic astrocytoma, is more aggressive and relatively rare, mostly seen in children and commonly found in brain. Primary intramedullary pilomyxoid astrocytoma of spinal cord (PIPASC) is extremely rare. The distinct aggressive and pathological behavior, poor prognosis and the diversity in response to various treatment modalities makes the PIPASC an oncologic enigma. We aim to evaluate the clinical manifestations, histopathologic spectrum and onco-surgical management of this neoplasm.

MATERIALS AND METHODS
After an extensive literature search using PubMed Central and Google Scholar, eight case reports and one case series of patients with spinal PA were retrieved and included using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines without applying any filter of time, study type or place. Case presentations of 12 patients were analyzed in this review.

RESULTS
Pediatric preponderance of the neoplasm (75%) with the mean age of 7.90 ± 4.51 years was noted. Sensory deficits and scoliotic deformity were the most common presenting symptom and sign in 83.33% and 33.33% of patients, respectively. Thoracic spine (50%) was most commonly affected region. MRI showed the most consistent findings of cord compression in 100% cases and the lesion appeared hypointense on T1- weighted images (T1WI) and hyperintense on T2-weighted images (33.33%). The average post treatment survival duration was found to be more than 2 years.

CONCLUSIONS
Occurrence of PIPASC among pediatric population is rare. They have possibility of extraneural metastasis, can differentiate into more malignant glioma and get recurrent due to which they require a long-term follow-up of the patients. Further studies are required to investigate the utility of chemotherapy and radiotherapy in its management.
EPID-21. PRIMARY INTRAMEDULLARY LYMPHOMA OF SPINAL CORD (PILSC): A SYSTEMATIC REVIEW OF CASE REPORTS AND CASE SERIES FROM 2000 TO 2023
Authors: Qadri Haseeb Mehmood , Bashir Asif 
Published: November 2024

Abstract

BACKGROUND AND OBJECTIVE
Primary CNS lymphoma accounts for three percent of all newly diagnosed CNS tumours and 1-3% of all non-Hodgkin’s lymphomas. The oncologic origin of primary intramedullary lymphoma of the spinal cord (PILSC) is an enigma. We aim to determine the clinical manifestations, disease course and management of PILSC.

MATERIALS AND METHODS
A comprehensive literature search using PubMed Central and Google Scholar, was done, retrieving 17 case reports and two case series of 21 patients with PILSC and included using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, published between 2000 and 2023.

RESULTS
About 90.48% patients inflicted with PILSC were adult, with male predominance, 61.90%. The most common complaint at presentation was neurological deficit of motor type in 32.14% patients. MRI proved to be helpful in 76.19% cases, with spinal cord enlargement and high signal intensity in 19.04% cases. Adjuvant chemotherapy and radiotherapy was acquired by 52.38% and 38.09% patients. Non-Hodgkin type was reported in 90.47% cases and Hodgkin lymphoma was seen in 9.52% patients. Diffuse large B cell lymphoma was culprit in 41.10% cases. Five out of 21 cases had variable post-operative complications. The average follow-up was 16.16 months.

CONCLUSION
PILSC is a multifaceted neoplasm in all its clinico-pathological aspects of presentation. Although rare, PILSC can involve adult and paediatric populations with a clear male preponderance. The MRI findings are not reliable to make a preliminary diagnosis. Like other lymphomas, the role of chemoradiotherapy is clearly more significant than surgical intervention in improving patient prognosis. Histopathologically, it can be Non-Hodgkin or Hodgkin, B-cell type or T-cell type and has a wide array of immunohistochemistry positivity.