bluuebunny/crossref_metadata_2025_split huggingface dataset:
EPCO-37. IDENTIFICATION OF KEY EPIGENETIC REGULATORS FOR MEDULLOBLASTOMA INVASION AND METASTASIS
Authors: Jangde Nitish , Walter T Jordan , Ruiz Luz , Ayad Nagi 
Published: November 2022

Abstract
Medulloblastoma (MB) is most common type of pediatric brain cancer. It starts from the hind brain or cerebellum. It is actually an embryonic malignant cancer of the cerebellum is mainly reported over 20% of all central nervous system (CNS) neoplasms in children. MB frequently affected the 3.8-6.9 per million children population in North America and Europe. MB embracing four subgroups: Sonic Hedgehog, Wingless, Group 3, and Group 4. However, the molecular and cellular factors and their mechanism in compelling the maintenance of malignancy are have not well understood. Invasion of tumor cells across the extracellular matrix to the other neighboring tissues is main key event critical for metastasis of the medulloblastoma metastasis. Several factors affect the medulloblastoma genesis, progression, invasion and metastasis. But epigenetic regulators are the crucial regulators MB progression, invasion and metastasis. In order to identify the key regulators for medulloblastoma progression, invasion and metastasis we are doing CRISPR epigenome library screening targeting more than 500 epigenetic genes and 4 guide RNAs targeting each for brain medulloblastoma cells (ONS76 and D425 cells). Initially we have transduced cells with epigenome CRISPR library with different titers to determine the effective viral titer to transfect 30% or lesser number of cells. So that each transduced cell has each guide RNA targeting each gene. Further the transduction was scaled up and after selection the cells were expanded. Further in vitro invasion assay the invaded and un-invaded cells were collected across the Matrigel matrix coated membrane. Along with further enrichment and expansion of these cells we isolated the genomic DNA and sequenced them. The present CRISPR epigenome sequencing analysis targeting invasion property of medulloblastoma cells may provide novel key epigenetic factors affecting the medulloblastoma invasion and eventually metastasis might be the novel and more effective therapeutic target for medulloblastoma treatment.
DISP-06. POPULATION-LEVEL DETERMINANTS OF SOCIO-DEMOGRAPHIC, TUMOR, AND TREATMENT FACTORS IN GLIOBLASTOMA USING SEER DATABASE (1997-2016)
Authors: Yoo Wonsuk , Garcia Michael , Kennedy William , Sanai Nader 
Published: November 2022

Abstract

BACKGROUND
Although socio-demographic and treatment factors have been separately linked to impact on prognosis in several GBM studies, no studies to date have collectively evaluated many potential individual patient and treatment-related factors and their impact on survival in GBM in a comprehensive, multi-institutional, population-based manner. The purpose of this study is to identify sociodemographic, tumor, treatment, and clinical characteristics affecting survival in GBM using a large cancer registry database, the Surveillance Epidemiology End Results (SEER) registry, and identify strategies to reduce risk and disparities for patients with GBM.

METHODS
Individual-level data were obtained from SEER 18 program (1997-2016) using SEER*Stat software. New variables on urban-rural area and treatment combination among surgery, radiotherapy, and chemotherapy were created to comprehensively identify determinants affecting survival in GBM. Univariate and multivariate survival analyses were performed to estimate median survival time using Kaplan-Meier methods and to evaluate the relative risks of potential determinants using Cox hazard methods.

RESULTS
(1) The important determinants include age, gender, race, rural-urban area, diagnostic confirmation, tumor size, resection type, metastases, laterality, treatment effects and combined effects. (2) In addition to the standard treatment on GBM, the socio-demographic and clinical factors like rural-urban area (access to hospital), diagnostic conformation, and report type were important to reduce the risk to GBM patients. (3) Coming to modern times, survival time and survival rate have improved, especially in terms of socio-economic factors of people living in metro areas and married people (HR = 0.897 to 0.813 for metro area and HR = 0.999 to 0.918 for married status).

CONCLUSIONS
Our findings of higher risk determinants in GBM might lead to better prognosis in GBM with socio-demographic and clinical factors affecting the survival in GBM. The future investigation including MGMT promoter methylation might be beneficial with better understanding of determinants affecting risk in GBM.
DISP-07. SURVIVAL ANALYSIS OF GLIOBLASTOMA PATIENTS IN PENNSYLVANIA ACCORDING TO AREA DEPRIVATION INDEX AND IDH STATUS
Authors: Baroz Angel , Stahl Caleb , Bhanja Debarati , Wilding Hannah , Mansouri Alireza 
Published: November 2022

Abstract

INTRODUCTION
Glioblastoma (GBM) is the most aggressive primary brain tumor with a universally poor prognosis. Living in disadvantaged neighborhoods is associated with poor health outcomes, including increased cancer incidence. This study was designed to elucidate the relationship between GBM patients’ survival, isocitrate dehydrogenase (IDH) mutation status, and residential areas of deprivation in the state of Pennsylvania.

METHODS
Patients from Pennsylvania with a pathological diagnosis of GBM WHO Grade IV between January 2007 and December 2018 were retrospectively reviewed in the Penn State Health database. Demographic variables and molecular features were assessed. Area Deprivation Index (ADI) is a validated measure of regional socioeconomic deprivation that indexes neighborhoods by percentile, with low ADI scores representing less deprivation. Patients were assigned to low ( &lt; 50) or high ( ≥ 51) ADI groups. Survival was measured against IDH status and ADI score; log-rank tests were performed.

RESULTS
121 GBM WHO Grade IV patients were identified (median age at diagnosis: 63, 39.7% female, 60.3% male, 93.4% of white race). Among those, 64 (52.9%) had low ADI, and 57 (47.1%) had high ADI. Patients with high ADI had similar overall survival (OS) rates and progression free survival (PFS) at 18 months (56% OS, 95% confidence interval [CI]: 48-64%; 37.4% PFS, 95%CI: 30-44%; P=0.27) compared to patients with low ADI (50% OS, 95%CI: 43-57%; 32.4% PFS, 95%CI: 26-39%; P = 0.27). Further classification by IDH status resulted in 17 (14%) IDH mutant (IDHm) and 104 (86%) IDH wildtype (IDHwt) patients. Survival analysis demonstrated no significant difference in OS between IDHwt and IDHm patients, regardless of ADI score.

CONCLUSION
The aggressive nature of GBM requires early diagnostic approaches to impact survival. Living in socioeconomic disadvantaged areas may diminish survival outcomes; however, our data indicate that GBM may be too aggressive for ADI to have a significant impact on prognosis.
DISP-12. RACIAL DISPARITY IN LENGTH OF STAY FOLLOWING CRANIOTOMY FOR PRIMARY BRAIN GLIOMA
Authors: Lockard Gavin , Gordon Jonah , Alayli Adam , Tran Nam 
Published: November 2022

Abstract

Introduction
The racial disparities of opportunity to receive the appropriate surgical intervention and insurance coverage for adjuvant care may result in surgical outcome and survival disparities among different races. Length of stay (LOS) is an important quality metric measure for determining the distribution of medical resources and their consumption. This study aims to provide a perspective on racial disparities in the overall length of stay and complications for patients undergoing craniotomy for primary brain glioma.

METHODS
The authors performed a retrospective chart review of all patients who underwent craniotomies for resection of primary brain tumors at the Moffitt Cancer Center from 2004-2018. Patients age, race, tumor type, comorbidities, length of stay and complications were reviewed.

RESULTS
A total of 701 patients underwent craniotomies for primary brain glioma, but 66 were excluded due to insufficient follow-up or incomplete records. The racial categories include Caucasians, African American, Asian, Hispanic, and other. Due to the prevalence of Caucasians, the minorities groups were pooled as non-Caucasians. Both cohorts were similar in baseline comorbidities, KPS, tumor characteristics, and surgical factors. Mean LOS remained lower for Caucasians versus non-Caucasians (3.6 vs. 5.5 d). The differences in LOS remain among different tumor types, including GBM (4 vs. 6.7 d), anaplastic astrocytoma (2 vs. 4.4 d), and oligodendroglioma (2.3 vs. 3.7 d). Interestingly, among astrocytoma, Caucasians had a longer LOS (3 vs 1.2 d).

CONCLUSION
Our results highlight disparate treatment patterns that reflect in LOS among patients undergoing craniotomies for primary brain gliomas. These findings warrant further investigation regarding current health-care practices and policies.
DISP-16. NUTRITIONAL SCREENING OF PEDIATRIC CENTRAL NERVOUS SYSTEM TUMOR SURVIVORS REVEALS HIGH PREVALENCE OF MALNOURISHMENT WITH SOCIODEMOGRAPHIC AND CLINICAL RISK FACTORS
Authors: Wilson Rebekah , Soja Jacqueline , Yunker Alexandra , Aziz-Bose Rahela , Gordon Erin , Dieli-Conwright Christina , Cooney Tab 
Published: November 2022

Abstract
Adult survivors of pediatric central nervous system (CNS) tumors are at the highest risk for morbidity and late mortality among all childhood cancers, partially due to chronic health conditions intersected with environmental and lifestyle factors. We aimed to study the prevalence of and risk factors for malnourishment (underweight, overweight, obese) amongst adult survivors of pediatric CNS tumors. We conducted a cross-sectional study assessing young adults (18-39 years) previously treated for pediatric CNS tumors who were followed in our survivorship clinic during 2016-2021. Sociodemographic, clinical, and treatment information was extracted from medical records with BMI status, per CDC guidelines, obtained from the most recent clinic visit. Data was assessed using one-way ANOVA, fishers exact test, and multivariable logistical regression. We identified 198 survivors (53% female, 84.3% white) categorized as underweight (4.0%), normal weight (40.9%), overweight (26.8%), obese (20.2%), and severely obese (8.1%). Patients were median age 8 years [4-12] at diagnosis and 24 years [20-28] at follow-up. Most common primary diagnosis and tumor location was low grade glioma (50.5%) and posterior fossa (39.4%) with 90.4% receiving surgery, 51.5% chemotherapy, and 52.5% radiotherapy. Male sex (OR 2.376, p = 0.006), hypothalamic/optic pathway tumor location (OR 2.362, P = 0.031), and radiation therapy (OR 2.844, p = 0.005) were associated with increased overweight/obesity risk, while chemotherapy (OR 0.363, p = 0.006) was associated with decreased risk. Male sex (OR 0.511, p = 0.007) and white ‘race’ (OR 0.166, p = 0.022) were associated with decreased underweight risk. The majority of young adult survivors seen in our clinic were not healthy weight by BMI, and the distribution of BMI groups appears comparable to contemporary studies of the general young adult U.S. population. The prevalence of malnourishment amongst PNO survivors warrants universal screening efforts with more accurate determinants of body composition than BMI, risk stratification, as well as targeted interventions.
IMMU-03. ANALYSIS OF EXPRESSION SIGNATURES OF MATCHED PRIMARY GASTROINTESTINAL CANCER AND BRAIN METASTASES USING NANOSTRING NCOUNTER TECHNOLOGY
Authors: Cheko Azad , Burnside Georgiana , Vogel Hannes , Gephart Melanie Hayden , Petritsch Claudia 
Published: November 2022

Abstract

BACKGROUND
Brain metastases from the gastrointestinal tract are a rare event (less than 10% of all brain lesions), but their impact on prognosis is remarkable. Their incidence is increasing due to earlier diagnosis and prolonged survival because of more effective treatment modalities. Because of the lack of evidence-based recommendations, no optimal treatment strategy has been defined. Hope might come from the discovery of new prognostic and predictive factors and their biological inhibitors. The aim of this study was to create a repository of matched primary cancer and brain metastases samples for clinicopathologic and molecular correlations of gastrointestinal tumors and to analyze changes in expression signatures between both samples. The main goal was to study the metastatic process and characterize the immune response by characterizing features such as invasiveness, vascular co-option, proliferation, stemness and cell-type heterogeneity between the matched tissues.

METHODS
We searched for patients at Stanford hospital with matched brain metastases from gastrointestinal tumors from 2008 to 2020 using the STARR database (The STAnford Research Repository, or STARR, is Stanford Medicine's approved resource for working with clinical data for research purposes.). Matched specimens mean that both brain metastases and gastrointestinal tumors were studied at Stanford University. FFPE blocks from these matched patients were sectioned and sections analyzed for gene expression analysis using nanoString nCounter technology and the immune-oncology panel.

RESULTS
Expression data from 32 matched patients with primary tumor and brain metastases will be discussed at the meeting.

CONCLUSION
We believe that analysis of changes in expression signatures between the matched primary gastrointestinal cancer and brain metastases will provide novel insights into the role for tumor factors, such as invasiveness, proliferation and stemness, and the tumor microenvironment in progression.
IMMU-10. EXPLORING THE IMMUNOLOGIC CONSEQUENCES OF ATRX DEFICIENCY IN GLIOMA
Authors: Whitfield Benjamin , Huse Jason , Irvin David , Dharmaiah Sharvari , Malgulwar Prit Benny , Roberts Hannah 
Published: November 2022

Abstract
ATRX is a key chromatin regulator, which is mutated in large subsets of both adult and pediatric gliomas. Despite being a common mutation, little is known about the biological ramifications of ATRX deficiency. Recently, it has been demonstrated that ATRX deficiency drives increased replication stress, DNA damage, and global epigenetic dysregulation. Despite these advances, little is known about the impact of ATRX deficiency on the tumor microenvironment (TME). In order to explore the impact of ATRX deficiency on the TME we utilized the RCAS/nTVa system to generate a novel murine model of ATRX deficient glioma. Mice bearing allografts of these tumors displayed significantly increased survival relative to the ATRX intact lines. This survival benefit persisted in Nu/nu mice, which lack an adaptive immune system, but not in SCID mice, which lack both adaptive and innate immunity. Bulk RNA sequencing revealed the ATRX deficient tumors displayed increased expression of inflammatory and innate immune gene sets, and western blotting revealed increased phosphorylation of tank binding kinase 1 (TBK1), a key innate immune regulator. Multiplex cytokine analysis of conditioned media also revealed increased expression of inflammatory cytokines such as CCL2, CCL5, and CXCL10 in the supernatant of ATRX deficient cell lines. Taken together, these results indicate that ATRX deficiency can drive innate immune activation, and that this activation can increase survival in vivo. Further exploration is needed to characterize the upstream drivers of TBK1 activation and elucidate alterations to immune cell infiltration in ATRXdeficient tumors.
IMMU-11. NONO IS A NEW ADENOVIRUS SENSOR: IMPLICATION FOR VIROTHERAPY
Authors: Gillard Andrew , Shin Dong Ho , Laspidea Virginia , Singh Sanjay K , Jiang Hong , Kim Debora , Fan Xuejun , Yi Yanhua , Lang Frederick , Alonso Marta M , Fueyo Juan , Gomez-Manzano Candelaria 
Published: November 2022

Abstract
The median survival for GBM patients is 15 months with a five-year survival rate of less than 10%. Current conventional and experimental treatments, including immune checkpoint blockade, have not improved outcomes in the vast majority of glioma patients. Oncolytic viruses (OVs) are designed to specifically infect and lyse cancer cells to elicit an anti-tumor immune response. In a clinical trial developed by the MDACC team, 20% of GBM patients treated with the oncolytic adenovirus Delta-24-RGD showed complete response and survival longer than three years (NCT00805376). Although these studies have shown that robust immune responses can be invoked using oncolytic virotherapy, the molecular mechanisms underlying OV-mediated anti-tumor immunity remain elusive. Exposure to viruses by innate immune sensors induces protective antiviral immunity. Using bulk RNA sequencing of cells infected with adenovirus we identified the main upstream regulators of the innate immune response including IFN gamma, Interferon responsive genes 3 and 7, and STAT3. However, RNAseq unexpectedly uncovered NONO (Non-POU Domain Containing Octamer Binding) as the most relevant upstream regulator. In agreement with the RNAseq data, Protein analyses demonstrated the upregulation of NONO after adenovirus infection. In addition, immunofluorescence and confocal microscopy examination of the infected cells showed the overexpression and translocation to the nucleus of NONO upon virus infection. We are the first laboratory that has identified NONO as a sensor of adenovirus infection, which may have great significance for the future development of oncolytic viruses. Importantly, we discovered the network of proteins that are upregulated after NONO activation and, finally, we have established that changes in the expression level and subcellular localization of NONO are coincident in time during the infection of cultured cells. Future work is focused on examining the immunomodulatory functions of NONO in adenoviral infected tumors and subsequent generation of NONO-resistant oncolytic adenovirus.
IMMU-32. SPERMIDINE DRIVES GLIOBLASTOMA PROGRESSION VIA SELECTIVE MODULATION OF THE IMMUNE SYSTEM
Authors: Kay Kristen , Bayik Defne , Wang Zeneng , Brown J Mark , Hazen Stanley , Lathia Justin 
Published: November 2022

Abstract
Glioblastoma (GBM) is incurable despite aggressive standard of care treatments (maximal safe surgical resection, radiation, chemotherapy). GBM therapeutic resistance is due to multiple factors, including tumor heterogeneity and a highly immunosuppressive environment. Naturally occurring polyamines have been identified as a putative therapeutic target in other cancers based on their increased presence and function in normal conditions; they are critical for cell growth and proliferation and cellular functions including autophagy and apoptosis. While polyamines are increased in GBM patients, little is known about their impact on GBM growth. In syngeneic immune competent mouse glioma models (GL261, SB28), mass spectrometry data revealed that spermidine (SPD) – a member of the polyamine family – is increased in tumor tissue as compared to non-neoplastic control brain tissue (sham implanted animals). To test the impact of SPD on tumor growth, we treated mouse glioma models with exogenous SPD and found treatment significantly decreased survival. However, in immunocompromised host mice, no such difference was observed, indicating the mechanism through which SPD is driving GBM progression likely involves immune system alterations. Depletion of myeloid derived suppressor cells in vivo via anti-Gr-1 antibody rescues the decrease in survival caused by exogenous SPD, indicating that SPD drives GBM by affecting immune-suppressive cell subsets, namely MDSCs. To assess if SPD is associated with more aggressive GBM growth in human patients, we are currently analyzing polyamine levels in human GBM samples of long vs short term survivors. We are also exploring the effect of dietary polyamines on GBM via the gut-brain-microbiome axis, as polyamines are enriched in many foods and produced by a subset of commensal gut microbes. Understanding the interactions between polyamines, the tumor microenvironment, and the immune response provide a new mechanism for GBM regulation and identify opportunities to alter the environment in the body to enhance immunotherapeutic efficacy.
INNV-03. THE YIELD OF SCREENING MRI AMONG STAGE IV NON SMALL CELL LUNG CANCER PATIENTS
Authors: Waizman Efraim , Lavie Inbar , Amiel Alexandra , Siegal Tali , Dudnick Elizabeth , Yust-Katz Shlomit 
Published: November 2022

Abstract

BACKGROUND
Brain metastases are a common complication of non small cell lung cancer (NSCLC). Approximately 10 percent of newly diagnosed patients with advanced NSCLC have brain metastases. The purpose of this study was to determine whether using magnetic resonance imaging (MRI) for early screening of brain metastases can improve survival. Material and

METHODS
A retrospective analysis of newly diagnosed stage IV NSCLC treated at Davidoff Cancer Center, Israel, between the years 2019-2020. Only patients who were neurologically asymptomatic were included in the study. The study population was divided into two groups. Group A included patients who underwent screening MRI within 12 weeks form diagnosis and group B included those who did not undergo screening MRI. Clinical and radiographic data were collected form the medical records.

RESULTS
379 patients were included in the study, of whom 170 underwent screening MRI. Of the patients who underwent screening MRI 54 were diagnosed with brain metastases. On univariate analysis screening MRI was corelated with better survival [group A median survival 24 month, group B median survival 18 month, p=0.003 HR 1.4 CI 1.12-1.75]. On multivariate analysis that included functional status (ECOG 0-2 compared to 3 and above) and age- screening MRI corelated with survival (p=0.04 HR 1.28 CI 1.02-1.6). Subgroup analysis according to molecular subgroup will be presented in the conference.

CONCLUSION
In this study screening MRI among stage IV NSCLC correlated with better survival even when adjusted to functional status and age.
INNV-04. PRIMARY TREATMENT OF SMALL-TO-MEDIUM(&lt; 3CM) SPORADIC VESTIBULAR SCHWANNOMAS: SYSTEMATIC REVIEW & META-ANALYSIS (2010 TO 2020)
Authors: Savardekar Amey , Terrell Danielle , LeLe Saudamini , Kosty Jennifer , Wang Chiachien Jake , Guthikonda Bharat 
Published: November 2022

Abstract

INTRODUCTION
Over the past two decades, the treatment of small-to-medium (&lt; 3cm) sporadic vestibular schwannomas (VS) has experienced a definite shift to stereotactic radiosurgery vis-a-vis microsurgery. We performed a systematic review and meta-analysis of VS patients primarily treated with stereotactic radiosurgery (SRS) or microsurgery (MS), with particular attention to hearing preservation outcomes (HPO), tumor control (TC), and facial nerve dysfunction (FND). Materials and

METHODS
A systematic review was conducted (Medline database) for the period, 2010 to 2020. Studies with mean/median follow-up of &gt;/= 3 years were included. Studies had to report an acceptable standardized hearing metric. HPO, TC, and treatment complications (with special attention to FND) were compared between the MS and SRS groups.

RESULTS
Thirty-two studies met our inclusion criteria: 10 for microsurgery and 23 for radiosurgery (one comparative study included in both arms). HPO were comparable between MS group and SRS group (56% and 59%, p=0.1527). TC was significantly better in MS group (98%) versus SRS group (92%) [p &lt; 0.0001]. FND was significantly higher in MS group (11%) versus SRS group (2%) [p &lt; 0.0001].

CONCLUSION
The ability to diagnose small sporadic VS earlier, allows patients time to consider all possible treatment options which include observation, radiosurgery, or microsurgery. The data presented in this study will assist physicians in their ability to appropriately counsel patients on the benefits and risks of both treatment modalities with the most recent evidence on the factors that contribute greatly to patients’ quality of life: HPO, TC and FND.