bluuebunny/crossref_metadata_2025_split huggingface dataset:
EPCO-47. HETEROZYGOUS CDKN2A LOSS IS ASSOCIATED WITH HIGHER RECURRENCE AND LOWER SURVIVAL IN HIGH-, BUT NOT LOW-GRADE MENINGIOMAS
Authors: Tabor Joanna , Chavez Miguel Millares , O'Brien Joseph , Morales-Valero Saul , Pappajohn Alexandros , McGuone Declan , Erson-Omay Zeynep , Yasuno Katsuhito , Gunel Murat , Moliterno Jennifer 
Published: November 2023

Abstract

INTRODUCTION
Homozygous loss of CDKN2A/B is known to be associated with more aggressive meningiomas and is now considered in the updated criteria for WHO grading. The relevance of heterozygous loss (hetloss) of CDKN2A/B is less clear and the potential association of hetloss CDKN2A with aggressive meningioma phenotype remains underexplored.

OBJECTIVE
We sought to understand the clinical associations of hetloss CDKN2A meningiomas.

METHODS
Clinical and whole exome sequencing (WES) data for patients who underwent resection of sporadic meningiomas were reviewed and analyzed.

RESULTS
Of the 564 meningiomas included, 16 tumors harbored a heterozygous mutation of CDKN2A; 6 of these were low-grade (WHO grade I) and 10 were high-grade (grade II or III). CDKN2A hetloss meningiomas were more likely to be high-grade (p=0.03) and to be diagnosed at older ages (p=0.04) than wild type (WT). Compared to high-grade hetloss meningiomas, low-grade ones were more likely to have elevated proliferative index (p=0.04) and were more common along the skull base (p=0.04). Low-grade meningiomas with hetloss CDKN2A compared to WT ones were more likely to be symptomatic (p=0.023); there was no difference in the tumor make-up or progression free survival (PFS) (p=0.4). High-grade hetloss CDKN2A meningiomas, however, had higher mitotic count (p=0.014), increased chromosomal instability (p=0.004), and higher recurrence rates (p&lt; 0.001), as well as shorter PFS (p&lt; 0.001) and decreased overall survival (OS) (p=0.002), compared to high-grade WT meningiomas. These findings remained significant amongst high-grade hetloss CDKN2A meningiomas even when controlling for underlying NF2 mutation.

CONCLUSION
Heterozygous loss of CDKN2A is associated with more aggressive histological and genomic characteristics in high-grade meningiomas. Additionally, high-grade meningiomas with hetloss CDKN2A differ from those without the mutation with higher recurrence rates and shorter PFS and lower OS, irrespective of underlying somatic NF2 mutation. These findings may have clinical implications for management.
EPCO-51. FUNCTIONAL ANALYSIS OF REGULATORY MUTATIONS IN PEDIATRIC BRAIN TUMORS
Authors: Narta Kiran , Verhey Theodore , Manoharan Varsha Thoppey , Morrissy Sorana 
Published: November 2023

Abstract
Pediatric brain tumors are the primary cause of cancer related mortality in children and are characterized by low mutations burden. The known somatic drivers reside in the coding regions of the genome. The role of non-coding mutations in brain tumors is important yet underexplored. In this study we investigate the impact of regulatory region mutations in pediatric brain tumors. We studied 1.3 million open chromatin regions (OCRs) genome-wide from 9 studies including developing/adult brain, and cancer. Within these OCRs we identified recurring mutations in whole genome sequences from 1003 pediatric brain tumors from CBTN and PCAWG cohorts. A total of 567 OCRs with significantly recurring mutations were found, showing enrichment in brain-specific enhancers and in repressed polycomb regions in stem cells. The mutations in these OCRs resulted in motif disruption or creation of 217 transcription factor binding sites. Differential expression analysis of mutated vs nonmutated samples identified perturbations of gene or protein expression in 67 (RNA) and 16 (protein) OCR-gene pairs. Furthermore, 17 mutated OCRs were found to correlate with alterations in gene expression programs, indicating a potential regulatory role affecting multiple downstream genes. We further performed network analysis to explore clusters of OCR associated genes that share biological networks and pathways, and identified 24 clusters. Among these, OCR mutation-associated genes in 6 clusters showed a survival impact in patients. These 6 clusters mapped to pathways including mRNA decay and degradation, longevity regulating pathway, autophagy, p53 pathway, HIF2-alpha transcription factor network, pathways in cancer among others. In summary, we report functionally important regulatory elements in the genome that impact the biological processes in pediatric brain tumors.
EPCO-53. MULTI-SCALE REGULATION OF SIGNALING CASCADES AND TUMOR EVOLUTION IN HIGH GRADE ASTROCYTOMAS
Authors: Chheda Milan , Liu Jingxian , Cao Song , Imbach Kathleen , Gritsenko Marina , Lih Tung-Shing , Kyle Jennifer , Yaron Tomer , Li Yize , Strunilin Ilya , Binder Zev , Wang Yi-Ting , Tsai Chia-Feng , Ma Weiping , Chen Lijun , Clark Natalie , Wyczalkowski Matthew , Wang Liang-Bo , Deen Nataly Al , Caravan Wagma , Houston Andrew , Rykunov Dmitry , Cottingham Sandra , Chu Rosalie , Weitz Karl , Moore Ronald , Wiznerowicz Maciej , Hostetter Galen , Jewell Scott , Newton Chelsea , Ketchum Karen , Thangudu Ratna , Barnholtz-Sloan Jill , Wang Pei , Fenyö David , An Eunkyung , Nasrallah MacLean P , Thiagarajan Mathangi , Robles Ana , Mani D R , Smith Richard , Porta-Pardo Eduard , Cantley Lewis , Iavarone Antonio , Mesri Mehdi , Zhang Hui , Resnick Adam , Rodland Karin , Liu Tao , Ding Li 
Published: November 2023

Abstract
The National Cancer Institute Clinical Proteomic Atlas Consortium (CPTAC) herein reports our deep characterization of 228 grade IV IDH1 WT and mutant astrocytomas (including 28 matched primary and recurrent GBMs) using 15 proteogenomic and metabolomic platforms. Major advances over our first CPTAC GBM report (Wang et al., 2021, Cancer Cell), are the inclusion of many more samples including paired primary and recurrent tumors, application of new platforms, including glycoproteomics and targeted mass spectrometry methods, development and application of new computational techniques, and the integration of an atlas of experimentally determined, functional, kinase substrate interactions from Kinase Library. Paired primary-recurrent GBM analyses showed increased clonal diversity in recurrent tumors as a function of time, and treatment-induced mutation signatures. Proteomic and metabolomic analyses showed that different drivers can cause similar downstream effects. Only EGFR altered tumors were associated with dual EGFR glycosylation (N352 and N603) and EGFR phosphorylation (Y316) events. IDH1 mutation was associated with activated RTK signaling and decreased hypoxia pathway activities, concordant with epigenetic and metabolic profiles. Protein-protein interaction and kinase/phosphatase-substrate analyses uncovered detailed signaling events from different upstream drivers (e.g., EGFR, PDGFRA, and IDH1) converged through a PTPN11 hub to downstream effectors, including GAB1, IRS1, MAP3K5, and PTK2B. In summary, this multiscale resource presents new and deeper biological insights regarding treatment impact on tumor evolution, shared downstream consequences of independent drivers, and the potential importance of PTPN11 signaling circuitry across high-grade gliomas. We hope that reporting this new international resource to the SNO community will advance therapeutic development, including targeted therapies that may avoid known mechanisms of resistance.
DISP-01. THE IMPACT OF COVID-19 PANDEMIC ON THE HEALTHCARE DELIVERY OF RACIAL/ETHNIC MINORITIES WITH BRAIN METASTASIS BY FACILITY TYPE
Authors: Zhu Ping , Chen Clark ,   NC Consortium
Published: November 2023

Abstract

OBJECTIVES
Brain metastases (BM) are the most common form of adult brain cancer and one of the most devastating complications of cancer. We propose to characterize the effect of the pandemic on health care delivery for racial/ethnic underserved populations on BM care in general and stratifying by facility type.

METHODS
We utilized two national-scale datasets - the National Cancer Database (NCDB) and one of the largest COVID-19 real-time centralized data in the world - the National COVID Cohort Collaborative (N3C) database. Multivariable binary logistic regression models were performed to determine whether the pandemic (three-dimensional measures: pre-pandemic vs. during-pandemic, COVID-19 positivity, and density of COVID-19 prevalence) influence BM care delivery [including stereotactic radiosurgery (SRS), chemotherapy, and immunotherapy], especially for race/ethnicity minorities and patients receiving treatments at non-academic centers (NACs).

RESULTS
Compared to pre-pandemic years, the proportions of receiving BM care significantly decreased across all racial/ethnic groups during the pandemic using two nationwide datasets (NCDB: N=5238; N3C: N=13106), but non-white patients were still significantly less likely to undergo SRS than non-Hispanic whites (NHW) in N3C (total: aOR-0.76, p&lt; 0.001; Black: aOR-0.78, p&lt; 0.001, Hispanic: aOR-0.75, p=0.013; APAA: aOR-0.62, p=0.002) and NCDB (Black: aOR-0.78, p=0.006). Similarly, the odds of receiving chemotherapy for race/ethnicity minorities BM patients were significantly lower than NHW in N3C (Black: aOR-0.71, Hispanic: aOR-0.63, APAA: aOR-0.46, all p&lt; 0.001) and NCDB (Black: aOR-0.86, p=0.028). Furthermore, such inequality in SRS receipt by race/ethnicity was exacerbated during the pandemic at NACs over academic centers (ACs) (esp. Hispanic vs. NHW at NACs: aOR-0.58, p=0.004; Hispanic vs. NHW at ACs: aOR-0.88, p=0.380) in NCDB.

CONCLUSION
Our study suggests that BM healthcare delivery has been significantly reduced in general during the pandemic, but racial/ethnic disparities in BM care and inequality in healthcare access by facility type still exist and have been even exacerbated.
DISP-06. EXAMINING THE INFLUENCE OF NEUROSURGICAL ONCOLOGY PROVIDER ACCESS ON DIFFUSE GLIOMA SURVIVAL OUTCOMES: A NATIONWIDE COUNTY-LEVEL APPROACH
Authors: Sibih Youssef , Perera Sudheesha , DiGiorgio Anthony , Hervey-Jumper Shawn 
Published: November 2023

Abstract
Neuro-oncology as a field has markedly improved understanding of the molecular underpinnings of brain cancer, yet fundamental concepts driving patient outcomes such as access to neuro-oncology subspecialty care remain poorly understood. The aim of this study was to determine the density of neuro-oncologist in the US and correlate disease-specific mortality with provider density. The data was calculated from two national data registries: Centers for Medicare & Medicaid Services (CMS) and Surveillance, Epidemiology, and End RESULTS: (SEER) database. Linear regression modeled three primary outcomes of interest: neurosurgical oncologist per capita, average distance to subspecialist care, and incidence-based mortality of diffuse glioma. Neurosurgical oncologists were classified as providers who billed for CPT code “61510” with at least 10 total services per year over the 5-year duration. In the US, a total of 113 catchment areas were constructed. Mean number of subspecialty providers per capita was 1.80 and the average distance traveled to the nearest provider across the US was 49.9 miles (range 5–151 mi). The mean age-adjusted incidence-based mortality rate among all catchment areas represented was 5.42 deaths per 1000 person-years. Catchment areas with a higher average income were associated with a greater number of subspecialty providers (95% CI 2.13 to 3.44, p &lt; 0.027). Among all US regions, there was no correlation between mortality and provider density or average distance to care. However, Hispanic ethnicity displayed highest incidence-based mortality (r = 0.601, 95% CI -5.02 to -0.944, p &lt; 0.0051). US regions associated with higher poverty and lower average income were associated with greatest mortality (r = 0.45, p &lt; 0.0058). This population study illustrates differences in provider density throughout the United States. Additional research is needed to devise strategies that ensure equitable geographic access in order to optimize patient care and reduce disease burden.
DISP-09. HISTOPATHOLOGIC AND MOLECULAR PROFILE OF GLIOMAS: A 9-YEAR RETROSPECTIVE STUDY OF CASES DIAGNOSED IN LAGOS NIGERIA
Authors: Odukoya Lateef , Kollmeyer Thomas , Eckel-Passow Jeanette , Ida Cristine , Lachance Daniel , Fonkem Ekokobe , Badmos Kabir , Bankole Olufemi , Kitange Gaspar , Daramola Adetola , Anunobi Charles , Jenkins Robert 
Published: November 2023

Abstract

BACKGROUND
The diagnosis and management of patients with brain tumors currently uses WHO defined morphologic and molecular features. However, neuro-oncology practice in low resource settings relies on histomorphology. This study aims to reclassify glioma cases diagnosed in the Department of Anatomic and Molecular Pathology Lagos University Teaching Hospital using the 2021 WHO classification.

METHODS
Fifty-six cases of glioma diagnosed between 2013 to 2021 were evaluated. Morphologic diagnosis was reassessed. Five-micron sections were obtained for immunohistochemistry (IHC), and genetic testing (DNA and RNA); after manual macrodissection for tumor enrichment using 10μm sections. IHC for IDH1-R132H, ATRX, BRAFV600E, P53,Ki67, and H3K27M and OncoScan chromosomal microarray analysis were performed. NGS mutation/fusion analysis and EPIC methylation array profiling are in progress.

RESULTS
Of 56 cases evaluated, median age was 22 years (range=1-60 years); 71% were males. The initial morphologic diagnosis include 21 pilocytic astrocytoma, 11 glioblastoma, 9 ependymoma, 7 diffuse astrocytoma, 3 anaplastic astrocytoma, 2 high-grade gliomas, 1 oligodendroglioma, 1 diffuse midline glioma, and 1 pleomorphic xanthoastrocytoma (PXA). Histomorphologic re-evaluation revealed discordant diagnosis in 29% (16/56) of cases. Of the 56 cases, 73% (41/56) had usable DNA yield and 38% (21/56) had DNA yield of ≥ 750ng. Chromosomal microarray analysis was completed for 50% (28/56) cases. The revised 2021 WHO diagnosis were: 5 glioblastoma, IDH-wildtype, 5 pilocytic astrocytoma, 4 glioma NEC, 3 posterior fossa ependymoma, group B, 3 PXAs, 3 astrocytoma, IDH-mutant, 2 pediatric low-grade glioma, 2 supratentorial ependymoma, ZFTA fusion-positive, 1 posterior fossa ependymoma, group A. In 71% (20/28) of cases, diagnosis was revised using the 2021 WHO criteria.

CONCLUSION
Most cases had usable DNA yield. Overall, hsitologic re-evaluation and molecular testing based on the 2021 WHO classification guidelines refined the diagnosis in 48% (27/56) of cases.
DISP-13. ENHANCING HISPANIC PARTICIPATION IN BRAIN TUMOR TRIALS
Authors: Tajera Dalissa , Marino Irene , De Gennaro Geoffrey , Martinez Adriana , Wright Leonela , Trent Jonathan , de la Fuente Macarena 
Published: November 2023

Abstract

BACKGROUND
Hispanics represent 18.9% of the U.S. population, 26.8% of Florida population, and is the fastest growing ethnicity in the country. Hispanic representation in clinical trials remains extremely low at less than 3%. Increasing the Hispanic participation rate in clinical trials has been a priority for the University of Miami (UM), who has implemented various initiatives to improve diversity and inclusion of underrepresented ethnic minorities (URM) within our clinical trials, especially brain tumor trials. Efforts such as community outreach raising awareness of clinical trials, translation of informed consents to Spanish, use of bilingual staff trained in cultural communication diversity and inclusion, dedicated social workers and community seminars have played a crucial role at enhancing Hispanic participation within our brain tumor studies. Method Retrospective review using UM’s clinical trial registry to analyze demographics of brain tumor patients consented to therapeutic/non-therapeutic trials between May 2017 to May 2023.

RESULTS
A total of 431 patients were consented of which 313 (72.4%) actively participated in therapeutic/non-therapeutic trials and 118 (25.1%) screened-failed. Of the accrued participants, 283 (90.42%) self-identified as White, 16 (5.11%) Black/African American, 5 (1.60%) more than one race, 4 (1.28%) Asian, 4 (1.28%) unknown/unreported and 1 (0.32%) American Indian/Alaskan Native. For ethnicity, 160 (51.12%) self-identified as Hispanic/Latino, 148 (47.28%) as non-Hispanic, and 5 (1.60%) were unknown/unreported. 143 (45.69%) were females and 170 (54.31%) were males. For age, 43 (13.73%) were 18-39, 191 (61.02%) 40-64 and 79 (25.24%) were 65 and over.

CONCLUSION
There is extensive evidence that patients from URM’s groups may not be afforded the same opportunity to participate in clinical trials and thus benefit from advanced therapies offered via them. Efforts to ensure meaningful representations of Hispanics in our brain tumor trials have led to a high accrual rate of Hispanics above national norms to better represent our community's demographics.
DISP-14. THE ASSOCIATION BETWEEN MEDICAID ENROLLMENT CONTINUITY AND CHILDHOOD, ADOLESCENT, AND YOUNG ADULT BRAIN TUMOR SURVIVAL
Authors: Johnson Kimberly , Brown Derek , Thompson Tess 
Published: November 2023

Abstract

BACKGROUND
Disparities in younger cancer patient survival between individuals with Medicaid and private insurance have been reported. To further understand this association for brain tumor survival, we used Surveillance, Epidemiology, and End

RESULTS
(SEER)-Medicaid-linked data to test two hypotheses: 1) those enrolled in Medicaid have lower brain tumor survival than those not enrolled, and 2) those with discontinuous enrollment in Medicaid around the time of diagnosis have lower survival than those with continuous enrollment.

METHODS
SEER-Medicaid linked data on individuals diagnosed with a first malignant primary brain cancer between 0 to 39 years from 2006 to 2013 were obtained with follow-up through 2018. Medicaid enrollment was classified as continuous (enrolled six months before through six months after diagnosis) and discontinuous (enrolled non-continuously in the twelve months surrounding the diagnosis month). We used Kaplan-Meier (KM) curves and Cox Proportional Hazards (PH) regression models with SEs clustered on state to evaluate survival differences in association with Medicaid enrollment timing after adjusting for age, race/ethnicity, and a measure of census tract poverty.

RESULTS
Our analytic dataset included 10,110 children, adolescents, and young adults, including 3,148 brain tumor deaths. Consistently lower survival probabilities over time were observed for those enrolled in Medicaid, particularly those with discontinuous enrollment for both age groups. Higher hazards of death were observed for those enrolled in Medicaid vs. not enrolled (HR0-19 =1.66 95% CI 1.41-1.95; HR20-39=1.38, 95% CI 1.27-1.51) and with discontinuous vs. continuous in Medicaid enrollment (HR0-19 =1.60, 95% CI 1.43-1.81; HR20-39=2.03, 95% CI 1.75-2.36).

CONCLUSIONS
These results indicate Medicaid enrollment continuity has an impact on the risk of death, with discontinuous enrollment associated with an over two times higher risk of death for young brain tumor patients. These results further support the critical need for consistent health insurance coverage for children, adolescents, and young adults.
IMMU-04. LOW-INTENSITY PULSED ULTRASOUND ENHANCES CAR T CELL THERAPY BY INDUCING TWO-WAY IMMUNE CELL TRAFFICKING – T CELL INTO TUMOR AND MYELOID CELL INTO PERIPHERY IN A SYNGENEIC MOUSE GLIOBLASTOMA MODEL
Authors: Yamamichi Akane , Chen Tiffany , Phyu Su , Young Jacob , Kyewarabye Keith , Hatae Ryusuke , Gallus Marco , Canney Michael , Sonabend Adam , Okada Hideho 
Published: November 2023

Abstract
Chimeric Antigen Receptor (CAR) T-cell therapy has been successful against hematological malignancies. However, it has not established efficacy in glioblastoma (GBM) patients. Significant challenges currently limiting the effectiveness of CAR T-cell therapy for patients with GBM include poor CAR-T cell trafficking to GBM due to the blood-brain barrier, and the presence of highly immunosuppressive and pro-tumoral tumor-associated macrophages (TAMs) in the tumor microenvironment. Furthermore, the heterogeneous expression of target antigens in GBM can lead to antigen escape and therapeutic resistance. Low-intensity pulsed ultrasound with microbubbles (LIPU/MB) has been shown to enhance CAR T-cell trafficking and improve survival in immunocompromised xenograft mice GBM models. In this study, we investigated whether multiple rounds of LIPU/MB can improve not only CAR T-cell but also endogenous T-cell infiltration into the tumors and induce myeloid cell trafficking into lymph nodes (LNs), thus enhancing CAR T-cell therapy against GBM in the immunocompetent syngeneic mice model. We recently developed a novel immunocompetent transgenic (Tg) mouse that expresses an anti-EGFRvIII CAR on T-cells and enables us to investigate the interaction between CAR T-cells and the endogenous immune environment. C57BL6/J mice bearing intracerebral EGFRvIII+ GBM received an intravenous administration of anti-EGFRvIII CAR T-cells derived from Tg-mice. The mice were stratified to receive single-LIPU (1 min before CAR T-cells administration) or triple-LIPU/MB (1 min before CAR T-cells administration, then two and four days later). Triple-LIPU/MB significantly suppressed tumor growth and improved survival and was associated with increased CAR T-cells and endogenous T-cells infiltration into the tumors compared with single-LIPU/MB or without LIPU. Furthermore, draining cervical LNs showed increased macrophages trafficking after triple-LIPU/MB. Moreover, TAMs isolated from triple-LIPU/MB mice brains showed higher levels of MHC-II expression. These results suggest that LIPU/MB may promote the tumor antigen presentation to endogenous T-cells and enhance the efficacy of CAR T-cell therapy for GBM.
IMMU-05. CD8 IMMUNOPET IMAGING IS ABLE TO MONITOR THE IMMUNE RESPONSE SENSITIVELY AND SPECIFICALLY IN GBM PATIENTS FOLLOWING NEOADJUVANT CHECKPOINT BLOCKADE IMMUNOTHERAPY
Authors: Prins Robert , Konik Arda , Sun Lu , Markus Lauren , Herrera Gilbert , Qin Lei , Everson Richard , Lee Eudocia , Reardon David , Shah Hina , Huang Raymond Y , Ellingson Benjamin , Cloughesy Timothy , Wen Patrick , Van den Abbeele Annick D 
Published: November 2023

Abstract
The sensitive and specific evaluation of treatment response in glioblastoma (GBM) patients following immunotherapy is a clinical dilemma. Traditional MRI assessments to visualize and quantify intracranial tumor burden following immunotherapy cannot reliably differentiate tumor progression and pseudo progression remains a complicating factor. In this study, we provide an early report on the use of an investigational new functional imaging PET tracer (CD8 ImmunoPET, 89Zr-crefmirlimab berdoxam, ImaginAb) prior to and immediately following neoadjuvant checkpoint blockade immunotherapy in five patients with recurrent GBM. Tumor samples were collected from each patient at surgery following a two-week neoadjuvant checkpoint blockade to assess gene expression changes and TIL density. We then evaluated how such tumor measurements correlated with PET metrics obtained at baseline and within 2 weeks after treatment initiation which included standardized uptake values (SUVmax, SUVpeak, and SUVmean), and two proposed new metrics indicating the Volume of Immunometabolism (VIM), and the Total Lesion or Lymph nodes’ T cells called TLTc (TLTc = VI x SUVmean) in the tumor bed and lymph node basins (neck, axillae, and inguinal regions). CD8 ImmunoPET demonstrated tracer uptake in the intracranial tumor at both time points, as well as specific physiologic uptake in lymph node basins, spleen, liver, and bone marrow. Neoadjuvant checkpoint blockade with PD-1 +/- CTLA-4 mAb (Nivolumab, Ipilimumab, BMS) at 2 weeks induced variable changes in SUV, but in four of the five initial patients studied in this clinical trial, an increase in VI and TLTc was observed within the tumor bed. Tracer uptake was associated with elevated T cell infiltration into the tumor bed and gene expression changes indicative of interferon signaling and immune cells in these same patients. Our early findings identify a noninvasive functional imaging platform to evaluate the immunometabolism secondary to T cell infiltration and/or activation changes following immunotherapy in GBM patients.