bluuebunny/crossref_metadata_2025_split huggingface dataset:
EPCO-36. INVESTIGATING THE BAIAP2-CDC42 INTERACTION IN MEDULLOBLASTOMA
Authors: Ruiz Luz , Jangde Nitish , Ayad Nagi 
Published: November 2022

Abstract
Medulloblastoma is the most common malignant brain tumor found in children. The standard of care is surgical removal, radiation, and chemotherapy. Despite advancements in treatment, there is still no significant improvement of survival rates using chemotherapy compared to no treatment. This indicates novel, more effective treatment options are necessary. In addition, there is a worst mortality rate when medulloblastoma is metastasized outside the central nervous system. Recent studies have identified that medulloblastoma tumors can disseminate via the bloodstream and cerebral spinal fluid. However, not much is known about the properties of metastasis and invasion in medulloblastoma. We set out to identify potential key regulators for the pathophysiology of medulloblastoma. I mined and analyzed Medulloblastoma patient tumor data along with data obtained from a 10X Genomics Chromium single-cell RNA sequencing experiment performed in the laboratory from a Tg (Neurod-Smoothened*A1) mouse to investigate cellular heterogeneity and identify potential regulators in the metastasis and invasion of medulloblastoma. We identified BAIAP2 and CDC42 to be differentially expressed in our data. Previous studies show that these genes are implicated in oncogenic properties, such as motility, filopodia, and invasion. We hypothesize that distinct cell populations within medulloblastoma should show different expressions of BAIAP2 and CDC42 and that there will be different expressions when compared to non-tumor brain cells. We determined that BAIAP2 and CDC42 have higher expression in medulloblastoma tumors compared to the control. Interestingly, BAIAP2 is enriched in the cell population for microtubule depolymerization. Moreover, we show the role BAIAP2 and CDC42 have in the invasion and metastasis of medulloblastoma. This study is important because BAIAP2 and CDC42 have yet to be characterized in medulloblastoma. We suggest that BAIAP2 and CDC42 have a role in the metastasis and invasion of medulloblastoma indicating it could be a possible target for future studies.
EPCO-38. TYPE B ULTRA LONG-RANGE INTERACTIONS IN PFAS (TULIPS) ARE RECURRENT EPIGENOMIC FEATURES OF PFA EPENDYMOMA
Authors: Johnston Michael , Lee John J Y , Hu Bo , Nikolic Ana , Baguette Audrey , Paik Seungil , Chen Haifen , Kumar Sachin , Chen Carol , Jessa Selin , Balin Polina , Fong Vernon , Zwaig Melissa , MichealRaj Kulandaimanuvel , Chen Xun , Zhang Yanlin , Varadharajan Srinidhi , Billon Pierre , Juretic Nikoleta , Daniels Craig , Giannini Caterina , Thompson Eric , Hauser Peter , Kim Seung-Ki , Wang Kyu-Chang , Lee Ji Yeoun , Grajkowska Wieslawa , Agnihotri Sameer , Mack Stephen C , Ellezam Benjamin , Weil Alex , Bourque Guillaume , Chan Jennifer , Lupien Mathieu , Ragoussis Jiannis , Kleinman Claudia , Majewski Jacek , Jabado Nada , Taylor Michael , Blanchette Mathieu , Gallo Marco 
Published: November 2022

Abstract
Posterior Fossa Group A (PFA) ependymomas are pediatric brain tumors with extremely poor survival outcomes. As protein-coding mutations in PFA are exceedingly rare, the underlying etiology of these tumors remains elusive. Elevated CpG island methylation and depletion of H3K27me3 have been described in PFA, leading to the hypothesis that PFA may be driven by a dysregulated epigenetic state. In this study, we sought to determine how three-dimensional (3D) genome features (such as DNA loops, domains, and compartments) differ between pediatric brain tumors. We performed Hi-C sequencing on a collection of 64 patient specimens and patient-derived primary cultures that collectively span multiple subgroups of ependymoma, medulloblastoma, high-grade glioma, and non-neoplastic brain. For certain samples, we further performed RNA-seq, histone modification ChIP-seq, or whole-genome bisulfite sequencing to allow multiomic data integration. Overall, the 3D genome organization of PFA samples appeared distinct from other tumor types. We identified and defined TULIPs: a subset of type B compartments, separated by genomic distances greater than 10 Mbp, that exhibit a striking fivefold increase in reciprocal interaction strength. These TULIPs recurred at the same genomic positions across the vast majority of PFA samples with minimal representation among other tumor or non-tumor samples. TULIPs displayed enrichment for heterochromatic features such as H3K9me3 and late replication timing and were depleted of euchromatic features such as H3K27ac and protein-coding genes. By using immuno-fluorescence for H3K9me3 and oligo-FISH to label TULIP regions, we demonstrated that TULIP regions are more compact in PFA than other tumors. Finally, by applying inhibitors of H3K9 lysine methylation to PFA cultures we showed that TULIPs become more diffuse and cell viability is reduced. Altogether, this work defines TULIPs as highly recurrent epigenetic features of PFA tumors.
EPCO-41. DNA METHYLATION PROFILING OF MENINGIOMAS FROM 17 PATIENTS, A CASE SERIES
Authors: Shen Erica , Leclair Nathan , Herlth Kristi , Soucy Melissa , Renzette Nick , Zhuo Xinming , Kelly Kevin , Omerza Gregory , Wolansky Leo , Becker Kevin , Li Lei , Wu Qian , Bulsara Ketan 
Published: November 2022

Abstract

BACKGROUND
Meningiomas are the most common intracranial tumors. According to the World Health Organization’s (WHO) classification guidelines, they can be classified into 15 subtypes with three grades of malignancy based on histology alone. In recent years, analysis of tumor methylomes that reflects both cell-origin methylation signatures and somatically acquired DNA methylation changes has been utilized to better classify meningiomas with great success. Method: In our case series, we report DNA methylation profiling on meningiomas from 17 patients. Formalin fixed paraffin embedded (FFPE) meningioma tumor samples were processed, loaded onto the Infinium Methylation EPIC array, and scanned using the Illumina IScan system. Raw IDAT files were then processed through the v12b6 version of the CNS tumor classifier developed by the Molecular Neuropathology group at the University of Heidelberg. Classifier output consisted of assigned methylation classifications along with confidence scores, with scores ≥0.84 classified as “high confidence.” Result: Among our meningioma samples from 17 patients (18 samples total), 14 samples are classified as “benign,” one sample is classified as “intermediate,” and the remaining three samples from two patients are classified as “malignant.” In addition to tumor methylation profiling, we also present information that includes patient demographics, clinical presentations, tumor characteristics (size, location), surgical approaches, and mutational analysis. Genomic analysis has revealed variants in NF2, SLX4, ARID1A, KDM4C, ERCC2, EP300, ERBB2, KMT2D, LRP1B, FANCE, CRKL, and SPEN in multiple patients. The three meningioma samples from the two patients that are classified as “malignant” all have a high MIB1 indexes consistent with WHO Grade II meningiomas. Both patients had tumor recurrence reflecting the aggressiveness of the tumor in their disease course.

CONCLUSION
In accordance with prior reports, our case series provides support that tumor DNA methylation profiling can provide useful classification information and can be correlated to both tumor pathology and patient clinical presentation.
EPCO-43. CHROMATIN REMODELERS LOST IN TRANSLATION
Authors: Van Rechem Capucine 
Published: November 2022

Abstract
The chromatin remodeler complexes mammalian SWI/SNF (SWItch/Sucrose Non-Fermentable) are altered in more than 40% of cancers and are involved in therapeutic resistance. In children,SMARCB1 is mutated in 95% of rhabdoid tumors, and the remaining 5% present mutations in SMARCA4. These tumors are typically identified in children younger than three years old and have a very poor prognosis with a survival under one year following diagnosis. SMARCB1 expression is also lost in more than 90% of epithelial sarcomas, a rare and aggressive tumor affecting young adults, and in 50% of pediatric chordomas. Additional mSWI/SNF subunits are also highly mutated in childhood cancers such as ARID1A and ARID1B in neuroblastomas, the most common solid tumor in children, and the ARID subunits and SMARCA4 in medulloblastomas, the most common brain cancer in children. To date, mSWI/SNF roles in normal and cancer cells are still largely undetermined and focus on nuclear functions. However, our assessment of genetic dependencies and drug sensitivity screens revealed that cancer cells mutated for mSWI/SNF are genetically dependent and exclusively sensitive to translation factors and translation pathway inhibitors. We demonstrate that mSWI/SNF complexes are extensively localized in the cytoplasm and that they interact with the translation initiation machinery. Furthermore, short-term inhibition, depletion and cancer mutations of specific subunits alter protein synthesis and increase sensitivity to translation inhibitors. Most mutations in these complexes being considered loss of function, these results suggest a potential therapeutic opportunity for diseases presenting mutations in these complexes. In conclusion, our work demonstrates the chromatin remodelers mSWI/SNF have direct roles in translation that will not only be relevant for the molecular understanding of cancer but also lead to new therapeutic opportunities.
DISP-08. DISPARITY OF RADIATION TREATMENT AND CLINICAL OUTCOME AMONG ADULT MEDULLOBLASTOMA PATIENTS
Authors: Yang Kailin , Dinh Mina , Nam Kireem , Madishetty Sanjana , Kilic Sarah , Scott Jacob , Chao Samuel , Murphy Erin , Suh John 
Published: November 2022

Abstract

OBJECTIVES
Medulloblastoma is the most common malignant pediatric brain neoplasm, but its pattern of care among adult patients has not been standardized. Disparity in socioeconomic factors influence treatment decision and prognosis in many cancers. This study aims to analyze the impact of insurance and socioeconomic status on the clinical outcome of adult patients with medulloblastoma in the United States.

METHODS
Adult patients (age 18 or older) with medulloblastoma in the brain diagnosed from 2004 to 2016 were identified from the National Cancer Database (NCDB). OS was evaluated with the Kaplan-Meier and Cox proportional hazards methods. Logistic regression was performed to assess the effect on dichotomized dependent variable.

RESULTS
A total of 1,282 adult patients with medulloblastoma were identified. The mean age was 29 years (range 18-85). 30.9% of patients were uninsured or had Medicaid, 83.2% were white, 81.9% received radiation therapy, and 59.9% received chemotherapy. Using univariate analysis, insurance status, radiation, and chemotherapy were statistically associated with OS. Uninsured/Medicaid patients were associated with poorer OS (HR 1.36, 95% CI 1.08-1.71, p &lt; 0.01) compared to those with private insurance. Treatment with radiation therapy (HR 0.43, 95% CI 0.34-0.55, p &lt; 0.01) or chemotherapy (HR 0.51, 95% CI 0.41-0.62, p &lt; 0.01) portended improved OS. After adjusting for age, sex, race, and Charlson-Deyo comorbidity score, statistically significant differences in OS were seen for patients with no insurance/Medicaid. Using multivariate logistic regression, patients with either no insurance or Medicaid were less likely to receive radiation therapy (OR 0.69, 95% CI 0.51-0.95, p = 0.02) compared to patients with private insurance.

CONCLUSION
Using a large national cohort of adult medulloblastoma patients, this study demonstrated the statistically significant disparity of patient outcomes with insurance status. An effort to address healthcare disparity and increase access to cancer care may improve the clinical outcome for adult patients with medulloblastoma.
DISP-09. THE GENOMIC PROFILES AND CLINICAL MANIFESTATIONS OF MENINGIOMAS VARY AMONGST DIFFERENT RACES
Authors: Vetsa Shaurey , Vasandani Sagar , Jalal Muhammad , Yalcin Kanat , Youngblood Mark , Marianayagam Neelan , Elsamadicy Aladine , Qureshi Hanya , Nadar Arushii , Sandhu Mani Ratnesh , Aguilera Stephanie , Mishra-Gorur Ketu , McGuone Declan , Fulbright Robert , Jin Lan , Erson-Omay E Zeynep , Günel Murat , Moliterno Jennifer 
Published: November 2022

Abstract

BACKGROUND
While socioeconomic factors for racial disparities amongst sporadic meningioma patients have been explored, other potential influences are poorly understood. We sought to identify whether the genomic make-up is different amongst meningioma patients of different races and how they correlate with clinical variables.

METHODS
All patients who underwent surgery for sporadic meningioma and consented for whole exome sequencing were eligible. Genomic and clinical data were reviewed and analyzed.

RESULTS
537 intracranial meningiomas from 483 patients with the following racial profile were included: 75% White, 14% Black, 8% Latinx, 3% Asian. Compared with others, Whites were older at the time of diagnosis (p = 0.038) and surgery (p = 0.015). Black and Latinx patients were more likely to present with vision abnormalities (p = 0.006). Whites were more likely to have convexity meningiomas (p = 0.003), while Blacks were more likely to have tumors along the anterior fossa (p = 0.002) with associated somatic Hedgehog (HH) driver mutations (p = 0.008). Both Black and Latinx patients were more likely to have TRAF7 mutated meningiomas (p = 0.006). The highest number of copy number variations was seen in Blacks (p = 0.011) and this correlated with Blacks being more likely to have high-grade tumors, followed by Whites, Asians, and then Latinx (p = 0.020). Black patients trended toward decreased progression-free survival than others (median survival: 57 vs. 130 months; p = 0.06) despite similar extent of resection.

CONCLUSION
Overall, when mutational subgroup and location are considered, Black patients are more likely to have anterior skull base meningiomas with associated visual issues and corresponding somatic HH and TRAF7 mutations. With regards to tumor grade, Blacks harbor more aggressive sporadic meningiomas with a larger prevalence of high-grade meningiomas and associated underlying chromosomal instability compared to others. These findings have implications for meningioma care especially in minority populations, who may harbor more aggressive tumors.
DISP-11. GENDER DISPARITY REGARDING WORK-LIFE BALANCE SATISFACTION AMONG GERMAN NEURO-ONCOLOGISTS: A YOUNGNOA SURVEY
Authors: Kebir Sied , Lazaridis Lazaros , Wick Wolfgang , Platten Michael , Tabatabai Ghazaleh , Combs Stephanie , Schmidt Teresa , Agkatsev Sarina , Blau Tobias , Mäurer Irina , Kahlert Ulf , Sagerer Andre , Berberich Anne , Heider Sina , Müther Michael , Bodensohn Raphael , Behling Felix 
Published: November 2022

Abstract

PURPOSE
Satisfaction with work-life balance (WLB) is an essential factor for persistent motivation of early career researchers. However, WLB satisfaction in the neuro-oncological landscape is not well characterized. We present the results of an interdisciplinary survey focusing on WLB satisfaction among neuro-oncologists in Germany.

METHODS
The questionnaire was sent to 351 physicians, all of whom were members of the Neuro-oncology Working Group “Neuroonkologische Arbeitsgemeinschaft” (NOA) of the German Cancer Society (Deutsche Krebsgesellschaft, DKG). The participants were asked for personal information, individual motivations, scientific interests, activities, individual workload, and job satisfaction. The questionnaire was accessible from 18 March 2021 to 1 April 2021.

RESULTS
Ninety-six physicians (36 female, 60 male) participated in this survey. Age, gender and relationship status were significantly different between participants who were satisfied and those not satisfied with their WLB. Female participants were less likely to be satisfied with their WLB than male participants (25% vs 75%, p = 0.005). In a logistic regression model, the finding that female participants were less likely to be satisfied with their WLB than male participants remained statistically significant (odds ratio [OR] 0.32; 95% confidence interval [CI] 0.21–0.84, p = 0.023) after accounting for possible confounding variables such as age (OR 1.06; 95% CI 1.01–1.11, p = 0.025), childlessness (children available vs not available, OR 0.40; 95% CI 0.10–1.35, p = 0.156), and relationship status (unmarried vs single, OR 2.49; 95% CI 0.50–13.98, p = 0.275; married vs single, OR 6.18; 95% CI 1.29–35.46, p = 0.029).

CONCLUSIONS
This survey demonstrates that WLB satisfaction is significantly decreased among female neuro-oncologists in Germany. It highlights the importance of programs such as “Diversity in Neurooncology” (DivINe), founded by the NOA and aiming to address gender disparities.
DISP-15. TRENDS IN LASER INTERSTITIAL THERMAL THERAPY (LITT): HOW RACE AND SOCIOECONOMIC FACTORS IMPACT ACCESS
Authors: Terrell Danielle , Kandregula Sandeep , Caskey Joshua , Newman Christopher 
Published: November 2022

Abstract
Introduction This study seeks to examine the trends of laser interstitial thermal therapy (LITT) access in the pre-and post-Medicaid expansion time periods; and more specifically, how racial and socioeconomic factors impact access. Methods The National Inpatient Sample (NIS) database was queried for all patients who received LITT from 2010 to 2019 for any indication. Age, gender, race, payer status, and median income by zip code were obtained and compared for the pre-Medicaid expansion (2010-2014), and post-Medicaid expansion (2015-2019) groups. Chi-square analysis was performed for categorical variables, and the student t-test was used to analyze continuous variables. Results The pre-Medicaid expansion (n = 915) and post-Medicaid (n = 3205) time periods were similar in that Whites were the overwhelming majority of LITT recipients (78.7% and 70.8%, p &lt; 0.001). In 2010, all races had low rates of LITT, as would be expected with a new emerging treatment. Although the absolute value of the percentages seems similar, between 2013 and 2014, the proportion of Whites receiving LITT nearly doubled (from 45% to 75%); while all other groups had no significant increase in utilization. Utilization of LITT by Black Americans remained stable, 5.4% and 5.6% in the pre- and post-Medicaid expansion eras, while Hispanics and Others saw slight increases in utilization (8.8% to 10.1% and 7.1% to 13.4% respectively). Although Medicare and Medicaid usage increased over the years, private insurance remained the primary payer for LITT (53.8% and 49.3%, p 0.018). Lastly, patients within the highest income quartiles comprised over half of LITT procedures done in the study period (56.8% and 52.8%, p 0.029). Conclusion Despite nearly a decade and the effects of Medicaid expansion via the Affordable Care Act, LITT is still difficult to access for patients of color, Medicare and Medicaid users, and patients in low-income locales.
IMMU-01. DEFINING THE IMMUNE PROFILE OF RADIATION NECROSIS THROUGH SINGLE-CELL ANALYSIS OF INTRACRANIAL LESIONS
Authors: Robert Stephanie , Lu Benjamin , Kiziltug Emre , Estape Anna , Nguyen Don , Chiang Veronica 
Published: November 2022

Abstract

INTRODUCTION
The incidence of radiation necrosis (RN), a common and morbid side effect of radiosurgical management of brain metastases, is growing as patient survival and use of immunotherapy increases. RN is thought to be immunologically driven; however, its pathophysiology remains poorly understood. Further, difficulty distinguishing it radiographically from recurrent metastatic disease often necessitates invasive brain biopsies for diagnosis. We sought to define the neuroimmune profile of RN to better understand the underlying pathophysiological mechanisms and improve patient diagnosis.

METHODS
Over 12 months, we collected intraoperative samples from patients undergoing craniotomy for RN and/or metastatic tumor. We created a bank of these 16 patient samples and processed them for scRNAseq analysis. Using fluorescence-activated cell sorting (FACS) and 10x Genomics single cell RNA sequencing, we analyzed the cellular immune profile of lesional tissue and time-matched blood from each patient.

RESULTS
Compared to metastases, RN demonstrates decreased expression of FOXP3, NKG7, and GZMB, markers of regulatory and cytotoxic T, and natural killer (NK) cells, and increased expression of interleukin-7 receptor (IL7R), a marker of naïve and memory T cells – profiles reflective of bystander transcriptional signatures. In contrast, metastatic tissue demonstrates an antigen-reactive profile, including commonly observed exhaustion signatures. Importantly, blood samples from patients also reflect these differences. Interestingly, increased IL7R is implicated in autoimmune disorders, suggesting an iatrogenically-induced autoreactive process underlying RN.

DISCUSSION
These findings demonstrate, firstly, the feasibility of extracting live cells from RN tissue, and, secondly, suggest RN and metastases have unique immune profiles that can be detected in patient blood. Therefore, in addition to beginning to define the immune landscape of this poorly understood pathology, this work has the potential to open new avenues for the development of improved diagnostic and therapeutic approaches to allow for earlier detection and more effective treatment of RN in metastatic brain tumors patients.
IMMU-07. HUMANIZED BI-SPECIFIC ANTIBODY SHOWS POTENT ACTIVITY IN PATIENT-DERIVED XENOGRAFT MODELS OF GLIOBLASTOMA
Authors: Duffy Joseph , Zannikou Markella , Levine Rebecca , Stupp Roger , James David , Balyasnikova Irina 
Published: November 2022

Abstract

BACKGROUND
Advancements in bioengineering have allowed bispecific Abs to develop with therapeutic applications in immuno-oncology. Here we describe a fully humanized bispecific t cell engager (BiTE) that binds the GBM-associated antigen interleukin 13 receptor alpha 2 (IL13Rα2) and the T Cell receptor CD3 epsilon (CD3ε) to elicit an anti-tumor immune response in patient-derived models of GBM.

METHODS
In vitro, BiTE-mediated activation of T Cells was assessed via flow cytometry as measurements of T cell activation markers CD25 and CD69 and cytokines IFNγ and TNFα. BiTE-directed T cell-mediated cytotoxicity was assessed in GBM 6 and GBM12patient-derived xenograft lines. In vivo, GBM6 patient-derived xenograft cells were intracranially implanted in NSG-MHC I/II DKO mice, reconstituted with HLA-matched donor peripheral blood lymphocytes (PBMC), and subsequently treated with 2.5 mg/kg BiTE via i.p. injection x 4 days/week of therapeutic BiTE for three weeks. Animals were followed for survival, and the brains of long-term survivors were analyzed for residual disease and T cell infiltration.

RESULTS
In vitro, BiTE potently activated T cells as determined by a high expression of CD25 and CD69 and the production of TNFα and IFNγ. BiTE also directed T cell-mediated cytotoxicity against GBM cells in a dose-dependent manner, with significant activity still seen in the low nanogram range. In vivo, BiTE significantly extended the survival of tumor-bearing animals in GBM6patient-derived xenograft models. Histological analysis of long-term surviving mice shows complete absence of tumor and robust presence of CD8+ T cells localized to the original site of tumor implantation.

CONCLUSIONS
Our data demonstrate the efficacy of humanized BiTE in patient-derived GBM models, and our results support the investigation of this novel therapeutic in a clinical trial setting.FUNDING: R01 NS122395-01 and R01 NS095642-01