bluuebunny/crossref_metadata_2025_split huggingface dataset:
EPCO-29. EPIGENOMICS OF THE GLIOMA LONGITUDINAL ANALYSIS (GLASS) CONSORTIUM
Authors: Sabedot Thais , Wells Michael , Datta Indrani , Malta Tathiane , Castro Ana Valeria ,   GLASS Consortium, Poisson Laila M , Verhaak Roel , Iavarone Antonio , Noushmehr Houtan 
Published: December 2020

Abstract
Adult diffuse gliomas are central nervous system (CNS) tumors that arise from the malignant transformation of glial cells. Nearly all gliomas will recur despite standard treatment however, current histopathological grading fails to predict which of them will relapse and/or progress. The Glioma Longitudinal AnalySiS (GLASS) consortium is a large-scale collaboration that aims to investigate the molecular profiling of matched primary and recurrent glioma samples from multiple institutions in order to better understand the dynamic evolution of these tumors. At this time, the cohort comprises 946 samples across 11 institutions and among those, 864 have DNA methylation data available. The current molecular classification based on 7 subtypes published by TCGA in 2016 was applied to the dataset. Among the IDH wildtype tumors, 33% (16/49) of the patients showed a change of subtype upon recurrence, whereas most of them (9/16) were Classic-like at the primary stage but changed to either Mesenchymal-like or PA-like at the recurrent level. Among the IDH mutant tumors, 15% (22/142) showed a change of subtype at recurrent stage, in which 16 out of 22 progressed from G-CIMP-high to G-CIMP-low. Although some tumors progressed to a different subtype upon recurrence, an unsupervised analysis showed that the samples tend to cluster by patient instead of by subtype. By estimating the copy number alterations of these tumors using DNA methylation, the overall copy number profile of the recurrent samples remains similar to their primary counterpart. From this initial analysis using epigenomic data, we were able to characterize some aspects of glioma evolution and how the DNA methylation is associated with the progression of these tumors to different subtypes. These findings corroborate the importance of epigenetics in gliomas and can potentially lead to the identification of new biomarkers that can reflect tumor burden and predict its development.
EPCO-31. EPIGENOMIC INTRATUMORAL HETEROGENEITY OF GLIOBLASTOMA IN THREE-DIMENSIONAL SPACE
Authors: Mathur Radhika , Iyyanki Sriranga , Hilz Stephanie , Hong Chibo , Phillips Joanna , Chang Susan , Yue Feng , Costello Joseph 
Published: December 2020

Abstract
Treatment failure in glioblastoma is often attributed to intratumoral heterogeneity (ITH), which fosters tumor evolution and generation of therapy-resistant clones. While ITH in glioblastoma has been well-characterized at the genomic and transcriptomic levels, the extent of ITH at the epigenomic level and its biological and clinical significance are not well understood. In collaboration with neurosurgeons, neuropathologists, and biomedical imaging experts, we have established a novel topographical approach towards characterizing epigenomic ITH in three-dimensional (3-D) space. We utilize pre-operative MRI scans to define tumor volume and then utilize 3-D surgical neuro-navigation to intra-operatively acquire 10+ samples representing maximal anatomical diversity. The precise spatial location of each sample is mapped by 3-D coordinates, enabling tumors to be visualized in 360-degrees and providing unprecedented insight into their spatial organization and patterning. For each sample, we conduct assay for transposase-accessible chromatin using sequencing (ATAC-Seq), which provides information on the genomic locations of open chromatin, DNA-binding proteins, and individual nucleosomes at nucleotide resolution. We additionally conduct whole-exome sequencing and RNA sequencing for each spatially mapped sample. Integrative analysis of these datasets reveals distinct patterns of chromatin accessibility within glioblastoma tumors, as well as their associations with genetically defined clonal expansions. Our analysis further reveals how differences in chromatin accessibility within tumors reflect underlying transcription factor activity at gene regulatory elements, including both promoters and enhancers, and drive expression of particular gene expression sets, including neuronal and immune programs. Collectively, this work provides the most comprehensive characterization of epigenomic ITH to date, establishing its importance for driving tumor evolution and therapy resistance in glioblastoma. As a resource for further investigation, we have provided our datasets on an interactive data sharing platform – The 3D Glioma Atlas – that enables 360-degree visualization of both genomic and epigenomic ITH.
EPCO-32. AN EPIGENETIC SINGLE-CELL ATLAS OF IDH-MUTANT GLIOMA REVEALS THE ROLE OF ATRX IN SHAPING TUMOR COMPOSITION
Authors: Babikir Husam , Wang Lin , Shamardani Karin , Sudhir Sweta , Kohanbash Gary , Aghi Manish , Philips Joanna , Diaz Aaron 
Published: December 2020

Abstract
Recent single-cell RNA-sequencing studies have identified a hierarchy of cell types that is common to all isocitrate dehydrogenase (IDH) -mutant gliomas. This finding is somewhat paradoxical since the genetic differences between IDH-mutant astrocytomas and IDH-mutant oligodendrogliomas are prognostic, predictive of therapeutic response, and correlated with differences in immune infiltrates. To integrate these disparate findings, we constructed a single-cell atlas of 28 human IDH-mutant primary untreated grade-II/III gliomas. All specimens were profiled by single-cell assay for transposase-accessible chromatin, with additional cohorts profiled via single-cell RNA-sequencing and single-cell spatial proteomics. We determined the cell-type specific differences between IDH-mutant gliomas in transcription-factor utilization, associated targeting and cis-regulatory grammars. To elucidate the role of the chromatin remodeler ATRX (inactivated in over 86% of IDH-mutant astrocytomas) in shaping observed differences in open chromatin, we knocked out ATRX in an immunocompetent model of IDH-mutant glioma and subjected murine tumors to single-cell profiling. We found: 1. ATRX-deficient, IDH-mutant human and murine gliomas both upregulate an astrocytic regulatory program driven by Nuclear Factor I genes and downregulate an oligodendrocytic program driven by basic helix-loop-helix transcription factors. 2. Both human and mouse ATRX-deficient, IDH-mutant gliomas up-regulate genes that promote myeloid-cell chemotaxis and both have significantly higher percentages of myeloid-derived immune-suppressive cells than controls; 3. A transcription-factor program is conserved between human and murine ATRX-deficient tumors that shapes glial identity and promotes local immunosuppression. These studies elucidate how IDH-mutant gliomas from different subtypes can have distinct cellular morphologies and tumor micronenvironments despite a common lineage hierarchy.
EPCO-33. MULTI-OMICS ANALYSIS REVEALS SUBTYPE-SPECIFIC ENHANCER-TARGET NETWORKS AND TUMOR CELL OF ORIGIN IN GROUPS 3 AND 4 MEDULLOBLASTOMA
Authors: You Zhen , Huang L Frank 
Published: December 2020

Abstract
Medulloblastoma (MB), one of the most common malignant childhood brain cancer, consists of heterogeneous subgroup of cerebellar tumors. Four molecular subgroups are classified, of which Groups3 and 4 are poorly characterized. Additionally, MB subtype tumorigenesis and cellular composition remain elusive. Here, we combined multi-omics data, including bulk ChIP-Seq, RNA-Seq data, and scRNA-Seq from medulloblastoma patients with primary tumors, and integrated with whole-genome sequencing data, to address the tumors development and cellular heterogeneity in MB subgroups. First, we identified subgroup-specific enhancers and their targets based on the differential accessibility of H3K27ac signatures and further acquired subgroup-enriched transcription factors. Three distinct transcriptional signatures were extracted from RNA-seq of groups 3 and 4 MB respectively using non-negative matrix factorization and consensus clustering. To illustrate the subtype-specific expressed genes in those subtypes, we applied the Shannon entropy approach to discover genes and lncRNAs that are exclusively active or quiescent in a certain subtype. Single-cell transcriptome analysis demonstrated that SHH subgroup mostly consisted of mature and proliferating GNPs; Group3 tumors contained divergent cells, e.g. GNPs, UBCs, and excitatory CN; while Group4 subgroup derived mainly from UBCs and GluCN. Moreover, deconvolution of bulk RNA-Seq revealed that Group3 subtype1 mostly resembled mitosis and mature GNPs; and subtype2 resembled mitosis GNPs, excitatory CN, and OPCs; while subtype3 resembled UBCs, mitosis and mature GNPs, indicating the cellular origin difference within Group3 tumorigenesis. Genes and lncRNAs specifically expressed in subtype and cell type linked to the subtype MB tumor development and intertumoral cellularity. Taken together, these data enabled us to constructed novel enhancers-target networks that give rise to MB subtyping and cellular heterogeneity and permits the discovery of novel driver genes and pathways in medulloblastoma.
EPCO-38. PRIMARY CNS DIFFUSE LARGE B-CELL LYMPHOMA WITH CIC-REARRANGEMENT IDENTIFYING FROM PAN-CANCER PATIENTS EXCLUDING SARCOMAS
Authors: Cai Linbo , Shan Changguo , Hong Weiping , Wang Hui , Ai Ruyu , Song Chao , Qin Huijuan , Zhang Xing , Sun Jiaxing , Ji Yuhang , Yang Xueyu , Ren Yong 
Published: December 2020

Abstract

BACKGROUND
CIC-rearrangements most commonly occur in patients with Ewing-like sarcomas, an emerging class of round cell sarcomas. CIC sarcoma has considered being a new entity in CNS tumors by cIMPACT-NOW conform classification of tumors of soft tissue and bone. However, not all patients harbor CIC fusion are sarcoma cases. Herein, we firstly report a case of primary CNS diffuse large B-cell lymphoma (DLBCL) harboring CIC-rearrangement with a novel partner.

METHODS
CIC fusions were screened in the tumor tissue or peripheral blood from 3,961 cases with different types of cancer excluded patients with sarcomas. Comprehensive genomic profiling with a 539 cancer-related genes panel was administrated based on next generation sequencing (NGS) which is adept in finding novel fusion mutations. The pathology diagnosis of every case was confirmed via hematoxylin and eosin (H&E) stained.

RESULTS
Among the whole 3,961 cases, 3 CIC-rearrangements were observed. One case has been reported yet, one was a patient with lung adenocarcinoma, the last one was a patient harboring POU2F2 (Exon5) -CIC (Exon 11) with CNS arisen tumor, primary DLBCL. Literature review revealed only CIC-LEUTX was reported not only in sarcomas, but also in anaplastic ganglioglioma and CNS embryonal tumors. The partners of CIC sarcomas included DUX4, NUTM1, NUTM2A, FOXO4 and LEUTX, and whether specific partner affected biology of CIC-rearrangement tumors.

CONCLUSIONS
CIC-rearrangement arises in another type of brain cancer besides glioma and embryonal tumor, primary CNS DLBCL. Observation of novel partner provides new basis for further study of biology function of them in CIC fusions. Our study also indicates the presence of a specific tumor type with distinct histopathology driven by CIC fusions can be classified via CIC molecular pathology.
EPID-03. SINGLE INSTITUTIONAL CLINICAL AND GENETIC ANALYSIS OF METASTATIC PROSTATE CANCER WITH AND WITHOUT BRAIN METASTASES
Authors: Jaeger Ellen , Jang Albert , Xie John , Barata Pedro , Ledet Elisa , Trevino Christopher 
Published: December 2020

Abstract

BACKGROUND
Brain metastases (BMs) from metastatic prostate cancer (mPCa) are rare so little is known about clinical, genetic, and anatomic risk factors (RFs) for developing BMs. This single-center review of mPCa patients evaluates RFs for BM development.

METHODS
We reviewed records of mPCa patients at Tulane from 1991 – 2020 to evaluate disease, treatment, cell free DNA, and germline mutations between men with mPCa without confirmed BMs (smPCa) and men with mPCa and confirmed BMs (mPCaBMs).

RESULTS
We reviewed 580 patients with mPCa, of whom 11 had BMs (1.9%). Median age of stage 4 disease was 60.9 and 67.6 for men with mPCaBMs and smPCa respectively. Most mPCaBMs patients had Gleason 8 disease (81.8%) and higher median initial PSA (32 ng/mL) compared to 52.5% and 22.5 ng/mL for patients with smPCa. The development of castrate resistant disease (p=0.30) and overall survival (p=0.53) did not differ between the two populations. There were no differences in frequency of pathogenic mutations for the 68.9% (mPCaBMs) and 72.7% (smPCa) of patients with available genetic testing. Among the 11 mPCaBMs patients, 81.8% had supratentorial and 45.5% had infratentorial involvement (36.4% both). Forty-five percent had adjacent bony metastasis. Median time from SMs to BMs was 65 months (5.28 – 163.63 months), and median survival after diagnosis of BMs was 6.23 (0.49 – 70.82) months after treatment with WBRT, SRS, or GK.

CONCLUSIONS
The higher incidence of BMs likely reflects Tulane’s aggressive mPCa population. Interestingly 45% of BMs occurred from direct bony extension. Although 45% had infratentorial disease reflecting posterior fossa predilection, 82% of patients with BMs had supratentorial metastases. Our data suggest that men with mPCaBMs have aggressive disease and younger age at diagnosis. Due to sample size, no clinical or genetic statistically significant RFs for BMs were identified.
EPID-05. COMPARATIVE EFFICACY OF FIRST-LINE ALK-INHIBITORS IN ALK+ LUNG CANCER BRAIN METASTASES: A NETWORK META-ANALYSIS
Authors: Haddad Philip , Hammoud Dalia , Gallagher Kevin 
Published: December 2020

Abstract

BACKGROUND
Lung cancer has been the leading cause of cancer death for both men and women worldwide. Non-small-cell lung cancer (NSCLC) displays an array of molecular abnormalities most commonly involving ALK and EGFR pathways. NSCLC with ALK rearrangements comprises close to 5% of cases. Several ALK inhibitors (ALKI) have been approved with activity in brain metastases. However, there have been limited comparative studies exploring their relative efficacies. This meta-analysis was conducted to compare the relative efficacy of ALKIs against ALKI-naïve ALK+ lung cancer brain metastases.

METHODS
A review of the medical literature was conducted using online databases. Inclusion criteria consisted of English language; diagnosis of ALKI-naïve ALK+ lung cancer trials with brain metastases; treatment with Crizotinib (CRZ), Alectinib (ALC), Brigatinib (BRG), and Ceritinib (CER); and comparative studies reporting brain metastases specific responses/events. A Bayesian and a frequentists network meta-analysis were conducted using netmeta package and the random-effects model.

RESULTS
Eight studies comprising a total of 665 participants with ALKI-naive ALK+ lung cancer brain metastases were included. When compared pair-wise to CRZ, ALC (RR=0.49;95%CI:0.36–0.66), BRG (RR=0.39;95%CI:0.24–0.64), and CER (RR=0.36;95%CI:0.19–0.68) demonstrated significantly superior response rates in patients with untreated or previously treated lung cancer brain metastases. When the efficacy of each ALKI was compared to each other, BRG and CER were ranked the highest, followed by ALC and CRZ in decreasing order.

CONCLUSIONS
This network meta-analysis is the first to compare and rank approved ALKIs used in treating metastatic ALK+ lung cancer. It indicates that BRG, CER, and ALC are better therapeutic options for patients with ALK-naive ALK+ lung cancer brain metastases when compared to CRZ.
EPID-09. QUANTIFYING SOCIAL DETERMINANTS OF HEALTH AMONG GLIOMA PATIENTS
Authors: Hutchinson Angelica , Marshall Alexandria , Hsu Fang-Chi , Weaver Kathryn , DeTroye Alisha , Houston Kristin Strickland , Carter Annette , Chan Michael , Cramer Christina , Laxton Adrian , Tatter Stephen , Lesser Glenn , Canzona Mollie , Strowd Roy 
Published: December 2020

Abstract

BACKGROUND
Social determinants of health (SDH) are modifiable factors that contribute to health outcomes. Despite studies linking SDHs with cervical, ovarian, and prostate cancer outcomes, few studies have explored SDHs in glioma patients. We conducted a cross-sectional survey to characterize and contextualize SDHs in glioma patients by community income, rural/urban residence, and treatment status.

METHODS
Two validated instruments: PRAPARE (Protocol for responding to and assessing patents’ assets risks and experiences) and AHC (accountable health communities instrument) quantified SDHs; along with study-specific supplemental questions. Risk scores were calculated and combined into an overall and domain-specific (economic, education, neighborhood environment, social context, and healthcare) SDH risk, with a higher score being indicative of higher SDH risk. Scores were compared between low-income (LIC) vs high-income (HIC) communities (defined by median household income), urban vs rural (defined by zip code), and active treatment vs surveillance (determined by patient medical record) using Wilcoxon rank-sum test.

RESULTS
100 glioma patients were enrolled: mean age 53 years (range: 22–78); 49% male; 18% oligodendroglioma, 34% diffuse astrocytoma, 38% glioblastoma, 10% other glioma; 68% resided in LICs, 27% in rural zip codes, and 51% were on active treatment. Overall, SDH risk scores were low (mean= 4.43-out-of-38). Scores in the healthcare domain were the highest. Compared to patients from LICs, patients from HICs had higher healthcare risk scores (p&lt; 0.05). Surveillance patients had higher overall SDH risk on the AHC than patients in active treatment (p&lt; 0.05), with age being a confounder. In multivariable analysis, younger age, and astrocytoma histology were associated with higher social health risk.

CONCLUSION
Glioma patients report relatively few SDH risk factors on standardized instruments designed for general clinic populations. The higher health risk observed in patients in HICs and higher AHC risk for those in surveillance will be further explored in planned qualitative analysis.
EPID-23. A SYSTEMIC REVIEW OF CENTRAL NERVOUS SYSTEM TUMORS IN AFRICA FROM 1960 – 2017 AND THE NEED FOR A CENTRAL BRAIN TUMOR REGISTRY IN AFRICA
Authors: Mbi Feh Marilyn , Brahmaroutu Ankita , Lyon Kristopher , Fonkem Ekokobe 
Published: December 2020

Abstract

PURPOSE
Central Nervous System (CNS) tumors pose a substantial health problem. Although data on specific time periods and regions of Africa has been previously reported, no study has yet to provide a systemic review on the frequency of CNS tumors for the entire continent of Africa. This study aims to analyze the frequency of CNS tumors in Africa from 1960 to 2017.

METHODS
A comprehensive literature search on CNS tumors in Africa was performed using multiple online scientific databases. The following keywords were queried in combination with the phrase “CNS tumors in Africa”: incidence, frequency, epidemiology, prevalence, brain, and cancer. A total of 26 articles met the inclusion criteria. Each selected article reported incidence and mortality rates from different regions of Africa between 1960 to 2017. SPSS21 statistical software was used to analyze the data.

RESULTS
Nigeria, Egypt, and Uganda were found to have the highest incidence of CNS tumors in Africa. Total incidence was 5902, the majority were males, 3190 with mean rate 122.67 (95% CI: 29.27, 216.07) compared to females, 2501 with a mean rate of 96.19 (95% CI: 26.24, 166.15). The most common CNS tumors found were astrocytoma (24.70%), meningioma (22.22%), pituitary adenoma (8.4%), medulloblastoma (4.26%), craniopharyngioma (4.07%), and other not specified (25.17%).

CONCLUSION
Given the large population of Africa, the reported total incidence may be underestimated when compared to other continents due to the lack of a central brain tumor registry in Africa. Comprehensive knowledge of CNS tumors in Africa is critical to research and the entire healthcare system.
EPID-33. PRACTICE VARIATION OF STEROID DOSING AND TAPERING SCHEDULES AMONG THE NEURO-ONCOLOGY COMMUNITY
Authors: Jessurun Charissa , Hulsbergen Alexander , Tewarie Rishi Nandoe , Smith Timothy , Broekman Marike 
Published: December 2020

Abstract

INTRODUCTION
Steroids are commonly used for treatment of peritumoral edema and increased intracranial pressure in brain tumor patients. However, despite the widespread use of steroids, relatively little evidence is available about the optimal dosing scheme in brain tumor patients.

PURPOSE
The aim of this study is to increase insight in the practice variation of steroid dosing and tapering schedules among the neuro-oncology community.

METHODS
An electronic survey consisting of 27 questions regarding dosing and tapering schedules and adverse events of steroids was conducted among neurosurgeons internationally between 6 December 2019 and 1 June 2020. The survey was distributed by the electronic mailing lists of the Europeans Association of Neurosurgical Societies and via social media platforms. Collected data was assessed for quantitative and qualitative analysis using the Kruskal-Wallis test.

RESULTS
The survey obtained 175 responses. 87% of respondents answered all questions. Steroids are prescribed routinely perioperatively by 80% of respondents. Prescribed doses range from 2 to 64 mg/day in dosing schedule ranging from one to four times a day. The most prescribed steroid is dexamethasone in a dose of 16 mg/day. No significant association is seen between the prescribed dose and frequency of adverse events, years of experience, country, type of institution or having an institutional guideline.

CONCLUSION
Steroids are routinely prescribed perioperatively in brain tumor patients. However, there is a great practice variation in steroid dosing and tapering schedules among neurosurgeons. Future investigation is needed to identify an optimal dosing scheme and implement (inter)national guidelines for the dosing of steroids.
EPID-35. CLINICAL TRIAL ENROLLMENT RATE AMONG ADOLESCENT AND YOUNG ADULTS WITH CENTRAL NERVOUS SYSTEM TUMOR AT DANA-FARBER CANCER INSTITUTE (DFCI)
Authors: Sarvode Supriya , Warren Katherine , Reardon David , Yeo Kee Kiat 
Published: December 2020

Abstract

BACKGROUND
Adolescents and young adults (AYAs; 15–39 yrs.) are a population recognized as facing significant challenges in cancer care and research, characterized by historically poor participation in clinical trials. The clinical trial enrollment rate among AYAs with CNS tumor is unclear. We report the findings from our study evaluating the clinical trial enrollment rate of AYAs with CNS glioma at DFCI, comparing the rates between its affiliated adult and children’s hospitals.

METHODS
We performed a retrospective cohort study of patients with primary CNS glioma treated at our center between 2008–18. Eligible patients were identified using institutional databases at Boston Children’s Hospital and Brigham and Women’s Hospital. Manual chart review and data abstraction from the electronic medical record were performed to obtain key variables. Clinical trial enrollment rates were reported, followed by univariate and multivariate logistic regression models to identify factors affecting clinical trial enrollment.

RESULTS
In the adult setting, a total of 608 AYA patients with glioma were identified to meet our inclusion criteria and presented with a median age of 32 years (range:15–39). 92 out of 608 (15%) patients enrolled in a clinical trial during their treatment course. Within this cohort, tumor type was significantly associated with clinical trial enrollment, with higher-grade tumors associated with better enrollment rates (p&lt; 0.001). On the contrary in the pediatric setting, a total of 52 AYA patients were identified from the children’s hospital, with a median age of 17.2 years (range:15–25.4) of whom, 19 out of 52 (36.5%) patients were enrolled on a clinical trial.

CONCLUSION
Clinical trial enrollment rate remains poor among AYAs with CNS tumors, with tumor type/histology grade associated with enrollment rate. Higher enrollment rates were seen among early AYAs treated at the children’s hospital.