bluuebunny/crossref_metadata_2025_split huggingface dataset:
INNV-38. COVID-19 INDUCED TELEMEDICINE LESSONS FOR CLINICIANS CARING FOR PATIENTS WITH PRIMARY BRAIN TUMORS
Authors: Komlodi-Pasztor Edina , Brady Amy , Grossman Stuart 
Published: November 2021

Abstract

BACKGROUND
The COVID-19 pandemic triggered a rapid conversion from in-person to video-visits for new patient consultations and follow-up visits. Now with available vaccines and declining case rates efforts are underway to return to in-person visits as they provide more revenue and are viewed as best for patients and clinicians. This abstract reviews these assumptions.

METHODS
Electronic medical records from seven full-time faculty neuro-oncologists at Johns Hopkins Hospitals were retrospectively reviewed from 4/1/20 to 3/31/21 to examine the use of video visits over time and their patient demographics.

RESULTS
From 4/1/20 to 3/31/21, 279 new patients were seen (57% video-visits) with a median age of 52 years for both video and in-person visits. Patients came from 15 states for video and 17 states for in-person visits. There were also 2247 follow-up visits (85% video-visits) with a median age of 47 yrs for video and 50 yrs for in-person visits. Patients came from 28 states for video and 14 for in-person visits. No show visits were more frequent for in-person visits. During early months of the pandemic, few patients were seen in the clinics. Thereafter, video-visits rose sharply comprising 93% of follow-up visits in June 2020 and 62% of new patient consultations in September 2020. These rates have remained high (in March 2021, 72% of all follow-up visits and 59% of new patient consultations).

CONCLUSIONS
Despite reductions in COVID-19 infection rates, our neuro-oncologists continue to favor video-visits for new patient consultations and follow-up visits. Video-visits save patients and caregivers travel time, parking costs, and time away from work. They also allow an acceptable history and neurological exam, participation by many family members, easy sharing of MRI scans and laboratory data, and discussions unencumbered by face masks and shields. These advantages to video-visits remain significant even as the pandemic recedes.
INNV-41. MY STORI – A SYMPTOM TRACKING AND REPORTING INSTRUMENT MOBILE APPLICATION FOR BRAIN TUMOR PATIENTS
Authors: Celiku Orieta , Odom Kristin , Ramidi Mahendar , Armstrong Terri 
Published: November 2021

Abstract

INTRODUCTION
Managing symptom burden is an integral part of brain tumor patient care, but tools to facilitate tracking symptoms and self-management for this population are lacking. Reporting is often limited to self-report as part of clinical follow-up care, or episodic between visits if symptoms are severe. While general-purpose and cancer-specific mobile applications that track medical symptoms are becoming more prevalent, they may not cover the entire range of symptoms experienced by patients with brain tumors or allow tracking of self-management strategies.

METHODS
We developed an iOS operating system mobile application using Apple’s UIKit, Foundation, WebKit, and Core Graphics frameworks. Core Data and iCloud were used to implement local and cloud-based data storage for personal use. Findings from our Outcomes Surveys informed selection of core symptoms to track. A multidisciplinary team of neuro-oncology scientists, providers, and communication specialists developed self-care content from evidence-based sources.

RESULTS
We developed My STORI, a free mobile application to capture the experiences of brain tumor patients. Patients and their family members can track daily symptoms and their impact on function and record any actions that were taken to mitigate them. Evidence-based self-care information on how to recognize, manage, and report symptoms is provided. Graphical summaries of how these symptoms evolve over time, and how they are impacted by clinical appointments, treatment, and self-care activities can be displayed and compiled into reports that can be shared with their care team, family, or health care record.

CONCLUSIONS
Mobile applications have the potential to promote self-care, facilitate symptom management, and enable intuitive, frequent, and convenient reporting of clinically relevant data to the health-care team. The My STORI application is an innovation in patient care guided by evidence-based research and can be used to track symptom management, promote self-care, and enhance communication to improve clinical care and research.
PATH-03. FERROPTOSIS-RELATED LONG NON-CODING RNA SIGNATURES PREDICT PROGNOSIS IN PATIENTS WITH GLIOMA
Authors: Lai Donglin , Zuo Xiaojia , Yang Xintong , Zheng Yanjun , Duan Baoyu , Li Yanfei , Wan Guoqing , Lu Changlian , Gu Xuefeng 
Published: November 2021

Abstract
Ferroptosis, with iron-dependent and ROS-dependent, is a novel type of cell death in a variety of diseases and some studies confirmed that ferroptosis-related lncRNAs are involved in the occurrence and development of several cancers. However, the ferroptosis-related lncRNA in the role of gliomas is unclear. Here, we constructed a prognostic scoring model of ferroptosis-related lncRNAs in gliomas. Data were downloaded from the Chinese glioma genome atlas (CGGA), the cancer genome atlas, and FerrDb database. In this study, we found 1051 lncRNAs associated with ferroptosis by Spearman's rank correlation analysis in CGGA653, and 547 lncRNAs were related to prognosis in gliomas. Subsequently, we identified 9 ferroptosis-related signatures (AC010729.2, AC062021.1, FAM225B, FAM66C, HOXA-AS2, LINC00662, LINC00665, MIR497HG, and TMEM72-AS1) by least absolute shrinkage and selection operator and Cox proportional hazards model. Next, all glioma patients were divided into high- and low-risk groups based on the median risk score based on these signatures, and the low-risk group had better prognosis significantly than the high-risk group by Kaplan-Meier curve. Moreover, the risk score can predict survival status with high sensitivity and specificity by receiver operating characteristic curve (area under the curve at 1, 3, 5 years: 0.791, 0.84, 0.856, respectively). In addition, some pathways (cell cycle, p53 signaling pathway, apoptosis, and oxidative phosphorylation) significantly enriched in KEGG enrichment pathway, and a nomogram was constructed by integrating some independent prognostic clinicopathological features to predict the overall survival in gliomas (C-index: 0.786). In summary, these 9 ferroptosis-related signatures have potential prognostic value and could be crucial factors for treating malignant gliomas.
PATH-12. CLINICAL AND PATHOLOGICAL ANALYSIS OF 43 PATIENTS WITH EPITHELIOID GLIOBLASTOMA
Authors: Zhen Junjie , Lai Mingyao , Zhou Jiangfen , Li Shaoqun , Cai Linbo 
Published: November 2021

Abstract

BACKGROUND AND PURPOSE
Epithelioid glioblastoma (eGBM) is a rare and aggressive subtype of glioblastoma. The clinical characteristics, pathological features and radiological findingsare still not well characterized.

METHODS
The clinical data of 43 patients with eGBM confirmed pathologically after surgery in Guangdong Sanjiu Brain Hospital from June 2015 to January 2021 were reviewed, and to investigate the clinical, pathological and imaging characteristics of the eGBM.

RESULTS
The range of patients' age was from 5 to 70 years (median 39 years). There were 24 males and 19 females. The median karnofsky performance score (KPS）at diagnosis was 70 (40-90). The most common symptom were headache (81.4%), and other common symptoms included nausea or vomiting (44.1%), limb weakness (30.2%), disturbance of consciousness (20.9%) and seizures (9.3%). Most of the tumors (97.6%) were located in the cerebral hemisphere ,except for one case located in the cerebellum,and with an average diameter of 5.3 cm (2.5-9.4 cm). There were 2 cases of intracranial metastasis and 7 cases of spinal cord metastasis in MRI. In pathologic examination, immunohistochemistry showed all the patients were IDH1 wild-type (43/43) and H3K27M wild-type(34/34). 25 (58.1%) of cases harbored BRAF mutation and 19 (44.2%) cases of MGMT positive. Most of patients were positive for GFAP, P53, Olig-2 and ATRX.

CONCLUSION
Epithelioid glioblastoma is more common in adults, most of which are located on the supratentorial, intracranial and spinal cord dissemination may occur. Half of patients showed BRFA mutation and maybe benefit from targeted therapy.These findings may help clinicians understand and treat epithelioid glioblastoma better.
PATH-14. ALPHA CARDIAC ACTIN EXPRESSION IS OBSERVED IN AGGRESSIVE GLIOMA SUBTYPES AND GLIOBLASTOMA STEM CELLS
Authors: Suresh Rahul , Fiola Sophie , Beaulieu Jamie , Diaz Roberto 
Published: November 2021

Abstract

BACKGROUND
Alterations in actin subunit expression have previously been observed in multiple cancers. In glioblastoma (GBM), the expression of ACTC1 has been associated with a more invasive phenotype and with shorter survival. We sought to explore the diversity of actin subunit expression across glioma subtypes and patient derived glioblastoma stem cells (GSCs).

METHODS
Bioinformatic analysis of multiple glioma databases was performed to profile actin subunit (ACTA1, ACTA2, ACTC1, ACTG1, ACTG2, and ACTB) mRNA levels. Expression levels were also evaluated in normal brain in comparison to liver and heart tissue. Western blot was used to analyze protein expression in GSCs, surgical tissue and human fetal astrocytes.

RESULTS
The primary actin subunits expressed in normal brain are beta actin (ACTB) and gamma actin (ACTG1). RNA sequencing of tissue from multiple glioma subtypes or different brain regions reveals a global increase in ACTG1 and ACTB abundance in gliomas compared to normal brain. LGG-GCIMP high and LGG-co-deleted glioma subtypes have the lowest ACTC1 expression. LGG-GCIMP low (HR 9.75, P&lt; 0.001), LGG-mesenchymal-like (HR11.1, P&lt; 0.001), LGG-classic-like (HR10.96, P&lt; 0.001) subtypes are associated with ACTC1 expression. ACTC1, ACTCB, and ACTG protein expression was observed in GSCs, freshly resected GBM tissue, and human fetal astrocytes.

CONCLUSIONS
Gliomas have a specific pattern of actin subunit expression that differs in actin subunit type and abundance when compared to normal adult brain. Expression of ACTC1 is found in aggressive glioma subtypes and is shared by GSCs and human fetal astrocytes. Investigation into the neurodevelopmental role of ACTC1 and its contribution to oncogenic transformation in GBM is warranted.
PATH-15. NON-CANONICAL IDH 1 AND IDH 2 MUTATIONS ARE ASSOCIATED WITH IMPROVED SURVIVAL IN PATIENTS WITH GLIOMAS: RESULTS OF A META-ANALYSIS
Authors: nunno Vincenzo Di , Franceschi Enrico , Tosoni Alicia , Gatto Lidia , Mura Antonella , Acquaviva Giorgia , De Biase Dario , Bartolini Stefania , Brandes Alba Ariela 
Published: November 2021

Abstract

BACKGROUND
Non-canonical isocitrate dehydrogenase (IDH) mutations are uncommon among patients with grade 2 and 3 gliomas and their clinical significance is still unclear.

METHOD
We carried out a systematic review and meta-analysis to evaluate the prognostic impact of IDH1 and IDH2 non-canonical mutations. We searched English-written articles published on PubMed/Medline, Cochrane library, and Scopus until the 1st May 2021. Keywords adopted for the research were: ‘’IDH’’ OR ‘’IDH1’’ OR ‘’IDH2’’ OR ‘’Isocitrate dehydrogenase’’ AND ‘’glioma’’.

RESULTS
We selected 13 of 3513 studies reporting data of 4007 patients with a diagnosis of grade 2 and grade 3 including 3091 patients with a molecular proven IDH 1 or IDH 2 mutations. Between patients with IDH mutated gliomas, 479 (15.5%) patients showed non-canonical IDH 1 or IDH 2 mutations. The presence of IDH 1 non-canonical mutation occurred in younger age and in non codeleted 1p19q as compared to canonical IDH 1 mutation. However, patients with IDH 2 mutations showed more frequently 1p19q codeletion as compared to those with canonical IDH 1 mutated glioma. Four studies reported complete data survival for patients with non-canonical (n= 160) and canonical mutations (n= 1019). The pooled HR of these studies was 0.47 (95% CI, 0.28-0.81) confirming a positive prognostic role for non-canonical IDH 1 and IDH 2 mutations.

CONCLUSION
The presence of non-canonical IDH 1 and IDH 2 mutations defines a specific subgroup of gliomas occurring at younger age with improved survival. Patients with a non-canonical IDH 1 mutation showed less frequently 1p19q codeletion as compared to those patients harboring a canonical or IDH 2 mutation.
PATH-19. TERT PROMOTER MUTATION, NOT H3K27M MUTATION IS A PROGNOSTIC FACTOR FOR ADULT THALAMIC GLIOMAS
Authors: Nitta Masayuki , Muragaki Yoshihiro , Komori Takashi , Masui kenta , Saito Taiichi , Tsuzuki Shunsuke , Fukui Atsushi , Koriyama Shunichi , Onitsuka Hiromi , Ikuta Soko , Kuwano Jun , Kawamata Takakazu 
Published: November 2021

Abstract

Purpose
Thalamic diffuse glioma is classified as WHO grade 4 as Diffuse midline glioma, H3K27M mutation if H3K27M mutation was found regardless of its histological findings, but the significance of H3K27M mutation is not clear compared with pediatric cases. We aimed to find genetic prognostic factors in adult thalamic diffuse gliomas.

METHODS
Pathological diagnosis, genetic abnormalities, and clinical course of adult newly diagnosed thalamic gliomas diagnosed and treated at our institution from July 2007 to March 2020 were retrospectively analyzed.

RESULTS
The number of cases was 41 (24 males, 17 females), median age was 47 years (20-75 years). Tumor localization was 20 cases on the left, 14 cases on the right, and 7 cases on both sides. The pathological diagnosis was GBM 15 cases, DMG 15 cases, AA-IDH WT 7 cases, DA-IDH WT 4 cases, all of which were IDH wild type, and none of them had IDH mutation and 1p/19q co-deletion. H3K27M mutations were found in 15 cases and TERT promoter mutations were found in 12 cases, both of which were completely mutually exclusive. Tumor resection and biopsy was performed in 33 and 8 cases, respectively, and the median removal rate was 95% for those who underwent tumor resection. The median PFS and OS of all cases were 14.3 months and 38 months, respectively, and the median OS by pathological diagnosis was GBM 12.4 months, DMG 47.4 months, AA-IDH WT 37.3 months, DA-IDH WT not reached. The median OS in the H3K27M mutant group (47.4 months) was significantly better (p=0.02) than that in the TERT promoter mutation group (13.5 months).

CONCLUSION
There was no IDH mutation in adult thalamic gliomas, the H3K27M mutation and the TERT promoter mutation were mutually exclusive. The H3K27M mutation was not a prognostic factor, but the TERT promoter mutation was the strongest prognostic factor.
PATH-20. SPATIAL MAPPING OF THERAPY-INDUCED, PATHOLOGICAL CHANGES IN GLIOBLASTOMA AT SINGLE-CELL RESOLUTION
Authors: Vanmechelen Maxime , Beckervordersandforth Jan , Pey Jon , Antoranz Asier , Nasari Pouya , Pantano daniele , Bevers Sien , Leunissen Daphne , Moors Wout , Messiaen Julie , Sebastian Ivey , Milli Giorgia , Van Herck Yannick , Geens Emma , Verduin Maikel , Hoosemans Linde , Claeys Annelies , Derweduwe Marleen , Zurhausen Axel , Bosisio francesca , Eekers Danielle , Weyns Frank , Daenekindt Thomas , Van Eyken Peter , Goovers Mark , Hovinga Koos , De Vleeschouwer Steven , Clement Paul , Broen Martijn , Vooijs Marc , Sciot Raf , Hoeben Ann , Speel Ernst Jan , De Smet Frederik 
Published: November 2021

Abstract
Glioblastoma (GBM) remains a highly malignant, intrinsically resistant and inevitably recurring brain tumor with dismal prognosis. The aggressiveness and lack of effective GBM treatments can be attributed to the highly heterogeneous and plastic nature of GBM tumor cells, which easily confer resistance to standard-of-care (SOC) therapy. While tumor progression has also been attributed to interactions with the tumor microenvironment, quantitative data describing these interactions are still largely missing. Here, we used high-dimensional, multiplexed immunohistochemistry to map evolutions in the spatial, single-cell tissue architecture of 120 paired adult GBM tumor samples derived from 60 patients at diagnosis (ND) and upon recurrence (REC) following SOC treatment. We mapped the spatial distribution of a multitude of GBM tumoral subtypes across this multicentric cohort, through which we identified a high level of heterogeneity defined by specific tumoral niches within and across patients and which evolved when subjected to SOC therapy. In addition, we describe the relationship of the various tumoral niches with their local immune-infiltrates, highlighting an even more immunosuppressive environment following SOC resistance. Finally, by aligning these findings to the observed genomic aberrations and the clinical data of the patients, we are now able to more precisely describe the heterogeneous landscape of glioblastoma and how it evolves under SOC treatment at spatial, single-cell resolution.
PATH-24. COPY NUMBER ALTERATIONS IN NOTCH PATHWAY GENES ARE PROGNOSTIC IN A SUBSET OF DIFFUSE ASTROCYTIC GLIOMAS
Authors: Nuechterlein Nicholas , Cimino Patrick 
Published: November 2021

Abstract
Inactivating mutations in NOTCH1 occur in many cancer types and are frequently observed in IDH-mutant, 1p/19q-codeleted oligodendroglioma. Although the role of NOTCH1 as a tumor suppressor in diffuse glioma has become appreciated in human tissue and small animal models, the spectrum of inactivating mutations in Notch pathway genes in diffuse astrocytic gliomas has not been well described. To address this, we queried the TCGA lower-grade glioma and glioblastoma datasets to establish the extent of inactivation of Notch pathway genes, specifically by cataloging single nucleotide variants and those with copy number loss or deletion. Key alteration frequencies were found to be similar in two-independent glioma cohorts (Col, MSK). Notch pathway genes with inactivating alterations (overwhelmingly copy number loss) were present in 77% of TCGA diffuse gliomas. Across all diffuse gliomas, DLL3 loss was the most common alteration (TCGA 31%). For IDH-mutant diffuse astrocytic gliomas, JAG2 loss was the most common alteration (TCGA 23.0%, Col 35%, MSK 27%). DLL1 loss and MAML1 loss were mutually exclusive (p&lt; 0.001) in TCGA IDH-mutant astrocytomas with a combined frequency of 39% (Col 47%, MSK 56%). The presence of any alteration in the top 10 altered Notch pathway genes indicated a shorter progression-free survival (p = 0.028) for TCGA IDH-mutant diffuse astrocytomas. For IDH-wildtype diffuse astrocytic gliomas, EP300 loss was the most common inactivating alteration (TCGA 35.4%, Col 49%, MSK 38%). EP300 loss, DLL1 loss, DLL4 loss were mutually exclusive (p = 0.006) in TCGA IDH-wildtype diffuse astrocytic gliomas with a combined frequency of 61% (Col 72%, MSK 66%). The presence of alterations in any of these three genes indicated a decreased overall survival (p = 0.045) in TCGA IDH-wildtype diffuse astrocytic gliomas. Overall, loss of differential Notch pathway genes has prognostic implications in both IDH-wildtype and IDH-mutant diffuse astrocytic gliomas.
PATH-31. METHYLATION SUBCLASS RECEPTOR TYROSINE KINASE II AS A DRIVER FOR SEIZURES IN IDH-WILDTYPE GLIOBLASTOMA
Authors: Drexler Richard , Eckhardt Alicia , Westphal Manfred , Schüller Ulrich , Dührsen Lasse , Ricklefs Franz 
Published: November 2021

Abstract

BACKGROUND
Seizures are a common symptom of patients suffering from glioblastoma and there is evidence that these tumours are morphologically different. However, the relationship of DNA methylation and glioblastoma-related seizures has not been well characterized. Only one study described an amplification of genes encoding receptor tyrosine kinases (RTK) as a positive predictor for intraoperative seizures during craniotomy.

METHODS
59 patients who underwent surgery with confirmed IDH-wildtype glioblastoma, WHO grade 4, were included. Genome-wide DNA methylation profiling was performed using an 850k Illumina EPIC array and classified by the DKFZ brain tumor classifier. Methylation glioblastoma subclasses and gene alterations were correlated with clinical characteristics including preoperative and long-term seizures.

RESULTS
Overall, 18 of 59 patients (30.5%) presented with seizures of whom suffered 8 (44.4%) from a focal and 10 (55.6%) from a generalized seizure. Correlation of preoperative seizures with glioblastoma subclasses and DNA genes identified a higher incidence of preoperative seizures in patients with the glioblastoma subclass of receptor tyrosine kinase II (RTK; EGFR amplified) (p=0.031). In addition, these patients were more likely to present with generalized seizures (p=0.05). In multivariate analysis, temporal location (p=0.014, OR 5.785) but moreover RTK II (p=0.024, OR 7.052) was most predictive for preoperative seizures. Furthermore, recurrent seizures with an increased antiepileptic medication at last follow-up (mean: 9.2 months) occurred more often in RTK II-glioblastoma (p&lt; 0.05). Kaplan-Meier curves showed no significant association between the presentation of seizures and overall or progression-free survival. In addition, further survival analyses did not reveal a correlation of methylation glioblastoma subgroups with the outcome.

CONCLUSION
Our study showed a strong correlation of the RTK II methylation subclass with preoperative and long-term seizures in patients suffering from glioblastoma.
PATH-34. MOLECULAR AND CLINICAL HETEROGENEITY WITHIN SPINAL EPENDYMOMAS
Authors: Al-Kershi Sina , Kresbach Catena , Pohl Lara , Dorostkar Mario M , Suwala Abigail K , Wefers Annika K , Schweizer Leonille , Engertsberger Lara , Mohme Theresa , Mynarek Martin , Lamszus Katrin , Kluwe Lan , von Deimling Andreas , Benesch Martin , Hagel Christian , Mautner Viktor , Rutkowski Stefan , Schüller Ulrich 
Published: November 2021

Abstract
Ependymomas encompass multiple clinically relevant tumor types based on localization, genetic alterations, as well as epigenetic and transcriptomic profiles. Distinct global DNA methylation signatures serve as the most powerful diagnostic tool to distinguish these types. The methylation class of spinal ependymomas (SP-EPN) comprises mostly WHO°II tumors with slow progression and incomplete surgical resection rate. Molecular data of SP-EPN are scarce and clear treatment recommendations are lacking although these neoplasms represent the most common intramedullary tumors in children and adults. The only known recurrent genetic events in SP-EPN are the loss of chromosome 22q and mutations of the NF2 gene. However, data on the frequency of NF2 mutations range from 16 % to 71 % and originate from small series that lack epigenetic or transcriptomic characterization. Furthermore, it remains unclear whether SP-EPN with germline or sporadic NF2 mutation or with NF2 wild type status display clinical and other molecular differences. Finally, the underlying genomic and transcriptomic changes of SP-EPN without NF2 mutations are fully unclear. To provide a comprehensive molecular profile of SP-EPN, we integrated genomic and epigenetic analyses and clinical data of 170 cases. Unsupervised hierarchical clustering and t-SNE analyses of methylation data revealed three distinct molecular SP-EPN subtypes. Of the three subtypes, only subtype 1 and subtype 2 contained tumors with NF2 mutations, either as previously known germline mutations or as sporadic mutations without evidence for a syndromic disease (p&lt; 0.0001). Besides the lack of NF2 mutations, subtype 3 tumors showed a higher frequency of MGMT promoter methylation (p= 0.0015) and occurred in significantly older patients compared to tumors of subtypes 1 and 2 (p= 0.0038). Further investigations such as whole-exome sequencing, copy number variation profiling, gene expression analysis, and histological evaluation are ongoing and will add to the picture of molecular and clinical heterogeneity within SP-EPN.