bluuebunny/crossref_metadata_2025_split huggingface dataset:
COVD-11. THE BRAIN TUMOR AND NOT FOR PROFIT AND CHARITY EXPERIENCE OF COVID 19: REACTING AND ADJUSTING TO AN UNPRECEDENTED GLOBAL PANDEMIC IN THE 21ST CENTURY
Authors: Ellen Maher Mary , Amidei Christina , Arzbaecher Jean , Oliver Kathy , Mungoshi Christine , Cashman Rosemary , Farrimond Stuart , Kruchko Carol , Granero Anita , Tse Chris , Daniels Maureen , Lovely Mary , Payne Sally , Lamb Sharon , Baker Jenifer 
Published: December 2020

Abstract
The COVID-19 pandemic has not only affected individuals, but also disease specific not-for-profits and charities. Brain tumor not-for-profit and charitable organizations around the world exist in all shapes and sizes, and address unmet needs of the patients and caregivers they serve. The International Brain Tumor Alliance(IBTA) carried out an international survey to identify organization changes brought about by the virus and the approaches adopted to address operational challenges created by COVID-19. A 37-question survey was sent across the world. In total, 77 organizations from 22 countries responded. Descriptive statistics and content analysis were used to present RESULTS: Responses fell into three categories: 1) organizational characteristics, 2) the impact of COVID-19 on services, and 3) how COVID-19 has affected the financial and human resources in these organizations. Although organizational characteristics vary widely, common concerns reported across organizations were primarily: a) the disruption of activities which impacted organizations’ abilities to offer their usual services and b) challenges to sustaining funding. Although brain tumor organizations have been impacted by the COVID-19 pandemic, organizations quickly adjusted to this unprecedented global healthcare crisis.
COVD-17. TUMOR TREATING FIELDS FOR GLIOBLASTOMA THERAPY DURING THE COVID-19 PANDEMIC: EXPERT CONSENSUS ON USE AND EXPERIENCE
Authors: Tosha Gatson Na , Barnholtz-Sloan Jill S , Drappatz Jan , Henriksson Roger , Hottinger Andreas , Hinoul Piet , Kruchko Carol , Puduvalli Vinay , Tran David , Wong Eric , Glas Martin 
Published: December 2020

Abstract

BACKGROUND
The COVID-19 pandemic has placed excessive strain on health care systems and this is especially evident in treatment decision-making for cancer patients. Glioblastoma (GBM) patients are among the most vulnerable due to increased incidence in the elderly (median age 64 years, peak between 75–84 years) and the short survival time. A virtual meeting was convened on May 9, 2020 with a panel of international neuro-oncology experts with hands-on experience using Tumor Treating Fields (TTFields). The objective was to assess the risk-to-benefit and to provide guidance for using TTFields in GBM during the COVID-19 pandemic.

PANEL DISCUSSION
Topics discussed included support and delivery of TTFields during the COVID-19 pandemic, concomitant use of TTFields with chemotherapy, and any potential impact of TTFields on the immune system in an intrinsically immunosuppressed GBM population. Special consideration was given to TTFields’ use in elderly patients and in combination with radiotherapy regimens (standard versus hypo-fractionated). Finally, we discussed the need to better capture COVID-19 positive brain tumor patients to analyze longitudinal outcomes and subtle changes in treatment decision-making during the pandemic.

EXPERT CONSENSUS
TTFields is a portable home-use device which can be managed via telemedicine and safely used in GBM patients during the COVID-19 pandemic. TTFields has no known immunosuppressive effects and is a reliable treatment modality with a relatively favorable side-effect profile. This is important during a crisis where other treatment methods might be limited, especially for elderly patients and patients with multiple co-morbidities. It is too early to estimate the full impact of COVID-19 on the global healthcare system and on patient outcomes and strongly recommended the need to collaborate with existing cancer COVID-19 registries (i.e. CCC19, ESMO-CoCARE, etc.) to follow CNS tumor patients. These efforts would have implications in assessing lessons-learned from this crisis and future guideline development.
COVD-18. POTENTIAL TO HARNESS SARS-COV-2 NEUROTROPISM IN THE DELIVERY OF ONCOLYTIC VIROTHERAPY FOR THE TREATMENT OF HIGH-GRADE GLIOMA
Authors: Immidisetti Amanda , Munier Sean , Patel Nitesh 
Published: December 2020

Abstract

BACKGROUND
High-grade gliomas (HGG) pose therapeutic challenges stemming from blood brain barrier, infiltrative growth, suppressed immune function, and tumor heterogeneity. Oncolytic viruses (OVs) are gaining traction for addressing these challenges. There is evidence that the SARS-CoV-2 glycoprotein spike binds the ACE-2 receptor in nasal epithelium and reaches the brainstem and thalamus via axonal transport through the olfactory pathway, making it an attractive candidate for OV therapy. Prior studies on chimerization of pathogenic virus-derived glycoprotein spikes with non-pathogenic strains exploit neurotropism of a wild-type virus while improving the safety profile of the resulting OV. We review, 1) the engineering of chimeric OVs used in the treatment of HGG; 2) potential for a novel chimeric virotherapy in which the SARS-CoV-2 glycoprotein spike can be used to deliver OV therapy intranasally; and 3) areas which warrant further investigation to develop this approach for clinical use.

METHODS
We performed an extensive review of chimeric OVs and specific modifications engineered to optimize safety and efficacy. Additionally, we assessed potential to use these principals to engineer the SARS-CoV-2 glycoprotein spike onto a non-pathogenic, replication competent virus to yield a novel chimeric for noninvasive, intranasal delivery.

RESULTS
Viruses with pathogenic properties in wild-type have been successfully used as components of OVs and have demonstrated potential in both preclinical and clinical trials. Outcomes show that despite wild-type virulence, notable toxicities were not observed in clinical trials, highlighting the potential of viral pseudotyping as a safe therapeutic approach.

CONCLUSIONS
The proposed method to utilize the SARS-CoV-2 glycoprotein in a novel chimeric poses advantages including 1) potential for non-invasive delivery, 2) therapy without need for maximal or uniform tumor coverage due to replication competence, 3) ability to reach infiltrative glioma cells, 4) potential to reach the brainstem, and 5) stimulation of host immunity through tumor cell lysis and antigen presentation
COVD-20. COVID-19 INFECTION DURING CHEMOTHERAPY FOR MALIGNANT GLIOMA: OUTCOMES AMONG 3 PATIENTS
Authors: Kim Esther , Koshy Amily , Higgins Shannon , Lassman Andrew , Iwamoto Fabio 
Published: December 2020

Abstract

BACKGROUND
Chemotherapy may increase risk of SARS-COV-2 infection and COVID-19 severity.

METHODS
A patient developed COVID-19 during chemotherapy for glioma. We retrospectively identified others diagnosed with COVID-19 during temozolomide or lomustine for glioma.

RESULTS
(1) A 64 year-old woman (index patient) with anaplastic oligodendroglioma received PCV 22 months previously. Baseline White Blood Cell (WBC) count was 4.2 and Absolute Neutrophil Count (ANC) was 2.7 K/uL. KPS was 90 without comorbidities. For recurrence she initiated temozolomide but developed fever on cycle 1 day 2. SARS-COV-2 PCR was positive. Further temozolomide was held. She is recovering as an outpatient. (2) A 27 year-old man with anaplastic astrocytoma received concurrent RT/temozolomide then 1 cycle of adjuvant temozolomide. Baseline WBC was 8.3, ANC 5.2, and KPS 90. Obesity, asthma, and pre-diabetes were comorbidities. Hyposmia/hypogeusia and low-grade fever began, in retrospect, during concurrent RT/temozolomide. PCR for SARS-COV-2 was negative 2 months after symptom onset; serology detected both IgG and IgM when WBC was 6.6 and ANC 4.0. Cycle 2 of adjuvant temozolomide was held until fever resolved (spontaneously); hyposmia/hypogeusia persist. (3) A 53 year-old man with glioblastoma previously received RT/temozolomide, then lomustine and bevacizumab for progression. WBC was 5.1, ANC 4.0, and KPS 60. He was obese. Fever, chills, and dyspnea developed on lomustine cycle 2 day 38. SARS-COV-2 PCR was positive. He was hospitalized and chemotherapy held; symptoms resolved 12 days after onset, but PCR continued to show detectable virus 32 days later. PCR became negative after 50 days total, and treatment resumed uneventfully.

DISCUSSION
All 3 patients recovered from SARS-COV-2 infection despite active temozolomide or lomustine chemotherapy. Normal ANC, high KPS, and early detection may have contributed to limited symptom severity and duration, despite obesity and other comorbidities in 2 cases. Detection changed management by delaying additional cycles of immunosuppressive chemotherapy until recovery.
COVD-25. THE PARADOXICAL EFFECTS OF COVID-19 ON CANCER CARE IN THE NEURO-ONCOLOGY SETTING
Authors: Cort Nicole , Broom Alex , Kenny Katherine , Page Alexander , Durling Jennifer , Brown Casey , Lipp Eric , Ashley David , Walsh Kyle , Johnson Margaret , Khasraw Mustafa 
Published: December 2020

Abstract
COVID-19 has caused ongoing interruptions to healthcare systems worldwide, shifting care to virtual platforms, and placing significant economic and logistical burdens on clinical practice. The pandemic has created uncertainty in delivering the standard of care, both in areas of cancer diagnosis and treatment, especially within neuro-oncology. Due to the pandemic, care and operational planning goals have shifted to infection prevention, modifying recommendations to decrease viral transmission and increasing telemedicine use, potentially creating a burden on implementing evidence-based medicine. These dynamics have since begun to redefine traditional practice and research regimens, impacting the comprehensive care that cancer patients can and should receive; and the enduring consequences for the delivery of healthcare. The impact of COVID-19 on oncology practice and trials might endure well beyond the short- to mid-term of the active pandemic. Therefore, these shifts must be accompanied by improved training and awareness, enhanced infrastructure, and evidence-based support to harness the positives and offset the potential negative consequences of the impacts of COVID-19 on cancer care. To address these paradoxical effects, we will conduct iterative, qualitative (face-to-face/video conference) interviews with neuro-oncology clinical and research professionals and adult brain tumor patients receiving care during the pandemic. We will capture unique aspects of oncology care: the lived, subjective, situated, and contingent accounts of patients and medical professionals, especially during a pandemic. We will also specifically compare the impact of telehealth during the pandemic on delivery of care to complex neuro-oncology patients. A summary of this in-depth, qualitative approach will result in a sophisticated understanding of neuro-oncology care on the frontline at a time of crisis, as experienced during a pandemic, to articulate best practices for future implementation.
COVD-27. THE COVID-19 PANDEMIC AND NEURO-ONCOLOGICAL PATIENTS
Authors: Norman Sofya , Juthani Rupa 
Published: December 2020

Abstract

INTRODUCTION
The Coronavirus disease 2019 (COVID-19) pandemic has uprooted healthcare systems worldwide, disrupting care and increasing dependence on alternative forms of health care delivery. It is yet to be determined how the pandemic affected neuro-oncology patient outcomes, given that the majority of even “elective” neurosurgical oncology procedures are time-sensitive. This study quantifies changes in neuro-oncological care during the height of the pandemic in New York City and investigates patient outcomes in 2020 compared to a historical control.

METHODS
We performed a retrospective review of patients with brain tumor diagnoses (primary or secondary) who were seen at the Weill Cornell Brain and Spine Center between March 13, 2020 and May 1, 2020. A control cohort from the corresponding time period in 2019 was also reviewed. Alterations in care, including shift from in-person to telehealth, delays in evaluation and intervention, and treatment modifications were evaluated. These variables were analyzed with respect to brain tumor control and mortality.

RESULTS
114 patients from 2020 and 171 patients from 2019 were included, with no significant difference in baseline demographics between the groups. There was no significant difference in outcomes between the cohorts, despite significantly more treatment delays (p= 0.0154) and use of telehealth (p&lt; 0.0001) in 2020. For patients treated during the pandemic in 2020, patients who experienced delays in care did not suffer from worse outcomes compared to those without delays. Patients who utilized telehealth visits had significantly more stable tumor control (P = 0.0027), consistent with appropriate use of in-person visits for patients with progression.

CONCLUSION
Our study showed that use of telehealth and selective alterations in neuro-oncological care during the COVID-19 pandemic did not lead to adverse patient outcomes. This suggests that adaptive physician-led changes during the pandemic were successful and effective. Further studies are needed to evaluate impact on long-term survival.
COVD-28. IMPACT OF COVID-19 IN CHILDHOOD CENTRAL NERVOUS SYSTEM TUMORS IN ARGENTINA. REPORT FROM THE NATIONAL PEDIATRIC CANCER REGISTRY, ROHA NETWORK
Authors: Baroni Lorena , Chaplin Agustina , Alderete Daniel , Fraqueli Lidia , Gallardo Patricia , Moreno Florencia 
Published: December 2020

Abstract
Introduction: The true impact of COVID-19 infection on children undergoing cancer treatment is unknown. At the present time, data on the clinical spectrum and outcome of children with cancer and concurrent COVID-19 are limited, and further data are awaited. Monitor the incidence and survival across this pandemic is critical to understanding the extent to which this occur and to prepare contingency plans. Results: Ninety-seven pediatric patients with cancer and COVID-19 infection have been identified by the Argentinian Oncopediatric Register since April 2020. Sixteen of them had diagnosis of CNS tumor (female=7, male=9); 5 Medulloblastoma, 3 DIPG, 2 GBM, 2 LGG, 2 anaplastic ependymoma, 1 anaplastic ganglioglioma and 1 germinoma. Most frequent aged was between 1–4 years old (6 patients), followed by 15 to 19 (4p), 5–9 (3p) and 10–14 (3p). Most patients were asymptomatic (9p) and the screening was performed regarding a virus exposed (5p), previous to a procedure with anesthesia (2p) and previous a mandatory travel (2p). The most frequent symptom was isolated fever (6p); only 1 patient presented fever with others symptoms. None received specific treatment for COVID infection. No death related to COVID-19 infection was found; 1 patient with metastatic medulloblastoma and COVID-19 infection passed away due to a rapidly tumor progression. Conclusion: Although COVID-19 infection is a new challenging in the management of pediatric brain tumor patients, our experience showed a relative indolent course in this specific population.
COVD-31. THE STATE OF NEURO-ONCOLOGY DURING THE COVID-19 PANDEMIC: A WORLDWIDE ASSESSMENT
Authors: Mrugala Maciej , Ostrom Quinn , Pressley Shelley , Thomas Alissa , Wefel Jeffrey S , Coven Scott , Acquaye Alvina , Haynes Chas , Agnihotri Sameer , Lim Michael , Peters Katherine , Butowski Nicholas , Hervey-Jumper Shawn , Porter Alyx , Oliver Kathy , Dunbar Erin , Taylor Jennie , Schiff David , Nassiri Farshad , Hegi Monika , Armstrong Terri , van den Bent Martin , Chang Susan , Zadeh Gelareh , Chheda Milan 
Published: December 2020

Abstract
To assess the impact of the pandemic on the field, we performed an international web-based survey of practitioners, scientists, and trainees from 21 neuro-oncology organizations across 6 continents from April 24 through May 17. Of 582 respondents, 258 (45%) were in the US, and 314 (55%) were international. 80.4% were affiliated with academic institutions. 94% respondents reported changes in clinical practice; 95% reported conversion to telemedicine for at least some appointments. However, almost 10% practitioners felt the need to see patients in person specifically because of billing concerns and perceived institutional pressure. Over 50% believed neuro-oncology patients were at increased risk of contracting COVID-19. 67% practitioners suspended enrollment for at least one clinical trial: 53% suspended phase II and 62% suspended phase III trial enrollment. 71% clinicians feared for their or their families’ safety, specifically because of their clinical duties. 20% percent said they did not have enough PPE to work safely; about the same percentage were unhappy with their institutions’ response to the pandemic. 43% believed the pandemic would negatively affect their academic career, and 52% fellowship program directors were worried about losing funding for their training programs. While 69% respondents reported increased stress, 44% were offered no psychosocial support. 37% had their salary reduced. 36% researchers had to temporarily close their laboratories. In contrast, the pandemic created positive changes in perceived patient and family satisfaction, quality of communication, and use of technology to deliver care and interactions with other practitioners. CONCLUSIONS: The pandemic has altered standard treatment schedules and limited investigational treatment options for patients. In some cases, clinicians felt institutional pressure to continue conducting billable in-person visits when telemedicine visits would have sufficed. A lack of institutional support created anxiety among clinicians and researchers. We make specific recommendations to guide clinical and scientific infrastructure moving forward.
CSIG-02. R-RAS SUBFAMILY PROTEINS ELICIT DISTINCT PHYSIOLOGIC EFFECTS AND PHOSPHOPROTEOME ALTERATIONS IN NEUROFIBROMIN-NULL MPNST CELLS
Authors: Weber Shannon , Brossier Nicole , Prechtl Amanda , Brosius Stephanie , Barnes Stephen , Wilson Landon , Carroll Steven 
Published: December 2020

Abstract
Loss of the Ras GTPase-activating protein neurofibromin promotes the development of aggressive spindle cell neoplasms known as Malignant Peripheral Nerve Sheath Tumors (MPNSTs) in patients with the genetic disorder neurofibromatosis type 1 (NF1). Currently, the available chemotherapeutic regimens and radiotherapy are ineffective against MPNSTs, so the prognosis for patients with these neoplasms is poor. Neurofibromin loss dysregulates multiple Ras proteins in the classic (H-Ras, N-Ras, K-Ras) and R-Ras (R-Ras, R-Ras2/TC21, R-Ras3/M-Ras) subfamilies. Consequently, it is unclear which Ras proteins or pathways regulated by these Ras proteins should be therapeutically targeted in MPNSTs. We have previously shown that classic Ras proteins drive MPNST cell proliferation and survival. However, the role(s) of the R-Ras subfamily of proteins in MPNSTs have not been elucidated. To determine how R-Ras proteins contribute to the pathogenesis of neurofibromin-null MPNSTs, we introduced dominant negative (DN) R-Ras mutants, which are pan-inhibitors of the R-Ras subfamily, into MPNST cells and assessed the impact of R-Ras subfamily inhibition on mitogenesis, migration and the phosphoproteome. A panel of MPNST cell lines (STS-26T, YST-1, ST88-14, 90–8, NMS2, NMS-PC, S462, T265-2c) was used. Methodologies utilized include immunoblotting, PCR, Transwell migration, 3H-thymidine incorporation, and mass spectrometric analysis of phosphoprotein-enriched specimens. We found that R-Ras and R-Ras2 are widely expressed and can be activated in neurofibromin-null MPNST cells. In contrast to classic Ras proteins, we found that R-Ras proteins drive MPNST both mitogenesis and migration. Using mass spectrometry-based phosphoproteomics, we identified thirteen protein networks that were regulated by DN R-Ras, including networks affecting cellular movement via effects on microtubules. We chose to further study changes in ROCK1 phosphorylation and found that R-Ras subfamily proteins function, at least in some part, through the same pathways as ROCK1. We conclude that R-Ras proteins promote tumorigenesis by regulating distinct signaling pathways that regulate MPNST mitogenesis and migration.
CSIG-03. RECONCILING TUMOR HETEROGENEITY IN GLIOBLASTOMA USING A PATHWAY-BASED APPROACH
Authors: Alvarado Alvaro , Tessema Kaleab , Patel Kunal , Kawaguchi Riki , Everson Richard , Ellingson Benjamin , Swarup Vivek , Goldman Steven , Kornblum Harley 
Published: December 2020

Abstract
Despite efforts to gain a deeper understanding of its molecular architecture, glioblastoma (GBM) remains uniformly fatal. While genome-based molecular subtyping has revealed that GBMs may be parsed into several molecularly distinct categories, this insight has yielded little progress towards extending patient survival. In particular, the great phenotypic heterogeneity of GBM – both inter and intratumorally – has hindered therapeutic efforts. To this end, we interrogated tumor samples using a pathway-based approach to resolve tumoral heterogeneity. Gene set enrichment analysis (GSEA) was applied to gene expression data and used to provide an overview of each sample that can be compared to other samples by generating sample clusters based on overall patterns of enrichment. The Cancer Genome Atlas (TCGA) samples were clustered using the canonical and oncogenic signatures and in both cases the clustering was distinct from the molecular subtype previously reported and clusters were informative of patient survival. We also analyzed single cell RNA sequencing datasets and uniformly found two clusters of cells enriched for cell cycle regulation and survival pathways. We have validated our approach by generating gene lists from common elements found in the top contributing genesets for a particular cluster and testing the top targets in appropriate gliomasphere patient-derived lines. Samples enriched for cell cycle related genesets showed a decrease in sphere formation capacity when E2F1, out top target, was silenced and when treated with fulvestrant and calcitriol, which were identified as potential drugs targeting this genelist. Conversely, no changes were observed in samples not enriched for this gene list. Finally, we interrogated spatial heterogeneity and found higher enrichment of the proliferative signature in contrast enhancing compared with non-enhancing regions. Our studies relate inter- and intratumoral heterogeneity to critical cellular pathways dysregulated in GBM, with the ultimate goal of establishing a pipeline for patient- and tumor-specific precision medicine.