bluuebunny/crossref_metadata_2025_split huggingface dataset:
BIOM-63. DIAGNOSIS AND PROGNOSTIC SIGNIFICANCE OF CIRCULATING miR-2276-5p IN PLASMA OF GLIOMA PATIENTS
Authors: Zhao Shiguang 
Published: December 2020

Abstract
Circulating microRNAs (miRNAs) in plasma have the potential to become diagnostic and prognostic biomarkers for various cancers. This study hopes to use plasma circulating miRNAs as biomarkers for diagnosis and prognosis of glioma patients. METHOD: In this study, the plasma circulating miRNAs of 124 patients with glioma and 36 controls was collected to detect the relative expression of miR-2276-5p, and the specificity and sensitivity of the diagnosis were verified by ROC curve. The follow-up survival status was analyzed by cox regression analysis. RESULT: In the GSE 139031 database, it was found that the expression of circulating miR-2276-5p in plasma of glioma patients was significantly lower than that of patients with non-gliomas. Using our plasma samples, and it is indicated that the expression of circulating miR-2276-5p in plasma is lower than that of healthy patients, and compared with low-grade gliomas, patients with high-grade gliomas have a lower expression of circulating miR-2276-5p. ROC curve analysis found that the AUC value was 0.851. The low expression of circulating miR-2276-5p in plasma of glioma patients indicates a poor prognosis of glioma patients, After univariate and multifactorial cox regression analysis, which can be used as an independent prognostic risk factor for glioma patients (P&lt; 0.05). CONCLUSION: The expression of circulating miR-2276-5p in plasma of glioma patients was significantly lower than that of the control group, compared with low-grade gliomas, patients with high-grade gliomas have a lower expression of circulating miR-2276-5p. The lower the relative expression of circulating miR-2276-5p indicated that glioma patients had a worse prognosis.
CBIO-01. THERAPEUTIC IMPLICATIONS OF CONDITIONAL VULNERABILITIES CAUSED BY TTFIELDS EXPOSURE IN NOVEL COMBINATION THERAPIES FOR NON-SMALL CELL LUNG CANCER AND BRAIN METASTASES FROM NON-SMALL CELL LUNG CANCER
Authors: Kumar Karanam Narasimha , Story Michael 
Published: December 2020

Abstract
Tumor Treating Fields (TTFields) are low-intensity, intermediate frequency, alternating electric fields which are FDA-approved for glioblastoma and malignant pleural mesothelioma. Clinical trials are ongoing for other solid tumor cancers, including lung, pancreatic, and ovarian cancers. The initial mechanism for tumor cell killing identified for TTFields exposure was through the disruption of mitosis. Subsequently, it has been shown that TTFields causes replication stress and down-regulates DNA repair and cell cycle checkpoint genes. Here, relative quantitative proteomics were employed to elucidate the cause for the downregulation of DNA repair and cell cycle checkpoint genes. STRING database analysis of differentially expressed proteins revealed interaction networks that included cell cycle, DNA damage repair and replication, and transcriptional and translational regulation. Upstream analysis of key genes associated with cell cycle checkpoint and DNA repair identified reduced expression of the transcriptional activators E2F1 and E2F2 and increased expression of the transcriptional repressor E2F6, suggesting that TTFields affects the CDK–RB–E2F axis. This axis is known to control the transcriptional machinery of the key regulators of cell cycle progression and genome replication fidelity, hence may explain the reduced DNA repair capacity and replication fork maintenance in TTFields-exposed cells. The current study results suggest that TTFields-exposure causes a conditional vulnerability environment that renders cells more susceptible to chemotherapeutic agents that block interfere with the E2F-RB-CDK4/6 axis, inducing DNA damage and replication stress. TTFields-exposure synergistically enhanced the efficacy of the E2F inhibitor HLM006474 with or without the CDK4/6 inhibitor abemaciclib. TTFields plus either or combination of cisplatin and etoposide (known enhancers of replication stress) synergistically enhanced cell killing. These results suggest that the combination of cisplatin and etoposide together with TTFields would be beneficial for non-small cell lung cancer patients and patients with brain metastases from non-small cell lung cancer.
CBIO-03. ATRX LOSS IN GLIOMA RESULTS IN EPIGENETIC DYSREGULATION OF CELL CYCLE PHASE TRANSITION
Authors: Mullan Brendan , Qin Tingting , Siada Ruby , Ravindran Ramya , Thomas Chase , Harris Micah , Muruganand Ashwat , Pyaram Kalyani , Miklja Zachary , Reiber Mary , Garcia Taylor , Tran Dustin , Danussi Carla , Brosnan-Cashman Jackie , Pratt Drew , Zhao Xinyi , Rehemtulla Alnawaz , Sartor Maureen , Venneti Sriram , Meeker Alan , Huse Jason , Morgan Meredith , Lowenstein Pedro , Castro Maria , Yadav Viveka Nand , Koschmann Carl 
Published: December 2020

Abstract
Gliomas are a leading cause of cancer mortality in children and adults, and new targeted therapies are desperately needed. ATRX is a chromatin remodeling protein that is recurrently mutated in H3F3A-mutant pediatric glioblastoma (GBM) and IDH-mutant grade 2/3 adult glioma. We previously showed that loss of ATRX in glioma results in tumor growth and additional tumor mutations. However, the mechanism driving these phenotypes has not been fully established. We found that in ChIP-Seq/ChIP-qPCR of mouse neuronal precursor cells (NPCs) and GBM cells with isogenic ATRX loss, ATRX binds regulatory elements for cell cycle phase transition gene sets, and ATRX loss subsequently results in reduced expression. Furthermore, human GBM cells with ATRX knock-out demonstrate higher rates of cells in S and G2/M phases, with clusters of cells demonstrating reduced expression of cell cycle regulatory gene sets by single-cell sequencing (scSeq) analysis. In human and mouse GBM in vitro models, ATRX-deficient cells exhibit a seven-fold increase in mitotic index at 16 hours after sub-lethal radiation and enhanced activation of the master cell cycle regulator ATM with radiation. Treatment of ATRX-deficient gliomas with ATM inhibitors results in a selective increase in dysfunctional cell cycling and increased radio-sensitization in ATRX-deficient glioma cells. Using an ATM-luciferase reporter in orthotopically-implanted human GBM cells, both AZD0156 and AZD1390 demonstrate in vivo pathway inhibition. Mice intra-cranially implanted with ATRX-deficient GBM cells demonstrate a doubling of median survival compared to radiated controls (p=0.0018) when treated with AZD0156 combined with radiation; this is not seen in ATRX-sufficient models. This study demonstrates that ATRX-deficient high-grade gliomas display epigenetic dysregulation of cell cycle phase transitions, which opens a new window for therapies targeting this unique phenotype.
CBIO-14. ELUCIDATING THE MECHANISM OF TEMOZOLOMIDE-INDUCED ATR ACTIVATION IN MGMT-METHYLATED GLIOBLASTOMA MULTIFORME
Authors: Ganesa Sachita , Sule Amrita , Sundaram Ranjini , Bindra Ranjit 
Published: December 2020

Abstract
Glioblastoma multiforme (GBM) is an aggressive, malignant brain tumor in adults. The current standard of care for GBM is surgical resection, radiation therapy and chemotherapy with temozolomide (TMZ). It is well established that GBM patients with a methylated MGMT promoter (MGMT-) who are treated with TMZ have a better overall survival than patients with an unmethylated MGMT promoter (MGMT+). The enzyme produced by the MGMT gene is responsible for removing cytotoxic O6-methylguanine (O6-meG) lesions formed by TMZ. In the MGMT- setting, the O6-meG lesion activates the mismatch repair (MMR) pathway which functions to remove the damage. Published work from our group reported differential activation of the ataxia telangiectasia and RAD3 related protein (ATR) in MGMT- and MGMT+ GBM cells in response to TMZ treatment, as demonstrated through the phosphorylation of CHK1. It is known that MMR proteins are involved in ATR activation, however, this project aims to unravel the specific MMR proteins required for ATR activation by TMZ-induced alkyl lesions. To accomplish this, we treated an shMSH2 MGMT- GBM cell line with TMZ and an ATR inhibitor (ATRi) compared to treatment in an MSH2-proficient MGMT- GBM cell line. We observed decreased cell death in the shMSH2 setting compared to the MSH2-proficient cells, suggesting that MSH2 is integral in the activation of ATR upon TMZ treatment in the MGMT- setting. This study elucidates a potential role for MSH2 in ATR activation. Mechanistic understanding of how the MMR system is involved in ATR activation by TMZ can ultimately be exploited for therapeutic gain in the treatment of patients with GBM.
COVD-04. REAL-WORLD PERSPECTIVES: TUMOR TREATING FIELDS (TTFIELDS) UTILITY TO OPTIMIZE TREATMENT OF PATIENTS WITH GLIOBLASTOMA (GBM) AMIDST COVID-19 PANDEMIC
Authors: Frongillo Peggy , Shackelford Melissa , Rain Lindsay 
Published: December 2020

Abstract

INTRODUCTION
Due to the unprecedented, COVID-19 pandemic and resulting health/safety guidelines, rapid-adjustments to treatment plans for patients battling glioblastoma (GBM; debilitating, aggressive cancer) were critical. Tumor Treating Fields (TTFields; FDA-approved for GBM; antimitotic device) are alternating electric fields (200 kHz) delivered through scalp-placed transducer arrays to target rapidly dividing GBM cells. Visitor restrictions at cancer-centers and often overburdened healthcare teams provided obstacles to cancer therapy. Health and safety of patients/caregivers, healthcare providers (HCPs), and patient Device Support Specialists (DSS) were prioritized. We evaluated the impact of Novocure® (device manufacturer) implemented strategies on overcoming limitations/restrictions to treatment-access during COVID-19.

TREATMENT/PROTOCOL
TTFields (Optune) offers a viable noninvasive, built-in-care system for convenient at-home use. TTFields provides survival benefit with continuous, portable-usage and is tolerable (no-related systemic effects) without overall impact on quality-of-life (except itchy skin). Novocure adopted/amended protocols to meet health guidance/regulation (ie, World Health Organization, Centers for Disease Control and Prevention, local, hospital/clinic directives).

PERSPECTIVES
COVID-19 forced a change in treatment patterns imposed by quarantine limitations. This, coupled with the vulnerabilities of immunocompromised patients with GBM, necessitated new-access to TTFields. A COVID-19 task force was created to monitor developments, providing directives to minimize risks to patients/caregivers and employees. Hygiene-practices/full-personal protective equipment were applied for live patient-appointments with DSS. Virtual education appointments were executed to guide patients/caregivers through treatment-initiation. New, no-contact, monthly-usage data downloads were employed. Communication measures were implemented, informing HCPs of process changes impacting patients. To date, no observed differences were noted for virtual to non-virtual patient starts, demographics, time-to-start (42-days), treatment discontinuations, percentage continuing therapy (90%), and overall complaints. No new safety signals were observed utilizing new approaches.

CONCLUSIONS
TTFields care-delivery has been transformed during COVID-19 and preemptively in regards to other future access-limiting events, with adoption of virtual-platforms/protocols, resulting in enhanced access and education for patients/caregivers and healthcare teams.
COVD-08. THE DIVIDED PRINCIPLE OF JUSTICE: ETHICAL DECISION-MAKING IN CANCER CARE DURING THE COVID-19 PANDEMIC
Authors: Brenna Connor , Das Sunit 
Published: December 2020

Abstract
The four-principle approach to medical ethics, balancing prima facie obligations to beneficence, nonmaleficence, autonomy, and justice, has supplied a common language for the application of ethical analysis to medical practice for the last four decades. The frayed edges of this edifice are made visible, however, by the ongoing COVID-19 pandemic (and other historical circumstances of severe resource limitation in the healthcare system). We interrogate ethical considerations involved in the state of medical care during the COVID-19 pandemic, as demonstrated by reconsiderations of cancer care, in which the pillar of justice is exposed as internally divided. Specifically, we identify both patient-oriented and system-oriented principles of justice constituting a broader collective, unique among the classical four principles. This leads us to suggest a formal recognition of justice as a divided category, and a reclassification of the term into two subcategories which serve fundamentally different interests. The result is a more cohesive four principle approach in which all principles favour the deontological relationships fostered between patients and providers, which exists in constant balance with the utilitarian interests of the broader medical system.
COVD-12. THE LONGITUDINAL IMPACT OF COVID-19 PANDEMIC ON NEUROSURGICAL PRACTICE
Authors: Alatar Abdullah , Bajunaid Khalid , Alqurashi Ashwag , Ajlan Abdulrazag 
Published: December 2020

Abstract

OBJECTIVE
This observational cross-sectional multicenter study aimed to evaluate the longitudinal impact of the coronavirus disease 2019 (COVID-19) pandemic on neurosurgical practice.

METHODS
We included 29 participating neurosurgeons in centers from all geographical regions in the Kingdom of Saudi Arabia. The study period, which was between March 5, 2020 and May 20, 2020, was divided into three equal periods to determine the longitudinal effect of COVID-19 measures on neurosurgical practice over time.

RESULTS
During the 11-week study period, 474 neurosurgical interventions were performed. The median number of neurosurgical procedures per day was 5.5 (interquartile range [IQR]: 3.5–8). The number of cases declined from 72 in the first week and plateaued at the 30’s range in subsequent weeks. The most and least number of performed procedures were oncology (129 [27.2%]) and functional procedures (6 [1.3%]), respectively. Emergency (Priority 1) cases were more frequent than non-urgent (Priority 4) cases (178 [37.6%] vs. 74 [15.6%], respectively). In our series, there were three positive COVID-19 cases. There was a significant among-period difference in the length of hospital stay, which dropped from a median stay of 7 days (IQR: 4 – 18) to 6 (IQR: 3 - 13) to 5 days (IQR: 2 - 8). There was no significant among-period difference with respect to institution type, complications, or mortality.

CONCLUSION
Our study demonstrated that the COVID-19 pandemic decreased the number of procedures performed in neurosurgery practice. The load of emergency neurosurgery procedures did not change throughout the three periods, which reflects the need to designate ample resources to cover emergencies. Notably, with strict screening for COVID -19 infections, neurosurgical procedures could be safely performed during the early pandemic phase. We recommend to restart performing neurosurgical procedures once the pandemic gets stabilized to avoid possible post-pandemic health-care system intolerable overload.
COVD-14. TELEMEDICINE REVIEW IN NEURO-ONCOLOGY: COMPARATIVE EXPERIENTIAL ANALYSIS FOR BARROW NEUROLOGICAL INSTITUTE AND GEISINGER HEALTH DURING THE 2020 COVID-19 PANDEMIC
Authors: Fonkem Ekokobe , Gatson Na Tosha , Tadipatri Ramya , Azadi Amir 
Published: December 2020

Abstract
Coronavirus disease 2019 (COVID-19) has grossly impacted how we deliver healthcare and how healthcare institutions derive value from the care provided. at increased infectious risk on immunosuppressive therapies and often have mobility limitations. Adapting to new technologies and reimbursement patterns were challenges that had to be met by the institutions while patients struggled with decisions to prioritize concerns and to identify new pathways to care. With the implementation of social distancing practices, telemedicine plays an increasing role in patient care delivery, particularly in the field of Neurology. This is of particular concern in our cancer patient population given that these patients are often at increased infectious risk on immunosuppressive therapies and often have mobility limitations. We reviewed telemedicine practices in neurology pre-/post-COVID-19 and evaluated the neuro-oncology clinical practice approaches of two large care systems, Barrow Neurological Institute and Geisinger Health. Practice metrics were collected for impact on clinic volumes, institutional recovery techniques, and task force development to address COVID-19 specific issues. Neuro-Oncology divisions reached &gt;67% of pre-pandemic capacity (patient visits and slot utilization) within 3-weeks and returned to &gt;90% capacity within 6-weeks of initial closures due to COVID-19. The two health systems rapidly and effectively implemented telehealth practices to recover patient volumes. While telemedicine will not replace the in-person clinical visit, telemedicine will likely continue to be an integral part of neuro-oncologic care. Telemedicine has potential for expanding access in remote areas and provides a convenient alternative to patients with limited mobility, transportation, or other socioeconomic complexities that otherwise challenge patient visit adherence.
COVD-15. COVIDNEUROONC: A UK MULTI-CENTRE, PROSPECTIVE COHORT STUDY OF THE IMPACT OF THE COVID-19 PANDEMIC ON THE NEURO-ONCOLOGY SERVICE
Authors: Fountain Daniel , Piper Rory , Poon Michael , Solomou Georgios , Brennan Paul M , Chowdhury Yasir , Colombo Francesca , Elmoslemany Tarek , Ewbank Frederick , Grundy Paul , Hasan Md Tanvir , Hilling Molly , Hutchinson Peter , Karabatsou Konstantina , Kolias Angelos , McSorley Nathan , Millward Christopher , Phang Isaac , Plaha Puneet , Price Stephen , Rominiyi Ola , Sage William , Shumon Syed , Silva Ines , Smith Stuart , Surash Surash , Thomson Simon , Lau Jun Yi , Watts Colin , Jenkinson Michael 
Published: December 2020

Abstract

BACKGROUND
The COVID-19 pandemic has profoundly affected cancer services. Our objective was to determine the effect of the COVID-19 pandemic on decision making and the resulting outcomes for patients with newly diagnosed or recurrent intracranial tumors.

METHODS
We performed a multi-centre prospective study of all adult patients discussed in weekly neuro-oncology and skull base MDTs who had a newly diagnosed or recurrent intracranial (excluding pituitary) tumor between 01 April and 31 May 2020. All patients had follow-up data at least 30-days after the index MDT date. Descriptive statistical reporting was used.

RESULTS
There were 1357 referrals for newly diagnosed or recurrent intracranial tumors across fifteen neuro-oncology centres. Of centres with all intracranial tumors, a change in initial MDT management was reported in 8.6% of cases (n=104/1210). Decisions to change the MDT management plan reduced over time from a peak of 19% referrals at the start of the study to 0% by the end of the study period. Changes in management were reported in 16% (n=75/466) of cases previously recommended for surgery and 28% of cases previously recommended for chemotherapy (n=20/72). The reported SARS-CoV-2 infection rate was similar in surgical and non-surgical patients (2.6% vs. 2.4%, p &gt;0.9).

CONCLUSIONS
Disruption to neuro-oncology services in the UK caused by the COVID-19 pandemic was most marked in the first month, affecting all diagnoses. Patients considered for chemotherapy were most affected. In those recommended surgical treatment this was successfully completed. Longer-term outcome data will evaluate oncological treatments received by these patients and overall survival.
COVD-16. THE COVID-19 PANDEMIC FROM A NEURO-ONCOLOGY PERSPECTIVE: STRATEGIES, PROTOCOLS, AND LESSON LEARNED
Authors: Burke John , Aghi Manish , Chan Andrew , Mummaneni Praveen , Berger Mitchel 
Published: December 2020

Abstract

INTRODUCTION
The COVID-19 pandemic has had an incalculable impact on our national healthcare system, and elective surgical procedures have been particularly affected. Given that brain tumors often straddle the line between elective and emergent procedures, the pandemic has presented unique challenges to the neuro-oncology community. Here, we present our institutional protocols to (1) maintain an active outpatient neuro-oncology practice, (2) triage surgical cases under limited operating room availability, and (3) safely resume research efforts.

METHODS
Given the rapidly evolving nature of the pandemic, we based the development of our protocols on the Delphi system to achieve consensus across a multi-disciplinary panel of experts. Specifically, we used this system to develop (1) a standardized physical examination that could be implemented over tele-medicine and (2) a triage system for surgical cases. Research efforts were largely suspended in the early days of the pandemic, however protocols for enrollment in clinical trials as well as the resumption of benchwork were also developed.

RESULTS
From the COVID-19 shelter-in-place order (March, 2020) through May 2020, our department performed 96 surgeries for the resection of brain tumors compared to 127 such surgeries from the three months prior. During this time, using a modified Delphi procedure, we developed detailed protocols to triage tumor cases. Implementation of telemedicine outpatient visits allowed the continuation of the neuro-oncology clinic and, ultimately, the resumption of clinical trials.

CONCLUSIONS
The protocols presented here offer several strategies to continue neuro-oncological care during the pandemic, including the surgical treatment of brain tumors. As we prepare for future outbreaks, these treatment algorithms will help ensure that patients with brain tumors receive the highest level of care independent of COVID-19.
COVD-23. PLANNED-USE GLUCARPIDASE FOR OUTPATIENT HIGH DOSE METHOTREXATE (HD-MTX) ADMINISTRATION IN PATIENTS WITH CNS LYMPHOMA (CNSL) DURING THE COVID-19 PANDEMIC
Authors: Schaff Lauren , Lobbous Mina , Bozza Alexis , Carlow Dean , Nabors Louis , Grommes Christian 
Published: December 2020

Abstract
Infection with SARS CoV-2 virus has resulted in a global pandemic of COVID-19, a respiratory illness with a crude mortality rate of 3–4%. Risk of death is higher in the elderly and in patients with underlying comorbid conditions. When local incidence of COVID-19 is high, hospital resources are scarce and elective admissions and procedures are placed on hold. Patients with CNSL receiving first-line HD-MTX require admission for monitoring and aggressive hydration to prevent toxicity. This study explores the feasibility of planned-use glucarpidase, a recombinant bacterial enzyme that rapidly reduces serum MTX levels, to facilitate outpatient administration of HD-MTX. Eligible adult patients had isolated CNSL and had previously tolerated inpatient HD-MTX. MTX 3.5 g/m2 was administered in the outpatient setting with hydration. Patients returned 24 hours after MTX administration for glucarpidase 2000u and additional hydration. MTX level was determined by high pressure liquid chromatography (HPLC) 48 hours following MTX administration. To date, seven outpatient HD-MTX treatments have been administered to a total of three patients. In all cases, MTX levels were reduced to &lt; 100 nmol/L at 48 hours. Three treatments resulted in grade 1 elevation of AST/ALT (two patients). One treatment resulted in a grade 2 creatinine increase. Creatinine returned to baseline following additional outpatient hydration. No patients required hospital admission. This study demonstrates feasibility of outpatient HD-MTX administration with planned-use glucarpidase during the COVID-19 pandemic. We are currently enrolling to a larger study of planned-use glucarpidase for repeated doses of outpatient HD-MTX.