bluuebunny/crossref_metadata_2025_split huggingface dataset:
QLTI-20. DIGITAL SOLUTIONS TO IMPROVE DATA QUALITY IN NEUROONCOLOGY RESEARCH
Authors: Ray Amit , Sanka Arka , Prathapa Kiran , Sreegiriraju Vijay , Kumar K V R N Kiran , Balagoni Yadagiri , Sunkara Samyuktha , Sunkara Ravi Teja , Nandoori Sharath Chandra , Vuyyuru Sarath , Mishra Pankaj , Madiraju Surya Prakash 
Published: November 2022

Abstract

PROBLEM
Data quality impacts the validity of results obtained through clinical research due to several reasons. These include degradation of tumor tissue and other biological samples while being transported across large distances. Other concerns related to data collection include breach in patient privacy and loss and corruption of data. Such issues lead to generation of results that are either unreliable or unsuitable for analysis. Blockchain based digital solutions for clinical trials may be an answer to the problem.

SOLUTION
In this abstract we review one such software ‘Elsy’ that we have used to collect around 1000 samples from more than 70 centres nationwide. Elsy had been deployed on the smartphone and desktop and used by clinical trial teams to plan, execute and monitor the trial across multiple geographical locations. Collection of tumor specimens was monitored from the time the specimens left the operating room by leveraging blockchain technologies. Patient data was imported into the system seamlessly by integration with hospital electronic medical records systems. Customised data forms were mapped to automatically import data fields that were relevant. Once recruited, all patient sensitive data was immediately obfuscated, and a bar code was assigned to the patient, which served as the unique patient identifier. Data was encrypted in transit and at rest on a cloud server, with access requiring 2-factor authentication. Data viewing and editing permissions were tailored to meet patient privacy and security requirements. Changes in data were logged and monitored, eliminating wilful or accidental manipulation of data. AI and ML tools were integrated with the system to perform advanced analysis.

CONCLUSION
Digital platforms may have the potential to revolutionise the clinical trials systems by enabling the collection of clean and secure data.
QLTI-23. BRAIN TUMOR-RELATED PAIN: INNOVATIVE APPROACHES TO DIAGNOSIS, TREATMENT, AND QUALITY OF LIFE ISSUES: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Ekhator Chukwuyem , Rak Ramin , Tadipatri Ramya , Fonkem Ekokobe , Grewal Jai 
Published: November 2022

Abstract

OBJECTIVE
The purpose of this systematic review and meta-analysis is to evaluate the various innovative approaches to diagnosing and treating patients presenting with brain tumor-related pain.

BACKGROUND
Brain tumors make up for lower than 2% of all cancers, which is heavily linked to high morbidity, deteriorated quality of life, and the death of the affected patients. Glioblastoma (GBM) makes up 38% of the malignant brain glioma.The main treatment approaches for gliomas are widely dependent on chemotherapy and radiation therapy. However, these methods have been associated with vast side effects which constitute the quality of life of the patient.

METHODS
This systematic review and meta-analysis conformed to PRISMA guidelines. A total of 3025 studies were assessed through the eligibility criteria to remain with twenty eligible studies. The included studies were then grouped into two categories; group one comprised 14 studies that focused on an innovative approach to diagnosis and treatment of gliomas, and six studies comprised of studies that focused on health-related quality of life (HRQoL) of patients with brain tumors.

RESULTS
Twenty studies that met the inclusion criteria were analyzed independently and in two groups: diagnosis and treatment and quality of life issues of brain tumor patients. In one group, one study revealed a relatively progression-free survival (PFS) going up to 57 weeks and overall survival (OS) time of more than 20 weeks after the initial surgery. Group two indicated HRQoL issues associated with symptoms such as headaches, fatigue, trauma, cognitive and personality dysfunction, leg weakness, and neurological deficits.

CONCLUSION
Timely diagnosis of the gliomas has significant improvements to the overall survival. Treatment approaches explored in the studies include Temozolomide (TZ), Gliadel Wafer, immunogeno-type, peptide vaccination, Bevacizumab, chemotherapy, radiation therapy, and Temsirolimus. Chemotherapy and radiation therapy have been linked to a deteriorated quality of life of the patients
QOL-01. RISK FACTORS FOR AND CONSEQUENCES OF PROLONGED DEXAMETHASONE USE IN PATIENTS WITH GLIOBLASTOMA (GBM)
Authors: Donovan Laura , Joanta-Gomez Adela , Furnari Julia , Mouton Brandi , Lassman Andrew 
Published: November 2022

Abstract

BACKGROUND
Dexamethasone is the primary treatment for tumor-associated edema. Prolonged use can have significant side effects and may negatively impact survival in GBM. Factors associated with steroid dependence and steroid associated side effects (SASEs) are not well established.

METHODS
We performed a retrospective study of patients with newly diagnosed, IDH-wildtype GBM at our center. Demographics, clinical and tumor characteristics, dexamethasone usage, and SASEs (infections, myopathy, hypertension, fractures, mood symptoms, weight gain, and hyperglycemia) were extracted through chart review. We compared survival outcomes (OS) between patients with and without steroid dependence. Risk factors for steroid dependence were identified through logistic regression analysis.

RESULTS
39/92 (35.9%) patients developed steroid dependence. Of these, 26/39 (66.7%) were on steroids at the start of initial treatment. Patients who developed steroid dependence were older, more likely to have STR/biopsy, bilateral disease, KPS &lt; 90, baseline neurological deficits, and to be obese (BMI ≥ 30). 94.9% of patients with steroid dependence experienced ≥ 1 SASE (vs. 34%) and 46.2% experienced ≥ 3 SASEs (vs. 3.8%). Mood symptoms (69.2% vs. 26.4%), hyperglycemia (53.8% vs. 7.5%) and infections (51.3% vs. 7.5%) were the most common SASEs. Median OS was inferior in steroid-dependent patients (18 vs 25 mo). Baseline obesity was identified as a risk factor for developing steroid dependence (OR 5.9).

DISCUSSION
SASEs are common in patients on prolonged steroids. Obesity may increase the risk of developing steroid dependence. Identifying patients at highest risk for steroid dependence may help guide future interventions to mitigate the negative effects of prolonged dexamethasone use.
QOL-05. OPIATE UTILIZATION AND PREDICTIVE FACTORS IN PATIENTS UNDERGOING SURGERY FOR GLIOMAS
Authors: Deleyrolle Phuong , Dagra Abeer , Mohamed Shahd , Chowdhury Muhammad Abdul Baker , McGrew Nina , Rahman Maryam 
Published: November 2022

Abstract

INTRODUCTION
Opiate dependence is a national crisis. The use of opiate in patients diagnosed with gliomas undergoing surgery is not well understood.

OBJECTIVE
The objective of this study was to evaluate opiate use in patients undergoing surgery for gliomas and risk factors for prolonged opiate use.

METHODS
A retrospective chart review was conducted on patients ≥ 18 years who underwent surgery for glioma from 1/2016 to 1/2020. Clinical data was collected and opiate dose was calculated as morphine equivalent dose (MED). Clinical data prior to surgery, during surgery, and post-operative setting were collected. Descriptive statistics (means, frequencies, and percentages) were used to characterize the study population. Chi-square, with Fisher’s exact test, was used to determine associations for categorical variables. Linear and negative binomial regression models were used to predict MED doses with patient characteristics.

RESULTS
180 patients were included in the analysis. The median MED at the time of surgery was 23.5 (IQR: 1.6, 72.5). 57 patients (46.04%) continued to take opiates after surgery. During adjuvant treatment the median MED was 45 (IQR: 45- 45) and the median length patients remaining on opiates was 59 days (IQR: 33- 168.5), with the longest usage being 1459 days. History of substance use, chronic headaches and other pain syndromes were not associated with increased use of opiates at the time of surgery. However, these factors were associated with higher morphine use after surgery. Male had a slightly higher dose (&lt; 0.001) at the time of surgery compared to women. Peri-operative use at the time of surgery did not predict the MED and length of opiate use as outpatient.

CONCLUSION
Nearly half of the patients continued to use opiate beyond the peri-operative setting as outpatient at a higher median MED on median period of 59 days suggesting opportunities for improvement in opiate management post operatively.
QOL-13. THE ROLE OF EPILEPSY IN ELDERLY PATIENTS WITH GLIOBLASTOMA: AN AUSTRIAN MULTICENTER ANALYSIS
Authors: Demetz Matthias , Hecker Constantin , Krigers Aleksandrs , Machegger Lukas , Kerschbaumer Johannes , Geiger Philipp , Pöppe Johannes , Spinello Antonio , Griessenauer Christoph , Thomé Claudius , Freyschlag Christian , Schwartz Christoph 
Published: November 2022

Abstract

BACKGROUND
With an aging population, acquisition of a better understanding of prognostic factors in elderly patients with Glioblastoma multiforme (GBM) is of utmost importance. Epileptic seizures have been found to correlate with improved overall survival (OS) in low-grade gliomas; however, the impact of epilepsy in GBM patients on outcome parameters is poorly defined. This study aims at specifically evaluating the impact of epilepsy in elderly GBM patients. Material &

METHODS
Two Austrian academic neurosurgical centers retrospectively analyzed all elderly (≥ 65 years) GBM patients with de-novo tumors, who underwent surgery between 09/2006 and 07/2021. Epidemiological, histopathological and survival data were gained from patients’ electronic charts and screened for presence of epilepsy preoperatively or during follow-up. Tumor volume was assessed using standardized software.

RESULTS
391 patients (55% males, 45% females) with a median age at surgery of 73 years (IqR 68.5-77.5) were analyzed. The mean predicted OS was 12.4 months (CI95% 10.9-14.0). Mean follow-up was 10.4 months (CI95% 9.1-11.6) in our cohort. Median tumor volume amounted to 26.47 cm3 (IqR 12.65-43.49). 95 patients (24%) suffered from preoperative epilepsy. 17 (18%) patients showed epilepsy after tumor resection. Four patients (1.0%) showed a worsening of already preoperatively diagnosed seizures. Patients with lower tumor volumes experienced significantly more often seizures compared to patients with larger tumors, p&lt; 0.001. Survival did not correlate with preoperative epilepsy (p &gt; 0.05). However, Cox-regression revealed that multifocal tumor location (HR=1.777, p=0.025) and thalamic involvement (HR=11.121, p=0.030) influenced OS. Surgery-associated complications shortened OS significantly (HR=1.945 [CI95% 1,296-2,916], p=0.025).

CONCLUSION
Even though epilepsy was not found to directly impact survival in elderly GBM patients, we found that surgery led to epilepsy freedom in a significant proportion of our patient cohort, thereby potentially leading to improved QoL. Greatest focus should be set on avoiding any surgery-associated deficits, since these severely influence the OS.
QOL-18. CAN QUALITY OF LIFE FOR BRAIN TUMOR SURVIVORSHIP CARE
Authors: Koehler Abigail , Rothman Yehudit , Enriquez Diego Gomez , Kirschner Michelle , Erickson Melissa , Rastogi Meera , Rebola Claudia , Sengupta Soma 
Published: November 2022

Abstract
Cancer survivorship is an important area of medicine as it focuses on the quality of life of patients after experiencing cancer and cancer treatment. Thankfully, many patients survive cancers and other benign tumor diagnoses but must live with the side effects and subsequent consequences of their treatment. These, sometimes lifelong, effects can diminish quality of life and interfere with day-to-day activities. A number of therapy tools have been developed to aid in survivorship care, but how can we advance new digital therapy tools for cancer survivorship and brain-related diseases, specifically quality of life? The University of Cincinnati has curated an innovative team of faculty and students across disciplines to develop digital applications to emphasize cancer and brain tumor survivorship and create new methods for health and wellbeing at the hands of people. This includes the CAN Quality of Life applications which use novel technologies to administer digital pre-existing therapies. The first, ARMCan, is a digital music therapy instrument used by breast cancer patients with post-chemotherapy brain fog. The second, ARTCan, is a digital art therapy platform in which vestibular schwannoma and NF2 patients with mood issues can complete self-guided art activities. ARTCan is partnered with ARCCan, animal robotic-like companions. A narrative application for cancer survivors and caregivers is being developed. These CAN applications hope to improve the quality of life for the people they serve by improving executive function and mood, respectfully. ARMCan and ARTCan/ARCCan pilot feasibility studies are currently accruing subjects at our institution.
RBIO-04. STEREOTACTIC RADIOSURGERY REPROGRAMS MACROPHAGE, MICROGLIA, AND CD8+ T CELL POPULATIONS IN THE GLIOBLASTOMA IMMUNE MICROENVIRONMENT
Authors: Young Jacob S , Cho Nam Woo , Lucas Calixto-Hope , Seo Kyounghee , Santos Raquel , Phillips Joanna J , Ozawa Tomoko , Berger Mitchel S , Raleigh David 
Published: November 2022

Abstract

INTRODUCTION
Fractionated radiotherapy is a first-line treatment for glioblastoma, but daily ionizing radiation prevents durable immune infiltration of the tumor microenvironment. Hypofractionated radiotherapy is used to treat glioblastomas at recurrence, but the impact of hypofractionated radiotherapy on the glioblastoma immune microenvironment is incompletely understood. Here we define immune microenvironment changes across multiple immunocompetent intracranial mouse models of glioblastoma after treatment with ionizing radiation mimicking stereotactic radiosurgery (SRS) in humans.

METHODS
Syngeneic GL261 (3x105 cells/mouse) or SB28 glioblastoma cells (3x104 cells/mouse) were implanted into the frontal lobe of immunocompetent C57BL/6J mice (18 mice/arm x 4 arms). Intracranial bioluminescence was used to assess glioblastoma growth. After tumor engraftment, glioblastomas were treated with conformal SRS (18Gy/1Fx) or sham. Glioblastomas were collected for histologic, single-cell, or molecular analyses 5 days after treatment (6 mice/arm) or at the time of euthanasia after monitoring for survival (12 mice/arm). Glioblastoma immune microenvironment responses were assessed using (1) H&E, (2) single cell mass cytometry (CyTOF) or IHC to define or validate immune cell changes, respectively, or (3) multiplexed cytokine assays to elucidate molecular mechanisms reprograming the glioblastoma immune microenvironment in response to SRS.

RESULTS
SRS attenuated glioblastoma growth and prolonged survival compared to sham treatment in both immunocompetent intracranial mouse models (GL261: 14 days versus 27 days, p&lt; 0.001, SB28: 19 days versus 22 days, p=0.001). CyTOF showed SRS decreased immunosuppressive macrophage infiltration and increased microglia or CD8+ T cell infiltration of the glioblastoma immune microenvironment. Histologic analyses validated T cell and microglia infiltration after SRS. Glioblastoma cytokine analysis revealed inhibition of pro-tumor/anti-inflammatory cytokines (IL6, LIF) after SRS.

CONCLUSIONS
Single-fraction SRS durably reprograms glioblastoma macrophage, microglia, and CD8+ T cell populations in preclinical models, suggesting SRS or inhibition of pro-tumor/anti-inflammatory mechanisms underlying the immunosuppressive glioblastoma microenvironment represent immunogenic therapies that may offer a benefit to patients with glioblastoma.
RTID-01. ONC108: A RANDOMIZED PHASE 3 STUDY OF ONC201 IN PATIENTS WITH NEWLY DIAGNOSED H3 K27M-MUTANT DIFFUSE GLIOMA
Authors: Arrillaga-Romany Isabel , Lassman Andrew , McGovern Susan , Mueller Sabine , Nabors L Burt , van den Bent Martin , Vogelbaum Michael , Allen Joshua E , Melemed Allen , Tarapore Rohinton , Yang Dewen , Wen Patrick Y , Cloughesy Timothy 
Published: November 2022

Abstract

BACKGROUND
H3 K27M-mutant diffuse midline glioma is a universally fatal malignancy primarily affecting children and young adults; while radiotherapy (RT) provides transient benefit, no effective systemic therapy is currently available. ONC201, a first-in-class imipridone, is an oral, blood-brain barrier penetrating, selective small molecule antagonist of dopamine receptor D2/3 (DRD2) and agonist of the mitochondrial protease ClpP. An integrated pooled analysis of objective response in ONC201-treated patients enrolled in one of five open-label trials has previously demonstrated efficacy in patients with recurrent disease. This phase 3 trial will be the first randomized, controlled study evaluating ONC201 in patients with H3 K27M-mutant disease.

METHODS
ONC108 is a randomized, double-blind, placebo-controlled, parallel-group, international Phase 3 study of ONC201 in patients with newly diagnosed H3 K27M-mutant diffuse glioma. Patients will be randomized to receive once-weekly ONC201 or placebo following standard frontline radiotherapy. Primary efficacy endpoints are overall survival (OS) and progression-free survival (PFS) in all participants; PFS will be assessed with the response assessment in neuro-oncology-high grade glioma by blind independent central review. Other objectives include assessments of safety, additional efficacy endpoints, clinical benefit, quality of life, pharmacokinetics, biomarkers, and healthcare resource utilization. Eligible patients will have histologically confirmed H3 K27M-mutant diffuse glioma, a Karnofsky/Lanksy performance status ≥ 70, and completed first-line radiotherapy. Eligibility will not be restricted based on age; however, patients must be ≥ 10 kg at time of randomization. Patients with a primary spinal tumor, diffuse intrinsic pontine glioma, leptomeningeal disease, or cerebrospinal fluid dissemination are not eligible.
RTID-02. A PHASE 1, SAFETY LEAD-IN AND RANDOMIZED, OPEN-LABEL, PERIOPERATIVE STUDY OF VORASIDENIB COMBINED WITH PEMBROLIZUMAB IN RECURRENT OR PROGRESSIVE ENHANCING IDH-1 MUTANT ASTROCYTOMAS: TRIAL IN PROGRESS
Authors: Wen Patrick , Mellinghoff Ingo , Clarke Jennifer , Puduvalli Vinay , de Groot John , Liu Hua , Tron Adriana , Chisamore Michael , Steelman Lori , Hassan Islam , Cloughesy Timothy 
Published: November 2022

Abstract

BACKGROUND
Astrocytomas are a subset of diffuse gliomas defined by intact 1p and 19q arms. Isocitrate dehydrogenase 1 mutations (mIDH-1) occur in ~70% of grade 2/3 gliomas, leading to accumulation of 2-hydroxyglutarate (2-HG). Vorasidenib (VOR) is an oral, brain-penetrant dual inhibitor of mIDH1/2 enzymes being investigated in a phase 3 study in non-enhancing gliomas. In an ongoing perioperative study in grade 2/3 gliomas, treatment with VOR was associated with interferon (IFN) signaling activation and increased T-cell infiltration, suggesting adequate 2-HG suppression renders the tumor immune microenvironment for immune checkpoint blockade, and supporting investigation of VOR in combination with an anti-programmed cell death (PD-1) antibody such as pembrolizumab in recurrent IDH-mutant gliomas treatment. This study will evaluate the safety and tolerability of VOR plus pembrolizumab to determine the recommended combination dose (RCD) of VOR, and evaluate CD3+ T-cell infiltration in tumors following preoperative treatment with the combination or VOR.

METHODS
This study will enroll ~70 patients with recurrent or progressive Grade 2/3 mIDH-1 astrocytoma. Key eligibility: enhancing disease, mIDH1-R132H, Karnofsky Performance Status ≥70, eligible for resection (perioperative phase only). Safety lead-in: Cohort 1 (Nf~6): VOR 40 mg QD plus pembrolizumab 200 mg Q3W in 21-day cycles. Based on DLT evaluation, cohort 2 may enroll an additional ~6 patients at VOR 20 mg QD plus pembrolizumab 200 mg Q3W. Randomized, perioperative phase (Nf~60): randomized 1:1:1 to the combination, VOR 40 mg QD, or untreated for 4 weeks preoperatively; all patients can opt to receive the combination postoperatively. Primary objectives: safety and tolerability, and VOR RCD with pembrolizumab; CD3+ T-cell infiltration in resected tumors following presurgical treatment with the combination compared to untreated tumors. Secondary objectives include clinical activity, VOR PK in tumor and blood, 2-HG concentration in tumors, and overall survival. This study will be active in the United States.
RTID-03. DSP-0390, AN ORAL EMOPAMIL BINDING PROTEIN (EBP) INHIBITOR, IN PATIENTS WITH RECURRENT HIGH-GRADE GLIOMA: A FIRST-IN-HUMAN, PHASE 1 STUDY
Authors: Reardon David A , Narita Yoshitaka , Arakawa Yoshiki , Goldlust Samuel , Anstass George , McMullen Dragana , Dow Edward , Seki Masataka , Furuta Yudai , Song Gregory , Colman Howard 
Published: November 2022

Abstract
The brain's cells are dependent on their own biosynthesis of cholesterol as the blood-brain barrier prevents uptake from the circulation. In normal glial cells, regulation of cholesterol synthesis depends on cell density and is turned off when density exceeds a certain level. Gliomas maintain high levels of cholesterol synthesis genes to support abnormal growth. Upregulation of cholesterol synthesis genes is associated with decreased survival in patients with glioblastoma (GBM). Therefore, gliomas are potentially sensitive to cholesterol synthesis inhibition. DSP-0390, an investigational small molecule, inhibits EBP, an enzyme in one of the last, crucial steps of cholesterol biosynthesis. By inhibiting cholesterol synthesis, cytotoxicity can be induced selectively against hyperproliferative GBM cells. DSP-0390 has shown significant antitumor activity in orthotopic xenograft models of human GBM (data on file).DSP-0390 will be evaluated in a phase 1 study in patients with recurrent, high-grade glioma (NCT05023551). Key eligibility criteria: age &gt;18 years; Karnofsky Performance Status score &gt;70%; adequate renal, hepatic, and hematologic function. Patients must not have multifocal disease, leptomeningeal metastasis or extracranial metastasis, abnormal electrocardiograms, or significant cardiovascular disease. In Dose Escalation, 21-30 patients with World Health Organization (WHO) grade III or IV malignant glioma who progressed after &gt;1 prior therapy will be enrolled. Dose level enrollment will be guided by a Bayesian Logistic Regression Model until identification of the maximum tolerated dose or recommended dose for expansion. Dose Expansion for clinical activity will enroll approximately 20-40 patients with WHO grade IV GBM who progressed after primary therapy and have measurable disease. Patients will receive oral DSP-0390 once daily. Study endpoints include safety (treatment-emergent adverse events [AEs], serious AEs, and dose-limiting toxicities), efficacy (6-month progression-free survival [PFS], objective response, PFS, duration of response, and 12-month overall survival), pharmacokinetics (PK), and pharmacodynamic biomarkers. This study is currently recruiting in the United States and Japan.