bluuebunny/crossref_metadata_2025 huggingface dataset:
EXTH-100. EVALUATION OF PANOBINOSTAT PLASMA AND CEREBROSPINAL FLUID (CSF) PHARMACOKINETIC PROFILE FOLLOWING ADMINISTRATION OF THE CAPSULE FORMULATION FARYDAK® IN A NON-HUMAN (NHP) PRIMATE PRECLINICAL MODEL
Authors: McCully Cynthia Lester , Warren Katherine , Zimmerman Sara , Peer Cody , Killoran Kristin , Garcia Rafael Cruz , Figg William , Widemann Brigitte
Published: November 2022

Panobinostat is an HDAC inhibitor with dose-dependent pre-clinical activity against pediatric glioma. Reported pharmacokinetic (PK) profiles of panobinostat, including CSF penetration, have varied. We hypothesized that this variability resulted from the utilization of differing panobinostat formulations. For comparison to the USP grade powdered formulation PK profile formerly reported (Rodgers, et al., Cancer Chemother Pharmacol. 2020 Apr;85(4):827-830) a plasma and CSF PK study was conducted with panobinostat administered as the capsule formulation, Farydak®, utilizing the same non-human primate (NHP) model, study design, analytical methods, and analysis.

METHODS

Three NHP previously developed for serial CSF access via a lateral ventricular CSF reservoir (n=2), or lumbar CSF port (n=1) received panobinostat orally (1.6 mg/kg, Human Dose Equivalent: 32 mg/m2) followed by serial paired plasma and CSF sample collections from 0-72 hours. Samples were quantified by LC-MS/MS. PK parameters were determined via noncompartmental analysis.

RESULTS

Mean plasma and CSF PK parameters Tmax (h), Cmax (nM), and AUCinf (h*nM/mg) are reported and compared to the corresponding PK parameters from the USP grade powdered formulation study formerly reported. Capsule Formulation: Plasma - Tmax: 5.3 □ 1.2, Cmax: 20 □ 1.9, AUClast: 14.5 □ 11.1, AUCinf: 15.2 □ 11.4 CSF - Tmax: 5.0 □ 3.6, Cmax: 1.7 □ 0.3, AUClast: 0.54 □ 0.47, AUCinf: unable to calculate Powdered Formulation – Mean PK of all dose levels formerly reported: Plasma -Tmax: 1.06 □ 0.13, Cmax: 1.27 □ 0.6, AUCinf: 7.7 □ 2.7 CSF - Cmax and Tmax: Unable to determine. Single quantifiable sample across all studies. AUCinf: unable to calculate.

CONCLUSION

The plasma and CSF Tmax, Cmax, the plasma AUCinf, and the CSF AUClast for panobinostat were increased following oral administration of the capsule formulation of panobinostat, Farydak®, compared to USP grade powder formulation of the drug.
QLTI-01. THE EFFECT OF COMPLETE RESECTION OF CONTRAST-ENHANCING TUMOR ON SURVIVAL IN PATIENTS WITH GLIOBLASTOMA OVER A 16-YEAR PERIOD IN A GEOGRAPHICALLY DEFINED POPULATION
Authors: Mendoza Mireles Eduardo Erasmo , Vik-Mo Einar Osland , Skaga Erlend , Helseth Eirik , Rønning Pål Andre , Server Andres , Brandal Petter
Published: November 2022

INTRODUCTION

The median survival for patients with glioblastoma is less than one year, and survival beyond five years is rare. Radiotherapy combined with chemotherapy has improved survival since its introduction in 2005. No new treatment modalities have been widely adopted after this, but treatment development has focused on achieving maximal resection and the introduction of coordinated clinical care pathways. We hypothesize that these changes in approach have resulted in an improved survival in surgically treated patients.

METHODS

Retrospective analysis of a prospectively collected database in the adult population (2.4 million habitants) of South-Eastern Norway. Patients were divided in three periods; radiotherapy- (2003-2005), temozolomide- (2006-2012), and resection focused-period (2013-2019). Patients were also stratified according to age and grade of resection. Relative survival, Cox hazard-ratio, 3- and 5- year survival were calculated.

RESULTS

We identified 1663 surgically treated glioblastoma patients eligible for the study. The median overall survival was 11.4 months. Complete resection of contrast-enhanced tumor (CRCET) was achieved in 387 (23.2%) patients. The frequency of CRCET increased during the observation time (32 - 116 - 239), but there was no increase in reoperation rates (13%). Significant improvement between the last period and the first two periods was observed (12.3 vs. 10.5 months, p < 0.006), with a significant increase in 3- and 5- year survival probability between the first two groups (p = 0.01). No difference was found in median survival in CRCET among periods. Patients with CRCET demonstrated significantly longer median survival than patients with non-CRCET (16.1 vs. 10.8 months; p < 0.001). Incidence in the elder group increased from 2.6 to 13.2 per 100,000 habitants, and median survival doubled when CRT was achieved.

CONCLUSIONS

There is an increase in median survival, 3- and 5- year survival probability when comparing time-periods. We suggest this survival benefit is related to improved CRCET rates.
QLTI-02. AUTOMATED INTRAOPERATIVE RESECTION TECHNOLOGY GENERATES INCREASED TISSUE YIELD AND IMPROVED BIOLOGICAL PRESERVATION OF BRAIN TUMOR SPECIMENS FOR NEURO-ONCOLOGY RESEARCH
Authors: Das Arabinda , Gunasekaran Arunprasad , Stephens Heather R , Sekerak Penny , Mark Joseph , McDonald Daniel G , Yazdani Milad , Stephenson Connor , Welsh Cynthia A , Infinger Libby Kosnik , Vandergrift William A , Mehrotra Shikhar , Varma Abhay K , Giglio Pierre , Patel Sunil J , Frankel Bruce M , Zukas Alicia , Cachia David , Lindhorst Scott M
Published: November 2022

Glioblastoma (GB) is an aggressive tumor showing extensive intertumoral and intratumoral heterogeneity. While preserving as much surrounding normal brain tissue as possible, neurosurgeons must aim to harvest maximal tumor tissue from a variety of tumor locations in an effort to capture heterogenic samples in high volume for molecular and pathologic diagnosis and translational research. A key challenge is the ability to consistently procure high-quality biologically active specimens. In this investigation, we implemented an automated intraoperative system to eliminate inconsistencies in the methodology of tissue collection, handling, and biological preservation immediately in the OR suite to establish a repeatable, standardized practice for obtaining high-quality tissue samples without the need for additional staff. Through this process, we were able to characterize matched specimens from GB patients or GB tumors from corresponding GB-allograft mice and compare the quality of traditional handling and collection processes of intraoperative tissue used in most neurosurgical operating rooms versus an automated resection, collection, and biological preservation system (APS) that captures, preserves, and biologically maintains tissue in a prescribed and controlled microenvironment. Matched specimens/or tissues were then processed in parallel at various time points and temperatures, evaluating viability, RNA and protein concentrations, and isolation of GB cell lines. We found that APS-derived GB slices stored in an APS modified medium remained viable and maintained high-quality RNA and protein concentration for up to 24 hours. Our results showed that primary GB cell cultures derived in this manner had improved growth over the widely used collection and preservation methods. Currently, we are continuing the investigation of collected samples in brain tumor animal models to further understand potential differences within the tumor region harvested and the cellular changes that occur over time. Our hope is this research will lead to new discoveries in the diagnosis and treatment of brain tumors.
QLTI-06. CHARACTERISTICS OF TERMINATED GLIOBLASTOMA-RELATED CLINICAL TRIALS: A REVIEW OF THE CLINICALTRIALS.GOV DATABASE
Authors: Shah Harshal , Mishra Akash , Gouzoulis Michael , Ben-Shalom Netanel , D'Amico Randy
Published: November 2022

Glioblastoma multiforme (GBM) is a devastating primary central nervous system tumor. Although past clinical trials have incrementally improved prognosis overall survival remains poor, emphasizing a need for further successful clinical trials. Terminated clinical trials are an inefficient use of financial, medical, and administrative resources and fruitlessly expose patients to the risks of experimental treatments. Therefore, premature trial terminations should be minimized whenever possible. GBM-related clinical trials in particular are known to suffer several inefficiencies in study design resulting in premature termination, and a 2019 Think Tank held by the Society of Neuro-Oncology intended to address this issue, suggesting optimizing participant accrual and efficacy assessments. The primary aims of the present study are to quantify terminated and completed GBM-related clinical trials and analyze reasons for premature trial termination. Using univariate and multivariate analysis we demonstrate factors associated with greater odds of trial termination. ClinicalTrials.gov, a clinical trial registry maintained by the National Library of Medicine, was queried to identify all completed and terminated GBM-related clinical trials. Trial characteristics pertaining to study design were abstracted from reported information on ClinicalTrials.gov for all trials, and the reason for trial termination was determined for those trials that were terminated early. Univariate analysis by Pearson’s chi-square and a multivariate logistic regression were performed to identify independent predictors of early trial termination. We identified 886 completed and terminated GBM-related trials between 2003 and 2020. Of these, 175 (19.8%) were terminated prior to completion. The most common reason for termination was participant accrual difficulties, accounting for 63 (36.0%) terminated trials. Trial termination was associated with trials that reported a primary purpose of diagnosis relative to treatment (OR = 2.952, p = 0.001). The identified predictors of trial termination should be considered when designing GBM-related clinical trials to minimize the odds of early trial termination.
QLTI-10. COST-EFFECTIVENESS OF SCRAMBLER THERAPY (CALMARE®) FOR THE TREATMENT OF CHRONIC CHEMOTHERAPY-INDUCED PERIPHERAL NEUROPATHY
Authors: Prakash Neal
Published: November 2022

BACKGROUND

Acute chemotherapy-induced peripheral neuropathy (CIPN) is a common and serious consequence of cancer treatment. However, for up to 30% of patients, CIPN persists beyond six months of completing chemotherapy, and is transformed to chronic (c)CIPN. Scrambler therapy (ST) is a therapeutic modality with emerging evidence supporting its ability to diminish CIPN symptoms, however, low reimbursement limits patient access to this potentially curative therapy.

METHODS

Data was from a convenience sample of 24 CIPN patients (with symptoms between 1-240 months after platinum-based, taxane, or combination chemotherapy) completing 10 sessions of ST using the Calmare® device in the City of Hope Outpatient Physical Therapy Department. Patients were treated for ~45 minutes per session over 10 sessions. Patients received a standardized assessment pre- and post ST that included: EORTC chemotherapy-induced peripheral neuropathy questionnaire (QLQ-CIPN20), mono-filament testing, pain intensity numerical rating scale, numbness scale, extensor hallicus longus strength, Timed Up and Go, Romberg, and single leg balance.

RESULTS

Significant changes were seen in post-treatment assessment of quality of life as measured by the QLQ-CIPN-20 and numbness scale. Post-treatment QLQ-CIPN-20 total scores decreased by an average of 7.1 points (n= 24, p< .01). Numbness in the left lower extremity decreased by an average of 1 point of the 0-4 point scale (n=24, p=.0007) and 1.09 points on the right lower extremity (n=24, p < .0004). There was a trend towards improvements in pain, monofilament testing, single leg balance, and Romberg test. Reimbursement for ST did not cover the costs to administer the therapy.

CONCLUSION

For patients with CIPN, scrambler therapy improves numbness and improves quality of life measures. However, reimbursement for ST did not cover the costs. Ways to improve this disparity are discussed.
QLTI-12. THE IMPACT OF MENTORING ON EARLY CAREER FACULTY: ASSESSMENT OF A VIRTUAL MENTORING PROGRAM
Authors: Sharma Akanksha , Leeper Heather , Bang Soo , Molaie Donna , Porter Alyx
Published: November 2022

BACKGROUND

Participation in mentorship programs for early career physicians is crucial to developing key skills and professional networks, but availability and opportunities for mentorship may be hampered by racial, ethnic and gender leadership disparities in medicine. A 6-month virtually facilitated peer mentorship program for women and diverse early career faculty was developed and piloted through the Society for Neuro-Oncology (SNO) Women & Diversity Committee.

METHODS

We designed and conducted a 6-month pilot open to SNO’s multidisciplinary early career members, leveraging peer-mentoring sessions with mid-to late-career physician mentors. A curriculum with online resources was provided and group assignments were based on time-zones and interests. Pre- and post-participation surveys assessed mentee experience and descriptive statistics assessed participant demographics and survey results. Results/

CONCLUSION

Twenty mentee applicants participated in 5 groups. Mentees were 90% women, 60% from diverse racial and ethnic backgrounds. Most were aged 31-40 (75%) and junior faculty (50%) in neuro-oncology (65%). Five mentors (2 female) practiced either neuro-oncology (3), neurosurgery (1) or radiation oncology (1). The proportion of mentees with a signature talk increased from 15% to 71% during the pilot. A large majority (64%) reported a positive impact of the program on their profile, career and networking, and reported participation was worthwhile (86%), and worth recommending to others (93%). Feedback themes included personal growth, peer support, networking, job opportunities, desire for late career female mentors, and scheduling constraints. The virtual environment during a global pandemic allowed participants to connect, creating a venue to discuss topics such as work-life balance, burnout, and self-advocacy. We did not have 100% post pilot follow up despite multiple attempts, limiting complete understanding of the pilot. This virtual mentorship pilot program proved feasible and of value in development of early career women and diverse individuals. A resource toolkit has been designed to scale and diffuse.
QLTI-13. FEASIBILITY OF SAMEDAY DISCHARGE AFTER BRAIN TUMOR RESECTION: A PROSPECTIVE QUALITY INTERVENTION STUDY
Authors: Vallejo Frederic , Eichberg Daniel , Morell Alexis , Shah Ashish , Di Long , Merenzon Martin , Berry Katherine , Luther Evan , Lu Victor , Patel Nitesh , Higgins Dominique , Kader Michael , Ivan Michael , Komotar Ricardo
Published: November 2022

INTRODUCTION

Cranial neurosurgery confers psychological stress, as well as the stress of being in the hospital rather than in one’s preferred surroundings. Compared with inpatient admissions, same-day discharges reduce patient exposure to nosocomial infection, thromboembolic complications, and medical error. Also, it reduces costs to the health care system.

OBJECTIVE

To report the results of a pilot study that prospectively evaluated for the first time in a United States hospital, the outcomes of patients that underwent brain tumor surgery and are discharged home the same day as surgery.

METHODS

A quality intervention study including patients who underwent outpatient craniotomy for brain tumors by a single neurosurgeon (R.J.K) at the University of Miami from August 2020 to August 2021 was performed. Patients included were between 16 to 85 years old, with a Karnofsky Performance Status score of ≥ 70, and with supratentorial tumors with a maximum diameter of 4 cm. Complete demographic and clinical data were collected prospectively for each patient. In all patients, the minimum observation period was 6 h after surgery.

RESULTS

37 of 334 patients met the inclusion criteria for the outpatient protocol. Thirty-two patients were discharged on the same day as surgery. Five patients (14%) were considered eligible for outpatient surgery but were ultimately admitted to the hospital postoperatively and were discharged after overnight observation. No postoperative complications were noted at two-week follow-up.

CONCLUSION

With appropriate selection and postoperative monitoring, same-day discharge can be considered a safe and feasible option for certain craniotomy cases. Establishing a multidisciplinary team of physicians, nurses, radiologists, and physical therapists is critical to achieving this aim. Physicians should have a low threshold to admit a patient with concerning exam findings, complications, or complicated past medical history
QLTI-14. PEDIATRIC CENTRAL NERVOUS SYSTEM TUMOR SURVIVOR AND CAREGIVER EXPERIENCES WITH MULTIDISCIPLINARY TELEMEDICINE
Authors: Cacciotti Chantel , Chua Isaac , Cuadra Jennifer , Ullrich Nicole , Cooney Tabitha
Published: November 2022

Central nervous system (CNS) tumors are the second most common pediatric cancer; survivors develop chronic medical conditions and complex care needs. While telemedicine is accelerating, its effectiveness has not been assessed in pediatric CNS tumor survivors. We evaluated the experiences of those seen through our Pediatric Neuro-Oncology Survivorship Clinic at Dana-Farber/ Boston Children’s Cancer and Blood Disorder Center. Patients and caregivers who had a multi-disciplinary telemedicine survivorship appointment from January 2021 through March 2022 were invited to participate in an anonymous survey which included questions on demographics, travel, equipment, experiences with telehealth, and preferences for telehealth utilization. Thirty-three adult survivors and 41 caregivers participated in the study (45% response rate). The majority of respondents agreed or strongly agreed that telemedicine visits started on time (97%, Nf65), scheduling was convenient (97%, Nf59), clinicians explained things in an easy-to-understand way (97%, Nf59), listened carefully and addressed concerns (93%, Nf56), and spent enough time with them (95%, Nf56). However, only 58% (Nf35) of respondents agreed or strongly agreed they would like to continue with telemedicine and only 48% (Nf32) agreed telemedicine was as effective as office visits. In our univariable analysis, the majority of respondents reported telemedicine as better with regards to travel time (82%, Nf60), convenience (68%, Nf50), wait time (70%, Nf50), and ease of scheduling (56%, Nf40), while the majority reported office visits as better with regards to personal connection (58%, Nf41). Survivors were more likely than caregivers to prefer office visits for personal connection (72% vs 46%, p=0.027). The most common telemedicine difficulties were using the system (15%, Nf11) and asking questions they would normally ask in clinic (19%, Nf14). While multi-disciplinary telehealth may improve care efficiency and accessibility for pediatric CNS tumor survivors, initiatives to improve personal connection are necessary to optimize patient satisfaction.
QLTI-16. ENHANCED RECOVERY AFTER LASER ABLATION SURGERY: A PRELIMINARY ANALYSIS OF A NOVEL PROGRAM
Authors: Merenzon Martin , Levy Adam , Eatz Tiffany , Morell Alexis , Higgins Dominique , Patel Nitesh , Kader Michael , Eichberg Daniel , Shah Ashish , Silva Michael , Lu Victor , Luther Evan , Bloom Marc , Komotar Ricardo , Ivan Michael
Published: November 2022

INTRODUCTION

The concept of enhanced recovery after surgery (ERAS) due to standardized interventions has been gaining more relevance within neurosurgery. Advances were made both in protocols for spine and cranial surgery. These experiences described many benefits such as less psychological stress, reduction in hospitalization days, and lower hospital costs, without increasing the incidence of complications. However, no experience has described to date the applicability of an ERAS program for laser ablation thermal therapy (LITT).

OBJECTIVE

To describe our initial experience with the first enhanced recovery program reported for laser ablation for brain tumors. Secondly, to summarize the perioperative clinical outcomes of ERAS applied to LITT.

METHODS

We performed a retrospective analysis of all adult patients who underwent LITT for oncological lesions from 2013 to 2021. A multidisciplinary program was created by protocolizing interventions carried out along the path of the patient's hospitalization. Each recommendation was individually assessed for its appropriateness for enhancing recovery and for its validity with a focused literature review process.

RESULTS

A total of 184 patients were included, with a mean age of 60.7 ± 13.5 years, 35% males. 167 tumors were located in the supratentorial compartment, and 17 were infratentorial; the mean tumor diameter was 1.84 ± 1.04 cm. Among the pathologies treated 50.0% were metastasis, and 36.9% were glioblastomas. The mean postoperative day discharge was 1.2 ± 0.8 days. The readmission rate due to surgical complications within 30 days of surgery was 2.7%. These readmission rates fall into what is expected according to published literature without an ERAS program and longer hospital admissions. One death was recorded in the perioperative period.

CONCLUSION

Clinical interventions that could constitute an ERAS program are feasible in laser ablation of brain tumors. This study could be useful as a preliminary framework for the development of future guidelines.
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

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

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

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 < 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

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 (< 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

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< 0.001. Survival did not correlate with preoperative epilepsy (p > 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

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

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< 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

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

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

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 >18 years; Karnofsky Performance Status score >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 >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.
SURG-01. DEVELOPMENT OF MURINE MODEL OF LASER INTERSTITIAL THERMOTHERAPY (LITT) FOR BRAIN TUMORS
Authors: Frain Matthew , Ebrahim Ghaidaa , Tomdio Macaulay , Mendez-Gomez Hector , Thomas Nagheme , Karachi Aida , Dastmalchi Farhad , Flores Catherine , Mitchell Duane , Bova Frank , Rahman Maryam
Published: November 2022

The objective of this study was to develop and test a murine system for delivery of laser interstitial thermotherapy (LITT). A system was built that allows for stereotactic placement of the laser into a mouse brain and real-time thermometry with a custom-made thermometer holder. Tissue heating curves for Laserglow Technologies 1064nm laser experiments testing tissue heating were performed by placing the laser in tissue and temperature monitoring via thermal probe. The laser was adapted for use with a stereotactic frame utilizing a system with a Hamilton syringe and a holder for consistent and precise placement of the thermal probe. The murine experiments were performed with C57BL/6 mice and samples were analyzed with H&E staining. First, ideal laser output was established using chicken breast. Laser dial setting of 4.38 successfully achieved slow tissue heating while a setting of 4.43 and 4.50 accomplished it rapidly, reaching a thermal ablative temperature of 43C in three and a half minutes. Next, a system for laser placement into the murine brain using the stereotactic frame was built revealing that the thermometer probe would require a separate system for consistent and precise measurements of heating. A thermometer probe holder was designed and fashioned via trigonometric calculations that allowed for thermal monitoring within 3mm spacing during laser ablation. Mice were anesthetized and treated with laser ablation at laser output of 4.38 and 4.43. H&E staining of the brain tissue demonstrated clear evidence of localized ablation identifiable by visible lesions on the H&E slides. The successful development of the stereotactic system for acquisition of tissue heating data coupled with evidence of successful live brain tissue ablation in a murine model via LITT proves that our protocol is ready for research of therapeutic combinatorial effects on live tumor bearing mice.