bluuebunny/crossref_metadata_2025_split huggingface dataset:
EXTH-98. ENHANCING T CELL TRAFFICKING OF CD3-ENGAGING IMMUNOTHERAPY TO TUMORS OF THE CENTRAL NERVOUS SYSTEM
Authors: Singh Kirit , Foster Matthew , Hotchkiss Kelly , Snyder David , Khasraw Mustafa , Sampson John 
Published: November 2022

Abstract

BACKGROUND
Effective immunotherapy against tumors of the central nervous system (CNS) requires that the drug the blood brain barrier (BBB) and encounter immune cells. We have previously described a mechanism which may facilitate transport of CD3-engaging therapeutics into the CNS, via carriage on activated T cells. Building on this, we sought to produce specific T cell phenotypes that rapidly enter and accumulate in the CNS.

METHODS
8–10-week-old C57/Bl6 mice (n=5-6 per group) were implanted with 30,000 CT2AvIII cells which established over 14 days. Mice received (1) CD45.1 lymphocytes activated with IL-7 and Concanavalin-A (single intravenous (IV) injection, 1 x 107 adoptive lymphocyte transfer (ALT)) or (2) CD45.1 lymphocytes activated with IL-2 and serial Con-A stimulation. Mice were sacrificed 3 hours following ALT and their brains analysed via flow cytometry. A follow-up timepoint of 48 hours was also analysed. Groups were compared using a Mann-Whitney U test.

RESULTS
Ex vivo culture in group 1 yielded a mixed population of T effector and T central memory cells whereas group 2 resulted in terminally differentiated T effector memory cells only. VLA-4, a migratory integrin involved in T cell entry into the CNS was upregulated in the IL-7 group. Mice in Group 1 demonstrated significantly enhanced entry of CD8+ effector and memory T cells into tumor bearing hemispheres 3- and 48-hours following administration compared to Group 2 (p = 0.005, p = 0.0159 respectively).

CONCLUSIONS
Varying the cytokine cocktail used for ex vivo activation and expansion of T cells results in markedly different trafficking properties and phenotype composition. Ongoing work will determine how enhanced T cell localization to tumor affects accumulation of immunotherapy via the hitchhiking mechanism. Further, we will evaluate the safety of combinatorial CD3-engaging immunotherapy and ALT in Phase I trials (NCT04903795) using a cGMP Brain Bi-specific T cell engager (BRiTE).
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

Abstract

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

Abstract

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 &lt; 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 &lt; 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

Abstract
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

Abstract
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

Abstract

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&lt; .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 &lt; .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

Abstract

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

Abstract

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

Abstract
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

Abstract

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.