bluuebunny/crossref_metadata_2025_split huggingface dataset:
EXTH-78. A NOVEL BISPECIFIC S100A4/TFR ANTIBODY TO REPROGRAM THE GLIOMA TUMOR MICROENVIRONMENT AND TARGET GLIOMA STEM CELLS
Authors: Wong Thomas , Leu Jia-Shiun , Fan Xuejun , Kang Reece , Abdelfattah Nourhan , Leonard Fransisca , Zhang Ningyan , Yun Kyuson 
Published: November 2024

Abstract
GBM (glioblastoma) is the most common and aggressive primary brain tumor in adults. While immunotherapy is a promising treatment modality for GBM, most clinical trials have thus far only provided a modest benefit to GBM patients. We propose that enhancing the efficacy of immunotherapy for GBM requires approaches that increase T cell infiltration and reprogram the myeloid cells to a more pro-inflammatory state. S100A4 is a major regulator of stemness, epithelial-mesenchymal transition, and a critical regulator of immune suppressive myeloid and T cell phenotypes in GBM. Targeting S100A4 in either glioma or stromal cells is sufficient to reprogram the tumor immune landscape and extend survival of glioma bearing mice, indicating that S100A4 is a promising immunotherapy target. We recently developed a S100A4 blocking monoclonal antibody; however, this antibody does not cross the blood brain barrier (BBB) efficiently to confer significant therapeutic benefit, limiting its efficacy in treating GBM. To overcome this challenge, we generated a bispecific S100A4-TfR antibody (BsA) that allows robust BBB penetration, and tested this in a pre-clinical syngeneic, orthotopic mouse model of GBM. Using ELISA, confocal immunofluorescent microscopy, flow cytometry, and bulk RNA sequencing, we report that systemic administration of the S100A4-TfR BsA results in increased immune cell infiltration with a preferential increase in CD4 T cell infiltration, and potent immune remodeling of the tumor microenvironment to a more pro-inflammatory state. Furthermore, the BsA is taken up by glioma cells intracellularly, which is correlated with depletion of intracellular S100A4 and decreased nuclear SOX2 localization, which would reduce stemness of glioma cells. Functionally, in vitro BsA treatment of primary glioma cell cultures shows decreased S100A4 expression, proliferation, and self-renewal. Our results suggest that S100A4-TfR BsA is a novel dual activity inhibitor to simultaneously reprogram the GBM immune landscape and reduce glioma stemness.
EXTH-85. ASSESSMENT OF ANTI-CD69 ANTIBODY THERAPY ALONE OR IN COMBINATION WITH ANTI-PD-1 IN MURINE GBM
Authors: Nisnboym Ziv Michal , Kohanbash Gary , Raphael Itay 
Published: November 2024

Abstract

BACKGROUND
Glioblastoma multiforme (GBM) is an aggressive central nervous system malignancy with a dismal prognosis. There is continued interest in trying multiple immunotherapy modalities for this intractable cancer. Cluster of differentiation 69 (CD69), is an early marker of T and NK cell activation. CD69 play multiple roles in T cell-mediated immunoregulation with immune inhibitory role in antitumor immunity. Previous preclinical work in non-CNS malignancies has demonstrated that targeting CD69 can improve clinical outcome and anti-tumor immunity. We aimed to assess anti-CD69 Ab therapy alone or in combination with anti-PD-1 in murine GBM.

METHODS
We explored transcriptomic data from 163 GBM patients using the TCGA database. We then tested the therapeutic value of anti-CD69 immunotherapy in a preclinical model of GBM and assessed the ideal timing of treatment with anti-CD69 Ab by evaluating survival and immune tumor-microenvironment by flow cytometry. Two treatment-timings with anti-CD69 Ab were further evaluated either alone, or in combination with anti-PD1 Abs and compared to control and to anti-PD1 only treatment. Survival data was collected.

RESULTS
CD69 expression was significantly increased in GBM patients tissues as compared with normal brains and increased CD69 expression was associated with worse progression-free survival. Treatment-timing with single dose anti-CD69 Ab at day 1 or three doses at days 4, 8 and 12 post tumor-injection minimally improved the median survival time of animals. In addition, effective CD69 blockage and significantly elevated PD-1 expression on NK cells was found in these timings, making them good candidates to evaluate anti-CD69 Ab therapy alone or in combination with anti-PD-1 Ab. However, when assessing these treatment-timings with anti-CD69 Ab alone or in combination with anti-PD1 no survival benefit was found.

CONCLUSION
This is the first study assessing anti-CD69 Ab therapy alone or in combination with anti-PD-1 in murine GBM. While some effect was found on the cellular level, this didn’t translate to survival benefit and results are overall negative.
QLTI-02. THE ROLE OF REOPERATION IN PAEDIATRIC PILOCYTIC ASTROCYTOMA
Authors: Kameda Michelle , Green Katherine , Hutton Dana , Jeelani Noor ul Owase , Thompson Dominic , Hargrave Darren , Aquilina Kristian 
Published: November 2024

Abstract

INTRO
Cerebellar pilocytic astrocytomas (cPAs) in childhood have long been recognized to have a good prognosis after total resection, but the outcome after incomplete resective surgery remains largely unpredictable, with the incidence of radiological progressive disease ranging from 18-100%. It has been traditionally thought that gross-total resection was required for long-term survival, and small residuals were classically resected in a subsequent operation.

OBJECTIVE
To determine the role of reoperation in residual or recurrent cerebellar pilocytic astrocytoma.

METHODS
The authors analyzed their pediatric low-grade clioma (PLGG) database for cases treated between 1985-2020 and filtered for intracranial PAs, to determine what clinical or radiological factors precipitated revisional resective surgery in their single quaternary care center cohort.

RESULTS
Using the PLGG database, 283 patients &lt;18 years of age were identified to have a histopathological diagnosis or intracranial PA between 1985-2020, of which, 200 were within the cerebellum (70.7%). The majority of patients with cPA were between 1 and 10 years of age (n=145, 72.5%) without gender preponderance (M/F=99:101) usually presenting with 1 lesion (n=197, 98.5%). Gross total resection was achieved in 74.5% (n=149) of initial surgeries for cPA. In patients with subtotal resection, the mean largest diameter of the postoperative residual tumor was 1.06cm (range 0-2.95cm). Seven patients with subtotal resection did not require a second resective intervention. In 31 patients the neuro-oncology multi-disciplinary team recommended a second resection at a mean time interval of 22.9 months (range 0.13-81.6 months) from the initial surgery. Proportionally, the children who underwent multiple resections were also more likely to receive adjuvant chemo/radiotherapy. Functionally, the children in the multiple operation cohort experienced more complications of therapy including ongoing endocrinopathy, treatment-associated hearing deficit, and neuro-cognitive deficits.

CONCLUSION
Residual disease in cPA should be maintained under clinico-radiological surveillance postoperatively with adoption of a more conservative approach when residual disease is not significantly changing over time.
QLTI-03. REAL-WORLD PARADIGM FOR TREATMENT OF PRIMARY CNS LYMPHOMA PATIENTS IN CLINICAL PRACTICE
Authors: Umemura Yoshie , Nayak Lakshmi , Nijland Marcel , Mohile Nimish , Batchelor Tracy , Strowd Roy 
Published: November 2024

Abstract
Although high-dose methotrexate (HD-MTX) is the foundation of induction therapy for primary CNS lymphoma (PCNSL), a gold-standard regimen has yet to be established. A 10-case-based survey, to assess the practice patterns at key decision-points in adult PCNSL management outside of clinical trials, was distributed through IPCG, HOVON, and AAN Neuro-Oncology Section. Eighty-five responses were collected from North American (N=42), European (N=33), Asian (N=7), and other countries (N=3) from neurologist neurooncologists (N=35), hem-onc neurooncologists (N=24), hematologist-oncologists (N=18), neurosurgeons (N=5), radiation-oncologist (N=2), and hematopathologist (N=1). The most common first-line induction regimen was R-MP+/-V: rituximab, HD-MTX, procarbazine, +/-vincristine (N=28) followed by MATRix: HD-MTX, cytarabine, thiotepa, rituximab (N=23), then R-MT: rituximab, HD-MTX, temozolomide (N=19). For elderly patients, R-MP+/-V remained most common (N=32). The majority preferred to omit intra-CSF chemotherapy (N=50). The most preferred consolidation after complete response was high-dose chemotherapy and autologous stem-cell transplantation (HDC-ASCT, N=57), or high-dose cytarabine (N=17) in elderly patients. In cases of partial response, the most common approach was still HDC-ASCT (N=24). For stable disease, participants would move to various salvage chemotherapy (N=33), continue additional induction (N=39), or to move to radiotherapy (N=10). If early progression was noted, the most preferred approach was non-methotrexate chemotherapy (N=31). For recurrences after previous complete response and HDC-ASCT consolidation, the majority preferred to try chemotherapy before moving to radiotherapy in scenarios &lt; 1 year (N=64) or &gt; 1 year from consolidation (N=68), and even if the performance status was poor (N=57). Close to half (N=34) participants felt there is a role for stereotactic radiosurgery in various clinical settings. This survey noted clear consensus to use multi-drug MD-MTX based chemotherapy, and common induction regimens, however, highlighted a great variety of treatment preferences after first-line therapy even amongst disease experts through clinical consortiums, suggesting likely wider range of treatments and disease response in larger community settings.
QLTI-06. NEXT GENERATION SEQUENCING SIGNIFICANTLY IMPROVES THE DIAGNOSTIC ACCURACY IN GLIOBLASTOMAS
Authors: Lath Devraj , Roy Vijaylaxmi , Sreegiriraju Vijay , Goel Pallavi , Ghanekar Yashoda , Sadasivam Subhashini , Kumari Neha , Pawar Vikas , Madiraju Surya , Ray Amit 
Published: November 2024

Abstract
The 2021 WHO Classification of CNS Tumours recognizes the presence of TERT promoter (pTERT) mutations, combined +7/-10 chromosome copy-number alterations, or EGFR amplification as a defining molecular feature(s) of glioblastoma, independent of histology. We evaluated these biomarkers in a cohort of Indian patients using a single-run next-generation sequencing (NGS) platform at a relatively low depth of 100. Seventy-four adult diffuse gliomas were selected from the Exsegen Genomics Research Pvt Ltd Biobank established during the trial CTRI/2021/09/036861 after reviewing their clinical and pathological data. Paired surgical tissue and blood samples underwent whole-exome sequencing on an Illumina NovaSeq-6000 (Illumina, San Diego, USA). Single-nucleotide variations (SNVs) were processed using the DRAGEN pipeline to generate Mutation Annotation Format (MAF) files. Copy number variations (CNVs) analysis was performed using GATK and GISTIC2.0. Thirty-nine glioma samples with IDH1R132H mutations were excluded. A total of 32/35 (91.4%) IDH-wildtype tumours met the 2021 WHO criteria for glioblastoma, IDH-wildtype and were included. Twenty-four glioblastomas also underwent whole-transcriptome analysis. Microvascular proliferation (n=24, 75%) and necrosis (n=30, 93.9%) were present in the majority. pTERT mutations were identified in 23 (71.9%) samples, with C228T mutations (n=15/23, 65.2%) being more common than C250T mutations (n=8/23, 34.8%). EGFR amplification, defined as ≥5 copies by NGS CNV, was seen in 15 (46.9%) samples, with a strong correlation between EGFR CNV and logEGFR expression (r=0.79; p=0.017). Whole-arm +7/-10 genotype was evident in 17 (53.1%) tumours, and another 5 (15.6%) showed partial copy-number alterations. Notably, two gliomas without necrosis and proliferation initially diagnosed as oligodendrogliomas due to misinterpretation of the IDH immunostain, were reclassified as glioblastoma, IDH-wildtype. The data was validated using Sanger Sequencing and targeted panel sequencing to a depth of 500. Even low depth NGS sequencing, that is cost effective and time efficient offers significant improvements in diagnostic molecular neuropathology.
QLTI-07. COLLABORATIVE RESEARCH SUITE FOR GENOMIC ANALYSIS, DATA REPORTING AND WORKFLOW CUSTOMISATION
Authors: Sreegiriraju Vijay , Roy Vijaylaxmi , Lath Devraj , Mishra Pankaj , Ghanekar Yashoda , Sadashivam Subhashini , Goel Pallavi , Pawar Vikas , Madiraju Surya , Ray Amit 
Published: November 2024

Abstract
The genomic analysis pipeline involves multiple stages, including data extraction, transformation, and loading (ETL), exploratory data analysis (EDA), machine learning (ML) modeling, and reporting. The ETL stage involves data profiling and quality control measures to ensure data integrity and consistency. The EDA stage employs statistical and visualization methods to understand data distribution, identify patterns, and detect anomalies. Machine learning modelling involves supervised classification techniques, such as logistic regression and support vector machines (SVMs), to predict tumour classification and develop gene signatures. Unsupervised classification techniques, such as K-means clustering and Hierarchical clustering, identify patterns and relationships in genomic data. Quality metrics evaluate data completeness, accuracy, and consistency, ensuring data reliability and validity. The integration of data science techniques into a comprehensive framework can be achieved with the development of Application Dashboards that provide real-time insights into genomic data across every stage of the analysis pipeline. This enables clinical researchers and bioinformaticians to make informed decisions quickly, improving turn-around time and accelerating the discovery of new insights. In contrast to conventional methods of using stand-alone scripts, these dashboards offer a reusable and scalable solution, allowing for easy modification and adaptation to new datasets and analysis pipelines, thereby reducing development effort and increasing productivity. The dashboards constitute a centralized platform for data visualization, exploration, and analysis, facilitating collaboration and communication among research team members. With customizable and interactive visualizations, users can explore genomic data from multiple dimensions and the integration of multiple sources, including genomic and transcriptomic data. The technologies used to power this Research suite include Streamlit for Web App development, Python for data analysis, Opensearch for data storage and other utility libraries for reporting.
QLTI-13. A REVIEW OF THE BEST TREATMENT STRATEGY FOR NEUROFIBROMATOSIS TYPE 2 PATIENTS THROUGH A SINGLE-CENTER RETROSPECTIVE STUDY: HOW TO ORCHESTRATE MULTIMODAL TREATMENT OPTIONS
Authors: Hee Chang Jong , Choi Seonah 
Published: November 2024

Abstract

PURPOSE
Neurofibromatosis type 2(NF2) is an autosomal-dominant tumor predisposition syndrome that affects the whole neuro-axis and causes various neurological symptoms decreasing the quality of life throughout the patient’s lifespan. However, due to the diversity of related diseases and the complexity of treatment, there are many cases in which only partial treatments are performed, the timing of the treatment is missed, and inappropriate treatment modality selection is made despite the intervention of many clinicians. Therefore, to increase the overall understanding of the disease, the single-institution experience was analyzed.

MATERIALS AND METHODS
Between 1998 and 2022, a total of 80 patients who clinically suspected NF2 visited our Brain Tumor Center. After excluding the patients with follow-up loss, the remaining 48 patients were finally analyzed. The patient’s symptoms, diagnosis process, treatment process, and outcomes were analyzed.

RESULTS
The average age at the time of symptom onset was 31.0(2-63) year-old. Hearing impairment was the major primary symptom(46.8%) among the patients. Five patients(10.9%) had family history of NF2. Thirty-five patients(76.1%) was clinically diagnosed as a NF2 for the bilateral vestibular schwannomas, and 34 patients(73.9%) had intracranial meningiomas, and 37 patients(80.4%) had spinal lesions at the time of diagnosis. Eleven patients were genetically confirmed as NF2. For vestibular schwannomas, 16 patients had surgical resection and 20 patients took gamma-knife surgery as a primary or secondary treatment. For intracranial meningiomas, 16 patients had surgical resection, 13 patients took gamma-knife surgery, and 15 patients took conventional radiation therapy as a primary or secondary treatment. Ventriculo-peritoneal shunt due to increased intracranial pressure was performed in 4 patients(8.7%). For spinal lesions, 16 patients had surgical resection.

CONCLUSION
NF2 is a disease group requiring a multidisciplinary team approach. The key to treatment is to set and implement a treatment sequence and method tailored to each patient. For this, an overall understanding of the disease and the treatment options is essential.
QOL-13. FROM SURVIVING TO THRIVING WITH A BRAIN TUMOR: THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO NEUROONCOLOGY MODEL FOR AN EMPOWERED AND ENGAGED PEER VOLUNTEER SUPPORT COMMUNITY
Authors: Hoffer Naomi , Rodriguez-Almaraz Eduardo , Fetting Mary Lacy , Choi Elizabeth , Destri Mary , Taylor Jennie , Chang Susan 
Published: November 2024

Abstract

BACKGROUND
Brain tumor patients often experience feelings of isolation, identity loss, and existential distress, and peer support can have a positive impact in these areas. Providing peer support, however, can be emotionally demanding and presents unique challenges for neuro-oncology patient volunteers, with little guidance available to address these issues. We describe an innovative program that supports volunteers and provides a roadmap for implementing peer volunteer programs in clinical neuro-oncology practices.

METHODS
In 2020, the UCSF Sheri Sobrato Brain Cancer Survivorship Program established an initiative to match brain tumor patients seeking support with trained patient volunteers. To address potential challenges, an optional, ongoing support community for volunteers was created by a health coach educator, with co-facilitation from a rehabilitation neuropsychologist and a social worker. The weekly meetings included supplemental training, personal check-ins, and group discussions. Volunteer feedback was collected through direct volunteer communication with the facilitator and an annual online survey.

RESULTS
From August 2020 through October 2023, 46 peer volunteers were trained in six cohorts. There were 116 patients requesting peer support. In total 132 volunteer-patient matches were made for an average of 2.87 matches per volunteer. Seventy percent of volunteers attended 11 or more meetings/year. Average attendance was 12 volunteers per meeting. All respondents to the annual online survey (n=31) reported a high level of satisfaction with the program. Volunteers highlighted benefits such as mutual support, impactful contributions, and personal growth and empowerment. Volunteers who reported higher levels of preparedness attended &gt;11 meetings per year.

DISCUSSION
In our experience, patient peer volunteer programs show promise in reducing isolation and restoring purpose. This unique 3-year pilot suggests that ongoing group support and training is a plausible and effective way to enhance a peer volunteer program. Future efforts will focus on developing a structured curriculum for neuro-oncology patient peer volunteers.
QOL-17. REFLECTIONS ON A PSYCHOEDUCATION INTERVENTION FOR PATIENTS WITH NEWLY DIAGNOSED BRAIN TUMORS (NEUROPATHWAYS): A QUALITATIVE STUDY
Authors: Whitman Jessica , Strander Sumita , Podgurski Alyx , Willis Kelcie , Chiu Daniel , Parsons Michael , Maguire Amy , Steele Sarah , Curtis Christopher , Warner Kara , McCone Joelle , Temel Jennifer , Traeger Lara , Forst Deborah 
Published: November 2024

Abstract

BACKGROUND
Patients with newly diagnosed primary malignant brain tumors (PMBT) face unique challenges processing and absorbing information regarding their diagnosis, often while contending with cognitive and communication deficits. Limited research exists regarding optimal information provision and support for this highly distressed population. We used input from clinician, patient, and caregiver stakeholders to design a population-specific, psychoeducation intervention (“NeuroPathways”) to address these needs.

METHODS
We conducted a single-arm study (N=12) to pilot and refine NeuroPathways in English-speaking patients within six-weeks of a PMBT diagnosis. Neuropathways comprises 1) a comprehensive (105 pages) handbook covering information about PMBT diagnosis, treatment, coping, self-care, and vetted resources, and 2) four brief, individual telehealth sessions with a trained interventionist (e.g., psychologist, physician) over 4-8 weeks to assist and empower patients to obtain information, support, and coping guidance at their preferred depth and pace, using the handbook as a resource. Ten participants completed all four sessions and participated in semi-structured exit interviews. We used rapid qualitative analysis to explore participants’ perceptions of intervention delivery, content, and benefit.

RESULTS
Participants (83% male, median age=52 years) uniformly described NeuroPathways as accessible, citing the telehealth format as particularly important for facilitating participation given logistical challenges related to cancer treatment. Perceived benefits of participation included: a) access to well-organized information targeting both current and future disease- and treatment-related concerns; b) increased skill in problem solving and communication with loved ones and/or medical providers; c) personalized emotional support from interventionists. While most felt the timing was appropriate, several who enrolled later in the eligibility window stated a desire for earlier intervention.

CONCLUSION
Participant feedback highlights the accessibility and potential benefits of this psychoeducation intervention for patients with newly diagnosed PMBT. These data will inform refinement of NeuroPathways in preparation for a pilot randomized controlled trial to formally assess feasibility and acceptability.