bluuebunny/crossref_metadata_2025_split huggingface dataset:
DDDR-17. A FACILE HIGH THROUGHPUT DRUG SCREENING PLATFORM ENABLES THE CONSTRUCTION OF A PHARMACO-PROTEOGENOMIC INTERACTION LANDSCAPE IN GLIOBLASTOMA
Authors: Zhang Ze-Yan , Ding Yingwen , Ezhilarasan Ravesanker , Graciani Melanie , Modrek Aram , Karp Jerome , Sulman Erik 
Published: November 2024

Abstract
Despite decades of intensive research, the number of treatment options for glioblastoma (GBM), a devastating disease, remains very limited. The vast tumor heterogeneity of GBM and the blood-brain barrier (BBB) represent major hurdles to developing effective therapeutics. Here, we present CARPOOL, a high-throughput therapeutic screening approach designed to facilitate accurate and parallel interrogation of numerous patient-derived GBM spheroid cultures (GSCs), capturing the disease’s heterogeneity. We validated CARPOOL in vitro and in vivo and then applied it for drug screening using a library of over 700 BBB-penetrating compounds across 23 omics-profiled GSCs. This screening identified numerous potential anti-GBM compounds, including previously non-oncology drugs. Clustering analysis provided insights into the mechanisms of action of some of the compounds. Coupling these results with omics data of the GSCs enabled the identification of genetic, subtype, and gene expression-based predictors of drug sensitivity. Our study presents a new approach for advancing drug screening and in vivo preclinical therapy evaluation for precision oncology. Furthermore, our construction of a pharmaco-proteogenomic interaction landscape offers a valuable resource for both basic and translational glioblastoma research.
DDDR-49. REPURPOSING OF THE ANTI-VIRAL DRUG RIBAVIRIN AS A POTENTIAL MENINGIOMA THERAPEUTIC
Authors: Casaos Joshua , Perryman Travis , Harary Maya , Vitte Jeremie , Shah Shilp , Na Brian , Giovannini Marco , Everson Richard 
Published: November 2024

Abstract

INTRODUCTION
High grade meningiomas provide significant challenges to treatment. Recent works have demonstrated meningiomas to express higher levels of the epigenetic regulator enhancer of zeste homolog 2 (EZH2), as well as the protein eIF4E, a key player in translation. These two molecules are demonstrated targets of the well tolerated antiviral drug, ribavirin, which has recently shown promise as an anti-neoplastic agent. Based on these findings we sought to investigate the effect of ribavirin on meningioma tumorigenesis utilizing in vitro and in vivo meningioma models.

METHODS
Several immortalized human meningioma cell lines, three immortalized mouse meningioma cell lines, and a panel of human primary cell cultures were assessed. Cell proliferation, cell colony formation, clonogenic assay, and cell death were assessed. Furthermore, we tested ribavirin efficacy in vivo utilizing two aggressive high grade syngeneic orthotopic allograft meningioma models in FVB WT mice.

RESULTS
We provide evidence that ribavirin significantly impairs meningioma cell growth and proliferation, and induces cell death in vitro. Most importantly, we demonstrate that ribavirin alone significantly improves the survival of mice orthotopically implanted with MGS2 cells. Ribavirin-treated animals exhibited a significantly increased median survival (67 days) compared to controls (41 days; p=0.0009;) in an orthotopic convexity meningioma xenograft model. Furthermore, ribavirin treatment resulted in increased survival in an orthotopic skull base meningioma xenograft model.

CONCLUSION
Our work establishes that ribavirin is effective against meningioma in vitro and in vivo. Ribavirin treatment reduced proliferation in all cell lines tested, in both high and low grade models, induced cell death, and prolonged survival in two aggressive in vivo models, potentially via modulation of the EZH2 and eIF4E pathways. Given the lack of medical therapy for high grade meningiomas, these findings provide a framework for further investigation into ribavirin’s effects on meningioma tumorigenesis, and demonstrate ribavirin as a potential new therapeutic option in the treatment of meningioma.
EOLP-01. PROPOSED FRAMEWORK FOR A PILOT MULTIDISCIPLINARY BEREAVEMENT FOLLOW-UP AND BRAIN AUTOPSY REVIEW FOR BEREAVED CAREGIVERS IN PEDIATRIC NEURO-ONCOLOGY
Authors: Wright-Nadkarni Mariah , Schaefer Megan , Moscato Emily , Stanek Joseph , Gerhardt Cynthia , Fouladi Maryam , Patel Priyal , Lazow Margot 
Published: November 2024

Abstract

INTRODUCTION
Brain tumors remain the leading cause of cancer-related death in children. The death of a child is distressing for caregivers and often associated with negative psychosocial outcomes. Bereaved caregivers frequently desire ongoing support after their child’s death. At our institution, brain autopsies with the option for tissue donation to research are offered to all families after the death of a child. Specific follow-up conducted to date and review of autopsy results have varied widely. We propose a pilot study to (1) evaluate feasibility of a comprehensive, multidisciplinary bereavement follow-up meeting with autopsy results review and grief supports for bereaved caregivers in pediatric neuro-oncology at Nationwide Children’s Hospital and (2) assess caregiver and provider perceptions regarding this follow-up meeting using mixed-methods design.

METHODS/DESIGN
Bereaved caregivers of children with a brain tumor who died and underwent brain autopsy through our institutional tissue donation protocol will be offered a follow-up meeting after their child’s death. The follow-up meeting will test an established PICU bereavement framework in the pediatric neuro-oncology setting with the addition of brain autopsy results review. Meetings will include caregivers and providers from neuro-oncology, palliative care, and psychosocial team (e.g., psychologist, social worker, chaplain). Caregivers will complete a Likert-scale questionnaire followed by a semi-structured interview via telephone. The goal is to conduct 7-10 meetings. Providers will participate in a focus group to provide feedback. Interviews and the focus group will be recorded, transcribed, and analyzed qualitatively. Concepts to be explored include perceived need for follow up; overall experience; satisfaction with structure, modality, and content; and perceived benefit and meaning of autopsy review.

LONG-TERM GOAL
To develop, evaluate, and formalize a comprehensive multidisciplinary bereavement follow-up meeting, guided by caregiver and provider feedback, that can be expanded to other institutions and become a “standard of care” for bereaved caregivers in pediatric neuro-oncology.
EPID-08. PATTERN OF EPIDEMIOLOGICAL DISTRIBUTION OF INTRACRANIAL NEOPLASMS IN NIGERIA FROM 1960: A SYSTEMATIC REVIEW AND POOLED ANALYSIS
Authors: Alare Kehinde , Alare Samson , Adetunji Busayo , Chukwumaeze Chukwunonso , Oluwumi Emmanuel , Periola Abdulazeez , Omoniyo Taiwo , Odesanya Okikioluwa , Adedokun Precious , Adedokun Stephen , Bakwa Nenkimun 
Published: November 2024

Abstract

BACKGROUND
Intracranial neoplasms, encompassing a range of benign and malignant tumors, pose significant health challenges worldwide. This study systematically reviews the epidemiological patterns of intracranial neoplasms in Nigeria from 1960 to the present, providing a comprehensive analysis of their distribution, demographic characteristics, and temporal trends.

METHODS
A systematic review was conducted following PRISMA guidelines, encompassing studies published from 1960 onwards. Databases including PubMed, Google Scholar, and African Journals Online were searched using relevant keywords. Eligible studies were those that reported on the incidence, prevalence, or demographic details of intracranial neoplasms in Nigeria.

RESULTS
A total of 45 studies met the inclusion criteria, encompassing 3,517 cases of intracranial neoplasms. The pooled analysis revealed a significant increase in the incidence of intracranial neoplasms over the study period. The pooled prevalence between the year 1960 to presences is 3.22 (95% CI: 1.66 – 5.22), while the pooled 10-yearly incidence was 3.66(95% CI: 1.67 – 6.32), the incidence rose from 2.18% in 1960-1969 to 4.08% in 2000-2009, and eventually to 4.84% in 2010 – 2019. The most common types of intracranial neoplasms identified were gliomas, meningioma pituitary adenomas; meningioma was the leading type found in adults followed by glioma and pituitary adenoma, while in pediatric age group glioma was leading followed by medulloblastoma, and craniopharyngioma. The demographic analysis indicated a higher prevalence in males compared to females with male-to-female ratio of 1.17:1, with the majority of cases occurring in the fourth to sixth decades of life. Geographic distribution showed higher incidence rates in southern Nigeria especially south east and south west compared to Northern Nigeria, potentially reflecting disparities in diagnostic facilities and healthcare access.

CONCLUSION
This review highlights an increasing trend in the incidence of intracranial neoplasms in Nigeria, with distinct demographic and geographic patterns. The findings underscore the need for improved diagnostic capabilities, enhanced public health strategies, and targeted interventions to address the burden of intracranial neoplasms in Nigeria.
DISP-01. FACTORS AFFECTING POST-ABLATION OUTCOMES AND TRIAL ENROLLMENT IN DIVERSE PATIENTS UNDERGOING LASER INTERSTITIAL THERMAL THERAPY
Authors: Haskell-Mendoza Aden , Gonzalez Ariel , Reason Ellery , Jackson Joshua , Seas Andreas , Zaidi Saif , Mohan Aditya , Lerner Emily , Srinivasan Ethan , Bradbury Claire , II James Herndon , Goodwin C Rory , Fecci Peter 
Published: November 2024

Abstract

BACKGROUND
Laser interstitial thermal therapy (LITT) is a surgical treatment for progressive brain metastases (BM) following stereotactic radiosurgery (SRS). Although LITT has been increasingly accepted, little is known regarding factors influencing presentation and outcomes of patients with diverse backgrounds.

METHODS
Retrospective review of all patients receiving their index LITT treatment for BM at a single center from 2015 – 2023. Patient demographics and geospatial data was used to compare differences in receipt of LITT by race or ethnicity, survival outcomes, and clinical trial enrollment.

RESULTS
From 2015-2023, 137 patients presented for LITT to 146 intracranial lesions. One hundred and six patients (77.3%) were non-Hispanic White (NHW), while among Hispanic or non-White (HNW) patients, 25 (18.2%) were Black or African American, 5 (3.6%) were Asian American, and 1 (0.7%) was Hispanic/Latino. Among HNW patients, women more frequently received LITT (p = 0.022), with skin cancers being a more frequent indication among NHW patients (P = 0.019). NHW patients traveled a median of 62.0 (6.2 – 1045.9) miles to receive LITT vs 25.9 (1.31 – 238.3) miles for HNW patients (p = 0.001). Length of stay, discharge location, or readmission rates did not differ between groups. In multivariate analyses, probability of clinical trial enrollment was less among those of female sex (P = 0.049), HNW race/ethnicity (P = 0.041), or external referral status (P = 0.035), while post-LITT overall survival was predicted by pre-LITT KPS (P = 0.0007) and recurrent tumor on biopsy (P = 0.0002).

CONCLUSIONS
Differences in presentation for LITT by race or ethnicity may be influenced by underlying patient factors, including sex, systemic disease histology, and distance from a treating center, which do not influence post-LITT procedural outcomes or survival. Accordingly, clinical trial enrollment should be prioritized for vulnerable patient populations to realize the full benefits of laser ablation.
DISP-15. FOLIC ACID SUPPLEMENTATION IN WOMEN OF REPRODUCTIVE AGE WITH HISTORY OF INTRACRANIAL TUMOR AND SEIZURES
Authors: Farrukh Alexandra 
Published: November 2024

Abstract

BACKGROUND
Meningiomas and gliomas are the most common intracranial brain tumors. The most common gliomas can be further classified as oligodendroglioma, astrocytoma, ependymoma and glioblastoma. These tumors often cause epilepsy and necessitate the use of anti-seizure medications, posing risks to reproductive-age women due to potential teratogenic effects. The most preferred anti-seizure medications used in pregnancy are levetiracetam and lamotrigine. The American Academy of Neurology advocates folic acid supplementation for women taking anti-seizure medications (ASMs) regardless of type to mitigate these risks.

OBJECTIVE
This retrospective chart review aims to assess the utilization of folic acid supplementation in women of reproductive age with a history of intracranial tumors and seizures.

METHODS
Data were extracted from The Ohio State University Wexner Medical Center’s Epic Electronic Medical Record database using Epic’s “Slicer Dicer” program, spanning a five-year period from March 2019 to March 2024. Inclusion criteria comprised women aged 18-50 years of age with a history of meningioma, oligodendroglioma, astrocytoma, ependymoma, or glioblastoma and a documented history of seizures. Diagnoses were obtained using Systemized Nomenclature of Medicine – Clinical Terms (SNOMED CT). Variables included demographics, tumor type, and anti-seizure medication usage, and folic acid supplementation. Anti-seizure medications included levetiracetam and lamotrigine.

RESULTS
Preliminary analysis of 182 patient charts revealed that less approximately 60% of these patients were prescribed anti-seizure medications. Of these, 3 patients received concurrent folic acid supplementation, despite recommendations from the American Academy of Neurology.

CONCLUSION
Our findings suggest a suboptimal utilization of folic acid supplementation in women of reproductive age with a history of primary brain tumor and seizures with ASM use, highlighting the need for improved adherence to clinical guidelines. Further research is warranted to explore barriers to implementation and strategies to optimize folic acid supplementation in this population.
DISP-19. ETHNIC DISPARITIES IN METASTASIS PATTERNS AND TREATMENT UTILIZATION AMONG METASTATIC BREAST CANCER PATIENTS WITH BRAIN METASTASIS: A RETROSPECTIVE ANALYSIS OF US HEALTH SYSTEMS DATA (2019-2023)
Authors: Podder Vivek , Ranjan Tulika , Bardhan Mainak , Jayram Diya , Mahtani Reshma , Ahluwalia Manmeet Singh 
Published: November 2024

Abstract

INTRODUCTION
The treatment landscape for metastatic breast cancer (MBC) with brain metastasis (BM) has evolved due to novel therapies. However, outcomes remain poor and vary among groups. This study investigated ethnic disparities in metastasis (mets) patterns and treatment use among MBCBM patients (pts).

METHODS
We analyzed deidentified data from seven US health systems in the Guardian Research Network from December 2019 to December 2023. Pts with MBC were categorized by IHC scores: hormone receptor+/HER2-, HER2-low (IHC 1+ or 2+ with negative FISH), HER2 positive, and Triple Negative (TNBC). We used descriptive and comparative statistical analysis.

RESULTS
Of 421 MBC pts, 200 (47.5%) had HER2+, 167 (39.7%) had HR+/HER2-, and 54 (12.8%) had TNBC. 159 (37.7%) were reclassified as HER2-low, primarily from HR+/HER2- (127; 76.0%) and TNBC (32; 59.3%). Bone mets developed in 29.6% of pts, more prevalent in HER2+ (39.5%), TNBC (25.9%), and HR+/HER2- (19.1%) groups. Non-Hispanics showed higher BM prevalence (74.4% vs. 25.6%). HR+/HER2- BM pts had higher bone mets (71.88%) than HER2+ BM (65.82%). TNBC BM pts had the highest rate of liver mets (57.1%). HER2-low BM pts showed mets across liver (40%), lung (34.29%), and bone (68.57%). In the HER2+ BM group, non-Hispanics had higher liver (40.13% vs. 32.35%) and bone mets (69.08% vs. 52.94%) than Hispanics. In TNBC BM group, Hispanics had higher liver mets (66.67% vs. 35%), while non-Hispanics had higher lung mets (32.5% vs. 11.11%). Both ethnic groups in HR+/HER2- category had high bone mets (78.95% vs. 73.33%). There were disparities in the use of CDK4/6 inhibitors, ICIs, and mTOR inhibitors, with Hispanics frequently using them.

CONCLUSION
HR+/HER2- BM pts were most affected by bone mets, followed by HER2+ BM. TNBC BM pts predominantly had liver mets. Non-Hispanics had higher BM prevalence. Hispanics frequently used ICIs, CDK4/6 and mTOR inhibitors, which were more frequently used by Hispanics. Further research should explore these disparities in mets patterns, treatment choices, and responses.
IMMU-02. INTRACRANIAL PROGRESSION IS LESS COMMON IN PATIENTS WITH ADVANCED NSCLC RECEIVING CANCER IMMUNOTHERAPY
Authors: Kemmotsu Naoya , Ninomiya Kiichiro , Otani Yoshihiro , Michiue Hiroyuki , Tanaka Shota , Togashi Yosuke 
Published: November 2024

Abstract

BACKGROUND
Intracranial metastases are common in patients with non-small cell lung cancer (NSCLC) and their prognosis is very poor. Furthermore, intracranial progression is common during systemic therapy due to the inability to cross the blood brain barrier, but the impact of cancer immunotherapy on intracranial progression remains unclear.

METHODS
We analyzed clinical data to evaluate the frequency of intracranial progression in patients with advanced NSCLC treated with PD-1 blockade therapies compared to patients not treated with PD-1 blockade therapies (Approval number: 2201-022). We also evaluated durable responses to PD-1 blockade and analyzed tumor-infiltrating lymphocytes using tumor-rechallenging murine models.

RESULTS
The clinical data analysis showed that the frequency of intracranial progression was significantly lower in patients with advanced NSCLC treated with PD-1 blockade than in patients treated with cytotoxic chemotherapy. In murine models, intracranial rechallenged tumors after initial rejection by PD-1 blockade therapy were suppressed, as observed for subcutaneous tumors. Accordingly, PD-1 blockade increased long-lived memory precursor effector T cells and antigen-specific T cells in intracranial lesions. In contrast, intracranial rechallenged different tumors were not suppressed.

CONCLUSIONS
The CNS has been considered a site in which cancer patients tend to experience progression during systemic therapies, however our results indicate that cancer immunotherapies can prevent intracranial progression, maintaining long-term effects intracranially as well as systemically. (Kemmotsu N. et. al., Int J Cancer, 2024)
IMMU-15. CD74/MIF SIGNALING AXIS DISRUPTION IN BONE MARROW-DERIVED MYELOID CELLS DELAYS MALIGNANT PROGRESSION IN A PRECLINICAL MODEL OF GLIOMA
Authors: Canella Alessandro , Rajendran Sakthi , Nazzaro Matthew , Schmitt Claire , Kreatsoulas Daniel , Wang Wesley , Rajappa Prajwal 
Published: November 2024

Abstract

INTRODUCTION
CD74, a chaperone associated with the major histocompatibility complex class II (MHC-II), plays a crucial role in assembling and transporting MHC-II molecules on the cellular surface. Beyond its physiological function in antigen presentation, CD74 is a negative regulator of inflammation, and its dysregulation is associated with inflammatory disorders and cancer. Notably, tumor stem cells release macrophage migration inhibitory factor (MIF) to trigger CD74 immunosuppressive signaling in tumor-infiltrating immune cells, thereby abrogating CD8+ T cell activation and promoting angiogenesis. While CD74 expression is known in dendritic cells, macrophages and B cells, our recent findings reveal its upregulation in immunosuppressive macrophages within the low-grade glioma (LGG) tumor microenvironment, and its negative correlation with the survival of adolescent and young adult patients with LGG. HYPOTHESIS. We hypothesize that inhibiting CD74/MIF in immunosuppressive myeloid cells may affect tumor progression and prevent malignant transformation (MT) to high-grade glioma (HGG).

METHODS
To test our hypothesis, we isolated bone marrow cells from immunocompetent RCAS n/tv-a LGG bearing animals, differentiated them into bone marrow-derived myeloid cells (BMDMs), silenced CD74 expression, and co-cultured them with primary CD8+T cells. Moreover, we inhibited CD74/MIF signaling in vivo. RESULTS. Deconvolution analysis of tumor-infiltrating immune cells revealed upregulation of CD74 and its network in myeloid cells during LGG compared to HGG. Silencing CD74 in LGG BMDMs in vitro resulted in the downregulation of genes associated with migration, proliferation, and immunosuppression. The co-culture of LGG CD74KD-BMDMs with CD8+ T cells increased the expression of T cell activation genes. In vivo treatment of LGG mice with MIF inhibitors significantly decreased myeloid cell infiltration in the tumor microenvironment (TME) and prolonged survival.

CONCLUSIONS
These preclinical studies highlight a role for the CD74/MIF signaling axis in glioma and present a novel immunotherapeutic target to modulate the activity of immunosuppressive myeloid cells in order to delay MT.
IMMU-19. PRECLINICAL THERAPEUTIC ACTIVITY AND PET IMAGING OF STING AGONIST 8803 IN GLIOBLASTOMA
Authors: Najem Hinda , Lea Spencer T , Tripathi Shashwat , Hurley Lisa , Chen Chao-Hsien , Sooreshjani Moloud , Bowie Michelle L , Hartley Genevieve , Pacheco Sebastian , Dmello Crismita , Lee-Chang Catalina , Procissi Daniel , Lukas Rimas V , Lesniak Maciej S , Ashley David M , Curran Michael A , Balyasnikova Irina , Heimberger Amy B 
Published: November 2024

Abstract
STING (stimulator of interferon genes) activation triggers interferon (IFN) release within the tumor microenvironment from myeloid cells and other cell types, inducing proinflammatory anti-tumor immune responses. The small molecule STING agonist, 8803, elicits long-term survival in 56% (QPP4; p=0.0003) to 100% (QPP8; p&lt;0.0001) of mice with orthotopically implanted immune checkpoint-resistant glioblastoma models after 2-3 doses. In humanized mice, in which glioblastoma-cell STING is epigenetically silenced, 8803 therapeutic activity is maintained. The combination therapy of 8803 with anti-PD-1 relatively further enhances survival in immune checkpoint-resistant models. Ex vivo flow cytometry and proteomic sequential multiplex profiling during the therapeutic window demonstrate global immunological reprogramming, specific tumor-antigen immune responses, increased tumor immune effector trafficking, and release of IFN. It has been shown that IFN signaling augments intracellular nucleotide metabolism and increases [18F]-FLT uptake in pancreatic cancer. We evaluated the longitudinal [18F]-FLT uptake in CT-2A-bearing mice using MRI/PET/CT at days 0, 2, and 4 after intratumoral 8803 delivery. Brain images were acquired before and after [18F]-FLT tracer and 8803 administrations. The CT was used for PET attenuation/correction, and the MRI was used for tumor segmentation. Regional analysis of PET-derived [18F]-FLT SUV maps used advanced image processing approaches as a function of time to enhance the voxel-by-voxel interpretation of the acquired images. [18F]-FLT uptake increased from baseline in all mice treated with 8803 compared to control mice with a peak at 48-96 hours. Concordant sequential multiplex immunofluorescence demonstrated that the STING expression was prominent along the tumor vasculature, myeloid, and tumor cells. p-IRF-3 expression, reflective of STING pathway activation, showed a diffuse pattern after treatment. Based on the preclinical data, PET imaging at 48-96 hours post-treatment represents the appropriate imaging modality and timepoint to maximize the ability to detect STING-dependent changes for a therapeutic strategy that reprograms the glioblastoma microenvironment and improves survival across multiple preclinical models of glioblastoma.