tbuckley/cabot-search huggingface dataset:
EPID-38. GLOBAL DISPARITIES AND PROJECTIONS IN PEDIATRIC BRAIN AND CNS CANCERS: A COMPREHENSIVE ANALYSIS THROUGH 2050
Authors: Sara Sennani, Ouassima Erefai, Fatine Hadrya, Abdelmajid Soulaymani, Abdelrhani Mokhtari, Hinde Hami
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Brain and other central nervous system (CNS) cancers are the most prevalent solid tumors and the leading cause of death among children worldwide. This study investigates trends in the incidence, mortality, and global distribution of pediatric brain and other CNS cancers projected through 2050. METHODS Data on pediatric brain and other CNS cancer incidence and mortality were extracted from Globocan 2022 for children aged 0 to 14 years. Age-standardized incidence and mortality rates were calculated by continent, country, and Human Development Index (HDI) categories. RESULTS The Globocan dataset revealed 24,677 new cases and 12,249 deaths, corresponding to age-standardized incidence rates (ASIRs) of 1.3 and age-standardized mortality rates (ASMRs) of 0.62 per 100,000 population. Significant geographic disparities were observed: North America reported the highest incidence rate at 3.6, followed by Europe (2.2), Latin America (1.7), Oceania (1.4), Asia (1.3), and Africa (0.67). Europe recorded the highest mortality rate at 0.89, followed by Latin America (0.87), North America (0.70), Asia (0.66), and Africa (0.40). A country-specific analysis revealed that the highest incidence rates were in Montenegro (3.7), Estonia (3.4), and Austria (3.2), whereas the highest mortality rates were in Lithuania (2.1), Angola (2.0), and Honduras (1.7). Additionally, 37.82% of new cases and 40.71% of deaths occurred in high-HDI countries. Projections: The annual increase in incidence and mortality rates for brain and other CNS cancers is projected at 1.3% through 2050, with new cases expected to rise to 25,004 and deaths to 12,404. CONCLUSIONS The findings indicate a 23% decrease in brain and other CNS cancer cases in high-HDI countries by 2050, contrasted with a 45.3% increase in low-HDI countries. These disparities underscore the critical need for global health strategies that promote equitable healthcare access and advanced treatments to reduce the global burden of these cancers and address inequities in health outcomes.
DISP-15. FOLIC ACID SUPPLEMENTATION IN WOMEN OF REPRODUCTIVE AGE WITH HISTORY OF INTRACRANIAL TUMOR AND SEIZURES
Authors: Alexandra Farrukh
Journal: Neuro-Oncology (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.
EXTH-73. TARGETING THE CELL ADHESION CLUSTER OF DIFFERENTIATION 44 TRANSMEMBRANE GLYCOPROTEIN SENSITIZES CRANIOPHARYNGIOMAS TO IMMUNOTHERAPY
Authors: Arturo Lujan, Jayati Chakrabarti, Jennifer Eschbacher, Gabriel Zada, Albert Kim, Andrew Little, Sandro Santagata, Yana Zavros
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Craniopharyngiomas are categorized as an adamantinomatous craniopharyngioma (ACP) or papillary craniopharyngioma (PCP) subtype with distinct histological, pathological and genetic differences. Studies propose the potential therapeutic benefit of targeting PD-L1 and/or PD-1 in both ACP and PCP subtypes using immune checkpoint inhibitors (ICI). The alternative mRNA splice variant of CD44, CD44v9, is expressed on cancer stem cells and plays multiple key roles including drug resistance and tumor cell invasiveness. CD44 positively regulates PD-L1, but the role of this transmembrane glycoprotein in craniopharyngioma tumorigenesis is unknown. Objectives: To replicate the complexity of the craniopharyngioma tumor microenvironment (TME) by developing a novel patient tissue-generated craniopharyngioma in vitro organoid preclinical model for the development of therapeutic strategies. Approach: NanoString CosMx™ Spatial Molecular Imager (SMI) was performed using FFPE tissue sections prepared from patient craniopharyngiomas. Quantification of PD-L1, and stem cell transmembrane glycoproteins CD44v9 and TROP2 was performed using multiplex immunofluorescence (MxIF). Craniopharyngioma patient-derived organoids (CranioPDOs) were generated and co-cultured with autologous immune cells (IMM) generated from patient peripheral blood mononuclear cells. CranioPDO/IMM co-cultures were used to predict the potential therapeutic benefit in response to tyrosine kinase inhibitor cabozantinib (Cabo) plus pembrolizumab (Pembro) or atezolizumab (Atezo) combinatorial therapy. RESULTS SMI analysis showed expression of CD44 and TROP2 positive cells, cancer-associated fibroblasts and myeloid-derived suppressor cells (MDSCs) consistent with the staining pattern of PD-L1. MxIF of matched tissues showed expression of CD44v9 and TROP2 within the same CD44 positive spatially mapped cell populations. Combinatorial treatment of CranioPDO/IMM co-cultures with Cabo plus Pembro or Atezo led to depletion of MDSCs correlating with decreased expression of CD44v9 and a significant increase in cytotoxic T lymphocyte proliferation and tumor cell death. CONCLUSION Our preclinical in vitro organoid data support the potential therapeutic benefit of ICI in combination with cabozantinib for the treatment of craniopharyngiomas.
CTIM-14. EARLY SAFETY DATA FROM A RANDOMIZED, MULTICENTER, DOUBLE-BLIND, PHASE 2B STUDY OF IGV-001, AN AUTOLOGOUS CELL IMMUNOTHERAPY, VERSUS PLACEBO, IN NEWLY DIAGNOSED GLIOBLASTOMA (NDGBM)
Authors: J Bradley Elder, Simon Hanft, Ian Y Lee, Christopher Farrell, John A Boockvar, Brad E Zacharia, Lyndon Kim, Michael Schulder, Carlos Eduardo Silva Correia, Rohan Ramakrishna, Eric T Wong, Julian Wu, Vijay Agarwal, Nduka Amankulor, Ankush Bhatia, Linton T Evans, Cameron Brennan, Brian J Gill, Soma Sengupta, Alfredo Quiñones-Hinojosa, Pierre Giglio, Kyle Wu, Synphen H Wu, Cristina Falo, Tobias Walbert, Adam Robin, Iyad Alnahhas, Morana Vojnic, A Gabriella Wernicke, Dawit Aregawi, Robert Maurer, Saadi Ghatan, Samuel Singer, Suriya Jeyapalan, Rajiv Magge, Athar N Malik, Nitesh Patel, Amy Chan, Fabio Iwamoto, Adilia Hormigo, Dominique Higgins, Mahua Dey, Nelson S Moss, Wendy Sherman, Leila Neese, Gregory K Pennock, Charles Scott, Raul Perez-Olle, David W Andrews
Journal: Neuro-Oncology (2024)

Abstract Standard of care (SOC) for ndGBM begins with maximal safe resection followed by adjuvant radiotherapy and temozolomide, and maintenance temozolomide. IGV-001 is an autologous biologic-device combination immunotherapy for the treatment of ndGBM that consists of autologous GBM tumor cells and an antisense oligonucleotide against IGF-1R mRNA, irradiated and administered via biodiffusion chambers implanted in the abdomen. In a phase 1b study, IGV-001 was well tolerated without unexpected adverse events in subjects with ndGBM. Multiple efficacy signals were observed, including significant improvements in progression-free survival (PFS), overall survival (OS), radiographic evidence of tumor response, and changes in immune response biomarkers. Here, we present early safety data from the phase 2b randomized, multicenter, double-blind, placebo-controlled study (NCT04485949) designed to assess efficacy and safety of IGV-001 in subjects with ndGBM across 20 sites in the United States. After surgical resection, subjects were randomized 2:1 and treated with IGV-001 or placebo followed by SOC. The primary outcome is PFS, defined as the time from randomization to first progression, as determined by blinded central radiology review, or death. Secondary outcomes include OS, defined as the time from randomization to death due to any cause, and safety. As of May 22, 2024, 99 subjects were randomized and 95 implanted with IGV-001 or placebo plus SOC. A total of 39/45 (86.7%) subjects had sufficient follow-up time after initiated treatment with concurrent radiation and temozolomide. Nine of 72 randomized (12.5%) discontinued treatment, including 7 who stopped during the SOC treatment period. None ceased treatment for adverse events, protocol deviations, or death. A total of 11/72 (15.3%) randomized subjects discontinued the study after randomization. A review of blinded safety data did not show any emerging risk and supports no change to the benefit-risk profile of IGV-001 versus placebo. Updated data will be presented.
NIMG-46. UNDERSTANDING PERMEABILITY CHANGES IN VESTIBULAR SCHWANNOMAS AS PART OF THE DYNAMIC RESPONSE TO RADIOSURGERY USING GOLDEN-ANGLE RADIAL SPARSE PARALLEL IMAGING, A RETROSPECTIVE STUDY
Authors: Ying Meng, Matthew D Lee, Assaf Berger, Roy Wiggins, James O’Callaghan, Kenneth Bernstein, Brandon Santhumayor, Kai Tobias Block, Girish Fatterpekar, Douglas Kondziolka
Journal: Neuro-Oncology (2024)

Abstract Vestibular schwannomas demonstrate different responses after stereotactic radiosurgery (SRS), commonly including a transient loss of internal enhancement on post contrast T1-weighted MRI thought to be due to an early reduction in tumor vascularity. We used dynamic contrast-enhanced based golden-angle radial sparse parallel (GRASP) MRI to characterize the vascular permeability changes underlying this phenomenon, with correlations to long-term tumor regression. Consecutive patients with vestibular schwannoma who underwent SRS between 2017-2019, had a transient loss of enhancement after SRS, and had long-term longitudinal GRASP studies (6, 12, and 24-36 months) were included in this retrospective cohort analysis (n = 19). Using GRAVIS, an analysis pipeline for GRASP studies, we extracted the key parameters normalized to the venous sinus from a region of interest within the tumor. The peak, area under the curve (AUC), and wash-in phase slope were significantly reduced at 6, 12, and 24 months after SRS (corrected p &amp;lt; 0.05), even while the internal enhancement returned in the tumors. Larger pre-SRS tumors were more likely to have a greater reduction in peak (p = 0.013) and AUC (p = 0.029) at 6 months. In a subset of patients (N = 13) with long-term follow-up, the median percentage reduction in tumor volume was 58% at median 62 months. These patients showed a strong correlation between changes in peak, AUC, and wash-in phase slope at 6 months and tumor volume at last follow-up. After SRS and loss of internal contrast uptake within the vestibular schwannomas, a slow vascular permeability dynamic found on GRASP studies persisted, suggesting the internal development of scar tissue. Moreover, the degree of reduction in GRASP parameters at 6 months positively predicted the degree of tumor regression long-term.
CTIM-13. D2C7-IT IN COMBINATION WITH AN FC-ENGINEERED ANTI-HUMANCD40 MONOCLONAL ANTIBODY (2141-V11) ADMINISTERED INTRATUMORALLY VIA CONVECTION-ENHANCED DELIVERY (CED) FOLLOWED BY CERVICAL PERILYMPHATIC INJECTIONS (CPLIS) OF 2141-V11 IN PATIENTS WITH RECURRENT GLIOBLASTOMA (RGBM)
Authors: Annick Desjardins, Vidya Chandramohan, James E II Herndon, Stevie Threatt, Chevelle Bullock, Claire Bradbury, Margaret O Johnson, Mustafa Khasraw, Justin T Low, Katherine B Peters, Madison Shoaf, Daniel Landi, Kristen Batich, Allan H Friedman, Henry S Friedman, David M Ashley, David Knorr, Juan Osorio, Jeffrey Ravetch, Darell D Bigner
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND The combination of D2C7-IT, an antibody toxin conjugate, and anti-mouseCD40 via CED generates robust antitumor immunity by killing tumor cells, activating microglia, reversing glioma-associated microglia and macrophage (GAMM)-mediated immune suppression, and empowering polyfunctional tumor antigen-specific CD8 T cells in glioma models. In addition to reprogramming GAMMs, anti-CD40 also activated dendritic cells and induced glioma-specific T cell responses in tumor draining lymph nodes. After establishing the phase 2 dose of the combination of D2C7-IT+2141-V11 when infused via CED, we initiated an assessment of the safety and efficacy of the combination of D2C7-IT+2141-V11 CED followed by repeated subcutaneous CPLIs of 2141-V11 ipsilateral to the tumor in patients with rGBM, IDH wild-type (NCT04547777). METHODS Eligible are adult patients with solitary supratentorial rGBM; ≥4weeks after chemotherapy, bevacizumab, or investigational agent; adequate organ function; and KPS ≥70%. Patients are treated with D2C7-IT (166μg) and 2141-V11 (3mg), both infused via CED, followed by CPLI of 2141-V11 at 2mg at weeks 2 and 4 post D2C7-IT+2141-V11 CED, followed by every 3 weeks for 1 year and then every 4-6 weeks. RESULTS As of May 22, 2024, 18 patients with rGBM (median age of 54) were treated with D2C7-IT+2141-V11 CED followed by CPLIs of 2141-V11. 83% patients remain alive (range 3.3-14.8 months from start of D2C7-IT CED infusion) with a median of 8 CPLIs of 2141-V11 received (range 3-19). No study related grade 4 or 5 adverse events (AEs) were observed. Grade 3 AEs related to D2C7-IT and/or 2141-V11 include one each of hydrocephalus, headache, seizure, and cerebral edema. AEs related exclusively to CPLIs of 2141-V11 consist of grade 1 injection site reaction (n=16). CONCLUSIONS The addition of CPLIs of 2141-V11 post CED of D2C7-IT+2141-V11 is feasible and has shown an acceptable toxicity profile. The safety and efficacy results will be updated.
DNAR-03. ONCOMAGNETIC TREATMENT KILLS GLIOMA CELLS BY INHIBITING MITOCHONDRIAL ELECTRON TRANSPORT AND BY INDUCING OXIDATIVE STRESS AND DNA DAMAGE
Authors: Shashank Hambarde, Arvind Pandey, David Baskin, Santosh Helekar
Journal: Neuro-Oncology (2024)

Abstract A new noninvasive cancer therapeutic device developed in our laboratory called the Oncomagnetic device involves repeated stimulation with oscillating magnetic fields (sOMF) produced by spinning permanent magnets. It is technologically and mechanistically distinct from the Optune® device approved by the FDA and provides a novel approach for CNS tumor treatment. In 7 end-stage GBM patients, this device reversed the progression of recurrent tumors causing &amp;gt;30% reduction in their contrast-enhanced volumes within 4 – 8 weeks of treatment. Immune-competent mice with implanted mouse glioma cells in their brains also showed marked reduction in tumor size, increased survival (p&amp;lt; 0.05, n = 9) and greater DNA damage (γ-H2AX foci) in implanted tumor after sOMF treatment. Normal mice exposed to sOMF for 4 months had no adverse effects on the brain and other organs. In-vitro, sOMF inhibited mitochondrial ETC complex-I and markedly increased reactive oxygen species (ROS) levels in GBM cells. Detection of γ-H2AX and 53BP1 foci showed that sOMF caused significant DNA damage in GBM cells and diffuse intrinsic pontine glioma (DIPG) cells but not in normal astroglial SVGp12 cells. GBM cells exposed to sOMF for 4 h caused cell cycle arrest in the G1 phase and 30% - 40% loss of surviving colonies detected by clonogenic cell survival assay, while normal SVGp12 cells were not affected. This loss of survival in GBM cells was rescued by the antioxidant Trolox. These results indicate that sOMF stimulation has high anticancer potency comparable to low dose radiation therapy at the cellular level with an underlying mechanism of action that is substantially different from that proposed for Optune® TTF.
DISP-04. SEX DIFFERENCES IN LUNG CANCER BRAIN METASTASES ADVERSE EVENTS
Authors: Mantas Dmukauskas, Gino Cioffi, Kristin Waite, Aaron Mammoser, Andrew Sloan, Patric Ma, Jill Barnholtz-Sloan
Journal: Neuro-Oncology (2024)

Abstract While sexual dimorphism is evident among adverse events (AEs) in response to treatments for many cancers, including brain tumors, little is known about sexual dimorphism among AE in brain metastases (BrM). As over 50% of BrM cases arise from lung cancer (LC), we examined sex differences in AEs associated with LC-BrM among individuals in the SEER-Medicare dataset aged ≥66 years at the time of LC diagnosis. Multivariable logistic regression models adjusted for demographic variables and Elixhauser comorbidity scores were used to analyze sex differences in AEs among individuals with BrM derived from primary LC. Analyses were stratified by the following histological subtypes: small-cell, adenocarcinoma, squamous cell carcinoma, or other non-small cell carcinomas. Additional variables analyzed included BrM treatment, age at BrM diagnosis, and year of diagnosis (at or before 2013/after 2013) to account for the introduction of targeted therapies. Differences in AE profiles, based by sex, in individuals diagnosed with LC-BrM were observed. Females diagnosed after 2013 with either small-cell, squamous cell, or other non-small cell carcinoma BrMs were more likely to experience headaches compared to males. Males diagnosed after 2013 with adenocarcinoma were more likely to experience brain herniation compared to females. Additionally, females aged 76 and older with small-cell BrM demonstrated an elevated risk of developing vision difficulties relative to males, whereas no significant sex difference observed in those under 76 years. Risk of most AEs decreased across all histological subtypes with receiving treatment after BrM diagnosis when compared to no treatment. This study underscores the existence of sex-specific differences in AEs among individuals aged 66 years and older diagnosed with LC-BrM. The AEs observed varied across histological subtypes, age cohorts, year of diagnosis, and treatment. Notably, receipt of treatment demonstrates consistent reduction in AE risk across all histological subgroups, underscoring the therapeutic benefit of treatment.
NCMP-15. MULTIPLE HEMORRHAGIC CNS LESIONS IN A PATIENT WITH RELAPSED SYSTEMIC CHRONIC LYMPHOCYTIC LEUKEMIA
Authors: Yi Li, Megan Mantica, Jan Drappatz
Journal: Neuro-Oncology (2024)

Abstract Although chronic lymphocytic leukemia (CLL) is the most common adult leukemia in Western countries, extramedullary CLL, characterized by the accumulation of clonal B cells outside of blood, bone marrow, and peripheral lymph nodes, remains rare. The central nervous system (CNS) is the most common site of extramedullary CLL involvement. However, clinically significant CLL in the CNS has been reported in fewer than 100 cases in the literature, and its true prevalence remains unknown with variable estimates. CLL in the CNS most often affects the meninges and usually spares the parenchyma unless there is a higher-grade/Richter transformation; in either case, it is typically not hemorrhagic. Furthermore, in the rare cases reported of hemorrhagic intraparenchymal CLL, patients present with isolated bleeding rather than multifocal hemorrhages. We present the case of a 63-year-old patient with multiply recurrent systemic CLL without Richter transformation who developed bilateral infratentorial and supratentorial micro and macrohemorrhages. Histopathology of a lesion showed focal subacute hemorrhage associated with reactive brain parenchyma containing CLL cells, though it was unclear whether the CLL predated the hemorrhage or if the hemorrhage introduced the CLL. Given the patient’s clinical stability, the lesions were ultimately attributed to coagulopathy in the context of CLL with subsequent secondary colonization of the hemorrhage by CLL cells. These lesions completely resolved after the patient underwent CLL-directed therapy three months after symptom onset. This case underscores the importance of considering bleeding risks associated with CLL and demonstrates that addressing the underlying CLL can lead to the improvement in bleeding sequelae.
NIMG-06. AUTOMATED VOLUMETRY OF MENINGIOMAS IN CONTRAST-ENHANCED T1-WEIGHTED MRI USING DEEP LEARNING
Authors: Ryuichi Hirayama, Takamitsu Iwata, Shuhei Yamada, Chisato Yokota, Noriyuki KIjima, Haruhiko Kishima
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND With the widespread use of MRI equipment and brain docks, there are more opportunities to perform follow-up observation for meningiomas. In recent years, attempts have been made to predict prognosis by using tumor volume as a highly objective imaging biomarker. On the other hand, manual lesion extraction by a reader with anatomical knowledge is indispensable for volume measurement, which requires a certain amount of labor and time. This is a major barrier to the generation of evidence and clinical application in this field. OBJECTIVE To establish the clinical significance of tumor volume as an imaging biomarker in meningiomas, and to develop a simple and highly reproducible application for automated volume measurement using artificial intelligence, and to investigate its accuracy and potential for clinical application. METHODS 178 patients with meningiomas who underwent MRI at Osaka University Hospital were included in the study. Contrast-enhanced T1-weighted images were used for manual lesion extraction by two neurosurgeons. These annotated image data were randomly divided into training (90%) and testing (10%). The deeplabV3 model was used to train the artificial intelligence, and leave-one-out cross-validation was used to train and validate the automated model. The test data were used for comparison, and the agreement rate (Dice index) on the images of the automatically extracted regions and the error rate of the calculated tumor volume (mean square error rate: RMSPE) were used as indices of measurement performance. RESULTS The average agreement rate between the automatically extracted area and the test data was 92.3±5.1%. The error rate of tumor volume was 9.5±1.2%. CONCLUSION This application using artificial intelligence was considered to have a certain validity in the accuracy of automatic lesion extraction. This method, which enables simple tumor volume measurement, is expected to create new imaging biomarkers that will contribute to the optimization and personalization of meningioma treatment.