bluuebunny/crossref_metadata_2025_split huggingface dataset:
SDPS-28 THE STUDY OF AN ANOIKIS-RELATED SIGNATURE TO PREDICT GLIOMA PROGNOSIS AND IMMUNE INFILTRATION
Authors: Zhang Dongdong , Wang Yu , Zhou Huandi , Han Xuetao , Hou Liubing , Lv Zhongqiang , Xue Xiaoying 
Published: August 2023

Abstract

BACKGROUND
Gliomas are the most common highly aggressive primary malignant brain tumors in adults with different biological behavior and clinically heterogeneous features. Method: We extracted the anoikis-related genes (ARGs) from GeneCards and obtained differentially expressed genes in normal and glioma tissues from the GSE4290 dataset by differential analysis to obtain intersect differentially expressed ARG in gliomas. KEGG and GO analysis were used to evaluate the potential pathways and molecular processes of these genes. Based on The Cancer Genome Atlas (TCGA) training cohort, we performed the Least Absolute Shrinkage and Selection Operator (LASSO) regression and Cox regression to construct an ARG prognostic model and validated them in the TCGA testing cohort and the Chinese Glioma Genome Atlas (CGGA) validation cohort. Subsequently, we further explored the differences in clinical characteristics, tumor mutation burden(TMB), and the immune microenvironment in the high- and low-risk groups. Univariate and multifactorial regression analyses and nomogram construction were also performed. Moreover, we assessed the expression levels and clinical prognostic value of prognostic key genes.

RESULTS
The regulatory model based on quantitative ARG prognostic models showed that patients in the high-risk group were associated with poorer survival prognosis, poorer clinical characteristics, and higher TMB levels. Moreover, the high-risk group had high levels of immune infiltration and upregulated immune checkpoint gene expression. The ARG prognostic model and the Nomogram showed good predictive performance. Expression and survival analysis of five prognostic ARG signatures (ETV4, HMOX1, MYC, NFE2L2, and UBE2C) showed that these genes except MYC were cancer-promoting genes.

CONCLUSION
Our constructed ARG prognostic risk model provides a potential therapeutic target and theoretical basis for predicting the prognosis of glioma patients and guiding individualized immunotherapy.
SDPS-45 PROGNOSTIC CHARACTERIZATION OF GENETIC MARKERS IN GLIOMA-ASSOCIATED EPILEPSY
Authors: Guo Lydia , Rilinger Ryan , Sharma Akshay , Lobbous Mina , Grabowski Matthew 
Published: August 2023

Abstract

BACKGROUND
High-grade gliomas are often associated with seizures, which impair quality of life and cause deleterious neurocognitive effects. Few molecular markers characterized in high-grade gliomas have prognostic capacity for glioma-associated epilepsy. Mutations in isocitrate-dehydrogenase 1 (IDH1) have been associated with glioma-associated epilepsy (Chen et al. Neurology 2017;88(19):1805–13), but other genetic and cell proliferation markers in glioma biopsies have inconclusive connections with glioma-associated epilepsy. Current AAN guidelines advise against prophylactic administration of anti-seizure medications in patients with newly diagnosed brain tumors. We sought to characterize common molecular markers in high-grade glioma-associated epilepsy.

METHODS
We retrospectively reviewed 241 patients diagnosed with grade IV gliomas between 2018 and 2021 at our institution. Analysis of genetic biomarkers in tumor biopsies included chromosome 1p/19q deletion, ki-67 expression, p53 expression, MGMT methylation, IDH1 mutation, and EGFR amplification. Multiple logistic regressions were utilized to examine the association between genetic biomarkers and seizure incidence at three intervals: preoperative, postoperative, and six months post-surgery. Other variables examined were age, tumor location (lobe, laterality, eloquence), and treatment type (radiation therapy, chemotherapy, immunotherapy).

RESULTS
Of 241 patients analyzed, 104 (43%) patients experienced seizures. EGFR amplification in high-grade gliomas was associated with preoperative seizures (β = .92, p = .013) but was not associated with postoperative seizures nor seizures six months post-surgery. Chromosome 1p/19q deletion, ki-67 expression, p53 expression, MGMT methylation, and IDH1 mutation were all not associated with seizure incidence.

CONCLUSION
The study results indicate that EGFR amplification is associated with preoperative seizures, suggesting EGFR to promote glioma epileptiform activity. As EGFR amplification is characteristic of the classical subtype of glioblastoma, these results further suggest that the pathogenesis of glioma-associated epilepsy is likely related to specific molecular tumor characteristics. These preliminary results will be expanded upon with further analyses that increase sample size and include next-generation sequencing

RESULTS
SPCR-01 CONCURRENT WOUNDED GLIOMA SYNDROME AND DISTANT WOUNDED GLIOMA SYNDROME FOLLOWING A GROSS TOTAL RESECTION OF GLIOBLASTOMA MULTIFORME - A CASE REPORT
Authors: Calubayan John Michael , Opinaldo Paul Vincent 
Published: August 2023

Abstract
Surgery is the initial form of treatment for glioblastoma, and a maximum resection without impairing neurological function improves survival. Wounded Glioma Syndrome (WGS) is a clinical picture observed after the resection of high-grade tumors. This syndrome, developing within hours or a few days after glioma surgery, is characterized by hemorrhage into the surgical bed and cerebral edema, and at times occurring in areas distant from the site of the resection, i.e., Distant WGS. We report a case of an elderly male presenting with an acute-onset left leg weakness, with a large peripherally-enhancing mass with central non-enhancement suggestive of necrosis in the right frontal lobe. A gross total resection of the tumor was done, and the histopathologic evaluation yielded a high-grade glioma, favoring a diagnosis of Glioblastoma WHO Grade-IV. During the postoperative period, he was drowsy and was able to move the right extremities. He had a series of generalized tonic-clonic seizures three hours after the operation. After eight hours, the patient became comatose with signs of increasing intracranial pressure. A cranial CT revealed diffuse cerebral edema, and hemorrhage into the operative site in the right frontal lobe, as well as subarachnoid hemorrhages in the bilateral fronto-parietal sulci. There were also small hemorrhages seen in the left caudate head, midbrain and left hemipons. Death occurred the following day. This case report demonstrates an unusual case of a WGS with a concurrent Distant WGS in the brainstem after a gross total resection of a frontal lobe glioma. This case shows a significant uncommon sequela that a patient undergoing glioma surgery can present, leading to rapid deterioration and death. Resection of a glioma carries a significant risk, and its impact in the immediate postoperative period merits evaluation when planning the perioperative management, taking prompt action if these syndromes occur.
SPCR-03 ACCESS TO CRITICAL GENOMIC TUMOR TESTING FOR GLIOBLASTOMA (GBM) PATIENTS
Authors: Pilkington Ed , Stebbins Alice , Wilke Martha , Duprey Kelli 
Published: August 2023

Abstract

PURPOSE
Assess whether GBM patients are being offered access to tumor testing at all stages of treatment as an essential first step toward personalized medical treatment of this fatal disease.Method: On-line survey sent to OurBrainBank Community.

RESULTS
More than 90 patients and/or caregivers completed the survey. Results revealed that 50 percent were never informed about tumor testing prior to their initial surgery, and some were never informed. Seventy percent were unsure or were never informed of the importance of storing tissue once collected. For the 30 percent who knew of tissue storage, only half actually had tissue stored. More than half did not know about tumor types or mutations. Only half felt that they received enough information and education to make good decisions. The best statistic was that those in urban areas were able to get care at a hospital that specialized in brain tumors. In addition, the survey revealed that 50 percent of participant GBM patients felt that they had an equal and collaborative relationship with their medical team, and 50 percent did not.

CONCLUSIONS
GBM patients and their caregivers are not treated consistently, particularly in regard to genomic tumor testing, which has become a vital first step toward personalized treatment. In this study, while some patients were provided information about their condition, 50 percent were not provided any information at all, or limited, and not based on individual patient needs. Geographical inequalities between urban and rural areas partly explain these disparities.
SYST-05 BETA-ADRENERGIC BLOCKADE LICENSES THE USE OF IMMUNOTHERAPY IN PRIMARY AND METASTATIC BRAIN TUMORS
Authors: Lorrey Selena , Wachsmuth Lucas , Ostrom Quinn , Fecci Peter 
Published: August 2023

Abstract
Brain tumors present a unique challenge to in the context of immunotherapy, as these patients are immunosuppressed not just at the tumor but also outside the CNS. The systemic immunosuppression observed in brain tumor patients limits the capacity of the immune system to respond to immunotherapy. Brain tumor patients, particularly those with metastatic disease, represent a patient population that is on the rise and in need of targeted treatment approaches. Through this work we present a novel axis of immunosuppression in brain tumor patients and demonstrate that overactive adrenergic signaling is a major barrier to immunotherapeutic success. Our data indicate that combining beta-adrenergic blockade with immunotherapy provides a survival benefit in the setting of brain tumors, where immunotherapy alone has proven ineffective. Using the SEER-Medicaid database, we retrospectively examined outcomes in patients with melanoma and lung adenocarcinoma brain metastasis who received checkpoint blockade therapy alone vs those concurrently on beta-blocker therapy. We found that patients receiving combination therapy showed increased overall survival compared to those receiving checkpoint blockade alone. We then validated these findings in preclinical models of both glioma and melanoma brain metastases, demonstrating that combining immunotherapy and propranolol, a widely-prescribed FDA-approved beta-blocker, extended survival. Moving forward, we suggest that combination therapy with propranolol and immunotherapy, particularly checkpoint blockade, represents a promising translational treatment platform for patients with primary or metastatic intracranial malignancies.
SYST-08 ROLE OF THE MICROBIOME IN BRAIN TUMORS
Authors: Omer Mohammed 
Published: August 2023

Abstract
A cross-sectional study was conducted to investigate the potential role of the microbiome in brain tumors. The study included 50 patients with histologically confirmed brain tumors and 50 healthy controls matched for age and gender. Fecal samples were collected from all participants and analyzed for bacterial composition using 16S rRNA gene sequencing. The results showed significant differences in the composition of the microbiome between the brain tumor patients and healthy controls. Specifically, patients with brain tumors had a higher abundance of certain bacterial species, including Fusobacterium and Porphyromonas, compared to the healthy controls. These bacterial species have previously been associated with inflammation and have been implicated in the development and progression of various types of cancer. Furthermore, the study investigated the potential interaction between the microbiome and the immune system in the context of brain tumors. Analysis of immune cell subsets in peripheral blood samples revealed differences between the brain tumor patients and healthy controls, with the tumor patients showing a lower proportion of CD8+ T cells and a higher proportion of regulatory T cells. Interestingly, there was also a correlation between the abundance of certain bacterial species and the proportion of immune cells, suggesting a potential role for the microbiome in modulating immune function in brain tumors. These findings suggest that the microbiome may play a role in the development and progression of brain tumors. Further studies are needed to investigate the mechanisms underlying this association and to determine whether interventions targeting the microbiome could have therapeutic benefit in brain tumors.
SYST-10 ENHANCING THE EFFICACY OF RADIATION THERAPY BY SURGICALLY TARGETED RADIATION-SENSITIZER LOADED FIBRIN GLUE
Authors: Nguyen Jane , Chandekar. Akhil , Hirschberg Henry 
Published: August 2023

Abstract
Radiation therapy (RT) forms an integral part of the treatment of brain tumors. Intrinsic, relative tumor radio-resistance, normal tissue tolerance and impact on neurocognitive function, all limit the efficacy of RT. Radiation sensitizers (RS) can potentially increase efficacy on tumor cells while maintaining normal tissue toxicity. Clinical trials, employing radiation sensitizers have been done, but so far, the results have been disappointing. An important factor that could account for the low efficacy of RS in clinical trials is the blood–brain barrier (BBB). The basis for this work was the development of a RS direct delivery system (DDS), that bypasses the BBB. This is implemented by the local implantation, into the tumor resection cavity, of RS loaded slow-release fibrin glue. Localized delivery significantly increases the concentration of RS reaching the remaining infiltrative tumor cells in the brain parenchyma, while avoiding systemic side effects. Additionally, the BBB would prevent retrograde flow of the RS into the circulatory system. and the RS is protected from degradation and clearance until locally released. FG has several characteristics that make it well suited for this form of agent delivery. It has been used clinically in surgery for decades, is FDA approved, its lack of toxicity has been clearly proven, it gels rapidly and spontaneously and is easily applied. Radiation protocols utilizing two sensitizers, 5FU and Motexafin-GD, have been optimized in vitro using 3D glioma spheroid models. The results obtained in vitro have been extended to an appropriate in vivo rat brain tumor model. The goal of this project is to improve the therapeutic index of radiation therapy and is therefore clearly aimed at eventually translating to new clinical treatment protocols.
SYST-16 ANXA5 PROMOTES GLIOMA PROGRESSION THROUGH THE FAK/PI3K/AKT PATHWAY
Authors: Zhang Xinyuan , Zhou Huandi , Han Wei , Zhang Dongdong , Han Xuetao , Hou Liubing , Li Haonan , Sun Guozhu , Xue Xiaoying 
Published: August 2023

Abstract
Annexin A5 (ANXA5) is a member of the calcium dependent phospholipid binding protein family and participates in the regulation of a variety of physiological and pathological processes. However, whether and how ANXA5 affects the growth and progression of glioma remains unclear.We analyzed the expression of ANXA5 in multiple public databases, and verified the expression in 50 glioma clinical samples with Western blotting to study the correlation between ANXA5 and prognosis, survival, and clinical characteristics. In vitro experiments, we up-regulated and down-regulated the expression of ANXA5 in glioma cells, then treated glioma cells with up regulated ANXA5 expression with Y397 FAK specific phosphorylation inhibitor Y15, and verified the effect of ANXA5 on proliferation, migration and invasion of glioma cells through CCK8, clone formation, EDU, migration and invasion assays, scratching,and Western blotting proved that the expression level of ANXA5 affected the protein level of upstream and downstream factors of FAk/PI3K/AK pathway. ANXA5 is highly expressed in glioma and is related to clinical features such as grade, age and molecular typing. The higher the expression of ANXA5, the worse the prognosis. The increased expression of ANXA5 can promote the proliferation, migration and invasion of glioma cells, activate FAk/PI3K/AK pathway, and Y15 can reverse the promotion of ANXA5 overexpression; when ANXA5 is knocked down, the result is opposite. ANXA5 is highly expressed in glioma and is an independent prognostic factor of glioma patients. ANXA5 can promote the proliferation, migration and invasion of glioma cells through FAk/PI3K/AK pathway, and this promotion can be reversed by Y15.
SYST-17 GOLD NANOSTARS ENHANCE THE EFFICACY AND SAFETY OF LASER INTERSTITIAL THERAPY FOR THE TREATMENT OF INTRACRANIAL TUMORS
Authors: Wachsmuth Lucas , Chongsathidkiet Pakawat , Liu Yang , Odion Ren , Srinivasan Ethan , Mendoza Aden , Edwards Ryan , Canning Aidan , Willoughby Gavin , Hinton Joseph , Norton Stephen , Fecci Tuan Vo-Dinh Peter 
Published: August 2023

Abstract
Laser interstitial thermal therapy (LITT) is a minimally-invasive technique for the treatment of intracranial tumors that uses a stereotactically-guided laser for ablation. Magnetic resonance thermal imaging is used to monitor ablation progress by measuring the cumulative heat energy exposure in both the tumor and the surrounding tissue to calculate thermal damage thresholds.Previous applications of GNS in laser ablation of tumors have studied extracranial tumors only and utilized externally administered near infrared radiation that cannot penetrate the cranial compartment. Herein, we present a novel platform for employing GNS in intracranial tumors. We developed GNS that exhibit maximum photothermal effects at the 1064 nm laser wavelength used in the FDA-approved clinical Neuroblate® LITT system. Monte Carlo simulations demonstrate that our GNS can accelerate and focus thermal energy distributions. Using ex vivo tumor phantom models, GNS-infused phantoms demonstrate more rapid heating, expanded ablation zones, and improved margin conformation, with surrounding areas exposed to lower temperatures than controls. In in vivo intracranial tumor models, we show that GNS selectively accumulate and are retained in CT2A glioma and B16F0 melanoma tumors at 24 and 72 hours post-injection. Using our in vivo heterotopic CT2A model, we demonstrate that systemically-delivered GNS dramatically augment laser ablation, with higher temperatures achieved in the tumor and more efficient temperature ramping. These results support the ability of GNS to optimize LITT for the treatment of intracranial tumors by improving the efficiency and safety of this platform.
SYST-20 TARGETED THERAPY MATCHED TO GENOMIC ALTERATIONS (BRAFV600E, NTRK, FGFR, ROS1, PIK3CA, PTEN) IN PATIENTS WITH RECURRENT IDH WILDTYPE GLIOBLASTOMA: A REAL-LIFE COHORT ANALYSIS FROM VENETO INSTITUTE OF ONCOLOGY, PADUA (ITALY)
Authors: Padovan Marta , De Toni Chiara , Maccari Marta , Bosio Alberto , Cerretti Giulia , Caccese Mario , Corrà Martina , Vizzaccaro Salvatore , Cestonaro Ilaria , Pittaro Alice , Guerriero Angela , Coppola Marina , Lombardi Giuseppe 
Published: August 2023

Abstract
We retrospectively analyzed 34 patients (pts) [19 males, 15 females, median age 54] with recurrent IDH wildtype glioblastoma treated with target therapy (TT) based on their next-generation sequencing (NGS) profile, between March2020 and December2022 at Veneto Institute of Oncology, Padua (Italy). ECOG PS was 0-1 in 29 pts. All pts received previous radiotherapy and temozolomide. NGS was obtained with FoundationOne®CDx on formalin-fixed paraffin-embedded samples. We identified 6 druggable genomic alterations, classified according to ESCAT (ESMO Scale for Clinical Actionability of molecular Targets): BRAFV600E mutation (IB), NTRK1-2-3 fusions (IC), FGFR1-2-3 alterations (IIB), ROS1 fusions (IIIA), PIK3CA mutations (IIIA) and PTEN loss/mutations (IIIA). The median line of therapy with TT was 3 (range 2-7). TT was dabrafenib/trametinib (9 pts), larotrectinib (2 pts), erdafitinib (4 pts), entrectinib (1 pt), alpelisib (6 pts), ipatasertib+/-atezolizumab (12 pts). At data cut-off (March2023), 19 patients had died. In the entire cohort, median overall survival and progression-free survival (PFS) after starting TT was 8.72 and 2.14 months, respectively. The dabrafenib/trametinib subgroup had the longest median PFS (5.23 months), a disease control rate (DCR) of 77%, an objective response rate of 22%, and a median duration of response of 22.5 months. 7/9 pt had died and 2 pts are continuing dabrafenib/trametinib. The pt with ROS1-GOCP fusion maintained a complete response for 12 months with entrectinib. Among the others, no complete/partial responses were detected. DCR due to stable disease was 50% in larotrectinib and erdafitinib subgroups and 8.3% in ipatasertib+/-atezolizumab subgroup. No toxicities were reported in dabrafenib/trametinib subgroup. Among all patients, no grade 4 drug-related adverse events were observed and in any case TT was interrupted for toxicity. Our results confirm the activity of dabrafenib/trametinib in BRAFV600E mutant glioblastoma pts and might suggest further explorations in targeting ROS1 and FGFR.
SYST-26 INVESTIGATING THE FUNCTIONAL ROLE OF GPNMB IN GLIOBLASTOMA AND THE TUMOR IMMUNE MICROENVIRONMENT AND ITS TARGETED ELIMINATION USING CAR-T CELLS
Authors: Savage Neil , Zemp Franz , Mikolajewicz Nicholas , Han Hong , Venugopal Chitra , Tatari Nazanin , Chokshi Chirayu , Kislinger Thomas , Mahoney Douglas , Moffat Jason , Singh Sheila 
Published: August 2023

Abstract

INTRODUCTION
Glycoprotein nonmetastatic melanoma protein B (GPNMB) is active in the extracellular matrix of glioblastoma and presents a promising immunotherapy target for both tumor cells and immunosuppressive macrophages.

METHODS
Immunohistochemistry was performed on patient derived xenograft (PDX) brains and tissue samples of 16 patient-matched primary/recurrent GBMs and 23 normal organ tissues. Whole cell proteomics was performed on 43 matched primary/recurrent GBM samples. CRISPR/Cas9 was used to eliminate expression in GBM lines and proliferation and mouse survival times measured. GPNMB knockout clones generated in GL261 were engrafted in immunocompetent mice to examine single cell transcriptomes using sciRNA sequencing at endpoint. A second-generation CAR-T was developed to target GPNMB-expressing populations, and efficacy was interrogated using in vitro assays and GBM PDX models.

RESULTS
GPNMB was absent in most normal tissues but detected in residual PDX tumors treated orthotopically with CD133 CAR-Ts. Tissue microarrays and whole cell proteomics showed GPNMB upregulation in recurrent GBMs compared to primary (p=0.0349 vs. p=0.0033) while absent in normal tissues. Single cell sequencing data of patient GBMs revealed GPNMB was also highly expressed in tumor-associated macrophages. Eliminating GPNMB in GBM cell lines decreased proliferation (P&lt;0.001) and prolonged survival times in all mouse models (P&lt;0.01). GPNMB knockout clones displayed downregulation of hallmark signaling pathways of GBM such as PDGFR, TGF-beta, Integrins and Stats, and decreased innate/adaptive immune activation. CAR-T cytotoxicity and activation was observed in vitro and in vivo resulting in decreased tumor burden (P&lt;0.001) and increased survival times (P&lt;0.001).

CONCLUSIONS
We show GPNMB influences tumor-intrinsic biology of GBM and is also active in macrophages in the recurrent GBM immune microenvironment. By targeting GPNMB alongside CD133, combinatorial therapeutic regimens could target both the cancer stem cell hierarchy and its supportive niche. Administration of both CAR-T cell therapies to humanized mice engrafted with patient-derived GBMs is underway.