tbuckley/cabot-search huggingface dataset:
NCMP-23. PATIENTS WITH BRAIN TUMORS HAVE DECREASED BILATERAL FINGER DEXTERITY COMPARED TO HEALTHY ADULTS
Authors: Brian Conway, Léon Taquet, Timothy Boerger, Kaitlin Goetschel, Sergey Tarima, Brian Schmit, Max Krucoff
Journal: Neuro-Oncology (2024)

Abstract Unilateral brain tumors are known to affect motor control of the contralateral hemibody, but ipsilesional effects are less frequently studied and may be just as impactful to quality of life. Hand dexterity, for example, is a critical skill that often requires both hands. Here, a cohort of 15 patients with unilateral brain tumors and 47 healthy adults performed individual finger movements with each finger (except the thumb) on each hand while tracked by a data glove (Cyberglove III, CyberGlove Systems, San Jose, CA). The ability to move each finger independently was quantified using a scale previously developed by our lab (individuation score) that represents dexterous ability. Repeated-measures two-way ANOVA with factors of group (brain tumor vs. healthy) and laterality (contralesional vs. ipsilesional) were performed for each finger. The lesional side was set to the left brain for cases in the brain tumor group for simplicity of analysis. There was a significant main effect of “group” for all finger individuation scores (index p-value&amp;lt;0.0001, middle p-value&amp;lt;0.0001, ring p-value&amp;lt;0.001, small p-value&amp;lt;0.01) with healthy volunteers scoring higher than patients. There was no main effect of “laterality.” Group-laterality interaction effects were not significant except for the small finger where healthy adults’ right but not left sided individuation scores were greater than the brain tumor group’s (p-value&amp;lt;0.01). Additionally, using cluster analysis incorporating data from both hands, we were able to differentiate patients with brain tumors from healthy adults with 97.9% specificity, 60% sensitivity, 90% positive predictive value, and 88.5% negative predictive value. Ultimately, these results suggest that unilateral brain tumors decrease hand dexterity bilaterally without a significant lateralizing difference except in the small finger. These results suggest unilateral lesions can have bihemispheric network effects, and/or that hand dexterity may rely on ipsilesional connections more than previously understood.
DNAR-16. TARGETING APOBEC CYTIDINE DEAMINASES TO ENHANCE RADIOSENSITIVITY IN GLIOMA
Authors: Bianca M Marin, Amit Gujar, Emre Kocakavuk, Kevin C Johnson, Samirkumar B Amin, Roel G W Verhaak
Journal: Neuro-Oncology (2024)

Abstract Glioma is the most common and aggressive primary adult brain tumor. Radiation therapy (RT) is a critical part of glioma treatment, but radioresistance severely limits its therapeutic efficacy. To better understand how radioresistance develops, we analyzed 212 paired primary and recurrent gliomas from the Glioma Longitudinal Analysis Consortium. We found a significant increase in mutational signatures associated with the activity of the Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like (APOBEC) family of cytidine deaminases in RT-treated recurrent gliomas (p&amp;lt;0.001, paired Wilcoxon signed-rank test). Further analysis of post-treatment mutations showed that RT increased APOBEC mutational signatures independent of other factors (p&amp;lt;0.001, multivariable log-linear regression), suggesting that APOBEC proteins become activated by radiation. However, their role in promoting tumor evolution and treatment resistance is currently unknown. Further analyses of extended signature contexts and expression data nominated APOBEC3B (A3B) and APOBEC3G (A3G) as candidates for creating these mutational signatures. To investigate their roles in RT response, we knocked out (KO) A3B and A3G individually in patient-derived glioma cell lines before RT. Compared to Control cells, irradiated A3B-KO and A3G-KO cells acquired significantly fewer APOBEC mutational signatures by whole genome sequencing (p&amp;lt;0.05, Kruskal–Wallis test) and exhibited enhanced radiosensitivity in vitro. Interestingly, the KO cells displayed a significant decrease in mutational signatures associated with Non-Homologous End-Joining (NHEJ), one of the main pathways for repairing the RT-induced DNA damage (p&amp;lt;0.05, Kruskal–Wallis test), suggesting that APOBEC deletion impaired DNA repair. This was further supported by persistent gH2AX DNA damage foci 48h post-RT and reduced autophosphorylation of DNA-dependent protein kinase (DNA-PK), a vital component of the NHEJ pathway, particularly in A3G KO cells. Overall, our results identify APOBEC proteins as potential targets for radiosensitizing gliomas and highlight the clinical utility of using mutational signatures to predict and monitor response to treatment.
SURG-10. SUPRATOTAL RESECTION: AN EMERGING CONCEPT OF GLIOBLASTOMA MULTIFORME SURGERY—SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Peer Aziz, Salma Memon, Hussain Mubarak, A Memon, Kiran Abbas, Shurjeel Qazi, Riaz Memon, Kanwal Qambrani, Osama Taj, Shamas Ghazanfar, Aayat Ellahi, Moiz Ahmed
Journal: Neuro-Oncology (2024)

Abstract The severe neurologic tumor known as glioblastoma (GBM), also referred to as a grade IV astrocytoma, is rapidly progressive and debilitating. Supratotal resection (SpTR) is an emerging concept within glioma surgery, which aims to achieve a more extensive resection of the tumor than is possible with conventional techniques. We performed a language-independent search of PubMed, Scopus, and Cochrane CENTRAL to identify all available literature up to August 2022 of patients undergoing SpTR assessing survival outcomes in comparison to other surgical modalities. After screening for exclusion, a total of 13 studies, all retrospective in design, were identified and included in our meta-analysis. SpTR was associated with significantly increased overall survival (hazard ratio 0.77, 95% CI 0.71–0.84; P &amp;lt; 0.01, I2 = 96%) and progression-free survival (hazard ratio 0.2, 95% CI 0.07–0.56; P = 0.002, I2 = 88%). SpTR is associated with greater overall survival and PFS when compared with other glioblastoma surgeries like GTR or SubTR.
BIOM-17. EVALUATION OF CARBONIC ANHYDRASE TYPE IX (CA IX) EXPRESSION AS TARGET FOR RADIOLIGAND THERAPY IN GLIOBLASTOMA
Authors: Maximilian J Mair, Erwin Tomasich, David Polten, Lisa Greutter, Georg Widhalm, Franziska Eckert, Adelheid Wöhrer, Anna S Berghoff, Matthias Preusser, Nathalie L Albert
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Glioblastoma represents an unmet need in neuro-oncology. Radioligand therapies are effective and approved in extracranial malignancies such as prostate cancer and neuroendocrine tumors, but data on their use is limited in brain tumors. In addition, rational target selection in gliomas is complicated by tumor heterogeneity. In extracranial tumors, clinical trials of radionuclide treatments targeting carbonic anhydrase IX (CA IX) are ongoing. METHODS Tumor samples of glioblastoma (isocitrate dehydrogenase [IDH]-wildtype) were retrieved from the Neuro-Biobank of the Medical University of Vienna. Formalin-fixed, paraffin-embedded tissue specimen were stained using rabbit anti-CA IX antibody (clone EP161, Cell Marque) on a Ventana Benchmark Ultra platform (Roche Diagnostics). CA IX expression was assessed semiquantitatively. RESULTS Overall, 29 patient samples were included in this study. Median age at surgery was 65 years (range: 55 – 74), and 22/29 (75.9%) were male. Median overall survival (OS) reached 11.6 months (95% confidence interval: 7.3 – 16.3). In total, 24/29 (82.8%) of specimen were positive for CA IX, of whom 20/29 (69.0%) exhibited moderate to high membranous CA IX expression and 4/29 (13.8%) showed weak immunoreactivity. CA IX staining displayed pronounced spatial heterogeneity, as positive areas were primarily seen in pseudo-palisading tumor cells around necrotic foci. Patients with stronger CA IX staining tended to have longer OS (median: 14.2 months) compared to those with absent or weak CA IX expression (median OS: 6.2 months; p = 0.075). Inclusion of further samples of different glioma subtypes is ongoing. CONCLUSIONS CA IX could represent a promising target for radioligand therapy in glioblastoma given the strong CA IX immunoreactivity in most samples. Intratumoral heterogeneity in CA IX expression should be considered in the design of appropriate compounds and the choice of optimal radionuclides to maximize efficacy.
DDEL-07. EFFICACY OF TEMOZOLOMIDE IN MEDULLOBLASTOMA PATIENTS: REVIEW OF SERIES OF TWO ADULT PATIENTS WITH RECENT UPDATES IN LITERATURE
Authors: Ruchi Raval, Khushi Desai, Aarya Raval, Jaspreet Behl, Om Raval, Aishwarya Gor4ty, Sakshi Parikh, Krishna Parikh, Meher Gupta, Sumul Raval
Journal: Neuro-Oncology (2024)

Abstract Medulloblastoma is a primary malignant CNS tumor commonly seen in children and rarely in adults (20% vs 1% of all primary brain tumors). Maximal safe resection and craniospinal irradiation followed by adjuvant chemotherapy have proven to be an effective treatment in children. Due to insufficient data available in adult patients, it is also the usual approach in them despite unclear long-term outcomes. Standard chemotherapeutic regimens consisting of vincristine, cisplatin, and lomustine are known to cause greater toxicity in adults making adequate dose titration a challenge. Temozolomide is a second-generation cytotoxic alkylating agent with favorable CNS penetration. It is a potential alternative that has yielded superior results in treating gliomas and preventing recurrence along with minimal toxicity. We discuss a series of two adult medulloblastoma cases which were given 24 cycles of Temozolomide monotherapy over two years following surgical resection and craniospinal irradiation. Serial MRIs did not report any signs of recurrence rendering one case cancer-free for seventeen years and the other for ten. Minimal toxicity in the form of nausea, vomiting, headache, and reversible, temporary pancytopenia was seen in contrast to other agents. Improved survival with minimal toxicity was demonstrated in both cases proving the efficacy of Temozolomide as adjuvant chemotherapy for adult Medulloblastoma. While a regimen of Temozolomide is recommended for recurrent Medulloblastoma, there is no optimal regimen available for initially diagnosed, localized tumors, especially in adults. Multi-institutional clinical trials are required to study its role as a monotherapy during an early yet critical phase of management.
EPCO-07. INTEGRATING SPATIALLY RESOLVED MULTI-OMICS DATA TO UNCOVER DYSFUNCTIONAL METABOLISM DRIVEN NETWORKS THAT ENHANCE INFILTRATION OF DIFFUSE GLIOMAS
Authors: Yanxia Ma, Nhat Nguyen, Sanjay Singh, Akshay Basi, Duncan Mak, Javier Gomez, Jared Burks, Erin Seely, Frederick Lang, Chibawanye Ene
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Diffuse infiltration is an aggressive feature of high-grade gliomas with survival implications. The contribution of crosstalk between non-neoplastic and neoplastic cells to tumor infiltration remains largely understudied due to the lack of profiling techniques that retain spatial information. Spatial multi-omic profiling is a promising approach to comprehensively analyze transcript-omics, prote-omics and metabol-omics on the same tissue section while preserving information about the spatial organization of cells. Integration of these spatial studies allows for inferring the consequences of complex cell-cell communication underlying tumor infiltration. We hypothesize that the glioma edge is enriched with pro-infiltration ligands-receptors driving tumor infiltration. Strategies that disrupt these ligand-receptor networks may suppress glioma infiltration and improve clinical outcomes. METHODS We utilized a glioma tissue micro-array (TMA) to establish the neoplastic and non-neoplastic heterogeneity in the GBM infiltration edge. Each TMA slide consists of pathologist annotated tumor core and edge samples of Glioblastoma (IDH Wildtype, WHO Grade 4; n=10), Diffuse Astrocytoma (IDH Mutant, WHO Grade 3; n=3), Oligodendroglioma (IDH mutant, WHO Grade 2; n=5) and 2 non-brain control samples. We performed spatial multi-omics profiling on adjacent sections of the TMA using 10x Xenium spatial transcriptomics, imaging mass cytometry (IMC) and mass spectrometry imaging (MSI). Integration, visualization, and quantification of the spatial data was done on VisioPharm. RESULTS In GBM, we identified candidate mRNA transcripts and proteins for ligands enriched at the infiltrating edge (compared to tumor core; p&amp;lt;0.0001) that correlated with a poor progression free survival (PFS; r2=0.22). These candidate ligands were also significantly enriched at the edge of oligodendroglioma WHO Grade 2 and astrocytoma WHO Grade 3. CONCLUSIONS Spatial multi-omics profiling on a TMA consisting of Glioma WHO grades 2-4 identified differentially expressed and targetable pro-tumor infiltration ligands associated with lower PFS in GBM. Functional studies to uncover the role of metabolites enriched at the glioma edge for the expression of the identified pro-infiltration ligands are ongoing.
CNSC-30. DETERMINING THE REGULATION AND FUNCTION OF ANGPT1 HIGH-GRADE GLIOMAS
Authors: Jaldeep Langhnoja, Xin Wei, Phonepasong Arounleut, Ipsita Kundu, Timothy Phoenix
Journal: Neuro-Oncology (2024)

Abstract Angiopoietin-1 (Angpt1) is a secreted protein that promotes angiogenesis and vascular stability in development and certain disease states through activation of the Tie2 receptor. However, little is known about its regulation and function in brain tumors. Angpt1 is upregulated in glial brain tumors, including high-grade gliomas and ependymomas. We find Angpt1 is expressed by specific cell populations within gliomas, along with non-tumor reactive astrocytes and perivascular mural cells. Leveraging an in vivo brain tumor modeling system we have generated glioma models to investigate how tumor cell state impacts Angpt1 expression, along with creating Angpt1 knock-out models. We find that Angpt1 expression is increased when glioma models are biased towards a more astrocytic and/or mesenchymal state, mirroring developmental expression patterns. Ongoing studies utilizing these models are being used to determine the mechanisms that regulate the dynamic expression of Angpt1 and its function in glioma pathogenesis, including tumor angiogenesis and blood-brain barrier function.
RADT-38. CLINICAL, MOLECULAR AND IMAGING FEATURES ASSOCIATED WITH LONG TERM SURVIVAL IN GLIOBLASTOMA PATIENTS
Authors: Muhammad Sharif, Carrie Andrews, Sophia Shah, Nilanjan Haldar, Louis Cappelli, Tingting Zhan, Iyad Alnahhas, Wenyin Shi
Journal: Neuro-Oncology (2024)

Abstract INTRODUCTION Glioblastoma (GBM) is the most common malignant brain tumor in adults and has poor prognosis despite standard of care treatment. Nevertheless, certain patients surpass survival expectations. This study seeks to identify the clinical, molecular, and imaging characteristics of GBM associated with extended patient survival. METHODS In this retrospective cohort study, we examined records of adult GBM patients (WHO 2016 classification) treated at Thomas Jefferson University Hospital from 2010 to 2023. Exclusion criteria included a preoperative Karnofsky Performance Status (KPS) below 60 and treatment with hypo-fractionated radiation therapy. Patients were categorized into two groups: short-term survivors (STS), who survived less than 36 months from diagnosis, and long-term survivors (LTS), who survived more than 36 months. We reviewed patient charts and pathology reports for comprehensive clinical and molecular data. For radiomics analysis, tumor segmentation was performed using CaPTk software on the initial diagnostic MRI (T1 pre and post-contrast, FLAIR and T2 sequences). The relationship between overall survival of more than three years was analyzed with univariable logistic models for potential predictors using R statistical software. RESULTS Of the cohort of 210 patients, 37 (17.6%) survived beyond three years. The median age at diagnosis was 55 years (range; 29-79) Twenty-two patients were male and 15 were female. Twenty-two percent had IDH mutation and 65% had MGMT methylation. Factors associated with long-term survival included younger age at diagnosis (p =0.007), MGMT hypermethylation (p =0.019), IDH mutation (p=0.001), absence of TERT mutation (p = 0.002), higher average number of adjuvant temozolomide cycles (10 vs. 5; p = 0.005), and smaller volume of enhancing tumor on T1 post-contrast imaging segmentation (p=0.022). But there was no significant difference in FLAIR abnormality or necrotic core volumes between the groups. CONCLUSION In our cohort of GBM patients, patients diagnosed at a younger age, MGMT hypermethylation, IDH mutation, absence of TERT mutation, receiving more cycles of adjuvant temozolomide treatment, and smaller enhancing tumor volume on preoperative T1 post-contrast imaging were associated with longer survival. Future research involving larger cohorts and validation of our findings is needed.
EPID-31. IMPACT OF THE COVID-19 PANDEMIC ON THE UTILIZATION OF STEREOTACTIC RADIOSURGERY AMONG RACIAL MINORITIES DIAGNOSED WITH BRAIN METASTASES
Authors: Ping Zhu, Clark Chen
Journal: Neuro-Oncology (2024)

Abstract OBJECTIVES Brain metastases (BM) is the most common form of adult brain tumors and one of the devastating consequences of cancer. Stereotactic radiosurgery (SRS) is an established and effective treatment for oligometastatic BMs. We examined how COVID-19 pandemic impacted clinical utilization of SRS in BM treatment and generalize such impact to outpatient care for patients with all cancer types. METHODS Three national-scale datasets were used: National Cancer Database (NCDB,N=5,238), the National COVID Cohort Collaborative database (N3C, N=13,106 for BM, N=203,706 for all cancer types), and SEER. Multivariable logistic regression models were performed to determine whether the pandemic affected clinical utilization of SRS in BM treatment and chemotherapy initiation for all cancer types. RESULTS Prior to 2019 (pre-pandemic), we observed no racial disparity in the odds of receiving SRS between non-Hispanic white (NHWs) and non-Hispanic black (NHBs) BMs in both NCDB and N3C. Between 2020 and 2021 (pandemic), however, NHBs were significantly less likely to receive SRS comparing to NHWs in both NCDB (NHB:aOR-0.77,p=0.002) and N3C (NHB:aOR-0.78,p&amp;lt;0.001). In SEER, the age-adjusted incidence rate of BM remained unchanged when comparing pre- and post-pandemic periods. Further substantiating the impact of COVID-pandemic on racial disparity in outpatient care for all cancer patients, we showed that NHB patients were more likely to receive delayed chemotherapy (&amp;gt;60 days since diagnosis of cancer) compared to NHWs during the pandemic (aOR-1.10, p&amp;lt;0.001), but such association was not detected before pandemic. Ratio of odds ratio (ROR) analysis confirmed that NHB patients comparing to NHWs during pandemic experienced 1.11-fold difference in the odds of delayed chemotherapy between NHBs and NHWs before pandemic [ROR=1.11, p&amp;lt;0.001]. CONCLUSION Racial disparity in SRS-receipt for BM patients has been exacerbated during COVID-19 pandemic and such impact could be generalized to outpatient care for all cancer types. Understanding the determinants giving rise to this disparity should augment the readiness of our cancer care infrastructure in anticipation of future pandemics or other public health crises.
SURG-28. THE IMPACT OF PERILESIONAL HEATSINK STRUCTURES ON ABLATION VOLUMES AND SYMMETRY IN LASER INTERSTITIAL THERMAL THERAPY FOR THE TREATMENT OF PRIMARY CENTRAL NERVOUS SYSTEM TUMORS
Authors: Chandler Berke, Cameron Rivera, Shovan Bhatia, David Levi, Adham Khalafallah, Victor Lu, Kate Stillman, Chase Delong, Eric Singh, Ashish Shah, Ricardo Komotar, Michael Ivan
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Laser Interstitial Thermal Therapy (LITT) has emerged as a minimally invasive treatment for primary CNS tumors. While LITT offers advantages over traditional approaches, perilesional intracranial heatsinks can lead to asymmetric ablation, impacting patient outcomes. Understanding heatsink effects is crucial for optimizing LITT efficacy. METHODS We retrospectively analyzed primary CNS tumors treated with LITT at a single tertiary care center. Ablation outcomes were quantified using the Heatsink Effect Index (HEI) measured on a scale of 0-1 (0=total symmetry; 1=complete asymmetry), and extent of ablation (EOA). Heatsink types evaluated were sulci, meninges, vasculature, and cerebrospinal fluid (CSF) spaces, inclusive of ventricles, surgical resection cavities, and CSF cisterns. Statistical analyses assessed the relationship between heatsink proximity and ablation outcomes. RESULTS A total of 99 patients satisfied all selection criteria. The cohort was 53% female, with a mean age of 61 years. Glioblastoma was the most predominant tumor type (78%), followed by low grade gliomas (15%), and meningiomas (4%). Heatsink proximity significantly correlated with ablation asymmetry (HEI) (p &amp;lt; 0.001), particularly at the midpoint of the catheter trajectory. The correlation between closest heatsink distance and HEI varied across the different heatsink types, with distance to vasculature and CSF spaces correlating the strongest with ablation asymmetry. When assessing the relationship between EOA and medial HEI during suboptimal ablations (EOA &amp;lt; 100%), we demonstrated a negative correlation showing improved EOA as HEI was reduced. Optimal cutoff catheter-heatsink distances for predicting ablation asymmetry ranged from 6.6-13.0 mm, emphasizing the impact of heatsink proximity on LITT efficacy. CONCLUSION We show that proximity to heatsinks, especially within a threshold distance of 13.0mm from the laser catheter, significantly predicts ablation asymmetry and volume in the setting of primary CNS tumors. Neurosurgeons should consider heatsink effects in pre- and intraoperative planning to optimize LITT outcomes and preserve normal brain tissue.