tbuckley/cabot-search huggingface dataset:
PATH-36. DO GENE EXPRESSION PROFILES BETTER PREDICT OLIGODENDROGLIOMA SURVIVAL?
Authors: Vijaylaxmi Roy, Devraj Lath, Vijay Sreegiriraju, Subhashini Sadasivam, Yashoda Ghanekar, Pallavi Goel, Neha Kumari, Vikas Pawar, Surya Madiraju, Amit Ray
Journal: Neuro-Oncology (2024)

Abstract The WHO 2021 classification of oligodendroglioma grade 2 (G2) and grade 3 (G3), is separated by histopathology alone and does not universally reflect survival outcome. DNA methylation-based profiling also fails to separate oligodendroglioma grades. Our aim was to define transcriptome-based molecular subgroups that predict survival of oligodendroglioma (IDH-mutant and 1p/19q-codeleted) patients. Clinical and whole-transcriptome data for oligodendroglioma were obtained from TCGA (n=132), CGGA (n=53), and the Exsegen Genomics Research Biobank (n=16) (CTRI/2021/09/036861); while that of control brain samples (n=9) were obtained from CPTAC. Overall survival (OS) was significantly different in TCGA samples between WHO CNS G2 and G3 oligodendrogliomas (log-rank test, p=0.0001); but, not in CGGA (p=0.1833) or Exsegen (p&amp;gt;0.06) samples. Genes with highly variable expression (Median Absolute Deviation, i.e. MAD&amp;gt;1; 1645 genes) across TCGA oligodendroglioma and CPTAC control brain samples were used to exclude 9 oligodendroglioma samples with Pearson’s correlation&amp;gt;0.75 with control brain samples. Consensus clustering (K-means and spectral) of remaining 124 TCGA oligodendroglioma samples identified three significantly different (SigClust, p&amp;lt;0.05) transcriptomic classes using 1347 highly variable genes (MAD&amp;gt;1) in these samples. Principal component analysis (PCA) on expression of 1347 genes in TCGA samples revealed partial overlap of G2 and G3 tumours; but transcriptomic classes with distinct OS could be identified at both extremes of survival. Gene expression signatures for each transcriptomic class were developed using core TCGA samples from each class. For further validation, gene signatures were used to predict the transcriptomic classes of CGGA and Exsegen samples based on highest cosine similarity between sample gene expression and gene signature of each transcriptomic class. OS was significantly different between the transcriptomic classes in TCGA samples and predicted ones in CGGA samples. Transcriptome profiling separated oligodendrogliomas into distinct classes which can predict survival and potentially augment grading and refine prognostication and treatment options.
EXTH-38. EVALUATION OF STORAGE CONDITIONS ON SERUM-DERIVED EXTRACELLULAR VESICLES IN BRAIN TUMOR SAMPLES
Authors: Pallavi Goel, Neha Kumari, Inderjeet Kaur, Yashoda Ghanekar, Subhashini Sadasivam, Vikas Pawar, Surya Madiraju, Amit Ray
Journal: Neuro-Oncology (2024)

Abstract Tumor-derived Extracellular Vesicles (EVs) are emerging as potential liquid biopsy tool in the field of cancer diagnosis and therapeutic targets. The functionality of EVs depends on its diverse cargo, which is known to alter host-receipient cells. Nevertheless, extracting EVs while preserving its integrity and functionality of its contents is challenging, specifically in Low-middle Income countries (LMIC) countries. Our study focussed on extraction of serum derived EVs analysis from brain-tumor samples encompassing Oligodendrogliomas, Astrocytomas and Glioblastomas. The stability of EVs were examined in serum stored for 2 years at -80°C to understand the effect of preservation and storage in different conditions, that were left exposed to room temperature for variable periods of time before freezing. To explore the optimal suitable conditions, EVs were isolated from serum samples using IZON column size-exclusion based-method, and evaluated for structural integrity and stability through nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM) technology. Interestingly, the majority of isolated vesicles exhibited round, intact structure with bilayer membrane of size varying between 30 - 250nm. Moreover, protein content of EVs positive markers (CD63, CD81 and CD9) was also detected with minimal contaminations evidenced by weak bands for negative marker (ApoB), as determined by Western blot analysis. Further, column-based EV-derived RNA demonstrated optimal yield and purity was confirmed by RNA integrity number (RIN) using Qubit. While cryopreservation had minimum detrimental effects on mRNA sample quality, leaving it exposed to room temperature before freezing had a significant effect on EV isolation, as samples were often haemolyzed. This will provide insights in optimizing pre-analytical and analytical procedures for more effective outcomes in the clinical setting
BIOS-04. THERAPIES FOR LEPTOMENINGEAL DISEASE: A NETWORK META-ANALYSIS
Authors: Vinay Suresh, Suhrud Panchawagh, Muneeb Muneer, Alireza Mansouri, Ahmad Ozair
Journal: Neuro-Oncology (2024)

Abstract INTRODUCTION Leptomeningeal disease (LMD) has limited head-to-head comparison of available therapies, including systemic chemotherapy (SysCT), intrathecal (IT) or intraventricular therapy (ITV), whole-brain radiotherapy (WBRT), or cranio-spinal irradiation (CSI). No network meta-analysis (NMA) of randomized controlled trials (RCTs) of LMD has been reported so far. METHODS NMA was conducted using published LMD RCTs and reported following PRISMA-NMA guidelines. Primary outcome was survival, assessed using hazard ratios (HRs) and 95% confidence intervals (95%CI). Survival times were converted to HRs under exponential distribution assumption. LogHR standard errors were calculated using deaths per RCT arm. P-scores were used to estimate probability of treatment being superior. Analysis was performed in R using frequentist approach, followed by back-transforming logHRs for indirect and direct comparisons. Incremental effects of individual treatment components were estimated using additive model. Heterogeneity and inconsistency were assessed using tau-squared (τ²), I-squared (I²), and Q-statistics. Analyses were performed separately for main subnetwork with disconnected subnetworks accommodated in additive model. RESULTS Seven studies were included, incorporating 7 pairwise comparisons and 9 treatments. 3 subnetworks were identified. Primary subnetwork analysis included 5 studies. Compared to SysCT±RT (reference), logHRs (95%CI) under random effects model were: IT/ITV DepoCyt±SysCT±RT -0.094(-0.468,0.281); IT/ITV methotrexate(MTX)±cytarabine(AraC)±SysCT±RT 0.8567(0.066,1.647). IT/ITV MTX±SysCT±RT 0.318(-0.163,0.798); ITV Thiotepa±SysCT±RT 0.438(-0.294,1.169). Heterogeneity and inconsistency were not detected (τ²=0,I²=0%,Q-statistic=0.57,P=0.45). P-scores were highest for IT/ITV DepoCyt±SysCT±RT (0.894), followed by SysCT±RT (0.769). Disconnected-component-NMA demonstrated incremental logHR: AraC 0.539(-0.347,1.425); IT/ITV DepoCyt 0.052(-0.566,0.670); IT/ITV MTX 0.179(-0.484,0.840); ITV thiotepa 0.298(-0.767,1.362); proton CSI -0.250(-0.726,0.225). No component demonstrated statistically significant incremental benefit, with moderate heterogeneity and adequate fit present (τ²=0.1017,I²=57%,Q-statistic=4.65,P=0.098). CONCLUSIONS IT/ITV DepoCyt±SysCT±RT and SysCT±RT were found most effective. Lack of significant incremental benefit warrants evaluating older therapies in contemporary RCTs.
EPID-24. OPTIMIZING PATIENT RECRUITMENT FOR BRAIN TUMOR STUDIES: LEVERAGING THE POWER OF GOOGLE ADS TO CONNECT WITH AFFECTED FAMILIES
Authors: Sofia Kakaizada, Matthew Bainbridge, Georgina Armstrong, Melissa Bondy
Journal: Neuro-Oncology (2024)

Abstract OBJECTIVE We assessed the effectiveness of using Google Ads to recruit individuals with familial glioma into a genetic research study. METHODS We conducted a comparative analysis between two periods: March 1 to June 30, 2023 (with Google Ads) and March 1 to June 30, 2021 (without Google Ads). We targeted individuals searching for brain tumor information using Google Ads, directing them to a study landing page. We analyzed metrics such as advertisement clicks, impressions, click-through rate, and cost per click. Our eligibility criteria included families with at least two members having glioma, with one currently living with the condition, aged 18 or older, and residing in the United States. RESULTS The 2023 Google Ads campaign generated 7,228 clicks, 82,242 impressions, an 8.79% click-through rate, and a cost per click of $0.62. The number of interested individuals increased from 13 in 2021 (without Google Ads) to 35 in 2023 (with Google Ads), with 20 indicating they found the study through Google Ads. However, the increase lacked statistical significance (x2=1.48, p=0.22). CONCLUSION Google Ads enhanced our participant outreach and recruitment for the glioma study, although the results were not statistically significant. This approach shows promise for recruiting participants for rare disease research. We recommend that future studies consider longer durations and larger sample sizes to better assess its impact. Additionally, due to the prevalence of misinformation about familial glioma, we submitted and conducted a survey to the Society of NeuroOncology to evaluate the attitudes and beliefs of physicians and other healthcare professionals towards familial glioma. This survey aims to address misconceptions and improve understanding within the healthcare community.
NIMG-78. THE ROLE OF FDG PET/CT IN MANAGING DIFFUSE MIDLINE GLIOMA WITH H3K27M MUTATION: A CASE STUDY AND PATHOLOGICAL CORRELATION
Authors: Yoon Choi, Xiao-Tang Kong
Journal: Neuro-Oncology (2024)

Abstract The clinical utility of fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) in the management of high grade gliomas has been a topic of ongoing debate, with limited cases reported that correlated FDG PET/CT findings with pathology, particularly in diffuse midline glioma with HdK27M mutation cases. We present the case of a 24-year-old male patient with diffuse midline glioma with H3K27M mutation centered in the left thalamus. Head FDG PET/CT was used for clinical management decisions with pathological correlation. Patient had stable follow up brain magnetic resonance images(MRIs) after initial Stupp protocol treatment comprised 6-week radiation therapy with concurrent temozolomide, followed by 12 cycles of adjuvant temozolomide. Despite stable MRI scans, subsequent evaluation using FDG PET/CT demonstrated a high standardized uptake value (SUV) of 13.8 that prompted craniotomy and partial resection of the lesion to confirm tissue diagnosis. Pathological findings confirmed the persistence of densely cellular malignant glioma, but with Ki-67 proliferation index of 4-5%. Following the surgery, the patient was closely monitored with surveillance MRIs for approximately four months post-surgery and follow up MRI’s showed slow growth of the tumor prompting additional therapeutic interventions. This case is an example of FDG PET/CT and pathological correlation and highlights the potential role of FDG PET/CT as an adjunctive imaging tool in the management of high grade gliomas.
PATH-32. THE PROGNOSTIC IMPACT OF CDKN2A/B HETEROZYGOUS DELETIONS IN IDH-MUTANT GLIOMA
Authors: Franziska Maria Ippen, Thomas Hielscher, Dennis Friedel, Kirsten Göbel, David Reuss, Christel Herold-Mende, Sandro Krieg, Andreas von Deimling, Wolfgang Wick, Felix Sahm, Abigail Suwala
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Homozygous deletions of CDKN2A/B have been shown to be a prognosticator for an unfavorable prognosis in gliomas, but the role of heterozygous CDKN2A/B deletions remains less well understood. The aim of this study was to assess the prognostic impact of CDKN2A/B heterozygous deletions in IDH-mutant low-grade astrocytoma and oligodendroglioma. METHODS Tissue samples diagnosed as astrocytoma, IDH-mutant and oligodendroglioma, IDH-mutant, 1p/19q co-deleted CNS WHO grade 2 and 3 were collected from the archive of the Institute of Neuropathology in Heidelberg. DNA methylation analysis was performed on formalin-fixed paraffin-embedded (FFPE) samples. Evaluation of the CDKN2A/B locus was performed by visual inspection of copy-number plots derived from methylation-array data for each case. Heterozygous and homozygous losses were assessed in relation to whole chromosomal or larger segmental losses and gains in the chromosomal profile. Survival probabilities were assessed using the Kaplan–Meier method. RESULTS A total of 334 low-grade glioma cases were identified. Those cases included 173 astrocytomas and 161 oligodendrogliomas. Heterozygous deletions in CDKN2A/B (37/173 in astrocytomas, 15/161 in oligodendrogliomas) did not confer worse survival outcomes compared to CDKN2A/B wildtype cases in neither low grade astrocytoma (p= 0.2556) nor oligodendroglioma (p= 0.2760), regardless of CNS WHO grade, which was further validated on a subgroup of astrocytoma, IDH mutant CNS WHO 4 cases (p= 0.1680). CONCLUSION In summary, our study suggests that heterozygous CDKN2A/B deletions do not confer worse survival rates with respect to OS and PFS in astrocytoma, IDH-mutant and oligodendroglioma, IDH-mutant, 1p/19q co-deleted CNS WHO grade 2 and 3.
NIMG-33. HIGH-RESOLUTION SODIUM MRI OF HUMAN GLIOMAS AT 3T USING PHYSICS-BASED GENERATIVE AI
Authors: Catalina Raymond, Jingwen Yao, Thorsten Feiweier, Bryan Clifford, Heiko Meyer, Xiaodong Zhong, Alfredo L Lopez Kolkovsky, Francesco Sanvito1, Sonoko Oshima, Nicholas S Cho, Noriko Salamon, Richard Everson, Timothy F Cloughesy, Benjamin M Ellingson
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Sodium neuroimaging is a promising technique for diagnosing and monitoring brain tumors, providing insights into microenvironment and metabolism. However, at 3T, it is limited by low signal-to-noise ratio and resolution, resulting in long acquisition times and low-quality images. To address these limitations, we developed a physics-informed generative adversarial network (GAN) approach for high-resolution sodium neuroimaging of brain tumors at 3T. METHODS 5,078 anatomical sequences from 1,330 brain tumor patients undergoing routine proton MRI were used to create a synthetic dataset with physics-based simulated artifacts, including B0 magnetic susceptibility artifacts, chemical shift artifacts, Nyquist aliasing artifacts, Gibbs artifacts, and low-resolution images, with Rician noise added during training to augment the dataset. By using multiple proton MRI contrasts, we hypothesized that the GAN model would learn to correct artifacts while preserving the inherent contrast information. We employed a transfer learning approach with a modified Pix2PixGAN architecture and an Attention-R2UNet generator. Twenty glioma patients consented to participate in this IRB-approved prospective study. Sodium and proton MRIs were acquired in the same sessions using a 3T Siemens scanner using a dual-tuned head coil, with a 3D spoiled gradient-echo sequence optimized for short TE. Sodium-proton exchanger (NHE1) expression was tested with immunohistochemistry from image-guided surgical biopsies. RESULTS High-resolution synthetic-sodium MR images were generated using the GAN model. The proposed method successfully reconstructed high-resolution synthetic-sodium MR images with improved SNR compared to traditional sodium images. Synthetic and native measurements were strongly correlated (R2=0.8539, P&amp;lt;0.0001). A significant correlation was seen between synthetic-sodium MR measurements and relative NHE1 tissue expression (ρ=0.5817, P=0.0036). CONCLUSION Results suggest that high-resolution synthetic-sodium MRI retains much of the inherent information from native sodium MR while accurately representing NHE1 expression. This approach could make high-resolution sodium neuroimaging at 3T feasible in the clinical environment, potentially improving diagnosis, monitoring, and treatment of brain tumors.
EPID-25. A SEER-MEDICARE ANALYSIS OF EXPOSURE TO COMMONLY USED MEDICATIONS AND 1-YEAR SURVIVAL IN GLIOBLASTOMA
Authors: Roshani Shah, Patrick Moeller, Scott Keith, Richard Hass, Wenyin Shi, Vittorio Maio, Iyad Alnahhas
Journal: Neuro-Oncology (2024)

Abstract OBJECTIVES Despite of research efforts, glioblastoma (GBM) remains a deadly disease. We aimed to evaluate the effects of commonly used medications on survival in GBM. METHODS We performed a retrospective cohort study and utilized the Surveillance, Epidemiology, and End Results (SEER) national cancer registry database linked with Medicare data to identify patients 66 years and older diagnosed with GBM between 1/1/2008 and 12/31/2019. Patients were excluded if they did not receive treatment after diagnosis. We evaluated several medication groups including metformin and oral hypoglycemics, insulin, fluoxetine, statins, beta-blockers, ACE inhibitors and NSAIDs. Mortality was captured within 1 year after diagnosis. Patients were identified as exposed to the medications if they filled at least 1 prescription between 3 months prior to and 9 months after diagnosis. RESULTS 9,641 GBM patients were included. 54.4% were male and the mean age was 73.8 ± 5.8 years. As expected, patients 66-70 years of age had the best survival compared to the older age groups. Similarly, patients diagnosed between 2017-2019 had the best survival compared to patients diagnosed in prior years. Moreover, patients with the highest Charlson Comorbidity Index scores had the worst prognosis. Obesity specifically had no effect on survival. Patients who underwent any resection had better survival and patients who received both radiation and chemotherapy had better survival compared to patients who received only one treatment modality. 15.5% of patients were exposed to insulin at 1 year and had worse prognosis (OR 1.65, CI 1.42-1.91). 3.4% of patients were exposed to fluoxetine at one year and surprisingly had worse prognosis (OR 1.35, CI 1.03-1.76). None of the other medication groups had significant effects on survival. CONCLUSION Our study suggests that exposure to insulin and fluoxetine negatively affects survival in GBM. Stratification of patients per molecular subgroups is necessary for more accurate conclusions.
NCMP-30. GLUCOCORTICOID-INDUCED HYPERGLYCEMIA IN BRAIN TUMOR PATIENTS: A SINGLE CENTER RETROSPECTIVE STUDY
Authors: Obiora Okoye, Katlyn Hurst, Brayan Corona-Macedo, Oluwamuyiwa Folarin, Morgan Jones, Atil Kargi, Yasmeen Rauf, Dominique Higgins
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Glucocorticoid (GC) therapies are integral in managing brain tumor-associated cerebral edema and neurological deficits in the neuro-oncology perioperative setting. Despite their effectiveness, GCs can induce significant morbidity, including hyperglycemia. METHODS This single-center retrospective study at the University of North Carolina neurological surgery department examines the incidence and risk factors for glucocorticoid-induced hyperglycemia in brain tumor patients treated with high-dose GCs. Data from clinical databases, electronic medical records, laboratory systems, and pathology information banks will be utilized. Documented glucose measurements, glycated hemoglobin test (HbA1c) and clinical outcomes (mortality, infection, hypoglycemia) in brain cancer patients treated with Glucocorticoid (GC) that developed hyperglycemia will be compared with brain tumor patient with normoglycemia. RESULTS We will document the total number of brain tumor patients referred over the study period, eligibility rates, and the percentage that developed glucocorticoid-induced diabetes (defined as two glucose measurements ≥200 mg/dL within the first week of treatment). Timing of hyperglycemia onset, treatments received, and risk factors for developing glucocorticoid-induced diabetes will also be analyzed. CONCLUSIONS The findings could underscore the necessity for proactive screening for glucocorticoid-induced diabetes in brain tumor patients to mitigate the associated morbidity. This study may guide future research on the benefits of optimized glucose control on clinical outcomes in patients with GC-induced hyperglycemia. Keywords: brain tumor, steroid-induced hyperglycemia, glucocorticoid-induced diabetes, dysglycemia, risk factors, outcomes.
EOLP-01. PROPOSED FRAMEWORK FOR A PILOT MULTIDISCIPLINARY BEREAVEMENT FOLLOW-UP AND BRAIN AUTOPSY REVIEW FOR BEREAVED CAREGIVERS IN PEDIATRIC NEURO-ONCOLOGY
Authors: Mariah Wright-Nadkarni, Megan Schaefer, Emily Moscato, Joseph Stanek, Cynthia Gerhardt, Maryam Fouladi, Priyal Patel, Margot Lazow
Journal: Neuro-Oncology (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.