tbuckley/cabot-search huggingface dataset:
RADT-29. ASSOCIATION OF ANATOMIC PROXIMITY OF BRAIN PARENCHYMAL METASTASIS TO THE CSF SPACE AND UPFRONT STEREOTACTIC RADIOSURGERY TO SUBSEQUENT LEPTOMENINGEAL METASTASIS DEVELOPMENT IN BRAIN METASTATIC NSCLC
Authors: Shoaib Bashir, Weiping Hong, Mingyao Lai, Linbo Cai
Journal: Neuro-Oncology (2024)

Abstract OBJECTIVE The most common solid systemic malignancies that metastasize to the leptomeninges are lung cancer, especially non-small cell lung cancer (NSCLC). Generally, patients develop leptomeningeal metastasis (LM) subsequent to brain parenchymal metastases (BM). However, its predictors remain unknown. Hence, the present study was carried out to explore the predictors of LM in brain metastatic NSCLC patients. METHODS The final analysis included 112 pathologically definite NSCLC patients with BMs treated in our center between July 1, 2014, and December 30, 2020. Of 112, one-half had LM. Three radiologists analyzed radiologic images independently. Anatomic proximity of BMs to the CSF space (dural-based metastases, periventricular or major CSF cisterns such as basal cisterns and cisterna magna) was measured and stratified into CSF space invading/bordering and detached lesions. The endpoint was the occurrence of LM or death, whichever occurred first. Univariable and multivariable logistic regressions were performed to identify potential predictors for LM. RESULTS Of 112, 48 (42.8%) were males, and 64 (57.2%) were females. Most patients (90.2%) had adenocarcinoma histology. The median follow-up time was 10.1 months (IQR, 4.2-18.4 months) following BM diagnosis. Univariate logistic regression analysis demonstrated that histology (OR 0.084, 95%CI 0.004-0.461, P=0.020), EGFR/ALK/ROS1 mutation (OR 3.868, 95%CI 1.583-10.079, P=0.003), CSF space invading/bordering lesion (OR 10.278, 95%CI 4.203-27.375, P=0.000), extracranial metastasis control (OR 2.7, 95%CI 1.191-6.309, P=0.019), upfront stereotactic radiosurgery (SRS) (OR 0.024, 95%CI 0.001-0.12, P=0.000), and target therapy (OR 4.476, 95%CI 1.877-11.464, P=0.001) were the potential predictor. CSF space invading/bordering lesion (OR 7.443, 95%CI 2.099-32.853, P=0.003) and upfront SRS (OR 0.035, 95%CI 0.002-0.212, P=0.003) remained statistically significant in the multivariate logistic regression analysis. CONCLUSION CSF space invading/bordering BMs may increase the risk of LM development in brain metastatic NSCLC patients, while upfront SRS targeting BM potentially decreases the risk. A prospective study is warranted to affirm.
EXTH-61. TOWARDS A QUANTUM THERAPY FOR GLIOBLASTOMA: A NEW THERAPEUTIC PARADIGM IN MEDICINE
Authors: Akhil Jain, Jonathan Gosling, Shaochuang Liu, Haowei Wang, Eloise Stone, Sajib Chakraborty, Padma-Sheela Jayaraman, Stuart Smith, David B Amabilino, Mark Fromhold, Yi-Tao Long, Lluïsa Pérez-García, Lyudmila Turyanska, Simona Campora, Alessandra Lo Cicero, Giulio Ghersi, Ruman Rahman, Frankie Rawson
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND A cell operates as an interconnected bioelectrical circuit, utilising electron transfer processes for intracellular communication, with cytochrome c (Cyt c) playing a pivotal role. The redox processes of Cyt c, occurring via electron tunnelling, are essential for its translocation into the cytosol and modulation of its conformation to bind apoptotic protease activating factor 1. This highlights the need for novel technologies capable of interacting with these processes at the atomic scale to control downstream effects and induce apoptosis in cancer cells. METHODS We demonstrate that ‘bio-nanoantennae’, when supplied with an electrical current, enable quantum biological tunnelling for electron transfer (QBET) and facilitate cellular apoptosis in patient-derived IDH wild-type glioblastoma from both the infiltrative tumour margin and proliferative core. The bio-nanoantennae were constructed from gold nanoparticles functionalised with reduced Cyt c and zinc porphyrin as a redox couple. RESULTS Electrical polarisation of these bio-nanoantennae via resonant alternating currents in preclinical glioblastoma cells led to decreased metabolic activity and reduced cell viability by oxidizing Cyt c, thus inducing cellular stress. No significant effect was observed in healthy human astrocyte counterparts. The cytosol localised bio-nanoantennae induced differential gene expression related to ion channels, apoptosis, cancer proliferation and tumour suppression upon activation, in tumour relative to astrocyte cell populations. The bio-nanoantennae were also tested in 3D glioblastoma spheroid models, showing similar effects, and in vivo studies demonstrated a significant reduction in glioblastoma xenograft tumour size. CONCLUSION We propose that bio-nanoantennae modulate the redox state of Cyt c under an electrical field through QBET. To validate this, we investigated the tunnel junction energy and plasmon resonance scattering, and developed a mathematical model to explain the system’s behaviour. This innovative wireless electrical–molecular nanodevice, capable of inducing cancer cell apoptosis, paves the way for further applications of quantum signalling as a new (non-pharmacological) therapeutic paradigm.
CTNI-80. 177LU-DOTATATE IN PATIENTS WITH RECURRENT MENINGIOMA
Authors: Elham Nasrollahi, Jan Drappatz
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND There are no effective medical therapies for patients with meningioma who progress after surgical and radiotherapeutic interventions. Somatostatin receptor type 2 (SSTR2) represents a promising treatment target in meningiomas. Here, we describe our experience with use of 177Lu-DOTATE in recurrent meningioma PATIENTS AND METHODS This is a retrospective study. All patients had progressive intracranial meningiomas and were heavily pre-treated. Patients underwent 68Ga-DOTATATE PET-MRI at baseline and received 177Lu-DOTATATE every eight weeks for up to four doses. We collected patient demographics, tumor grade, treatment history prior to starting 177Lu-DOTATATE, duration of treatment, toxicities, overall survival (OS) and progression-free survival (PFS). Descriptive statistics were used to summarize patient’s characteristics. RESULTS Seven patients (female = 2, male = 5) with progressive meningiomas (WHO 1 = 1, 2 = 1, 3 = 5) were enrolled. Median age was 56 (range 41-72) years. All patients previously underwent tumor resection and at least one course of radiation. Treatment with 177Lu-DOTATATE was well tolerated. Three patients achieved PFS-6. One patient with malignant meningioma remains progression free at 13 months. Three patients remain on active treatment. Best radiographic response was stable disease (SD) in six patients. CONCLUSIONS Treatment with 177Lu-DOTATATE was well tolerated and demonstrated encouraging efficacy. Updated survival data will be presented.
INNV-33. ADVANCING PRECISION TREATMENT FOR DIFFUSE MIDLINE GLIOMA: THE DMG LEARNING HUB INITIATIVE
Authors: Nicole Lyons, Misha Mehta, Lisa Ward
Journal: Neuro-Oncology (2024)

Abstract Diffuse Midline Glioma (DMG) poses a significant challenge in neuro-oncology due to its heterogeneous presentation and limited therapeutic options. Clinical trials often serve as the primary avenue for treatment, yet families encounter numerous barriers in navigating and selecting appropriate trials. Health disparities, including disparities in medical literacy and access to specialized medical centers, further complicate decision-making processes. Existing registries lack comprehensive data integration, focusing on isolated perspectives of either research or clinical data, neglecting the holistic patient profile. Evaluation of treatment endpoints beyond Progression-Free Survival (PFS) and Overall Survival (OS) remain inconsistent, despite being a priority for families. The DMG Learning Hub emerges as a transformative platform designed to empower families by offering informed options and guidance while fostering a collaborative environment where patient families actively contribute to shaping the landscape of clinical trials. Leveraging AI-assisted matching, the platform assists families in navigating the complex decision-making process surrounding clinical trial participation. The inclusion of a patient-reported outcome journal feature enables families to track vital information such as symptom changes and supplement usage, with autonomy over the timing of shared data. Using real-time data sharing facilitates invaluable insights for researchers, bridging gaps that would otherwise be overlooked and enriching the collective understanding of DMG. Harmonizing molecular, imaging, and clinical data within the platform equips care teams with comprehensive, near-real-time information crucial for personalized treatment strategies. This integrated approach not only supports the inclusion of n-of-1 arms in current trials but also extends therapeutic opportunities to patients previously ineligible for studies due to specific disease markers or progression patterns. The DMG Learning Hub represents a significant stride towards precision oncology by synergizing patient-centric priorities with cutting-edge technology, integrating harmonized data, and fostering collaborative efforts, the initiative heralds a promising era of personalized treatment for DMG and beyond the neuro-oncology community.
STEM-09. A GROUP 3 MEDULLOBLASTOMA STEM CELL PROGRAM IS MAINTAINED BY OTX2-MEDIATED ALTERNATIVE SPLICING
Authors: Olivier Saulnier, Jamie Zagozewski, Lisa Liang, Liam Hendrikse, Paul Layug, Victor Gordon, Kimberly Aldinger, Parthiv Haldipur, Stephanie Borlase, Ludivine Coudière-Morrison, Ting Cai, Emma Martell, Naomi Gonzales, Gareth Palidwor, Christopher Porter, Stephane Richard, Tanveer Sharif, Kathleen Millen, Brad Doble, Michael Taylor, Tamra Werbowetski-Ogilvie
Journal: Neuro-Oncology (2024)

Abstract Group 3 medulloblastomas (MBs) are highly metastatic pediatric brain tumors with limited therapeutic options. The transcription factor orthodenticle homeobox 2 (OTX2) is a known driver and molecular hallmark of Group 3 MB. We previously demonstrated that OTX2 regulates Group 3 MB cell fate decisions that favor self-renewal or stemness and the retention of a primitive cerebellar rhombic lip signature. Here, we show that OTX2-regulated alternative splicing (AS) is a major driver of Group 3 MB progression. Surprisingly, the functional role of post-transcriptional events, such as AS, in Group 3 MB development has never been explored. This gene regulatory layer represents an untapped source of therapeutic targets. Using a combination of TurboID, RNA-sequencing and single cell RNA-seq, we characterized the Group 3 primary MB AS landscape with a focus on genes that control MB stem cells. OTX2 associates with the multimeric Large Assembly of Splicing Regulators (LASR) complex through protein-protein interactions and can directly or indirectly bind RNA. Together, OTX2 and LASR complex proteins oversee a pro-tumorigenic splicing program that is mirrored in the human cerebellar rhombic lip origins and is associated with Group 3γ MBs that exhibit the worst prognosis. Among our core set of OTX2-regulated spliced genes, periphilin 1 (PPHLN1) is expressed in the most primitive cerebellar rhombic lip stem cells, and mimicking PPHLN1 AS by pre-treating cells with a splice blocking antisense morpholino reduces tumor growth while increasing survival in vivo. We propose that OTX2-mediated AS is a key determinant of cell fate decisions favoring the maintenance of the stem cell state. Targeting transcription factors like OTX2 is notoriously difficult; thus, our work offers fresh opportunities to exploit MB-specific AS events therapeutically to abrogate tumor progression.
NCOG-27. HIGHER LEVELS OF SERUM ICAM-1 AND IL-10 ARE ASSOCIATED WITH COGNITIVE DYSFUNCTION IN BOTH IDH-WILDTYPE AND IDH-MUTANT GLIOMA
Authors: Vivian A Guedes, Tito Mendoza, Kaitlynn Slattery, McKenzie C Kauss, Dhaivat Raval, Emory Hsieh, Michelle L Wright, Tara S Davis, Ann Choi, Kimberly Reinhart, Hope Miller, Elizabeth Vera, Marta Penas-Prado, Mark R Gilbert, Terri S Armstrong
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Cognitive dysfunction is common among glioma patients, but the contribution of specific mechanisms to the development of cognitive symptoms is unclear. Circulating levels of proteins linked to neurodegeneration, inflammation, and vascular damage have been associated with cognitive symptoms in neurological diseases and aging, but their prognostic value in glioma is unknown. Here, we examined associations between cognitive symptoms and serum levels of protein biomarkers in glioma patients. METHODS Cognitive function was evaluated using the Montreal Cognitive Assessment (MoCA, scores ≤ 25 = cognitive dysfunction). Cytokines (interleukin-1β [IL-1β], IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, interferon-γ [IFN-γ], tumor necrosis factor-α [TNF-α]), and neurodegeneration (neurofilament light chain [NfL], tau, glial fibrillary acidic protein [GFAP]), and vascular damage markers (Serum amyloid A [SAA], C-reactive protein [CRP], vascular cell adhesion molecule 1 [VCAM-1], and intercellular adhesion molecule 1 [ICAM-1]) were measured using ultrasensitive assays (Meso Scale Discovery). RESULTS Patients (n=73) were predominantly male (58%), white (74%), with a median age of 44 (range=24,74). Cognitive dysfunction was found in 53% of the patients. Levels of NfL (p=0.035), IL-6 (p=0.006), IL-10 (p=0.007), TNF-α (p=0.035), IFN-γ (p=0.011), CRP (p=0.016), VCAM-1 (p=0.012), and ICAM-1 (p&amp;lt;0.001) were higher in patients with cognitive dysfunction when compared to those with normal cognition. After adjusting for isocitrate dehydrogenase (IDH) tumor mutation status, age, tumor grade, and number of surgeries, higher levels of ICAM-1 and IL-10, but not other markers, remained associated with cognitive dysfunction. MoCA scores were negatively correlated with GFAP (r=-0.24, p=0.038), IFN-γ (r=-0.31, p=0.008), IL-6 (r=-0.29, p=0.014), IL-10 (r=-0.24, p=0.039), and ICAM-1 (r=-0.39, p&amp;lt;0.001). CONCLUSIONS ICAM-1 and IL-10 levels were higher in patients with MOCA determined cognitive dysfunction, suggesting an association between cognitive symptoms and inflammation and vascular impairment in glioma patients. Future analyses in larger longitudinal cohorts are warranted to assess the predictive value of protein biomarkers.
EPCO-36. INTEGRATIVE DEEP-LEARNING AND PHARMACOGENOMIC PROFILING OF MALIGNANT GLIOMAS USING PATIENT-DERIVED TUMOR CELLS
Authors: Seung-Won Choi, Vinay Swamy, Seung Yoon Hyun, Nam-Gu Her, Doo-Sik Kong, Jung Won Choi, Ho Jun Seol, Jung-Il Lee, Do-Hyun Nam, Raul Rabadan
Journal: Neuro-Oncology (2024)

Abstract Malignant glioma stands as a formidable cancer with limited therapeutic options due to many factors including pronounced genetic heterogeneity, the blood-brain barrier, among others. Precision medicine, tailoring treatment based on a patient’s unique molecular profiles, is a fitting approach for addressing intra- and inter-tumor heterogeneity. Previously, we have shown the advantage of using patient-derived tumor cells (PDCs) to evaluate drug efficacy across various cancer types. Unlike cancer cell lines, which significantly differ from primary tumors, PDCs capture the molecular features of primary tumors, showing predictive clinical responses in a retrospective study. Building on these encouraging results, we have expanded PDC-based drug screening to specifically target malignant gliomas. We have established an initial cohort of over 500 malignant glioma PDCs (~ 370 patients) and screened more than 100 drugs. We have complemented our cohort with molecular profiles, including genomic and transcriptomic data to infer the potential pharmacogenomic associations of malignant gliomas. We constructed a multi-modal deep-learning model that seamlessly integrates molecular features and drug structure to predict the drug sensitivity. By employing an explainable machine learning method, we retrospectively analyzed the model to investigate the potential molecular biomarkers and their contribution to drug sensitivity. Collectively, our study demonstrates the efficacy of using patient-derived tumor cells (PDCs) combined with deep-learning models to predict drug sensitivity in malignant gliomas. This integrative approach can potentially refine personalized treatment strategies and improve clinical outcomes for glioma patients.
QLTI-16. QUALITY IMPROVEMENT PROJECT (QIPR) FOR IMPLEMENTATION OF PSYCHOSOCIAL ASSESSMENTS FOR ONCOLOGY CLINICAL CARE
Authors: Anjelica Body, Hannah Johnson, Drashti Patel, Deidre Pereira, Ashley Ghiaseddin
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Patient-reported outcomes (PROs) have been used to assess individuals’ quality of life (QoL) throughout cancer treatment. Individuals with cancer often experience physical, psychological, and social challenges. It is crucial to evaluate their QoL to provide supportive care services to improve survival and treatment outcomes in real-world cancer clinical settings. Patients’ ability to engage with completing PROs is critical to ensuring PRO implementation efficacy. This QIPR (UF: 2216) examined these completion rates in coordinated medical-behavioral cancer care. METHODS Questionnaires delivered to neuro-oncology and psycho-oncology patients through the electronic health record (EHR) prior to scheduled office visits were: PROMIS – Anxiety, Depression, Pain Interference, Ability to Participate in Social Roles, and Cognitive and Physical Function. Data collection occurred from July 2023-January 2024. Descriptive statistics were calculated to assess battery completion rates. Information from the first 3 encounters following initiation of the battery into clinical practice were analyzed. RESULTS Of 906 scheduled encounters, 491 (54.2%) were attended by 280 unique patients. The battery was completed at least once by 106 (37.9%) patients. 72.6% (N=77) of these patients completed the battery at the first scheduled visit at which it was assigned. Of patients with 2 scheduled visits (N=25, 23.6%); 24.0% (N=6) completed the battery at both visits. Of patients that had 3 scheduled visits (N=12, 11.3%); 16.7% (N=2) completed it at all 3 visits. CONCLUSION Only approximately 38% of patients completed the battery at least once across 3 consecutive visits. The highest battery completion rate was at the first visit at which it was assigned. Completion rates were lower across additional visits. Future work will seek to understand barriers and facilitators of these completion rates to optimize implementation of PROs in coordinated medical-behavioral oncology care.
QOL-09. “I’VE DEFINITELY CHANGED WHO I AM”: A THEMATIC ANALYSIS OF CHALLENGES FACED BY PATIENTS WITH IDH-MUTANT GLIOMAS
Authors: Daniel Chiu, Jessica Whitman, Sumita Strander, Kelcie Willis, Jennifer Temel, Lara Traeger, Deborah Forst
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Despite their more favorable prognosis, patients with isocitrate dehydrogenase (IDH)-mutant gliomas experience significant psychological distress across their disease trajectory. The specific drivers of distress in this population are poorly understood, and interventions to support these patients are lacking. We sought to better characterize drivers of distress and ways to enhance support for patients with IDH-mutant gliomas as they confront potentially prolonged but ultimately unpredictable survival with an incurable, progressive brain tumor. METHODS Eligible individuals were English-speaking adults ages 65 and younger diagnosed with an IDH-mutant glioma at a single academic medical center. We conducted semi-structured interviews (N=20) to better understand the distress patients experience as they progress along their illness trajectories. We audio-recorded and transcribed interviews and analyzed interview content using reflexive thematic analysis. RESULTS Distress among participating patients (female = 7/20; age &amp;lt;40 years = 10/20) was linked to their struggles to maintain a coherent sense of identity while adapting to 1) neurocognitive changes and 2) altered life plans amidst prognostic uncertainty. Patients described feeling self-conscious and distrustful of their cognitive capacities, frequently comparing their current performance to their premorbid functioning (e.g. by checking their symptoms and indexing perceived deficits against scan results). Patients felt overwhelmed by the need to make decisions and set priorities (e.g., regarding family planning, retirement) due to the uncertain timing of their tumor’s progression and its unclear impact on their future functioning. Patients identified the transition from treatment to surveillance as a time of heightened worry, as they shifted their focus from the logistics of cancer care to the task of planning – financially, occupationally, socially – for an uncertain future. CONCLUSION These findings highlight the need for tailored supportive care to help patients with IDH-mutant gliomas cope with the distress caused by significant changes to identity and ongoing uncertainties regarding their future.
NIMG-54. AUTOMATED IMAGING RESPONSE EVALUATION SYSTEM (AIRES) FOR NEURO-ONCOLOGY: PROTOTYPE SOFTWARE TOOL FOR DETERMINING STANDARDIZED RADIOGRAPHIC RESPONSE ASSESSMENT FOR GLIOBLASTOMA CLINICAL TRIALS
Authors: Ashley Teraishi, Francesco Sanvito, Nicholas Cho, Catalina Raymond, Albert Lai, Phioanh Nghiemphu, Noriko Salamon, Timothy Cloughesy, Benjamin Ellingson
Journal: Neuro-Oncology (2024)

Abstract Standardized radiographic response assessment criteria like Modified Response Assessment in Neuro-Oncology (mRANO) and now the RANO 2.0 are utilized for evaluating progression-free survival and objective response rate during glioblastoma clinical trials. After measuring tumor size with either bidimensional diameters or volumetric segmentations, the crucial and final time-consuming step of categorizing progression, stable disease, and response based on multiple criteria and numerical thresholds (e.g. ≥40% volumetric growth = progressive disease) is currently done manually. We developed an application prototype, Automated Imaging Response Evaluation System (AIRES) for Neuro-Oncology, that uses the mRANO criteria to label each timepoint as treatment response, stable disease, or disease progression based on either bidimensional or volumetric measurements as well as optional inputs of clinical status and corticosteroid dosage. These inputs may be uploaded via CSV files, which can integrate with automated tumor segmentation volumetry workflows, or entered in the AIRES graphical user interface (GUI). The AIRES GUI displays a patient report consisting of a table and graph that contain the lesion size, percent change from baseline, percent change from nadir, and the mRANO response category for each timepoint. To test AIRES in a real-world application, tumor size measurements from 367 scans across 41 patients from NUTMEG, a phase II multicenter clinical trial, were used to perform mRANO reads and calculate progression-free survival and time to response. AIRES-assisted reads performed by reader 1 were significantly quicker than fully manual reads performed by reader 2 (37.1±8.6 vs 107.7±58.6 seconds, P&amp;lt;0.0001). These results show that the AIRES app can make the reads quicker and potentially feasible for non-trained personnel, while reducing the amount of error-prone manual steps. Additionally, the underlying logic of AIRES is easily adaptable to integrate other response criteria including but not limited to RANO 2.0 and other future response assessment updates.