tbuckley/cabot-search huggingface dataset:
CTNI-02. FLUORESCEIN-STAINED CONFOCAL LASER ENDOMICROSCOPY VERSUS CONVENTIONAL FROZEN SECTION FOR INTRAOPERATIVE HISTOPATHOLOGICAL ASSESSMENT OF INTRACRANIAL TUMORS
Authors: Arthur Wagner, Maria Charlotte Brielmaier, Charlotte Kampf, Lea Baumgart, Amir Kaywan Aftahy, Hanno-Sebastian Meyer, Victoria Kehl, Julius Höhne, Karl-Michael Schebesch, Nils Ole Schmidt, Saida Zoubaa, Markus Riemenschneider, Miriam Ratliff, Frederik Enders, Andreas von Deimling, Friederike Liesche-Starnecker, Claire Delbridge, Jürgen Schlegel, Bernhard Meyer, Jens Gempt
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND The aim of this clinical trial was to compare Fluorescein-stained intraoperative confocal laser endomicroscopy (CLE) of intracranial lesions and evaluation by a neuropathologist with routine intraoperative frozen section (FS) assessment by Neuropathology. METHODS In this phase II non-inferiority, prospective, multicenter, non-randomized, off-label clinical trial (Eudra-CT: 2019-004512-58), patients above the age of 18 years with any intracranial lesion scheduled for elective resection were included. The diagnostic accuracies of both CLE and FS referenced with the final histopathological diagnosis were statistically compared in a non-inferiority analysis, representing the primary endpoint. Secondary endpoints included the safety of the technique and time expedited for CLE and FS. RESULTS 210 patients were included by 3 participating sites between November 2020 and June 2022. Most common entities were high grade gliomas (37.9%), metastases (24.1%), and meningiomas (22.7%), A total of 6 serious adverse events in 4 (2%) patients were recorded. For the primary endpoint, the diagnostic accuracy for CLE was inferior with.87 versus.91 for FS, resulting in a difference of.04 (95% confidence interval -.10;.02; p=.367). The median time expedited until intraoperative diagnosis was 3 minutes for CLE and 27 minutes for FS, with a mean difference of 27.5 minutes (standard deviation 14.5; p&amp;lt;.001). CONCLUSION CLE allowed for a safe and time-effective intraoperative histological diagnosis with a diagnostic accuracy of 87% across all intracranial entities included. The technique achieved histological assessments in real-time with a tenfold reduction of processing time compared to FS, which may invariably impact surgical strategy on the fly.
NIMG-66. DEFINING PROGRESSIVE DISEASE: LOCALIZING VOXEL-AT-RISK ON MAGNETIC RESONANCE IMAGING USING DEEP LEARNING
Authors: Nicolas Freeman, Ian Pan, Gilbert Youssef, Patrick Wen, Raymond Huang
Journal: Neuro-Oncology (2024)

Abstract Follow-up magnetic resonance imaging (MRI) of post-treatment glioblastoma (GBM) can be diagnostically challenging in differentiating progressive disease (PD) from coexisting treatment-related changes. The study aim was to train a machine learning model using multiple MRI timepoints from treated GBM patients with subsequent PD or at least six months of tumor-like, persistently stable disease (SD) to estimate PD risk. A retrospective, post-treatment GBM cohort (n=189) with 453 timepoints was identified with available MRI sequences (T1-weighted with and without contrast, T2-weighted, and fluid-attenuated inversion recovery). PD cases (n=154) showed new, enhancing PD followed by death within 3-6 months; timepoints included the MRI on the PD diagnosis date and the one directly prior. SD cases (n=35) exhibited stable, tumor-like enhancement over timepoints. Cases underwent voxel-wise annotation of PD versus SD. A multiclass, three-dimensional nnU-Net was trained to label voxels as PD, SD, or neither using timepoint sequences with five-fold cross-validation. Model performance was assessed using the ratio of predicted PD/SD voxels compared to each case’s actual PD or SD status. Classification accuracy of PD versus SD status, PD case-wise sensitivity and specificity, and a Receiver Operating Characteristic (ROC) analysis using the PD/SD ratio were presented. The five-fold model ensemble was evaluated on a holdout test set. Validation set performance showed 74.3% accuracy, 0.73 PD case-wise sensitivity, and 0.80 specificity. The holdout set exhibited 79.8% accuracy, 0.81 sensitivity, and 0.78 specificity for PD cases. The ROC analysis showed an area under the curve of 0.80 and 0.83 on the validation and holdout sets, respectively. The model showed high performance and classification accuracy in predicting which voxels were at risk of PD in post-treatment GBM cases. The model also differentiated between PD and SD regions. The model’s predicted PD/SD ratio may be clinically used to stratify patients’ PD risk.
BIOM-07. SURVIVAL-ASSOCIATED GENETIC VARIATIONS IN TAIWANESE GLIOBLASTOMA MULTIFORME PATIENTS - A RETROSPECTIVE NGS STUDY
Authors: Yu-FEN Huang
Journal: Neuro-Oncology (2024)

Abstract This retrospective study, conducted at Taichung Veterans General Hospital in Taiwan, employed Next-Generation Sequencing (NGS) technology to analyze genetic variations associated with survival in patients with glioblastoma multiforme (GBM). The study encompassed 30 newly diagnosed GBM patients, divided into two groups based on survival duration: long-term (over two years) and short-term (under two years). The findings are outlined below: Key Mutations: Significant mutations included CHEK2, IDH1, and TP53, along with variations in the TERT promoter and TP53 RNA splicing sites. Correlation Between Mutations and Survival: Contrary to Western data, TP53 mutations were more prevalent in the long-term survival group, suggesting that regional genetic differences may influence GBM prognosis. Therapeutic Effectiveness: The application of bevacizumab was significantly associated with improved survival rates, indicating its potential efficacy in treatment. The study highlights the critical role of personalized medicine in the treatment of GBM in Taiwan and points to the necessity of further research into the genetic characteristics and treatment responses of GBM patients in Taiwan and potentially other non-Western regions. These insights underline the importance of continuing to explore effective personalized treatment strategies and enhancing our understanding of genetic determinants in diverse populations. Moreover, the prevalence of certain mutations in Taiwanese patients, which differ from those commonly observed in Western populations, prompts a reevaluation of global treatment frameworks and suggests the potential for region-specific therapeutic protocols. The implication of these findings extends beyond immediate clinical applications, providing a foundation for future clinical trials and research into genetic markers that could dictate treatment choices. In conclusion, this study not only underscores the importance of individualized treatment plans based on genetic profiling but also highlights the variations in genetic mutations across different populations, which could have profound implications for the management of GBM worldwide. Further investigation into these disparities and their implications on treatment efficacy is essential for advancing GBM treatment and improving patient outcomes globally.
NIMG-56. MAGNETIC RESONANCE SPECTROSCOPY IN THE POST-TREATMENT METABOLIC CHARACTERIZATION OF BRAIN TUMORS OF GLIAL ORIGIN OF CENTRAL NERVOUS SYSTEM
Authors: Pablo Moreno Acosta, Gina Malaver, Trinidad González Padin, Oscar Gamboa, Carla Singh, Cesar Rodriguez, Josep Balart, Camilo Zubieta, Wafa Bouleftour, Nicolas Magné, Pedro Penagos, Daniel Fino
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND and Purpose Central Nervous System tumors have a very low incidence worldwide, however they constitute an important source of mortality and morbidity. Treatment for these types of tumors in adults may include surgery, radiosurgery, radiation therapy, chemotherapy, and targeted treatment. These treatments in brain tumors of glial origen in adults can produce changes in the pathophysiology of the tumor. The purpose of this study was to characterize the different metabolic patterns as effect of treatment and identify tumor recurrences. Materials and METHODS A prospective study was conducted with patients with low- and high-grade tumors treated, subjecting them to the single-voxel MRS and multivoxel MRSI protocol at 1.5 T. RESULTS Of the 44 patients included, 21 were histopathologically diagnosed as low-grade tumors and 23 as high-grade tumors. Of the low-grade tumors, 11 were caracterized as low-grade (mean Cho/NAA and NAA/Cr ratios 1.49 ((p=0.036) and 0.92 (p=0.038) respectively), 8 cases presented gliosis (mean Cho/NAA and NAA/Cr ratios 1.57 (p=0.028) and 1.36 (p=0.026) respectively), and 4 cases presented radiation necrosis (mean Cho/Cr ratios 2.14 (p=0.03)), (mean Cho/Cr and NAA/Cr ratios 1.25 (p=0.01) and 1.25 (p=0.00)) respectively). Furthermore, tumor recurrence that presented high Cho/NAA ratio were observed in 11 cases. Of the high-grade tumors, 13 were caracterized as high-grade (mean Cho/NAA and Cho/Cr ratios 2.24 (p=0.026) and 4.48 (p=0.026) respectively), 13 cases presented gliosis (mean Cho/NAA and NAA/Cr ratios 1.82 (p=0.028) and 0.64 (p=0.026)) respectively) and radiation necrosis was detected in 10 cases (mean Cho/Cr ratio 1.47 (p=0.03), (mean Cho/Cr and NAA/Cr ratios 2.25 (p=0.01) and 0.97 (p=0.00) respectively). Moreover, tumor recurrence that presented high Cho/NAA ratio were observed in 9 cases. CONCLUSION MRS and MRSI contribute to identifying the recurrences, to characterizing the different metabolic patterns as an effect of the treatment and differentiate between low and high grade tumors.
NCMP-17. SPHENOID WING DIFFUSE LARGE B-CELL LYMPHOMA MIMICKING A MENINGIOMA: A RARE DIFFERENTIAL DIAGNOSIS
Authors: Aline Lariessy Campos Paiva, João Luiz Vitorino Araujo, Renan Maximillian Lovato, Jean Gonçalves de Oliveira, José Carlos Esteves Veiga
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Meningioma is the most frequent dural lesion and in most cases have a benign course and surgery usually is curative. Nevertheless, there are several dural lesions, neoplastic and non-neoplastic that may mimic meningiomas. Radiological features could help to perform this differentiation. Primary dural lymphoma (PDL) is a rare entity in which adjuvant therapy is required for proper therapeutic approach. CASE PRESENTATION A 67-year-old female patient presented with a clinical complaint of left exophthalmos and headache. During investigation, it was noticed the presence of a hyperintense left sphenoid wing lesion with orbital invasion. The diagnosis of meningioma was initially considered and she underwent neurosurgical approach aiming maximal extension. However, histopathological investigation disclosure that was a primary dural lymphoma (diffuse large B type) and she was referred to adjuvant therapy with a proper control of the disease. CONCLUSIONS Dural lesions could have neoplastic and non-neoplastic origin. Although meningiomas have a high prevalence, it must be considered other pathologies during evaluation and consideration of the differential diagnosis. This help to improve therapeutic management of the patients.
INNV-09. DISTANT PARENCHYMAL RECURRENCE DURING LONG-TERM USE OF TTFIELDS TREATMENT FOR GLIOBLASTOMA
Authors: Yuhei Takido, Fumiharu Ohka, Shoichi Deguchi, Kazuya Motomura, Koichi Mitsuya, Yoshiki Shiba, Kazuhito Takeuchi, Yuichi Nagata, Junya Yamaguchi, Yuji Kibe, Yutaro Fuse, Sachi Maeda, Hiroki Shimizu, Shota Nohira, Ryo Yamamoto, Shohei Ito, Akihiro Nakamura, Ryuta Saito
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Tumor treating fields (TTFields) treatment has been an important option for the treatment of glioblastoma. The introduction of novel treatment options may lead to distinct recurrence patterns compared to those observed with conventional therapies; however, the specific recurrence pattern during TTFields treatment has not been elucidated. METHODS AND RESULTS Here, we analyzed 39 cases of glioblastoma treated with TTFields. Although a usage rate of more than 75% is recommended, among 39 cases, 18 discontinued TTFields treatment owing to requests by patients with lower usage rates. In these discontinued cases, patients exhibiting sensory aphasia were more frequently included compared to those who continued TTFields (44.4%, p&amp;lt;0.001). Among 21 cases involving patients who continued TTFields, tumor recurrence was observed in 15 of those cases. Five out of 15 cases (33.3%) exhibited recurrence in distant parenchyma from the primary lesion. A higher usage rate and relatively longer use of TTFields were observed in these five cases, along with more favorable progression-free survival than those in the other 10 cases (p=0.019, p=0.040, and p=0.024, respectively). In one case, recurrent tumors with lower-grade glioma histology but molecular markers characteristic for glioblastoma, IDH-wildtype were identified. This tumor arose in an area that received a lower local minimum power density of TTFields compared to the primary lesion, following long-term TTFields therapy CONCLUSIONS Long-term use of TTFields might be correlated with a high frequency of distant parenchymal recurrence in cases with favorable response.
Medical Therapy Alone, Percutaneous Coronary Intervention, or Coronary Artery Bypass Grafting for Treatment of Coronary Artery Disease
Authors: Daniel K. Amponsah, William F. Fearon
Journal: Annual Review of Medicine (2024)

In this review, we describe how the management of coronary artery disease (CAD) has become increasingly complex due to the rapid evolution of pharmacotherapy and procedural techniques. The expanding array of treatment options has driven researchers to investigate the optimal combination of therapies; while the findings offer invaluable insights, the sheer volume and occasional contradictions can foster confusion. Given the diverse spectrum of CAD and its manifestations, a tailored treatment decision is critical for each patient. We hope to demonstrate that by integrating the key messages from clinical trials and prioritizing patient comprehension and preference, healthcare providers can guide their patients toward appropriate treatment options, ultimately leading to enhanced care.
QOL-26. GLIOMA PATIENTS’ COGNITION AND THEIR CAREGIVERS: THE GOOD, THE BAD, AND THE BURDEN
Authors: Giuliana Zarrella, Amber Fox, Ashlee Loughan, Autumn Lanoye, Farah Aslanzadeh, Paula Sherwood, Sarah Braun
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Cognitive decline, common in patients with gliomas, can contribute to reduced independence in daily functioning. Patients with gliomas often rely on informal caregivers for functional support, evidenced to cause distress in other caregiver populations (e.g., Alzheimer’s, terminal cancer, dementia). Few studies have investigated this relationship in neuro-oncology; thus, we explored whether patients’ neurocognitive function was associated with aspects of caregiver burden. METHODS Patients with glioma underwent neurocognitive testing including Auditory Verbal Learning Test-Delayed Recall (AVLT), Trail Making Test-Part B (TMT-B), Stroop Color-Word Interference (CWI), Controlled Oral Word Association Test (COWA), and the Grooved Pegboard (GPB). Caregiver burden was assessed using the schedule burden and self-esteem subscales of the Caregiver Reaction Assessment (CRA). Hierarchical regressions and independent samples t-tests evaluated whether neurocognitive performance predicted caregiver burden and differences in caregiver burden between patients with intact versus impaired (AVLT; ≥ -1.5 SD) memory. RESULTS Seventy-eight dyads were included for analyses (Patient: Mage=53.4, 65.4% male, 97.4% Non-Hispanic/White; Caregiver: Mage =52.5, 71.8% female, 96.2% Non-Hispanic/White). AVLT performance was significantly related to both caregiver schedule burden (β = -.63, p =.003) and self-esteem (β =.26, p =.046). Performance on TMT-B, COWA, GPB, and CWI and patient age were not related to caregiver burden in any model (ps&amp;gt;.05). There was a significant difference in caregiver schedule burden between those with (M=15.17, SD=5.84) and without memory impairment (M=18.50, SD=5.60) [t(72)=-2.44, p=.017] but not for self-esteem (p&amp;gt;.05). CONCLUSIONS Patient performance on verbal memory was sensitive to the changes that may contribute to increased caregiver burden. An amnestic profile may be the most salient cognitive predictor of strain on neuro-oncology caregivers. Our findings speak to the interdependence of patient outcomes and caregiver quality of life. Supporting patients’ neurocognitive capabilities, such as implementing individualized cognitive rehabilitation programs, may improve caregiver burden.
NIMG-68. A COMPREHENSIVE REVIEW OF THE USE OF FMRI IN EVALUATING FUNCTIONAL CONNECTIVITY AND ACTIVATION IN DISORDERS OF CONSCIOUSNESS
Authors: Sandra Leskinen, Neel H Mehta, Mica Quelle, Souvik Singha, Randy S D’Amico
Journal: Neuro-Oncology (2024)

Abstract PURPOSE Disorders of consciousness (DoC) like vegetative and minimally conscious states pose significant diagnostic and prognostic challenges, compounded by the inherent limitations in communicating with affected patients. We performed a scoping review of the literature to examine the application of functional magnetic resonance imaging (fMRI) to the assessment of functional connectivity (FC) and activation in DoC. METHODS We searched the MEDLINE/PubMed, Web of Science, and Embase databases between the years 2004 and 2024 for English-language studies involving fMRI and DoC in adult populations, adhering to PRISMA guidelines. Included studies were evaluated for study design, DoC subtype, fMRI subtype, cohort size, and FC and/or activation findings. RESULTS Our initial search identified 17,475 results, of which 82 studies were ultimately included with a total of 3917 patients. Only one of the included studies was a randomized controlled trial, 24 were prospective cohort studies, three were retrospective cohort studies, and 54 were observational in design. The majority of studies utilized resting-state fMRI (n=54, 65.9%), and the most commonly investigated disorders of consciousness were minimally conscious states (31.9%), vegetative states (14.4%), and unresponsive wakefulness syndromes (12.9%). Among studies with higher levels of evidence like prospective and retrospective studies, FC and activation findings were heterogeneous, with several studies reporting abnormal connectivity in the default mode and auditory networks. Activation responses among patients also varied, with some patients of the same DoC displaying expected activation patterns while others did not. Normal patterns of connectivity and activation were associated with improved prognosis in eight prospective studies and one retrospective study. CONCLUSIONS These findings underscore the complexity of using fMRI to evaluate consciousness in DoC patients. Though fMRI has the potential to identify residual cognitive function, the variability in responses also indicates the need for personalized approaches and further research to standardize fMRI protocols for this purpose.
IMMU-66. PHYSIOLOGICALLY RELEVANT MURINE GLIOMA MODELS THAT REPRESENT GBM HETEROGENEITY AND ENABLE THE NEXT GENERATION OF DISCOVERY AND THERAPY EFFICACY STUDIES
Authors: Jose Maldonado, Caiyi Wang, Jia-Shiun Leu, Han Nhat Tran, Nourhan Abdelfattah, Kyuson Yun
Journal: Neuro-Oncology (2024)

Abstract To transform cancer drug development pipelines and gain a deeper mechanistic understanding of cancer: immune interactions, we desperately need better experimental models that faithfully recapitulate the cellular heterogeneity, complex and dynamic cell:cell interactions, and therapy responses in humans. To address this need, we developed and characterized a cohort of five new mouse glioma models in the C57BL6/j background. These transplantable tumorsphere models were derived from spontaneous gliomas that formed in genetically engineered mouse models with different oncogenic drivers, including EGFRviii, PDGFA, PTEN, p53, and NF1 mutations. They show a range of responses to standard of care (TMZ+IR) similar to GBM patients and all are resistant, to immune checkpoint inhibitors, anti-PD1+CTLA4, treatment, unlike the GL261 model and similar to GBM patients. We deeply characterized each model, including immune phenotyping and single-cell RNA-sequencing analyses. We also performed a cross-species comparison of human and mouse GBM and stromal cell phenotypes at the single-cell level. Our results show that new mouse models recapitulate the heterogeneity of glioma cell states observed in individual patients and, importantly, also the complex and immune suppressive TME. We demonstrate at the single-cell level that glioma-associated T and myeloid cell types are molecularly similar and conserved across species. Leveraging these data sets and experimental models, we are testing now novel immunotherapy targets for GBM.
NIMG-57. EMBEDDED GRAPH DERIVED FROM PSEUDO-RESTING-STATE FUNCTIONAL MRI CAN PREDICT COGNITIVE IMPAIRMENT IN GLIOMA
Authors: Chencai Wang, Nicholas Cho, Kathleen Van Dyk, Francesco Sanvito, Sonoko Oshima, Jingwen Yao, Albert Lai, Noriko Salamon, Timothy Cloughesy, Phioanh Nghiemphu, Benjamin Ellingson
Journal: Neuro-Oncology (2024)

Abstract Resting-state brain network analyses are of great interest in studying the neurocognition and measuring the functional connectivity (FC) patterns of glioma patients. However, resting-state functional MRI (rs-fMRI) is not assessed in clinical routine due to the scan time and cost. The current study used pseudo-resting-state functional MRI (pseudo-rs-fMRI) derived from dynamic susceptibility contrast (DSC) perfusion MRI to predict cognitive impairment in glioma. 37 glioma patients were enrolled consecutively in the current study with DSC perfusion MRI acquired and neurocognition assessed, where 24 glioma patients also got rs-fMRI collected. The pseudo-rs-fMRI was created by voxel-wise subtracting the Gamma-variate modeled signal of contrast agent bolus from the original DSC perfusion signal. Following the pre-processing of pseudo-rs-fMRI and full rs-fMRI, the functional connectivity network (FCN) was established for each patient. Graph embedding was implemented to learn and extract features of each node in the binarized FCN, and the decision tree classification algorithm was applied to distinguish cognitive impairment. FCNs of 24 patients with DSC perfusion and rs-fMRI acquired were used to train the model, and FCNs of 13 patients with only DSC perfusion MRI acquired were used to test the model. The AUC (area under the receiver operating characteristic curve) was used to evaluate the model’s performance. The similarity and mean-square-difference between average FCNs extracted from rs-fMRI and pseudo-rs-fMRI were 0.6769 and 0.0263, respectively. Classifier trained using 24 FCNs of pseudo-rs-fMRI has an AUC of 0.750 in identifying cognitively impaired patients in the testing cohort. Combining FCNs of both rs-fMRI and pseudo-rs-fMRI to train the classifier resulted in a higher AUC of 0.833 in the testing cohort. To summary, DSC perfusion MRI-derived pseudo-rs-fMRI can be used to predict cognitive impairment in patients with gliomas. External validation would be required.