tbuckley/cabot-search huggingface dataset:
P20.21.A SPINAL CORD ASTROBLASTOMA WITH EWSR1-BEND2 FUSION IN FEMALE PATIENTS: A REPORT OF FOUR CASES FROM CHINA AND A COMPREHENSIVE LITERATURE REVIEW
Authors: L Fu, W Hu, S Xi
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Astroblastoma is an extremely rare central nervous system (CNS) tumor characterized by astroblastic pseudorosettes and vascular hyalinization. Despite these histologic hallmarks, its morphology can vary, occasionally resembling other CNS tumors like ependymoma. A novel tumor entity, astroblastoma, meningioma 1 (MN1)-altered, has been identified, featuring MN1 gene rearrangements typically involving BEN-domain containing 2 (BEND2) as a fusion partner. Most astroblastomas arise in the cerebral hemisphere. MATERIAL AND METHODS We present four cases of female patients with astroblastoma, focusing on their uncommon spinal cord location and the unique molecular feature of EWSR1-BEND2 fusion. All cases underwent next-generation sequencing (NGS), RNA sequencing (RNA-seq), and fluorescence in situ hybridization (FISH). Additionally, two cases underwent DNA methylation profiling. RESULTS These tumors displayed growth patterns akin to traditional intracranial astroblastomas, with three cases demonstrating high-grade histology, including elevated mitotic activity and necrosis. Interestingly, some cases exhibited positive staining for pan-cytokeratin (CK) and hormone receptors. Three out of the four patients experienced recurrence, underscoring the aggressive nature of this disease. CONCLUSION We suggest recognizing a new molecular subgroup of spinal astroblastoma and recommend testing newly diagnosed infratentorial astroblastomas for EWSR1-BEND2 fusion.
P19.13.A RESULTS FROM THE COSMIC PROJECT: CORE OUTCOME SETS FOR MENINGIOMA IN CLINICAL EFFECTIVENESS STUDIES
Authors: M D Jenkinson, C P Millward, A I Islim, S M Keshwara, N Srikandarajah, A R Brodbelt, A G Marson, P R Williamson
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND The minimum outcomes that should be measured and reported in all clinical trials for a specific health condition or health area can be defined by a Core Outcome Sets. The aim was to develop core outcome sets for cranial meningioma; for clinical trials (COSMIC: Intervention) and observational studies (COSMIC: Observation). MATERIAL AND METHODS An international study advisory group was formed with representation from charities (IBTA, TBTC, brainstust), neuro-oncology organisations (BNOS, EANO, EORTC, ICOM, RANO-PRO, SNO) and neurosurgery societies (SBNS, BIMS). Systematic literature reviews and trial registry searches were performed to identify outcomes reported in published and ongoing 1) meningioma clinical trials, and 2) studies of incidental/untreated meningioma. Outcomes were deduplicated and categorised. Individuals from stakeholder groups (including meningioma patients and carers, healthcare professionals, researchers) were invited to participate in 2-round, international, modified eDelphi surveys. The final core outcome sets were ratified through online consensus meetings. RESULTS The COSMIC: Intervention systematic review identified 660 verbatim outcomes, rationalized into 24 Delphi survey items. Following the consensus meeting, 15 outcomes were included in the final set. For COSMIC: Observation, 267 verbatim outcomes were identified and rationalized into 17 Delphi survey items. 16 outcomes were included in the final set. Eight core outcomes common to both COSMIC: Intervention and COSMIC: Observation COS: tumour growth, physical, emotional, and neurocognitive functioning, overall quality of life, progression-free survival, meningioma specific mortality and overall survival. Role and social functioning were core outcomes in COSMIC Observation but not COSMIC intervention. CONCLUSION COSMIC has defined the core outcome sets for use in future meningioma clinical trials and studies. Role and social functioning were important to incidental meningioma patients and likely reflects the anxiety and uncertainty around clinical treatment. The international stakeholder community will adopt and use these core outcome sets in future trials.
P17.27.B TOWARDS IMPROVED PROGNOSTICATION: A LOOK AT SURVIVAL SCORE ACCURACY IN ELDERLY PATIENTS WITH SURGICALLY TREATED BRAIN METASTASES
Authors: A Gubian, A Sulejmani, G Rinkel, N Etminan, S Brehmer
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Because of demographic changes in highly developed countries, the number of elderly patients requiring surgery for brain metastasis is increasing. However, concerns for risk-benefit ratio, ability to tolerate invasive treatment, and limited healthcare resources may explain why intracranial surgery is often declined in elderly patients. Although prognostic scores have been implemented to predict survival of patients with intracranial metastasis, no evaluation of those scores for the elderly population exist. We aimed to address the lack of data on the accuracy of prognostic scores in this specific population. MATERIAL AND METHODS Patients over the age of 65 who underwent surgery for intracranial metastases between 2015 and 2022 at the Department of Neurosurgery, University Hospital Mannheim (Germany) were retrospectively analysed. The evaluated prognostic scores included the recursive partitioning analysis (RPA) and the disease-specific grade prognostic assessment (ds-GPA). A log-rank analysis was conducted to assess differences in predicted versus observed survival. To further define the different model’s performance metrics, survival was classified into four classes (&amp;lt;6 months, 6-12 months, 12-24 months and &amp;lt; 24 months), and a confusion matrix was generated. The primary endpoint was the accuracy of prediction of survival in elderly patients with surgically treated intracranial metastases. RESULTS A total of 83 patients who underwent surgery for intracranial metastases between 2015 and 2022 were analysed. RPA and ds-GPA scores could be attributed for 83 and 77 patients, respectively. The mean age was 73.2 years. The 0.5-, 1-, 2- and 3-year probabilities of overall survival were 47%, 36%, 24% and 18% in the studied population, respectively. These probabilities were predicted to be 3%, 0%, 0% and 0% by the RPA model and 25%, 6%, 1% and 0% by the ds-GPA model. A statistically significant difference was observed between the predicted and actual survival rates in the studied population (p-value &amp;lt; 0.005). Using the categorised survival and a confusion matrix, the accuracy, recall, precision, and F1-score for the RPA model were 0.41, 0.17 and 0.24, respectively. The recall, precision, and F1 score for the DS-GPA model were 0.39, 0.36 and 0.31, respectively. Conclusion: Our analysis revealed a statistically significant discrepancy between predicted and actual survival in elderly patients with surgically treated intracranial metastases. These findings underscore the critical need for developing updated prognostic scoring systems specifically tailored to this population.
P20.19.A RARE CASE OF PRIMARY BRAIN AMYLOIDOMA
Authors: R Ivan, A Signate, S Puget, C A Sirbu
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Cerebral amyloidoma, composed of insoluble fibrillary proteins, is one of the rarest forms of amyloid deposition. It resembles a tumor, with a variable clinical presentation that can include vision loss, behavioral changes, cognitive issues, and recurrent headaches. It has a slow evolution pattern, without characteristics of dissemination. MATERIAL AND METHODS We present the case of a 56-year-old patient, who presented with a sensory loss on the right side of the body, progressive memory troubles of one-year duration, and later a left homonym hemianopsia. She underwent a cerebral MRI that showed a right parietal-temporal heterogenous lesion, with contrast enhancement as well as a right parieto-occipital smaller lesion, with a differential diagnostic of glial tumor or cerebral lymphoma. A stereotactic biopsy of the mass was made by the neurosurgeon with a subsequent anatomopathological examination. RESULTS The histopathological result was consistent with a cerebral amyloidoma AL with lambda chains, without an associated lymphatic lesion. The systemic extension was also evaluated, without signs of systemic amyloidosis (salivary gland biopsy, thoracic abdominal pelvic scan, myelogram, and a urinary analysis). Hematological and ophthalmological consults were also made. CONCLUSION Given the age and the progressive clinical course, the treatment proposed was with Revlimid and Dexamethasone, along with a periodical surveillance with cerebral imaging and neurological consultations. The evolution remained stable at the moment of the publication of this report.
P17.28.A TUMORAL INTERFERON BETA INDUCES AN IMMUNE-STIMULATORY PHENOTYPE IN TUMOR-ASSOCIATED MACROPHAGES IN MELANOMA BRAIN METASTASES
Authors: J Gellert, D A Agardy, S Kumar, K Jähne, L Bunse, M A Davies, M Platten, T Bunse
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Type I interferons (IFN) such as IFNβ are pro-inflammatory cytokines involved in antiviral immune responses. Increasing evidence indicates that the success of several anticancer therapies, including radiotherapy, relies on the immune-stimulatory effects of type I IFNs on innate and adaptive immune cells in the tumor microenvironment (TME). Tumor-associated macrophages (TAMs) are one of the most abundant innate immune cells in the TME of melanoma brain metastases (MBMs) and can exert potent immune-suppressive functions compromising effective antitumor immune responses. Here, we investigate the potential of tumoral type I IFNs to re-educate TAMs towards an antitumor M1-like phenotype to enhance the efficacy of immunogenic anticancer therapies in MBMs. MATERIAL AND METHODS In order to minimize confounding effects of immunogenic cell death associated with type I IFN-dependent anticancer therapies, we generated an inducible IFNβ-overexpressing MBM mouse model. Tumor growth was measured by magnetic resonance imaging (MRI) and changes in the TME were analyzed by flow cytometry. We confirmed our in vivo findings by mixed-leukocyte reaction assay and RNA sequencing of IFNβ-treated bone marrow-derived macrophages (BMDMs) and validated our myeloid type I IFN-response signature gene set in a recently published RNA sequencing dataset of treatment-naïve and previously irradiated MBM patient samples. RESULTS In this murine MBM model, tumoral IFNβ markedly impaired tumor growth and TAMs from IFNβ-expressing tumors exhibited a decreased expression of CD206, a widely used marker for immune-regulatory M2-like macrophages. Functional and transcriptomic analyses of IFNβ-treated BMDMs revealed an immune-stimulatory M1-like phenotype. Following radiotherapy, the myeloid type I IFN-response signature was upregulated in over 40 percent of MBM patient samples which was associated with a higher M1/M2-like TAM ratio and increased overall survival. CONCLUSION Our findings demonstrate the immune-stimulatory capacity of tumoral IFNβ in the context of type I IFN-inducing anticancer therapies in MBM by re-polarizing TAMs towards a pro-inflammatory M1-like phenotype.
P10.09.A BLOOD-BASED CLASSIFICATION OF IDH-STATUS OF NON-ENHANCING GLIOMAS: A MACHINE LEARNING APPROACH
Authors: S Hadad, G Warrier, L McCoy, H Hansen, J Chen, T Rice, M Wrensch, J Taylor, J Clarke, J Wiencke, A Molinaro
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Non-invasive determination of IDH mutational status in patients with glioma could offer significant therapeutic opportunities. While IDH wildtype tumors (e.g., GBM) typically show enhancement on MRI, IDH mutant tumors often lack this enhancement. However, relying solely on anatomic radiology may lead to misclassification, and currently, tissue acquisition is the primary method for assessing IDH status in gliomas. This limitation hampers the development of neoadjuvant or intraoperative therapeutic strategies based on IDH status; thus, more minimally invasive methods to determine IDH status are needed. In this study, we assessed immune cell proportions, which vary by glioma subtype, from pre-surgery peripheral blood samples as an alternative method of classifying the IDH status in gliomas without enhancement. MATERIAL AND METHODS First, we employed a highly accurate large language model (GPT-4-Turbo-128k) with over 99% accuracy to read radiology notes and exclude patients with enhancing gliomas. Then, we identified twelve immune cell subtypes from whole blood using deconvolution algorithms based on DNA methylation data. These immune cell subtypes, along with patient age, were integrated into a machine learning model (random forest) to predict IDH status (wildtype vs. mutant), leveraging conditional Generative Adversarial Networks to generate synthetic data and mitigate bias in the datasets. Two independent datasets were included for training and validating the model. RESULTS The random forest model had an area under the ROC curve (AUC) of 0.90 and accurately identified IDH status in 81% of a training set of 287 gliomas (65 wildtype and 222 mutant tumors at varied time points after diagnosis). In an independent validation data set of 99 gliomas (6 wildtype and 93 mutant) from pre-surgery blood samples, the AUC was 0.93, and accuracy predicted IDH status in 92% of cases with a sensitivity of 93% and specificity of 83%. CONCLUSION We could accurately predict IDH status in pre-surgical peripheral blood samples from patients with non-enhancing gliomas. This minimally invasive approach is a promising step toward reducing risk and exploring opportunities for earlier therapies based on IDH status.
P18.05.B ASSOCIATION OF CELLULAR DRUG RESPONSES AND METABOLIC PROFILES IN ADULT TYPE DIFFUSE GLIOMAS
Authors: S Stanzer, J Bandres-Meriz, N Harbusch, J Franz, K Mahdy-Ali, F Ferreira da Silva Souza Monedeiro, C Magnes, E Zügner, T Pieber, A El-Heliebi, T Urbanic Purkart, A Wöhrer, B Prietl
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Functional precision medicine is the next step in individualized patient centered medicine, seeking to guide treatment based on ex-vivo drug response of patient-derived tumor cells (PDCs). In this study we aimed to evaluate the drug response (combination of potency and efficacy) to a panel of cytotoxic and targeted agents in PDCs isolated from IDH-mutant (mut) and -wild type (wt) gliomas. Next, we integrated these assessed drug responses with corresponding metabolomic tissue signatures reflecting the in-vivo metabolic profile of IDH-mut and -wt gliomas. To gain further insight into the aggressive behavior of IDH-wt tumors, we aimed to characterize clonal and sub-clonal metabolic heterogeneity within IDH-wt gliomas to uncover potential therapeutic vulnerabilities. MATERIAL AND METHODS The tumor tissues of patients with glioma were used for PDC isolation prepared by mechanical and enzymatic tissue dissociation. After short-term cultivation (7-14 days) under standard culture conditions, spheroids (n=50) were dissociated into a single-cell suspension and subjected to drug screening using a high throughput screening platform. The drug panel consisted of 80 chemotherapeutics and targeted drugs. Dose response curve (DRC) fitting per drug was performed and the area under the curve (AUC) was evaluated. Corresponding tumor tissues obtained from surgical resections were analyzed by HILIC-HRMS. We then correlated the metabolomic profiles with the drug response. RESULTS First analysis within this cohort (n =18) showed significantly lower AUC values (i.e. enhanced drug response) of panobinostat and vorinostat (HDAC inhibitors), AMG232 and RG7112 (MDM2 inhibitors), selinexor (exportin-1 inhibitor) and temsirolimus (mTOR inhibitor) in IDH-wt gliomas (all p&amp;lt;0.05). Statistical correlation analysis between AUC values and metabolite levels showed substantially more significant correlations (criteria: |r|&amp;gt; 0.5, p&amp;lt;0.05) between drug responses and metabolites in IDH-wt tumors (1329 versus 926). CONCLUSION These first analyses showed an association between drug response and metabolism when using a holistic approach. Additionally, these results suggested a connection between metabolic pathways and drug susceptibility. In the next step, we plan to investigate the metabolic heterogeneity of IDH-wt gliomas within the tumor in more detail to find out whether there is an influence on the response to treatment.
P12.11.A IMMUNOTHERAPY WITH AUTOLOGOUS DENDRITIC CELLS IN THE TREATMENT OF GBM - RESULTS
Authors: A Rynda, D Rostovthev, V Olyushin
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Malignant gliomas are the most common primary brain tumor. Despite the variety of modern treatments, it is still a fatal disease with an extremely poor prognosis. The use of immunotherapy as a technique for the treatment of malignant tumors has great promise, retraining and exploiting the patient’s immune response against tumors. Evaluation of the effectiveness of dendritic cell vaccine in patients with malignant brain gliomas in the structure of complex treatment in comparison with the control group of patients without immunotherapy in the structure of treatment. MATERIAL AND METHODS In a single-center, prospective, cohort study, taking place on the basis of the RNSI named after prof. A.L. Polenov, 91 patients with morphologically established malignant glial tumor (glioblastoma) took part. The main group of 41 patients who, in addition to standard treatment (surgical, radiation and chemotherapy), underwent specific antitumor immunotherapy. 50 patients received only standard treatment, without immunotherapy. RESULTS Median survival was 21.7 months in the immunotherapy group (95% CI 4-37 months) and 15.8 months (95% CI 3-22 months) in the non-immunotherapy group (p = 0.002). The median relapse-free period in the group with immunotherapy was 13.8 months (95% CI 1-20 months), and in the group without immunotherapy 7.9 months (95% CI 1-12 months) (p = 0.003). CONCLUSION In general, the use of immunotherapy in the structure of complex treatment of patients with malignant gliomas demonstrates a clear positive trend in terms of overall survival and median relapse-free period. But nevertheless, immunotherapy requires further development as a therapeutic tool, study and improvement, which will take into account immunosuppression in malignant gliomas and means of overcoming it, optimization in terms of target antigen selection, cell preparation and integration of dendritic vaccines into other treatment regimens.
P19.08.B MENINGIOMA: A CHALLENGE FOR RADIOLIGAND THERAPY. THE INITIAL EXPERIENCE OF TWO EUROPEAN CENTRES
Authors: S Asadurova, A Flaus, A García-Burillo, C Lorenzo-Bosquet, B Lachachi, L Al Mansour, M Gonzalez, M Vieito, C Gamez-Cenzano
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Evaluation of the treatment with [177Lu}Lu-DOTA-TATE in patients with recurrent meningioma. MATERIAL AND METHODS International bicenter retrospective study including 6 patients with recurrent meningiomas treated with [177Lu}Lu-DOTA-TATE between 12/02/2019 and 11/03/2022. Prior to the treatment, the expression of somatostatin receptors has been confirmed by [68Ga]Ga-DOTA-TOC PET/CT. Patients received between two and four cycles of 7400 MBq of [177Lu}Lu-DOTA-TATE. To mitigate potential complications, 50% (3/6) received corticosteroids. We calculated the progression-free survival (PFS), the progression-free survival at 6 months (PFS-6) and the overall survival at 12 months (OS-12). As a secondary objective we assessed the somatostatin receptor expressing tumor volume (SSTR-TV), the total lesion somatostatin receptor expression (TL-SSTR), the SUVmax of the tumor, the pituitary gland and the liver on the [68Ga]Ga-DOTA-TOC PET/CT using Syngo.via software. RESULTS The mean age is 61±11.5 years, men:women 1:1. All patients were diagnosed with WHO grade II meningioma, 83% (5/6) with multifocal involvement, 83% (5/6) with intracranial location and 17% (1/6) had a spinal meningioma. One patient had the NF2 mutation. All patients have previously been treated with surgery and radiotherapy as first line treatment, achieving total resection (Simpson grade II) in 50%. 33.3% (2/6) of the patients received [177Lu}Lu-DOTA-TATE as a first line treatment post-recurrence, 33.3% (2/6) as a second line after proton therapy or [177Lu}Lu-DOTA-TATE (retreatment) and 33% (2/6) as a fourth line after somatostatin analogues, mTOR and angiogenesis inhibitors or others. The treatment has been well tolerated, showing asthenia in 50% (3/6), alopecia in 33% (2/6) and mild haematological toxicity in 50% (3/6) of the patients, two of them with multiple previous lines of systemic therapy. The PFS is 14.5 months, PFS-6 was achieved by 83%, and OS-12 is 100%. The patient with the lowest lesion SUVmax (5.2) and the lowest TL-SSTR (23.6 SUV-lbm x cm3) had the shortest PFS (6 months) and the patient with the highest SSTR-TV (68.2 cm3) and TL-SSTR (4206.78 SUV-lbm x cm3) had PFS of 7 months, significantly less than the cohort average. The best responder (17 months) had a small SSTR-TV (12 cm3) with a high TL-SSTR (165 SUV-lbm x cm3). CONCLUSION The treatment with [177Lu]Lu-DOTA-TATE in recurrent meningiomas is safe, well tolerated and demonstrates comparable PFS, PFS-6 and OS-12 with other systemic therapies. The total tumor burden (SSTR-TV) and the total lesion somatostatin receptor expression (TL-SSTR) might have an important role in patient selection and therapeutic outcome prediction.
P13.05.B DYNAMICS OF POST-RADIOTHERAPY MORPHOLOGICAL CHANGES IN THE BRAIN
Authors: A Turcas, A Tipcu, B Homorozeanu, D Cernea, A Turcas, D Leucuta, P Achimas-Cadariu
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Radiotherapy is essential in achieving local control for many brain tumours. However, it carries the risks of toxicities, including neuro-cognitive decline, with potential impact on quality of life. Several brain areas and structures are involved in cognition, but their radiosensitivity and clinical response to radiotherapy is not yet fully understood, and no dose-thresholds are yet established. We studied the dynamics of morphological changes on MRI imaging of 18 brain structures following radiotherapy and investigated predictive factors of their occurrence. Identifying such imaging biomarkers could help develop sparing strategies and improve treatment planning. MATERIAL AND METHODS We included 40 patients treated for gliomas in a tertiary cancer center between 2018-2022 and contoured a set of 18 structures on T1-MRI sequences acquired at 3, 6, 9 months, 1 and 2 years after treatment. Dosimetric data were extracted from dose-volume histograms of the delivered plan, and for each structure the baseline volume and volumes in dynamics were noted. Correlations were tested by calculating the Spearman coefficient (rho) and comparisons between different groups were made using the paired Wilcoxon test, with statistical significance for p&amp;lt;0.05 RESULTS The mean age at diagnosis was 47 years. All patients underwent pre-radiotherapy surgical resection. Twenty tumors were left-sided, 18 on right-sided, 1 infratentorial and 1 on the midline. Radiotherapy regimens were normo-fractionated (1.8-2Gy/fr) in 67.5% of cases, and the rest were hypofractionated (&amp;gt;2.67Gy/fr). Most structures registered a slight increase in volume at 3 months, followed by a gradual decrease over the two-year follow-up A correlation was observed between the dynamics of Hippocampal and Putamen volumes with Dmean, with loss of 0.55% of Hippocampal volume with each additional 1 Gy added to Dmean (rho = -0.293, p = 0.054) and 0.45% decrease in Putamen volume for every additional 1 Gy for Dmean (rho = -0.373, p = 0.018). The magnitude of volumetric changes was not significantly associated with dose per fraction, patient age, or overall treatment time. CONCLUSION In our cohort of patients, we identified a particular pattern of post-irradiation volume dynamics in selected structures, with a slight increase in volume as an acute effect, followed by progressive, dose-dependent, late atrophy. Our results pave the way for further exploration and validation in subsequent studies, including prospective neurocognitive testing and correlation of dosimetric, volumetric and clinical data.