tbuckley/cabot-search huggingface dataset:
P13.04.A CRANIOPHARYNGIOMA TREATMENT: PROTONS VS. PHOTONS - A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Y P Silva, E Sharma, P Łajczak, R Jabbar, M W Majeed, A R Ahmed, I N S Petry, D Chawla, A Chatterjee, W Fagundes
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Craniopharyngiomas are complex tumors that can present significant challenges for neurosurgeons, sometimes necessitating a range of treatment modalities, including radiotherapy. MATERIAL AND METHODS Through a systematic review and meta-analysis, this study evaluates the effectiveness and safety of proton beam therapy compared to traditional photon therapy for craniopharyngioma treatment. We searched major databases (Pubmed, Cochrane, and Scopus) for studies comparing proton and photon therapy for craniopharyngioma. Studies published up until April 2024 were included. We assessed event-free survival and endocrine dysfunction. The risk of bias in each study was evaluated. Pooled estimates of odds ratios using random-effects models were calculated for each outcome for patients undergoing proton versus photon therapies. RESULTS This systematic review analyzed data from three non-randomized studies, encompassing 375 patients who received subtotal resection followed by radiation therapy for residual tumors. Patients were divided into two groups: photon therapy (n=147, 39.2%) and proton therapy (n=228, 60.8%). With a median follow-up of 5.0 to 6.4 years, the meta-analysis revealed no significant difference in event-free survival (log OR=-0.28, 95%CI=-1.49-0.93, p=0.65) or endocrine dysfunction (log OR=0.12, 95%CI=-0.36-0.60, p=0.62) between the proton and photon therapy groups. Heterogeneity among studies was low to moderate (I²=50.59% for event-free survival, I²=0.00% for endocrine dysfunction). CONCLUSION This review suggests proton therapy offers comparable event-free survival and endocrine dysfunction to photon therapy for craniopharyngioma, which is especially relevant considering the substantial cost differential between these treatment options. However, further research with a greater sample size is warranted to confirm this survival outcome and explore long-term toxicity differences.
P19.14.A TARGETING TUMOR-ASSOCIATED MACROPHAGES IN THE IMMUNE-MICROENVIRONMENT OF MENINGIOMAS
Authors: C Lotsch, R Warta, P Dao Trong, S Krieg, F Sahm, A Unterberg, C Herold-Mende
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Meningiomas represent the most common primary brain malignancies in adults with a subset of tumors exhibiting aggressive clinical behavior. Immunotherapy might present a new treatment strategy but is highly dependent on the immunological composition of the tumor microenvironment. Our previous data have shown that tumor-associated macrophages (TAMs) make up the main immune cell population in meningiomas with a significant negative impact on patient outcome. In this study, we investigated whether TAMs from meningioma tissue could be reprogrammed to an immunologically active and tumoricidal phenotype. MATERIAL AND METHODS For this purpose, CD11b+ sorted macrophages derived from tumor samples from &amp;gt; 40 patients including a substantial number of clinically aggressive meningiomas were treated with small molecule inhibitors targeting the colony-stimulating factor-1 receptor (CSF-1R). In a first analysis, the direct treatment response of CD11b+ patient-derived macrophages has been investigated by various techniques including flow cytometry and bulk RNA-sequencing of treated TAMs and further analysis of the macrophage-conditioned media after treatment. In addition, we studied the influence of CSF-1R-targeted macrophage treatment on the phenotype and functional activity of T cells to assess a potential indirect treatment response in the tumor microenvironment. RESULTS Our data revealed that CSF-1R-targeted treatment of CD11b+ TAMs induced significant changes in the protein and gene expression of macrophage polarization markers towards a more immunologically active state and a significantly higher metabolic nitric oxide production as another sign of immunological activation. Subsequent analysis of indirect effects on T cells showed not only a significantly increased expression of the T cell activation marker CD69+, but also a significantly increased tumor cell killing by autologous T cells after macrophage-targeted treatment. CONCLUSION Together these data suggest both a direct and indirect CSF-1R-targeted macrophage treatment response in the local tumor microenvironment and give first promising results on the efficacy of macrophage-targeted immunotherapy in human meningiomas.
P20.16.A PEDIATRIC CENTRAL NERVOUS SYSTEM TUMOR WITH CIC-LEUTX FUSION: A DIAGNOSTIC CHALLENGE
Authors: W Hu, Y Hou
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND The fifth edition of the WHO Classification of Tumors of the Central Nervous System (WHO CNS5) recognized CIC-rearranged sarcoma as a distinct mesenchymal, non-meningothelial tumors, designated as CNS WHO grade 4. This entity is characterized by CIC fusion with various partners, notably NUMT1 or DUX4, serving as its key molecular feature and essential diagnostic criterion. However, due to their rarity, the genetic background, etiology and clinical implications of CIC-fused CNS tumors still remains elusive. In a recent study by Philipp Sievers et al., a set of CIC-fused pediatric high-grade neuroepithelial tumors exhibit a distinct DNA methylation profile (CIC-HGNET), differing from CIC-rearranged sarcomas and suggesting an intermediate malignancy grade.Does all the central nervous system CIC tumors are CIC sarcomas or CIC-HGNETs? In this multi-center study, we assembled a series of CIC-rearranged CNS tumors, specifically those with rare fusion partners. Our aim is to broaden the understanding and diversity of CIC-fused CNS tumors, and to discuss whether CNS tumors with CIC fusions merit classification as a unified entity. MATERIAL AND METHODS Using histological evaluation, immunohistochemistry, next generation sequencing and DNA methylation cluster analysis. RESULTS The final cohort included 13 CNS CIC-cases and 6 peripheral CIC sarcoma cases. We find that not all intracranial CIC tumors are CIC sarcomas. Unlike peripheral CIC sarcomas (common features are WT1 positive and GFAP/Olig2 negative with relatively abundant reticular fibers), pure intracranial CIC-LEUTX fusion tumors with some GFAP/Olig2/Syn expression, WT1 negative, and no reticular fibers are still neuroepithelial tumor, not sarcoma. CIC-HGNET does exist. However, CIC-HGNETs can’t include all the intracranial CIC tumors. There were still some cases that methylation failed to cluster, indicating new subtypes in CIC tumors (One case of PXA morphology clustered in GG and one case of embryonal tumor morphology clustered in independent group with near LGG-MYB and ependymoma-ZFTA). Although they are not CIC-HGNET, they also belong to CIC-NET, not sarcoma. This point requires special attention, because the two types of tumors have different treatments and different prognosis. The prognosis of neuroepithelial tumors with CIC-LEUTX fusion are much better than CIC sarcomas! CONCLUSION Pediatric central nervous system tumor with CIC fusion have heterogeneity. It manifests varied methylation signature and clinical characteristics. Whatever, there are two types in CNS tumor with CIC fusion. One is CIC sarcoma and the other is CIC-NET (including new type of CIC-HGNET).
P14.13.B IN VIVO EFFICACY OF TUMOR TREATING FIELDS (TTFIELDS) FOR GLIOBLASTOMA USING NOVEL MOUSE HEAD ARRAYS
Authors: S Zbidat, R Blatt, M Sellevoll, M Gabay, I Schlachet, S Cahal, S Davidi, I Tzchori, A Haber, M Giladi, Y Palti
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Tumor Treating Fields (TTFields) therapy is CE marked for the treatment of grade 4 glioma. TTFields therapy is based on continuous, non-invasive delivery of electric fields by two array pairs placed on the patient’s scalp. Preclinical animal studies of glioblastoma (GBM) - the most common type of grade 4 glioma - are mainly performed in mouse models. However, arrays for application of TTFields to the mouse head are lacking therefore limiting the possibility of conducting in vivo studies for GBM treatment. The small dimensions and specific geometries of the mouse head make the development of such arrays challenging. MATERIAL AND METHODS We tested various array layouts to identify one that will be suited to the specific structure of the mouse head and will minimally restrict head movement. We investigated adhesive tapes to allow good skin adherence but at the same time easy array removal. We performed field measurements using a floating scope to validate that the intensity was sufficient within the region to which the tumor was to be inoculated. Finally, we conducted an efficacy study with the new arrays, using GL-261 GBM cells intracranially injected into C57BL/6 mice. Eleven days following tumor inoculation we commenced treatment with sham-heat (control) or TTFields, continuously for 12 days. We measured tumor volume by magnetic resonance imaging (MRI) before and after treatment, and calculated tumor volume fold change. We also recorded electric currents and treatment usage throughout the study. RESULTS To overcome the limitations imposed by the small head size, we developed a layout with two arrays situated on the head and opposing arrays located on the torso of the mouse. In addition, the arrays for the head were divided into two smaller disks. We identified a thin and transparent adhesive tape (facilitating correct array positioning) with good tackiness and easy removal (without leaving residual adhesive on the skin). Field intensity was found to be higher in the posterior side of the mouse head, at a location more directly underneath the arrays, and overall the arrays met the minimum treatment requirements: current ≥ 50 mA, usage ≥ 75%, field intensity ≥ 1 V/cm RMS. Efficacy was detected for treatment of GBM, with 31% lower tumor growth at treatment end in TTFields-treated versus the control group. CONCLUSION Our newly developed arrays are flexible and strongly adhering to enable efficient electric field delivery. The new arrays allowed TTFields delivery to mice heads at sufficient intensities and showed efficacy for treating GBM in mice. The new arrays will facilitate continued preclinical studies to broaden the understanding of the effects of TTFields on GBM for further advancing this research field.
P12.10.B HYPOKINETIC MOVEMENT DISORDERS FOLLOWING ADOPTIVE IMMUNOTHERAPY WITH BCMA-DIRECTED CAR T-CELLS: A CONSECUTIVE CASE SERIES
Authors: J A Gudera, J M Baehring, R K Fulbright, J Dietrich, P Karschnia
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Chimeric Antigen Receptor (CAR) T-cells targeting the B-cell maturation antigen (BCMA) represent an emerging immunotherapy for refractory multiple myeloma. While acute neurologic toxicities frequently occur and are well-described, hypokinetic movement disorders are rare and ill-defined. Clinical experience and therapeutic management therefore remain to be elucidated. MATERIAL AND METHODS We retrospectively searched the institutional databases from the Sections for Neuro-Oncology at the Yale School of Medicine (New Haven, Connecticut) and the Massachusetts General Hospital (Boston, Massachusetts) to identify patients that presented for evaluation of movement disorders following transfusion of BCMA-directed CAR T-cells. RESULTS We identified four patients (females: n = 3, males: n = 1) with complex movement symptoms following transfusion of BCMA-targeting CAR T-cells. At presentation, median age was 74.5 ± 4.3 years (range, 67-77 years). All patients received a single transfusion of a commercially available CAR T-cell product (ciltacabtagene-autoleucel: n = 3; idecabtagene-vicleucel: n = 1). Parkinsonism-like symptoms were generally preceded by mild (maximal ICANS: grade 3) and transient (median duration: 4 days) neurotoxicity.Following resolution of acute neurotoxicity, all patients developed parkinsonism-like symptoms after a median of 23 ± 7 days (range, 19-35 days). Predominant motor symptoms were bradykinesia, oppositional paratonia, postural instability, and hypomimia. Psychiatric involvement was noted in three patients. Consistent with the potential on-target/off-tumor toxicity of the CAR T-cells against BCMA-positive basal ganglia, MRI revealed bilateral hyperintensities in the head of the caudate nucleus on FLAIR/T2-weighted or diffusion-weighted sequences in two patients. [18F]-FDG-PET scans revealed basal ganglia hypometabolism in one patient, diffuse frontal hypometabolism in another, and diffuse hypometabolism in a third patient.As symptoms progressed, treatment for movement symptoms was administered in all patients and included systemic immunosuppression (corticosteroids), interleukin-antagonists, aimed to reduce the number of circulating CAR T-cells (cyclophosphamide, intrathecal methotrexate, cytarabine) or symptomatic treatment (levodopa/carbidopa). At a median follow-up of 115 days (range, 69-198 days), one patient died of sepsis despite aggressive therapy while symptoms stabilized in three patients. CONCLUSION Given that parkinsonism-like movement disorders may develop weeks after transfusion of BCMA-directed CAR T cells, a high degree of suspicion is crucial to establish diagnosis. Since symptom stabilization may be achieved, early diagnosis may form the basis for more favorable outcomes. Thus, a multidisciplinary care team appears crucial to provide optimal care of affected patients.
P10.21.A MODELLING GBM RECURRENCE - THE INFLUENCE OF PERI-LESIONAL OEDEMA AND THE DISCONNECTOME
Authors: M Tariq, J Ruffle, S Mohinta, M R S Brothwell, S Brandner, P Nachev, H Hyare
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Residual tumour burden after surgery in GBM patients is a prognostic imaging biomarker, often involving the area of T2 signal elevation surrounding the tumour core, histopathologically representing infiltrative oedema with tumour cells. We present the first stage of a model to improve the prediction GBM recurrence by specifically investigating the perilesional oedema compartment. MATERIAL AND METHODS UK-wide sample of histologically proven IDHwt GBMs with MRIs at the time of diagnosis underwent state-of-the-art in-house tumour segmentation pipeline and radiomic feature extraction of whole-tumour, enhancing, non-enhancing and oedema components, and masked disconnectome map components. Of these, early GBM recurrence, within 6 months after completion of radiotherapy, was curated and distribution mapped across the brain. RESULTS 1464 patients were identified: male = 901, median age 63 years, average overall survival 597 days. The radiomic features: Compactness 1 and 2, Surface Area, Spherical Disproportion, Sphericity, and Maximum 2D Diameter column of the disconnectome-related perilesional oedema compartment were most predictive of survival outcome (p value &amp;lt;0.01). Of these, 47 patients with average overall survival 357 days and average time from end of radiotherapy to progression of 131 days were identified. CONCLUSION Our early results reveal the relationship between perilesional oedema, MRI features and survival, with disconnectome-related perilesional oedema features most predictive. This suggests that extended brain network aberrations caused by gliomas may also influence tumour recurrence. Further work will focus on the development of more robust predictive models of tumour recurrence that have potential for significant impact on surgical and radiotherapy planning.
P12.07.A DEVELOPING NOVEL, MORE STRINGENT EVALUATION PLATFORMS TO ACCELERATE RESEARCH TRANSLATION AND INCREASE SURVIVAL FROM BRAIN CANCER
Authors: Y Chen, S Bax, V Prior, K Hsu, B Kramer, T Goodhand, J MacLeod, G McCowage, S Gore, K Gowrishankar, G O’Neill
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND The high grade gliomas (HGG) are a collection of lethal brain tumours. Currently available therapies are unsuccessful and patient survival rates have not significantly improved over the last ~ 50 years. Preclinical models currently in use poorly predict subsequent activity in phase I trials and over-estimate anti-tumour activity in HGG. Fundamental research from many labs, including our own, has shown that the normal tissue environment controls cancer invasion, signalling and response to therapy. Yet most preclinical assays lack this vital element. We have developed a brain-organoid co-culture model to test potential Chimeric Antigen Receptor (CAR) T-cell therapies for brain cancer. METHODS We grew stem-cell generated cortical brain organoids derived from human embryonic stem cells (hESCs) using a directed organoid protocol to ensure uniform organoid generation. Organoids were then combined with spheroids of HGG cells that were transduced with lentiviral vector to express luciferase. Tumour cell viability was assessed by xCelligence electrical impedance assay or by IVIS Lumina imaging of luciferase activity in 3D cultures. Cytokine-mediated T-cell killing was confirmed by ELISA. RESULTS We evaluated Ephrin receptor A2 (EphA2)-directed CAR T cells in EphA2-positive HGG, comparing response in target cells grown in 2D monolayers, as 3D spheroids and as 3D spheroids co-cultured with cortical brain organoids. Critically, we show that CAR T cell efficacy reduces with increasing model complexity. CONCLUSION Thus the inclusion of the normal tissue in the form of the organoid modulates therapy response, and the co-cultures provide an important platform for evaluating novel therapies for brain cancer. The use of such biomimetic models may not only provide a more realistic reflection of in vivo responses but also increase successful transition of treatments to patients.
Addressing fairness issues in deep learning-based medical image analysis: a systematic review
Authors: Zikang Xu, Jun Li, Qingsong Yao, Han Li, Mingyue Zhao, S. Kevin Zhou
Journal: npj Digital Medicine (2024)

Deep learning algorithms have demonstrated remarkable efficacy in various medical image analysis (MedIA) applications. However, recent research highlights a performance disparity in these algorithms when applied to specific subgroups, such as exhibiting poorer predictive performance in elderly females. Addressing this fairness issue has become a collaborative effort involving AI scientists and clinicians seeking to understand its origins and develop solutions for mitigation within MedIA. In this survey, we thoroughly examine the current advancements in addressing fairness issues in MedIA, focusing on methodological approaches. We introduce the basics of group fairness and subsequently categorize studies on fair MedIA into fairness evaluation and unfairness mitigation. Detailed methods employed in these studies are presented too. Our survey concludes with a discussion of existing challenges and opportunities in establishing a fair MedIA and healthcare system. By offering this comprehensive review, we aim to foster a shared understanding of fairness among AI researchers and clinicians, enhance the development of unfairness mitigation methods, and contribute to the creation of an equitable MedIA society.
P11.07.B RELIABILITY OF POSTOPERATIVE NEUROPSYCHOLOGICAL SCREENING IN PATIENTS WITH PRIMARY BRAIN TUMORS BY VIDEO CONSULTATION AND IN-PERSON
Authors: W van Buijtene, E Butterbrod, G Rutten, K Gehring
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Since COVID-19 there has been an increase in consultations with patients in neuro-oncological practice via video teleconferencing (VTC). While VTC can increase access to care, the degree to which cognitive screening can be reliably conducted via VTC in brain tumor patients is unclear. The aim of this study is to investigate reliability of a predominantly computerized cognitive screening conducted via VTC (Teams) vs in-person in a Dutch hospital. MATERIAL AND METHODS Glioma and meningioma patients underwent an in-person neuropsychological screening as part of standard care before surgery. Between May 2020 and October 2022, patients underwent their 3-month follow-up as part of their standard care via VTC due to COVID. Before May 2020, patients underwent this follow-up in-person. The screening consisted of a computerized battery (CNS vital signs) and paper and pencil tasks (Fluency, Digit span forward and backward). We compared the stability of raw scores over time of patients undergoing VTC vs. in-person administration with intraclass correlation coefficients (ICCs, continuous scores) and absolute agreement (non-continuous scores). We also statistically compared percentages of patients showing reliable change between groups (α=0.05). RESULTS Compared to the in-person group (n=112), the VTC (n=112) group was younger (51±14 vs 58±14 years), contained more male patients (56% vs 34%) and more patients with higher education (49% vs 29%). The groups did not differ on other sociodemographic, tumor or treatment characteristics. The majority of test measures for both the VTC (13 out of 15) and in-person group (10 out of 15) had acceptable to excellent ICC values (range 0.50-0.91 vs 0.61-0.87). ICCs of reaction time scores on simpler tests, the Stroop test part 1 (0.45 vs 0.47), and a Continuous Performance test (0.37 vs 0.46), and of a Visual Recognition test (0.33 vs 0.44) were low for both groups. ICCs of a Verbal Recognition test (0.44 vs 0.65) and Digit Span test backward (0.44 vs 0.65) were low only for the VTC group. The degree of agreement on non-continuous measures was similar for both groups, except for Continuous Performance test accuracy. Significantly more patients in the VTC group showed reliable improvement on the Continuous Performance test (15% vs 11%). CONCLUSION Neuropsychological screening via video consultation is a promising method, as it can provide opportunities for more patients to receive care from home. Reliability was comparable for VTC and in-person administration for most measures. Performances over time assessed via VTC appeared less stable for Digit span backward, a paper and pencil test, and for Verbal Recognition accuracy, a computerized test. Future research into patient characteristics of the VTC group, and consequences for performances, is warranted.
P02.18.A MOLECULAR CHANGES UNDERLYING DECAY OF SENSORY RESPONSES AND ENHANCED SEIZURE PROPENSITY IN PERITUMORAL NEURONS
Authors: E De Santis, E Tantillo, M Scalera, N Meneghetti, C Cerri, M Menicagli, A Mazzoni, M Costa, C Mazzanti, E Vannini, M Caleo
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Glioblastoma growth impacts on the structure and physiology of peritumoral neuronal networks, altering the activity of pyramidal neurons which drives further tumor progression. It is therefore of paramount importance to identify glioma-induced changes in pyramidal neurons, since they represent a key therapeutic target. MATERIAL AND METHODS We longitudinal monitored visual evoked potentials after the orthotopic implant of murine glioma cells into the mouse occipital cortex. With laser microdissection, we analyzed layer II-III pyramidal neurons molecular profile and with local field potentials recordings we evaluated the propensity to seizures in glioma-bearing animals with respect to control mice. RESULTS We determine the time course of neuronal dysfunction of glioma-bearing mice and we identify a symptomatic stage, based on the decay of visual response. At that time point, we microdissect layer II-III pyramidal neurons and evaluate the expression of a panel of genes involved in synaptic transmission and neuronal excitability. Compared to the control group, peritumoral neurons show a decrease in the expression of the SNARE complex gene SNAP25 and the alpha1 subunit of the GABA-A receptor. No significant changes are detected in glutamatergic (ie, AMPA or NMDA receptor subunit) markers. Further reduction of GABA-A signaling by delivery of a benzodiazepine inverse agonist, DMCM (methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate) precipitates seizures in 2 mouse models of tumor-bearing mice. CONCLUSION These studies reveal novel molecular changes that occur in the principal cells of the tumor-adjacent zone. These modifications may be therapeutically targeted to ameliorate patients’ quality of life.