tbuckley/cabot-search huggingface dataset:
P21.01.A CEREBELLOPONTINE ANGLE EPIDERMOID CYST WITH MALIGNANT TRANSFORMATION TO SQUAMOUS CELL CARCINOMA: UNUSUAL COMPLICATION OF A BENIGN INTRACRANIAL TUMOR
Authors: Y J Garcilazo-Reyes, J O Navarro-Fernández, D Magos-Rodríguez, L F Arias-Ruiz, M L Pérez-Díaz, E Gómez-Apo, R Hernández-Montes de Oca, G A Gutiérrez-Aceves
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Intracranial epidermoid cysts (EC) account for approximately 0.2%-1.8% of all intracranial tumors. Extremely rare, these benign lesions may undergo malignant transformation into squamous cell carcinoma (SCC). The time frame for transformation can vary greatly, and the ideal management approach remains uncertain. MATERIAL AND METHODS 55-year-old female patient with history of migraines was diagnosed with an incidental cystic lesion suggestive of EC in right cerebellopontine angle (CPA) since the age of 30. She experienced a sudden onset in March 2023 of auditory decline in her right ear, tinnitus, vertigo, headache, dysgeusia, and gait disturbance. Examination revealed involvement of the VIII right cranial nerve with sensorineural hearing loss and complete right facial nerve palsy. She underwent surgery in June 2023 where the cyst was resected however, the capsule of the tumor was strongly adhered to the brainstem, unable to be removed. It showed positive immunohistochemistry for p63, p40, CK5/6, CK7, D2-40, S100, PD-L1, Ki67 was positive in 20% of neoplastic cells, brachyury was negative, consistent with EC with malignant transformation to SCC. She developed few days after the surgery, dysarthria, diplopia, IV and VI right nerve palsies and right dysmetria. Neuroaxis contrast-enhanced MRI was performed with no evidence of lesion otherwise. Brainstem auditory evoked potentials, blink reflex test and facial nerve conduction tests were completed and abnormal due to axonal right facial nerve neuropathy with side-to-side ≥ 90% difference and profound right hearing loss. RESULTS The one-month follow-up brain MRI showed the right CPA lesion with heterogeneous enhancement with increase in diameter and involvement of the auditory canal. 18FDG) PET/CT demonstrated focal hypermetabolism (SUVmax 10.3) in the right CPA indicative of progression. She underwent radiosurgery with a total dose of 30 Gy in 5 sessions (October 2023). The follow-up 18FDG PET/CT (April 19, 2024) showed no distant sites associated with abnormal hypermetabolism but persistent focal hypermetabolism that decreased compared to previous exam (SUVmax 7.2). The patient is currently 11 months apart from her diagnosis without new neurological findings. Chemotherapy or checkpoint inhibitors have not been used yet. CONCLUSION We report a case of intracranial SCC derived from an EC, the occurrence this malignant transformation is uncommon and typically indicates a poor prognosis. Small series and case reports are to date available in the literature. After surgery, radiotherapy or radiosurgery should be considered, close follow-up is recommended, chemotherapy or immunotherapy can be used but its effectiveness remains unclear.
P10.13.A DEMOCRATIZING QUALITY: A STRATEGY TO MAKE LEVEL OF EVIDENCE ASSESSMENTS QUICK, EASY, AND ACCESSIBLE TO ALL
Authors: A Badani, C Grzyb, E W Church, M Glantz
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Advances in clinical care depend decisively on evidence from high-quality clinical trials. EANO and other international societies have established systematic and transparent methodologies for assessing the quality of clinical trials, but the process is time-consuming and challenging to master. Using advanced computational strategies, we have developed three novel models—an Excel-based calculator, a machine learning (ML) model, and a permutation-based decision tree—designed to facilitate this assessment and make it easily accessible to clinicians and researchers. METHODS AND MATERIALS A PRISMA-compliant literature review was conducted to identify all therapeutic human trials involving adult neuro-oncology patients published in the last 12 months in high-impact journals. Articles fulfilling pre-specified inclusion and exclusion criteria were selected and a level of evidence was assigned independently by two investigators, with differences resolved by consensus. Simultaneously, an advanced ML model was created, employing a Support Vector Machine (SVM) algorithm renowned for its efficacy in classification tasks. The SVM model was configured with a 0.2 train-test split to validate its predictive accuracy and recursive feature elimination to evaluate the significance of input features, confirming their equal importance. Additionally, a permutation-based decision tree was developed, where a collaborative team analyzed all possible permutations of questionnaire responses to assign explicit quality ratings through a data-driven decision framework. Finally, an Excel-based tool was developed to calculate the level of evidence. The results of all four assessment strategies were statistically compared. RESULTS The ML model was developed and trained on a dataset of 225 categorized research papers and achieved a classification accuracy of 97%. The permutation-based decision tree tool was designed to map all possible questionnaire response permutations to specific trial quality levels, with 11,521 independently graded permutation response pathways. The Excel-based tool was programmed to use a phrase-matching algorithm to identify an evidence level based on a user’s provided answers. The permutation and Excel-based strategies provided excellent classification accuracy but were inferior to the ML model. As we will demonstrate, all three models were easy to use and provided rapid and reliable levels of evidence assessments. CONCLUSION By providing open access to these tools to clinicians and researchers and making the level of evidence assessments efficient, consistent, and transparent, we hope to democratize the ability to evaluate published trials, thereby improving the quality of clinical care. We also hope that clinical researchers will utilize these tools to enhance the quality of their clinical trials at the design stage.
OS04.7.A PRESERVATION OF FERTILITY AND FAMILY PLANNING IN PATIENTS WITH LOW-GRADE GLIOMA
Authors: A R Brüning, M Reischl, C Jungk, J Onken, D Mielke, K Kniese, M Nadji-Ohl, S Krieg, P Vajkoczy, V Rohde, A Nabavi, O Ganslandt, R Wirtz, R Gerlach, M Czabanka, J Coburger, M Forster
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Patients suffering from a Low-grade glioma (LGG) will require adjuvant treatment at some stage of their course of disease which is a mayor impact for fertility and family planning. Given the predominantly young age of patients at the time of LGG diagnosis and the high 5-year survival rate of up to 95%, we aimed at analyzing fertility preservation measures and the influence of glioma diagnosis on family planning in LGG patients. MATERIAL AND METHODS Adult LGG patients having been enrolled prospectively in the German LoG-Glio registry since 2015 underwent semi-structured interviews to retrospectively evaluate repercussions of glioma on their family life. RESULTS 199 LGG patients were contacted by phone, and 76 patients (38%), with 38 (50%) being females, completed the questionnaire. At the time of glioma diagnosis, 18 (47%) women and 14 (39%) men already were parents, and 13 (34%) women and 16 (42%) men desired to have (further) children. However, glioma diagnosis influenced family planning in 10 of each male and female patients, with most of them resigning their wish. Thus, fertility-preserving measures were initiated by 9 (24%) men but only 3 (8%) women by using sperm cryopreservation or egg freezing. In men, a total of 7 children were born after the diagnosis, with all pregnancies occurring naturally and all children been born healthy. Among female patients, 7 (18%) women became pregnant during the course of their illness; all pregnancies were uncomplicated and all children were born healthy and via vaginal delivery. Regarding relationship, at the time of the survey, 21 (55%) men and 26 (68%) women were still with the same partner as they had been at the time of diagnosis. However, 19 (50%) male and 24 (63%) female patients declared that tumor diagnosis had an impact on their relationship, with only 4 (20%) male and 10 (45%) female patients reporting on a positive influence. CONCLUSION Diagnosis of glioma has a major impact on family planning and on relationship in both, female and male patients. However, according to our data, fertility-preserving measures are only rarely taken, predominantly by male patients. Most importantly, pregnancies occurring after glioma diagnosis and treatment were uneventful and all children were born healthy. Further research in larger cohorts is necessary for better counseling patients and individual patient-centered therapy planning.
P18.52.B UNVEILING THE IMPACT OF CANCER-IGG ON GLIOMA: INSIGHTS FROM BIOLOGICAL BEHAVIOR AND TUMOR MICROENVIRONMENT
Authors: X Han, H Li, L Su, L Tian, W Wang, Z Xiao, H Guo, X Li, T Fan, H Zhou, X Xue
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Gliomas are the most common malignant brain tumor in the central nervous system, with high invasiveness and heterogeneity. In recent years, cancer derived immunoglobulin G (Cancer-IgG) has been drawing attention of researchers. Cancer-IgG was identified in tumors and could promote tumorigenesis and progression. MATERIAL AND METHODS In this study, we explored the expression pattern of Cancer-IgG using available datasets and validated with our own patient samples. A serious of loss- and gain-of function assays were performed to investigate the role of Cancer-IgG. Possible mechanisms were unveiled by co-immunoprecipitation and RNA sequencing. RESULTS Our result demonstrated that Cancer-IgG expresses in glioma. And the expression pattern is associated with poor prognosis and malignant molecular characterization. Functional assays confirmed that Cancer-IgG could promote glioma cells proliferation, migration, invasion and resistant to apoptosis. The cGMP/PKG/VASP pathway could be the underlying mechanisms by which Cancer-IgG has an effect. Evidence from co-culture assay suggest that Cancer-IgG could induce macrophages M2 polarization. CONCLUSION Collectively, Cancer-IgG could be identified in glioma cells and it could facilitate the malignant biological phenotype in vivo and in vitro. In glioma microenvironment, Cancer-IgG could induce M2 macrophages polarization.
P06.05.B FLYDENTIFICATION - CHARACTERIZATION OF NOVEL MOLECULAR DRIVERS IN GLIOBLASTOMA BASED ON FUNCTIONAL GENOMICS SCREENING IN DROSOPHILA MELANOGASTER
Authors: O Lewandowska, D Picard, B Hariri, T Klein, G Reifenberger, T Reiff, G Leprivier
Journal: Neuro-Oncology (2024)

Abstract Glioblastoma is an extremely aggressive form of brain tumor. The median overall survival of patients is only 15 to 18 months, and the five-year survival rate is less than 10% despite aggressive multimodal treatment that includes total resection of the tumor followed by a combination of radio-, chemo- and Tumor Treating Fields (TTF)-therapy. Therefore, new therapeutic interventions are urgently needed. For this reason, it is essential to define novel therapeutic targets for this tumor entity. To this aim, we developed a combinatorial approach, termed “ FLY dentification”, to identify and characterize novel driver genes in glioblastoma. This pipeline combines bioinformatics analysis of patients proteomics data together with functional screening in Drosophila models of glioblastoma, and validation with human glioblastoma cell models. This approach allowed us to initially uncover the top 300 most overexpressed proteins in glioblastoma tissues using in silico preselection algorithms. By taking advantage of a Drosophila model of glioblastoma ‒ driven by overexpression of the oncogenic forms of EGFR and PI3K ‒ and using an RNAi approach we tested the functional contribution of 192 of the gene candidates to glioblastoma lethality in vivo. This targeted screening allowed us to identify 41 clinically and functionally relevant gene candidates. Focusing on the top candidates with no reported function in glioblastoma, we demonstrated that the DNA binding and chromatin remodeling DEK protein contributes to human glioblastoma tumorigenesis in vitro. Some of these findings will be validated using in vivo models of human glioblastoma. Together, the established “FLY dentification” pipeline represents a combinatorial approach designed to uncover previously unrecognized glioblastoma driver genes, which has the power to reveal novel biomarkers and therapeutic targets for this tumor type.
P06.06.A HOXA1, A TRANSCRIPTION FACTOR UPREGULATED IN GLIOBLASTOMA, IS ABLE TO TRAVEL BETWEEN CELLS WITH THEIR NUCLEI AS TARGET
Authors: E Vigneul, M Finet, L Bridoux, E Renaux, R Rezsohazy, F Clotman
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Homeobox A1 (HOXA1) is a transcription factor overexpressed in glioblastoma and an independent prognostic marker. As a transcription factor crucial for proper neural proliferation and differentiation, dysregulated expression of HOXA1 can potentially accelerate glioblastoma growth and invasion. Furthermore, recent publications highlight HOX homeoprotein ability to travel between cells and to potentially alter neighboring cell transcriptional or non-transcriptional mechanisms. MATERIAL AND METHODS To investigate HOXA1 intercellular travel and their targeted intracellular compartment, human embryonic kidney 293 cells (HEK 293) and mouse N2a cells (a fast-growing neuroblastoma cell line) were transfected with plasmids containing Flag/V5-HOXA1 and Enhanced Green Fluorescent Protein (EGFP) coding sequences (producing cells), or untransfected (recipient cells). EGFP was used as positive control for transfection and as negative control of intracellular travel. Cell nuclei were marked using 4′,6-diamidino-2-phenylindole (DAPI). Flag immunohistochemistry was performed between 24 and 48 hours after cellular transfection. RESULTS Intercellular travel was assessed by immunofluorescence. Since cells were either cotransfected with HOXA1 and EGFP plasmids or untransfected, HoxA1 positive and EGFP-negative cells were considered homeoprotein recipients. On the recipient coverslips, the presence of HoxA1 was detected while EGFP was not, confirming the ability of HoxA1 homeoproteins to travel between cells. Moreover, colocalization with DAPI was detected in the receiving cells, suggesting the ability of HoxA1 to enter the nucleus of the target cells and potentially impact transcriptional mechanisms. CONCLUSION These results underscore the possibility for oncogene HoxA1 to be secreted by different types of cells, and to potentially influence the transcriptional activity of the surrounding cells.
P22.01.A “IT FEELS LIKE I’M GRIEVING FOR SOMEONE THAT IS STILL ALIVE”: A QUALITATIVE STUDY OF THE EXPERIENCES OF NEURO-ONCOLOGY CAREGIVERS
Authors: A Zanotto, K Goodall, M Ellison, C McVittie
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Informal caregiving of someone with a primary brain tumor is highly distressing and associated with an increased risk of depressive symptoms, anxiety, and caregiver burden. A brain tumor diagnosis poses unique symptoms and challenges, including an uncertain prognosis and related existential concerns, as well as neurological symptoms such as cognitive deficits or personality changes. Due to these characteristics and related care demands, family caregivers experience a different set of challenges compared to other types of cancer. The purpose of this qualitative study was to understand in-depth the experiences of informal caregivers’ coping, support needs, and changes in relationships while caring for a loved one with a brain tumor. METHODS In-depth interviews were conducted with 10 informal caregivers (3 spouses/partners, 4 parents, 2 children, and 1 sibling) of people with low- or high-grade tumor. The mean age of participants was 42 years (range 19-68 years), and 90% of participants were female (n = 9). Interviews were transcribed verbatim and analyzed using interpretative phenomenological analysis (IPA). RESULTS Participants experienced grief and feeling unappreciated, and were advocating for the person diagnosed. Caregivers described grieving for the loss of their loved one as they were before the diagnosis, but also for the loss of their previous lifestyle and the loss of a future together as they imagined it to be. There was a sense of uniqueness in caring for someone with a brain tumor. Participants felt unappreciated by society, particularly when comparing their current role to their professional identities. They were involved in the care decisions, researching treatment and support availability, and advocating for the needs of the person diagnosed. CONCLUSION The current findings highlight the importance of involving informal caregivers of persons with a brain tumor in the treatment process. It is crucial that their role is acknowledged and appreciated during interactions with healthcare professionals. Implications for communication with clinicians will be discussed.
OS03.4.A REPEATED INTRACRANIAL ADMINISTRATION OF ANTI-PD-1 ALONE OR IN COMBINATION WITH ANTI-CTLA-4 IMMUNE CHECKPOINT-BLOCKING MONOCLONAL ANTIBODIES IN PATIENTS WITH RECURRENT HIGH-GRADE GLIOMA
Authors: L Lescrauwaet, I Dirven, J Del’haye, W Geens, X Geeraerts, L Stevens, S Brock, M Kockx, L Seynaeve, H Everaert, a Vanbinst, S Tuyaerts, B Neyns, J Duerinck
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Recurrent high-grade glioma (rHGG) is an invariably fatal malignancy, currently lacking life-prolonging treatment options. Systemic administration of PD-1 and CTLA-4 immune checkpoint blocking monoclonal antibodies has shown limited efficacy. In the Glitipni multi-cohort dose finding phase I clinical trial, the primary aim is to establish safety and feasibility of intra- followed by postoperative intracranial (iCran) administration of nivolumab (NIVO), with or without ipilimumab (IPI), in patients with rHGG amenable for a maximal safe resection (MSR) or stereotactic core needle biopsy (SCNB). MATERIAL AND METHODS Sixty-one patients were enrolled (across 3 cohorts), receiving 10 mg NIVO IV within 24h prior to MSR or SCNB. Forty-three patients underwent MSR, followed by intracerebral (iCer) injection of NIVO (10 mg) and IPI (5 mg) in the brain tissue lining the resection cavity. Among them, 27 received an additional intracavitary injection of NIVO (10 mg) and IPI (1-, 5-, or 10 mg) (iCav, via an Ommaya reservoir) at the end of the neurosurgical procedure. Sixteen patients underwent SCNB followed by the intratumoral (iTum) injection of NIVO (10 mg) and IPI (5 mg). Postoperative iCav administrations were repeated bi-weekly for a maximum of 11 cycles, concurrently with 10 mg NIVO IV. Postoperatively, 1-, 5-, or 10 mg NIVO iCav was administered as a single agent in 28 patients. In the third cohort, postoperative administration of 10 mg NIVO iCav was combined with 1-, 5- or 10 mg IPI iCav in 22 patients. RESULTS No unexpected adverse events (AE) occurred related to the perioperative treatment. Dose limiting toxicity consisted of transient symptomatic grade 3 aseptic neutrophilic pleocytosis in 1- and 3 patients receiving iCav administration of 5- and 10 mg iCav IPI, respectively. The most frequent reported treatment related AE was fatigue (n=49,80%); no grade 5 AE occurred. PFS did not differ between cohorts. OS was superior in patients who underwent a MSR versus SCNB; but was not improved by the addition of iCav IPI (median OS: 15- [95% CI 0-53] vs. 42- [26-57] vs. 35 [29-40] weeks; 1y OS-rate: 12% [95% CI 0-28] vs. 37% [14-60] vs. 29% [12-46]). OS of pts who underwent a MSR compared favorable against a pooled historical control cohort (n=469) treated with VEGF(R)-inhibitors (log rank p.015). CONCLUSION This first-in-human, multi-cohort, phase I clinical trial on intracranial CTLA-4/PD-1 blockade in patients with rHGG, demonstrates that intra- and postoperative iCran administration of NIVO with or without IPI up to a bi-weekly postop iCav dose of 1 mg IPI and 10 mg NIVO can be safely performed. Promising survival is documented in patients amenable for resection.
P18.19.A EVOLVING STANDARDS: THE INTEGRATION OF NEW THERAPIES INTO NEUROONCOLOGY GUIDELINES
Authors: A Lawson McLean, A C Lawson McLean, J Walter, C Senft
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND In the swiftly progressing domain of neurooncology, continuously updated clinical guidelines are essential to integrate emerging therapeutic developments effectively. This study investigates the perspectives and challenges faced by neurooncology professionals regarding these guidelines, with an emphasis on their responsiveness to innovative treatments such as Tumor Treating Fields (TTFields). MATERIAL AND METHODS An electronic survey was distributed via the mailing list of the German Neuro-Oncological Working Group, encompassing demographic queries, attitudes towards clinical guidelines, and the assimilation of novel therapies like TTFields. The survey featured Likert-scale items, direct questions concerning the utility and adaptability of guidelines, and specific inquiries regarding the incorporation of TTFields into guidelines. Statistical validation was performed using chi-squared tests, Pearson’s correlations, and Fisher’s exact test. RESULTS Out of 87 valid responses, primarily from neurosurgeons (66.7%), a substantial majority (81.6%) affirmed that guidelines enhance the quality of treatment. Nevertheless, 32.2% expressed that these guidelines limit therapeutic freedom. With regard to TTFields, 78.2% were aware of its exclusion from the current DGN glioblastoma guidelines. Analysis indicated a positive correlation between the perception that guidelines enhance treatment quality and the advocacy for their regular revision. The survey also exposed variations in guideline perceptions across different demographic groups, illustrating diverse attitudes towards their utility and progressive adaptation. CONCLUSION Clinical guidelines in neurooncology are vital but must be frequently revised to accommodate the latest therapeutic advancements. The findings underscore the necessity for guidelines to adapt dynamically, maintaining their validity and applicability in clinical practice. This study highlights the critical balance between adhering to evidence-based standards and incorporating timely updates, particularly with the integration of innovative treatments such as TTFields.