tbuckley/cabot-search huggingface dataset:
OS02.6.A COORDINATION OF CARE IN THE CONTEXT OF PRIMARY BRAIN TUMOURS: HEALTHCARE PROFESSIONALS’ EXPLORATION OF THE UNSPOKEN IMPACT AND CLINICAL IMPLICATIONS
Authors: M S Jeon, J Shaw, H Banks, D M Legge, S He, T Carlick, E S Koh, G Halkett, B Kelly, M B Pinkham, T Ownsworth, R J Chan, H Dhillon
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND People with primary brain tumours (PwBT) and their families expereince high distress and face challenges navigating the disease, healthcare system, treatment, and/or survivorship. Coordination of care is an approach to achieving continuous, timely care according to individual care needs of PwBT. Within the Brain Cancer Rehabilitation, Assessment, Interventions for Survivorship Needs (BRAINS) program, we aimed to explore healthcare professionals’ (HCPs) practices and perceptions about neuro-oncology care coordination (NOCC). MATERIAL AND METHODS We conducted a qualitative study using semi-structured interviews via videoconferencing. Participants were HCPs involved in clinical neuro-oncology care. Interviews were audio-recorded and transcribed verbatim. Data were analysed thematically using interpretive description, following COREQ guidelines for conducting and reporting qualitative research. RESULTS We interviewed 12 HCPs from Australia and Aotearoa New Zealand between June and November 2023. The median interview duration was 58 minutes. Participants had a median of 13 years of clinical experience in neuro-oncology across medical, nursing, and allied health disciplines. NOCC models were not standardised. Often they were not clearly established and depended on HCPs’ knowledge, experience, and skillsets for triaging care or managing advanced illnesses. HCPs typically oversaw NOCC in either the neurosurgical or oncology care phases but not both. We identified five themes related to NOCC as perceived by HCPs: 1) Vulnerable and complex: PBT is a unique cancer generating pervasive, multifaceted disabilities; 2) Tailored coordination: Shaping and tailoring NOCC is in the best interests of PwBT and families; 3) Unfunded support: Care needs warrant unfunded proactive support; 4) Role limitations: Limited resources impact HCPs’ capacity to deliver the optimal standard of care; and 5) Emotionally demanding: HCPs manage emotional weight with limited support. CONCLUSION PwBT experience a unique and complex set of care needs requiring specialist skills and knowledge beyond general oncology care coordination. NOCC encompasses continuous coordination of multidisciplinary care to optimise functional living for PwBT. Recognising the NOCC role in managing a vast array of issues, better support infrastructure with training and resources for HCPs is needed to retain HCPs and prevent burnout, which will provide greater access to NOCC for PwBT and carers. The findings will inform further research to identify support, training and resource needs for HCPs and implement appropriate interventions. FUNDING The study is funded by the MRFF Australian Brain Cancer Mission Brain Cancer Survivorship Grant.
P17.12.B LEPTOMENINGEAL DISEASE FOLLOWING POSTOPERATIVE RADIOSURGERY IN RESECTED BRAIN METASTASES: LONG TERM FOLLOW UP OF A PHASE 2 STUDY
Authors: P Navarria, F Pessina, E Clerici, L Bellu, L Politi, V Vernier, L Raspagliesi, B Bono, A Franzini, M Scorsetti
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Brain metastases (BMs) affect about 20-40% of patients with solid primary tumors, and as many as 25% of patients will harbor large BMs. Surgical resection followed by postoperative stereotactic radiosurgery has become the standard modality to treat large BMs, given the ability to obtain a satisfactory local control with neurocognitive preservation. Notwithstanding the excellent outcome of a combined treatment approach, one concern is the potential risk of developing leptomeningeal disease (LMD) occurring in up to 30% of patients receiving surgical resection followed by postoperative SRS. We evaluated LMD in patients enrolled in prospective phase 2 study treated with surgery followed by hypofractionated radiosurgery (HSRS) on the tumor bed in oligometastatic patients with single large brain metastases (BMs). Local control (LC), brain distant failure (BDF), overall survival (OS), and prognostic factors related to LMD were analyzed too. MATERIAL AND METHODS A retrospective review of patients treated into a prospective phase 2 study with surgery followed by HSRS on the tumor bed from June 2015 and May 2018 has been performed. Patterns of LMD were determined radiographically based on the first MRI at which LMD was diagnosed. Prognostic factors for LMD have been evaluated as well. LC was assessed using Response Assessment in Neuro-Oncology criteria, BDF defined as the appearance of new BMs in other brain sites in respect to the treated ones. OS was calculated from BMs treatments. Cause of death was defined as neurologic in case of diffuse brain or meningeal progression, and systemic in case of diffuse extracranial progression with controlled brain disease. RESULTS One hundred and one patients were included in the present analysis. The median follow up time for the whole cohort was 25 months (range 3-109 months) and 79 months (range 67-91 months) for alive patients. LMD has been recorded in 20 (19.8%) patients at a median time of 9 months (range 3-47 months) from surgery. For patients with LMD the median OS time, 6-month, 1-year, and 2-year OS rates were 16 months, 95%, 75%, and 20%, respectively compared to 20 months, 93%, 80.6%, and 38.7%, respectively for those with BDF only without LMD. According to logistic regression analysis, the infratentorial site (p=0.04) and meninges not surgically removed (p=0.01) influenced the development of LMD. At long term follow up the 2, 5 years LC, BDF, and OS rates 87%, 78%; 50.4%, 56.8%; 49.5%, 23.8% respectively. The occurrence of LMD significantly influenced OS (p=0.01). CONCLUSION Surgery followed by HSRS on the tumor bed is an effective and safe treatment approach. LMD conditioned a worse outcome. In the future the employ of preoperative HSRS could represent a valid approach to potentially reduce this adverse event.
P17.11.B INTERIM ANALYSIS OF A PHASE II TRIAL OF INTRAOPERATIVE RADIOTHERAPY (IORT) WITH INTRABEAM AFTER SURGICAL RESECTION OF BRAIN METASTASES (BM) (NCT05084092)
Authors: M Macià i Garau, G Plans Ahicart, A Lucas Calduch, N García Expósito, A Rosselló Gómez, A Fernández Coello, N Vidal Sarró, C Majós Torró, A Pons Escoda, M Ventura Bujalance, R Martín Vaello, P Saldaña Gutiérrez
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND The addition of external radiotherapy (RT) improves local control after surgical resection of brain metastases (BM). IORT involves delivering of a single, high dose of radiation directly to the tumor bed during surgery offering several advantages: precise targeting of tumor bed, potentially reduction of radiation-related complications and rapid start of systemic treatment if indicated. MATERIAL AND METHODS We have analysed the results of the first 20 patients included in a Phase II trial. Inclusion criteria: KPS ≥ 70%, complete resection judged by Neurosurgeon, peroperative histological confirmation of BM, no dural attachment, adequate distance to organs at risk and informed consent. Previous RT was allowed. After en bloc resection, administration of a fixed dose of 15,40 Gy prescribed at 2 mm depth with INTRABEAM (X-ray 50 Kv) using the appropriated sized applicator was planned. Primary endpoint was local (cavity) progression free survival. RESULTS from June 2020 to March 2024 we have included 39 patients. 12 patients were excluded for various reasons. This communication reports the first 20 analysable patients. Median age was 58,8 years (40-78). 12 males (60%) and 8 females (40%). Lung cancer was the most frequent primary tumour (55%), followed by breast (15%) and melanoma (15%). Median DS-GPA was 2,9 (1-4). Median KPS was 87,4 (60-100). All patients except one were oligometastatic. Surgery was complete in 100% of cases. All patients received the prescribed dose with a median surface dose of 22,34 Gy (20,06-24,2) with a median applicator size of 23,25 mm (15-45) in a median time of 16,25 minutes (7,40-39,29). One patient suffered thrombocytopenia and cerebral bleeding. Another patient presented an asymptomatic distal jugular and lateral sinus thrombosis discovered in the postoperative MRI. Median hospitalization time was 5,6 days. After a minimum and median follow-up of 12 and 29,4 months, 4 patients died prematurely. Regional (brain) progression of the remaining 16 patients was 43,8% including 1 nodular leptomeningeal disease 6 month after surgery. Many patients received new local treatments with RT; 2 patients were treated with salvage WBRT. Local (cavity) control at 1 and 2 years was 93,8% and 92,9% with only one local relapse at 8 months after surgery that was treated with salvage SRS. We noted only one symptomatic radiation necrosis in a patient previously locally treated by FSRT. CONCLUSION IORT appears as a feasible, safe and highly effective option to ensure local control after surgery of BM with minimal risk of complications.
P12.12.B IMMUNOTHERAPY WITH CAR T-CELLS IN THE TREATEMENT OF RECURRENT GLIOBLASTOMAS: A SYSTEMATIC REVIEW
Authors: P H L Souza, N O Fracaroli, I M Almeida, R G Suaid, H A Guaresqui, R N T Motta, V C Monici, R C A Moysés, G A Moraes, A O Ramalho, C C Berriel, G K Bellotti, B V Nogueira
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Glioblastomas are common malignant tumors in the central nervous system. Currently, the standard of treatment (SOD) for this kind of disease is maximum surgical resection associated with postoperative chemotherapy. However, the current SOD for this tumor still promotes a strict prognosis, with a median Overall Survival (mOS) of less than 24 months. In consequence, many studies are carried out in order to explore new treatment strategies; among those studies, Chimeric Antigen Receptor (CAR) T-cell therapy stands out. This therapy offers a promising alternative for treating those neoplasias resistant to conventional treatment. Therefore, we conducted a systematic review aiming to consolidate and summarize current knowledge on the efficacy of CAR T-cell therapy specifically for glioblastoma. METHODS We searched Medline, Embase, and Web of Science databases following Cochrane and PRISMA guidelines. bThe endpoints of this systematic review were mOS, T-cell persistence, and maximum tolerated dose of CAR-T cell. RESULTS The analysis included 8 studies with a total population of 70 patients diagnosed with recurrent glioblastoma treated with CAR T-cells The pooled data of mean Overall Survival was 265,57 days. Of the 70 patients, only 5 had complete tumor regression, while 36 had tumor progression. CONCLUSION This systematic review showed that CAR T-cell therapy does not seen to be an optimal treatment for recurrent glioblastoma patients due to its low tumor regression rate and high tumor progression. However, current research needs to solidify the evidence base before its widespread clinical use in treating recurrent glioblastoma can be justified.
Microbiome research in autoimmune and immune-mediated inflammatory diseases: lessons, advances and unmet needs
Authors: Jose U. Scher, Renuka Nayak, Jose C. Clemente
Journal: Annals of the Rheumatic Diseases (2024)

The increasing prevalence of autoimmune and immune-mediated diseases (AIMDs) underscores the need to understand environmental factors that contribute to their pathogenesis, with the microbiome emerging as a key player. Despite significant advancements in understanding how the microbiome influences physiological and inflammatory responses, translating these findings into clinical practice remains challenging. This viewpoint reviews the progress and obstacles in microbiome research related to AIMDs, examining molecular techniques that enhance our understanding of microbial contributions to disease. We discuss significant discoveries linking specific taxa and metabolites to diseases such as rheumatoid arthritis, systemic lupus erythematosus and spondyloarthritis, highlighting the role of gut dysbiosis and host–microbiome interactions. Furthermore, we explore the potential of microbiome-based therapeutics, including faecal microbiota transplantation and pharmacomicrobiomics, while addressing the challenges of identifying robust microbial targets. We advocate for integrative, transdisease studies and emphasise the need for diverse cohort research to generalise findings across populations. Understanding the microbiome's role in AIMDs will pave the way for personalised medicine and innovative therapeutic strategies.
P20.03.B ASSESSING QUALITY OF LIFE IN SCHWANNOMATOSIS: A SYSTEMATIC REVIEW
Authors: A Lawson McLean, S Rosahl, A Lawson McLean, A Freier, D Löschner, M Kamp, A Neumeister, C Senft, A Demetriades
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND The term schwannomatosis refers to rare genetic disorders associated with the development of multiple tumours within the central and/or peripheral nervous system. Recent advancements in our molecular understanding of these disorders have led to a redefined conceptual framework within the field. This revised framework groups nf2-related schwannomatosis with other forms of schwannomatosis resulting from various causative pathogenic variants, highlighting their distinct nature compared to neurofibromatosis 1. MATERIAL AND METHODS A comprehensive search of electronic databases, including PubMed, MEDLINE, and Scopus, was performed in August 2023. The search methodology entailed variations of keywords such as “neurofibromatosis 2,” “schwannomatosis,” “quality of life,” and “patient-reported outcomes.” Inclusion criteria encompassed studies evaluating QoL in schwannomatosis patients, utilising validated QoL appraisal tools or patient-reported outcome metrics. Case studies and reviews were excluded. RESULTS Initial searches yielded 224 articles after removal of duplicates. Following screening, 37 articles met inclusion criteria. These studies employed diverse assessment instruments, including the SF-36 (n=7), PHQ-9 (n=8), GAD-7 (n=5), and the disease-specific questionnaire NFTI-QOL (n=13). Interestingly, patients with nf2-related schwannomatosis overall had worse physical and emotional well-being than the general population, while non-nf2-schwannomatosis patients mainly reported worse pain than the general population. CONCLUSION This systematic review provides a comprehensive synopsis of QoL literature pertinent to patients with schwannomatosis. The findings underscore the imperative of a holistic patient-care paradigm, addressing not only tumour management but also the augmentation of overall well-being and QoL among affected individuals.
OS05.5.A DOSE ESCALATED SPINE RADIOSURGERY FOR RADIORESISTANT SPINAL METASTASES UTILIZING SIMULTANEOUS INTEGRATED BOOST
Authors: A J Ghia, V Bernard, G Iskander, M Rooney, B De, T M Briere, C E Tatsui, A Bishop, S Perni, M Tom, C Wang, T Beckham, D N Yeboa, M McAleer, J Li, B Amini, L D Rhines
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Spine stereotactic body radiosurgery (SSRS) delivers ablative doses of radiation with sub-millimeter precision leading to high rates of local control with minimal toxicity. Treatment dose, fractionation and technique vary from institution to institution. We present our experience delivering single fraction SSRS using simultaneous integrated boost (SIB) for radioresistant spinal metastases. MATERIAL AND METHODS This is a single institution retrospective review analyzing patients treated from 2006-2021 with single fraction SSRS delivering 24 Gy to the gross disease (GTV) and 16 Gy to the clinical target volume (CTV) at risk of harboring microscopic disease per International consensus guidelines. We assessed clinical endpoints in relation to patterns of failure, including local control (LC) and overall survival (OS), using univariate and multivariate analyses. RESULTS From 2006-2021, 395 sites from 285 patients were treated with SSRS. With a median follow-up of 18 months, the actuarial 1- and 2-year local control (LC) was 93% and 89%, respectively. The most common pattern of failure was epidural (67%). Indeed, multivariate analysis revealed the presence of epidural disease as a significant predictor of local failure (HR 3.42, 95% CI 1.71-6.85 p=0.001). Of the 39 sites with local failure, only 2 sites were within the CTV volume outside of the GTV volume. The median overall survival was 26 months and no radiation myelopathy was noted. Grade 3 vertebral fracture was noted in only 5% of treated sites (20 fractures out of 395 sites). CONCLUSION This is the largest experience on SSRS using SIB for radioresistant spinal metastases. SSRS with SIB delivered to 24 Gy in 1 fraction is associated with a high local control rate with low toxicity. Failures outside the GTV and within the CTV were very rare and clinically significant fracture risk was 5% suggesting that SIB is a reasonable approach for radioresistant spinal metastases treated with SSRS.
KS01.5.A A BRAIN CANCER CELL ATLAS REVEALS SHARED ASTROCYTE-LIKE STEM CELL STATES DRIVE INTRATUMOURAL HETEROGENEITY AND SHAPE IMMUNE DYNAMICS IN ADULT-TYPE DIFFUSE GLIOMAS
Authors: A Zaman, W Muskovic, E Holton, M Pandya, R Zakanovic, V Chin, E Lam, J Yeung, M Sughrue, C Teo, J Powell
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Adult-type diffuse gliomas pose significant clinical challenges due to their complex cellular makeup and evolving nature. Understanding this heterogeneity is crucial for developing effective targeted therapies. MATERIALS AND METHODS To understand glioma heterogeneity, we performed single-cell and single-nucleus RNA sequencing on 66 tumours (single surgery) and 54 paired (two surgeries) longitudinal samples. This dataset comprises approximately 900,000 cells, enabling us to investigate both the conserved cellular landscape and dynamic cellular evolution across different glioma subtypes. RESULTS Employing a novel phylogeny-based approach, we showed that the astrocyte-like glioma stem cell (GSC) is the origin of diverse glioma lineages. This finding represents a paradigm shift in our understanding of glioma development, highlighting the GSC as a potential therapeutic target. The GSC’s resemblance to healthy adult neural stem cells provides insight into the roots of glioma heterogeneity and suggests a shared origin for intratumoral diversity. Our analysis revealed a consistent cellular architecture spanning astrocytomas, oligodendrogliomas, and glioblastomas (GBMs). This architecture comprises seven recurring malignant cell states: neuro-, oligo-, neuro-oligo-lineage, cycling (G1/S, G2/M), hypoxia-associated, and a quiescent astrocyte-like GSC. Notably, the proportions of these cell states differ among glioma subtypes. We further show that GBMs exhibit significantly higher T-cell and myeloid cell infiltration than IDH-mutant gliomas. Paradoxically, this correlates with a worse prognosis, suggesting profound T-cell dysfunction and a complex interplay between myeloid cells and the tumour. Longitudinal analysis underscored the evolving nature of the glioma’s malignant cell populations and immune landscape. We identified subtype-specific T-cell and myeloid gene expression profiles, including targets like PARD6G (GBM) and CXCL13 (astrocytoma), which offer a foundation for developing targeted immunotherapies and prognostic biomarkers. CONCLUSION Our study provides a model of glioma heterogeneity and evolution. This model integrates a shared astrocyte-like GSC driving cellular diversity alongside distinct, dynamic immune landscapes across different glioma subtypes. These findings offer unprecedented potential for developing transformative treatment strategies. Future research functionally validating the GSC and its impact on tumour dynamics will be crucial for translating these insights into improved patient outcomes.
P22.13.B QUALITY OF LIFE DISPARITIES AMONG VESTIBULAR SCHWANNOMA PATIENTS UNDER DIFFERENT TREATMENT REGIMENS: A SYSTEMATIC REVIEW
Authors: M Rutenkröger, L Brandes, H Führes
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Evaluating the quality of life in vestibular schwannoma patients is crucial for gaining insights into the broader impact of the condition and its treatments. Understanding how vestibular schwannoma affects physical, emotional, and social well-being is essential for comprehensive patient care. Quality of life assessments illuminate the unique challenges faced by patients, including hearing loss and balance issues, guiding healthcare professionals in tailoring treatment plans to improve overall well-being. Furthermore, such evaluations contribute to advancing medical knowledge and developing more patient-centered approaches to managing vestibular schwannoma. MATERIAL AND METHODS We conducted a systematic literature search across four databases— MEDLINE, Web of science, Cochrane Library and PSYNDEX—to identify pertinent studies reporting disease-specific quality of life measures (PANQOL) in patients with vestibular schwannoma. Stringent blinding procedures were implemented during the screening stage, yet determinations regarding study eligibility and data extraction were carried out independently by two reviewers. Our overarching goal is to systematically synthesize available data, offering a comprehensive overview of the variations in quality of life among individuals undergoing diverse treatment modalities for this condition. Should a sufficient volume of data be accessible, we intend to progress to a comprehensive meta-analysis. RESULTS During our screening process, we initially identified 548 articles, of which 317 have progressed to the ongoing stage of abstract screening. This extensive process aimed to include studies specifically reporting disease-specific quality of life measures in vestibular schwannoma patients. CONCLUSION We anticipate presenting comprehensive results from our systematic review at the upcoming conference. The results aim to enhance our comprehension of the multifaceted impact of vestibular schwannoma on patients and establishes a foundation for the development of more personalized, patient-centered strategies in managing patient education and post-treatment care for this condition.