Purpose: Since the 2021 World Health Organisation (WHO) classification, glioblastoma could be diagnosed based on classical histological features (hGBM) or molecular criteria (mGBM). However, prior studies included patients who required reclassification as a mGBM, potentially biasing survival analyses. The Histo-Mol GBM collaborative performed an international multicentre retrospective real-world cohort study of glioblastoma patients diagnosed according to WHO CNS 5. Methods: We identified consecutive patients diagnosed in 2021 with IDH wildtype glioblastoma according to WHO CNS 5. Clinicopathological, treatment, and survival data were collected and compared between mGBM and hGBM. Results: 1828 patients diagnosed with glioblastoma were included. 75 mGBM patients (8.4% of tested patients) were identified, with no difference in age (median 61 vs 64, p=0.057), gender (p=0.937), or proportion with performance status 0-1 (82.7% vs 68.3%, p=0.052) compared to hGBM. mGBM patients had an extended interval from MRI to surgery (median 23 vs 14 days, p<0.001) and more frequently underwent biopsy (69.3% vs 30.3%, p<0.001), but equivalent proportions received oncological treatment (80.0% vs 78.7%, p=0.784). Overall survival (OS) from surgery was not different (p=0.063). However, OS from initial MRI, stratified by surgical extent, demonstrated improved OS for mGBM patients (hazard ratio (HR) 0.56, 95% confidence interval (CI): 0.43-0.73). Propensity score matching identified improved survival following resection (HR 0.48, 95% CI: 0.24-0.95; median OS: 26.0 versus 14.0 months, p=0.031) but not biopsy (HR 1.10, 95% CI: 0.71-1.72). Conclusion: In this large real-world cohort, mGBMs had longer OS than hGBMs following resection with implications for prognostication and clinical decision making.

Glioblastoma is the most common primary brain cancer in adults, with half of cases diagnosed in patients aged ≥ 65 years. However, definitions of older adults vary, resulting in treatment variation between centres. This study aimed to report on the treatment intensity and survival outcomes in older patients with glioblastoma diagnosed according to WHO CNS 5 classification. We conducted a retrospective, multicentre cohort study (Histo-Mol GBM Collaborative) of consecutive patients with pathologically confirmed glioblastoma, IDH-wildtype diagnosed in 2021, according to the 2021 WHO CNS 5 classification, across 52 centres in the UK, Ireland, New Zealand, and Australia. Demographic, molecular, treatment, and survival data were analysed. Of 1,857 patients, 863 (46.5

Background: Clinical guidelines are central to safe evidence-based medicine in modern healthcare, providing diagnostic criteria, treatment options and monitoring advice for a wide range of illnesses. LLM-empowered chatbots have shown great promise in Healthcare Q A tasks, offering the potential to provide quick and accurate responses to medical inquiries. Our main objective was the development and preliminary assessment of an LLM-empowered chatbot software capable of reliably answering clinical guideline questions using University College London Hospital (UCLH) clinical guidelines. Methods: We used the open-weight Llama-3.1-8B LLM to extract relevant information from the UCLH guidelines to answer questions. Our approach highlights the safety and reliability of referencing information over its interpretation and response generation. Seven doctors from the ward assessed the chatbot's performance by comparing its answers to the gold standard. Results: Our chatbot demonstrates promising performance in terms of relevance, with 73 strong understanding of the clinical context. Importantly, our chatbot achieves a recall of 0.98 for extracted guideline lines, substantially minimising the risk of missing critical information. Approximately 78 satisfactory in terms of completeness. A small portion ( 14.5 unnecessary information, indicating occasional lapses in precision. The chatbot' showed high efficiency, with an average completion time of 10 seconds, compared to 30 seconds for human respondents. Evaluation of clinical reasoning showed that 72 demonstrates significant potential to speed up and improve the process of accessing locally relevant clinical information for healthcare professionals.

INTRODUCTION:There is a lack of evidence to guide the choice between stereotactic radiosurgery (SRS) and neuroablative procedures for patients with medically refractory trigeminal neuralgia (TN). This meta-analysis aims to identify the outcomes of these interventions for TN. METHODS:Studies identified through PubMed, MEDLINE, and Embase, were cohort studies or clinical trials, had ≥20 participants, and had a ≥12-month follow-up. All participants were ≥16 years old and had primary refractory TN. Studies reported outcomes using the Barrow Neurological Institute (BNI) scale. The Shapiro-Wilk test, Mann-Whitney U test, two-tailed T Test, Spearman's R, and ANCOVA were used to test statistical significance. Screening was done according to PRISMA guidelines. Bias assessment was according to the Newcastle-Ottawa Scale. RESULTS:3,288 patients from 37 studies were included (2,537 SRS, 751 neuroablative). Overall reporting of BNI I, II, III, IV, and V was 36.0%, 17.4%, 23.9%, 11.7%, and 10.9%, respectively, in the SRS cohort, and 63.6%, 10.4%, 11.1%, 7.3%, and 7.6%, respectively, in the neuroablative cohort (p < 0.0001). Recurrence was 41.6% in the SRS cohort and 22.5% in the neuroablative cohort (p < 0.001). The neuroablative cohort reported significantly higher rates of hypoesthesia (18.6% vs. 50.5%, p < 0.0001), and minor (19.6% vs. 2.2%, p < 0.0001) and major (3.4% vs. 1.3%, p < 0.001) adverse effects compared to SRS. CONCLUSION:The findings suggest improved pain relief and reduced recurrence with neuroablative procedures compared to SRS, albeit conferring a higher rate of adverse effects. Neuroablative techniques may be more appropriate for patients with medically refractory TN who are unsuitable for microvascular decompression.

Diffuse gliomas are the commonest malignant primary brain tumour in adults. Herein, we present analysis of the genomic landscape of adult glioma, by whole genome sequencing of 403 tumours (256 glioblastoma, 89 astrocytoma, 58 oligodendroglioma; 338 primary, 65 recurrence). We identify an extended catalogue of recurrent coding and non-coding genetic mutations that represents a source for future studies and provides a high-resolution map of structural variants, copy number changes and global genome features including telomere length, mutational signatures and extrachromosomal DNA. Finally, we relate these to clinical outcome. As well as identifying drug targets for treatment of glioma our findings offer the prospect of improving treatment allocation with established targeted therapies.

Glioblastoma (GBM) is the most common and aggressive brain tumour with starkresistance to available therapies, leading to relapse and a median survival of<15 months. A key cause of therapy resistance is diffuse infiltration oftumour cells into brain regions surrounding the tumour, which presents a majorclinical challenge as existing imaging techniques offer limited detection of theresectable margin. Here, we use diffusion weighted imaging (DWI) and apply themultiple echo time neurite orientation dispersion and density imaging(MTE-NODDI) model as a tool to detect tumour cells in the hard-to-distinguishmargin. We used the G144 patient-derived xenograft model, with characteristicinvasion along white matter tracts, in combination with MTE-NODDI. Tumourdevelopment was monitored, and magnetic resonance imaging (MRI) data wereacquired over a 4-week period, starting at 4 weeks after stereotactic injectionof tumour cells. MTE-NODDI demonstrated sensitivity to the developing tumour inthe invading margin, and changes in measured parameters were apparent from 6weeks after injection. In comparison to standard DWI, MTE-NODDI showed increasedsensitivity to the tumour-associated changes in the margin. Furthermore,extraneurite volume fraction (fen ) and neuritedensity index (NDI) measured from MTE-NODDI correlated with immunohistologicalmeasurement of tumour cells. These findings suggest that MTE-NODDI maynon-invasively detect infiltrating cells and tumour-induced pathology in marginregions without T2 or DWI changes in a patient-derived mouse model of GBM.MTE-NODDI is clinically translatable and could be a powerful tool forneurosurgeons to maximise surgical resection, resulting in better survivaloutcomes for patients with GBM.

Abstract AIMS Retraction is a critical step in surgical removal of brain tumours, enabling visualisation and resection. Conventional retraction applies focal pressure to overlying tissue, potentially resulting in retraction-induced injury. Tubular retractors (minimally invasive parafascicular surgery) circumferentially distribute pressure to theoretically minimise injury. Whilst previous reviews have provided insight into their potential, the literature has since significantly expanded, necessitating an update. The objective was to synthesise all current evidence regarding surgical outcomes of tubular retractors in resection of brain tumours. METHOD Studies reporting on use of tubular retractors to resect brain tumours in adult patients were eligible. PRISMA guidelines were followed. MEDLINE, Embase and the Cochrane Library were searched to 18th October 2023. Duplicate title/abstract screening, data extraction and risk of bias assessments were conducted. RESULTS Of the 2453 studies screened, 49 were included in the final synthesis, involving 690 patients. Tubular retractor systems assessed were: BrainPath (n=199), VBAS (n=198), METRx (n=63) and other (n=230). Pooled estimate of gross total resection rate was 75% (95% CI 0.65-0.84; I2=83%), whilst pooled estimate of complication rate was 17% (95% CI 0.11-0.24; I2=75%). Sub-group analysis of gross total resection rate was conducted for: glioma (150 patients, pooled prevalence 47%, 95% CI 0.36-0.57; I2=29%), colloid cyst (121 patients, pooled prevalence 100%, CI 0.99-1.00; I2=0%), and metastasis (114 patients, pooled prevalence 82%, 95% CI 0.67-0.94; I2=64%). There was no significant difference between tubular retractor systems with regards to gross total resection or complication rate (p>0.05). CONCLUSION There is mounting evidence for the utility of tubular retractors in resection of brain tumours. However, this evidence remains largely in the form of low-quality case-series, providing proof-of-concept, but limited in its ability to draw more robust comparisons to conventional retraction. Future studies with greater sample sizes and inclusion of control groups are now needed to consolidate the position of tubular retractors in neuro-oncology.

Objectives Build the theoretical and evidence-base for a digital platform (map-OR) which delivers intraoperative language tests during awake craniotomy and facilitates collaborative sharing of brain mapping data.Design Mixed methodology study including two scoping reviews, international survey, synthesis of development guiding principles and a risk assessment using failure modes and effects analysis.Setting The two scoping reviews examined the literature published in the English language. International survey was completed by members of awake craniotomy teams from 14 countries.Main outcome measures Scoping review 1: number of technologies described for language mapping during awake craniotomy. Scoping review 2: barriers and facilitators to adopting novel technology in surgery. International survey: degree of language mapping technology penetration into clinical practice.Results A total of 12 research articles describing 6 technologies were included. The technologies required a range of hardware components including portable devices, virtual reality headsets and large integrated multiscreen stacks. The facilitators and barriers of technology adoption in surgery were extracted from 11 studies and mapped onto the 4 Unified Theory of Acceptance and Use of Technology constructs. A total of 37 awake craniotomy teams from 14 countries completed the survey. Of the responses, 20 (54.1%) delivered their language tests digitally, 10 (27.0%) delivered tests using cards and 7 (18.9%) used a combination of both. The most commonly used devices were tablet computers (67.7%; n=21) and the most common software used was Microsoft PowerPoint (60.6%; n=20). Four key risks for the proposed digital platform were identified, the highest risk being a software and internet connectivity failure during surgery.Conclusions This work represents a rigorous and structured approach to the development of a digital platform for standardized intraoperative language testing during awake craniotomy and for collaborative sharing of brain mapping data.Trial registration number Scoping review protocol registrations in OSF registries (scoping review 1: osf.io/su9xm; scoping review 2: osf.io/x4wsc).

Abstract AIMS Glioblastoma (GBM), the most common primary brain malignancy in adults, remains incurable. Pervasive heterogeneity and plasticity underpin therapy resistance and lethal recurrence, suggesting that prevention or earlier intervention may be required. Improved understanding of GBM initiation is a prerequisite for achieving this goal. GBM frequently originates from neural stem cells (NSCs) of the subventricular zone, which, upon acquisition of mutations, migrate away from their niche and form tumours at distal sites through unknown mechanisms. Here, we explored GBM initiation and its microenvironment. METHOD We combined a murine somatic GBM model which faithfully recapitulates the human disease with PDX models and patient tissue datasets. We used immunohistochemistry, scRNA-sequencing, immuno-phenotyping, behavioural and survival studies and in vivo gain- and loss-of-function experiments in Sarm1-/- lines. RESULTS Time-course analysis of tumour development identified neuronal degeneration as an early event in GBM tumourigenesis, occurring preferentially in white matter, where we find mutated NSCs are immediately rerouted. Axonal loss was accompanied by a robust inflammatory response, marked by microglial and astrocytic activation. Neuronal degeneration played a causative role, in that transection injury of corpus callosum axons accelerated tumourigenesis and, conversely, GBM development was delayed in Sarm1-/- mice with impaired Wallerian degeneration, a major mode of neuronal death following injury. Consistently, terminal Sarm1-/- tumours were more diffuse, contained more immature tumour cells and were less immune-infiltrated than their WT counterparts. Strikingly, behavioural studies revealed that Sarm1-/- tumour-bearing mice also retained improved motor performance compared to WT mice, even at terminal disease stages. CONCLUSION Our work provides important insights into GBM development, identifying white matter injury as a key initiating event, elicited by early tumour cells and orchestrated by neuronal degeneration. It identifies Wallerian degeneration, a druggable pathway already in clinical trials for neurodegenerative diseases, as a therapeutic target for GBM, with the potential to extend survival and ameliorate cognition.

Background: Cerebral cavernous malformations (CCM) may undergo a period of clinical and/or radiographical surveillance that precedes or follows definitive treatment. There are no international guidelines on the optimal surveillance strategy. This study describes the surveillance strategies at our centre and explore the related clinical outcomes.Methods: We performed a retrospective study of adult patients with CCMs referred to a neurovascular service over an 8-year period, to determine the frequency and type of surveillance, intervention, and explore the associated outcomes. We report our findings adhering to STROBE guidelines. Results: 133 patients (Male:Female 73:60; men age 42 years; range 12-82) were included. CCMs were identified in patients first presenting with symptomatic intracerebral haemorrhage (42.11%); headache, focal neurological deficit, or seizure without haemorrhage (41.35%); or, as an incidental finding (16.54%). The most common CCM location was supratentorial (59.40%), followed by brain stem (21.80%), cerebellum (10.53%) and basal ganglia (6.02%). Of the 133 patients, 77 patients (57.89%) were managed conservatively, 49 patients (36.84%) were managed by surgical resection alone, and seven patients (5.26%) were managed with stereotactic radiosurgery (SRS).Patients follow-up had a mean duration of 65.94 months, and varied widely (SD = 52.59; range 0-265), for a total of 730.83 person-years of follow up. During surveillance, 16 patients suffered an ICH equating to a bleeding rate of 2.19 per 100 patient years. CCMs that increased in size had a higher bleeding rate (p = 8.58 x10- 4). There were 8 (6.02%) cases where routine clinic review or MRI resulted in a change in management.Conclusions: Our single centre retrospective study supports existing literature relating to presentation and sequalae of CCM, with an increase in CCM size being associated with higher rates of detected bleeding. There remains heterogeneity, even within a single centre, on the frequency and modality of surveillance. Further, there are no international guidelines or high-quality data that recommends the optimal duration and frequency of surveillance, and its effect on clinical outcomes. This is a future research direction.

Introduction:Brain biopsy provides important histopathological diagnostic information for patients with new intracranial lesions. Although a minimally invasive technique, previous studies report an associated morbidity and mortality between 0.6% and 6.8%. We sought to characterise the risk linked to this procedure, and to establish the feasibility of instigating a day-case brain biopsy pathway at our institution.Materials and methods:This single-centre retrospective case series study included neuronavigation guided mini craniotomy and frameless stereotactic brain biopsies carried out between April 2019 and December 2021. Exclusion criteria were interventions performed for non-neoplastic lesions. Demographic data, clinical and radiological presentation, type of biopsy, histology and complications in the post-operative period were recorded.Results:Data from 196 patients with a mean age of 58.7 years (SD+/-14.4 years) was analysed. 79% (n=155) were frameless stereotactic biopsies and 21% (n=41) neuronavigation guided mini craniotomy biopsies. Complications resulting in acute intracerebral haemorrhage and death, or new persistent neurological deficits were observed in 2% of patients (n=4; 2 frameless stereotactic; 2 open). Less severe complications or transient symptoms were noted in 2.5% of cases (n=5). 8 patients had minor haemorrhages in the biopsy tract with no clinical ramifications. Biopsy was non-diagnostic in 2.5% (n=5) of cases. Two cases were subsequently identified as lymphoma. Other reasons included insufficient sampling, necrotic tissue, and target error.Discussion and conclusion:This study demonstrates that brain biopsy is a procedure with an acceptably low rate of severe complications and mortality, in line with previously published literature. This supports the development of day-case pathway allowing improved patient flow, reducing the risk of iatrogenic complications associated with hospital stay, such as infection and thrombosis.

Glioblastoma a deadly brain cancer that is nearly universally fatal. Accurate prognostication and the successful application of emerging precision medicine in glioblastoma relies upon the resolution and exactitude of classification. We discuss limitations of our current classification systems and their inability to capture the full heterogeneity of the disease. We review the various layers of data that are available to substratify glioblastoma and we discuss how artificial intelligence and machine learning tools provide the opportunity to organize and integrate this data in a nuanced way. In doing so there is the potential to generate clinically relevant disease sub-stratifications, which could help predict neuro-oncological patient outcomes with greater certainty. We discuss limitations of this approach and how these might be overcome. The development of a comprehensive unified classification of glioblastoma would be a major advance in the field. This will require the fusion of advances in understanding glioblastoma biology with technological innovation in data processing and organization.

PurposeDespite advances in technology, stereotactic brain tumour biopsy remains challenging due to the risk of injury to critical structures. Indeed, choosing the correct trajectory remains essential to patient safety. Artificial intelligence can be used to perform automated trajectory planning. We present a systematic review of automated trajectory planning algorithms for stereotactic brain tumour biopsies.MethodsA PRISMA adherent systematic review was conducted. Databases were searched using keyword combinations of 'artificial intelligence', 'trajectory planning' and 'brain tumours'. Studies reporting applications of artificial intelligence (AI) to trajectory planning for brain tumour biopsy were included.ResultsAll eight studies were in the earliest stage of the IDEAL-D development framework. Trajectory plans were compared through a variety of surrogate markers of safety, of which the minimum distance to blood vessels was the most common. Five studies compared manual to automated planning strategies and favoured automation in all cases. However, this comes with a significant risk of bias.ConclusionsThis systematic review reveals the need for IDEAL-D Stage 1 research into automated trajectory planning for brain tumour biopsy. Future studies should establish the congruence between expected risk of algorithms and the ground truth through comparisons to real world outcomes.

Mathematical oncology provides unique and invaluable insights into tumour growth on both the microscopic and macroscopic levels. This review presents state-of-the-art modelling techniques and focuses on their role in understanding glioblastoma, a malignant form of brain cancer. For each approach, we summarize the scope, drawbacks and assets. We highlight the potential clinical applications of each modelling technique and discuss the connections between the mathematical models and the molecular and imaging data used to inform them. By doing so, we aim to prime cancer researchers with current and emerging computational tools for understanding tumour progression. By providing an in-depth picture of the different modelling techniques, we also aim to assist researchers who seek to build and develop their own models and the associated inference frameworks. Our article thus strikes a unique balance. On the one hand, we provide a comprehensive overview of the available modelling techniques and their applications, including key mathematical expressions. On the other hand, the content is accessible to mathematicians and biomedical scientists alike to accommodate the interdisciplinary nature of cancer research.

Abstract Aim Leptomeningeal Metastases (LM) is associated with altered CSF flow dynamics (50-70%), and 1-5% of patients will develop communicating hydrocephalus, adversely impacting quality of life (QoL), functional status, and overall survival (OS). There is equipoise for CSF diversion in LM-associated hydrocephalus (LM-H). This systematic review and meta-analysis aims to assess the effect of CSF diversion on OS and QoL in this context. Method This systematic review was conducted in accordance with PRISMA guidelines. Pubmed/MEDLINE, EMBASE, Web of Science, and Scopus were searched for articles evaluating the role of CSF diversion in adult patients with systemic cancer LM-H. A meta-analysis was conducted using random effects models, mean differences, and 95% confidence intervals (CI). Bias was assessed using the ROBINS-I tool. Results Ten eligible studies with a total of 494 patients were included. Two studies reported multivariate hazard ratios for median OS, suggesting no significant effect of shunting on OS (pooled HR = 0.42; p = 0.27; 95% CI 0.09-1.94). A pre-operative and post-operative Karnofsky Performance Status (KPS) mean difference of 17.6 points (CI 10.44-24.68; p<0.0001) was calculated from 4 studies. Across all studies, a symptomatic improvement rate of 67-100% was observed, with high rates of improvement of headaches and nausea and lower rates for cranial nerve palsies. Complication rates across nine studies ranged from 0-21.1%. Conclusions The present findings prompt the generation of a standardised decision-making tool, a critical analysis of individual patient risk-benefit ratios, and systematic measurements for QoL for these patients. Implementation of these will facilitate and optimise surgical management for LM-H patients.

OBJECTIVE:Leptomeningeal metastasis (LM) is associated with altered CSF flow dynamics in 50%-70% of patients. Approximately 1%-5% of patients develop symptomatic LM-associated hydrocephalus (LM-H), which adversely impacts quality of life (QOL), functional status, and overall survival (OS). There is equipoise for CSF diversion procedures in LM-H. This systematic review and meta-analysis aimed to assess the effect of CSF diversion on OS and QOL in this context.METHODS:This systematic review was conducted according to the PRISMA guidelines. PubMed/Medline, Embase, Web of Science, and Scopus were searched for articles that evaluated the role of CSF diversion for LM-H due to systemic cancer in adult patients. A meta-analysis was conducted using random effects models, with mean differences and 95% CIs reported. Bias was assessed using the Risk of Bias in Nonrandomized Studies of Interventions (ROBINS-I) tool.RESULTS:Ten eligible studies with a total of 494 patients were included. Two studies reported multivariate HRs for median OS, suggesting no significant effect of shunting on OS (pooled HR 0.42, 95% CI 0.09-1.94, p = 0.27). A difference between preoperative and postoperative Karnofsky Performance Status of mean 17.6 points (95% CI 10.44-24.68, p < 0.0001) was calculated from 4 studies. Across all studies, a symptomatic improvement rate of 67%-100% was observed, with high rates of improvement for headaches and nausea and lower rates for cranial nerve palsies. Complication rates across 9 studies ranged from 0% to 21.1%.CONCLUSIONS:Based on the present findings, shunting does not improve OS but does relieve symptoms, suggesting that individuals who exhibit certain symptoms should be considered for CSF diversion. The present findings prompt the generation of a standardized decision-making tool and a critical analysis of the individual patient risk-benefit ratio. Implementation of these will optimize surgical management of LM-H patients.

Introduction: Survival amongst posterior fossa tumour (PFT) patients is improving. Clinical endpoints such as overall survival fail to depict QoL. There is yet to be a review of current QoL instruments used for adult PFTs. Aim of this review is to outline the QoL reporting in the management of PFTs and measure participation level. Methods: This systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis. A search strategy to identify adult patients with PFTs who took part in QoL metrics was conducted. Observational and experimental studies published from 1990 to date were included. Studies with a sample size less than 10 and performance measures such as Karnofsky Performance Status were not considered. Results: A total of 116 studies were included in the final analysis. Vestibular schwannomas were the most common tumour pathology (n = 23,886, 92.6%) followed by pilocytic astrocytomas (n = 657, 2.5%) and meningiomas (n = 437, 1.7%) Twenty-five different QoL measures were used in the study pool. SF-36 was the most common (n = 55, 17 47.4%) QoL metric in the whole study pool, followed by the Penn Acoustic Neuroma QoL scale (n = 24, 20.7%) and Dizziness Handicap Inventory (n = 16, 13.8%). Seventy-two studies reported less-than 100% participation in QoL evaluation. The commonest reason for non-participation was a lack of response (n = 1,718, 60.8%), incomplete questionnaires (n = 268, 9.4%) and cognitive dysfunction (n = 258, 9.1%). Conclusion: Informed clinical decision-making in PFT patients requires the development of specific QoL outcomes. Core outcome sets, and minimal clinically important differences (MCID) are essential for these metrics to show clinically significant improvements in patient QoL.

Glioblastoma is the most common and aggressive primary brain cancer in adults and is almost universally fatal due to its stark therapeutic resistance. During the past decade, although survival has not substantially improved, major advances have been made in our understanding of the underlying biology. It has become clear that these devastating tumors recapitulate features of neurodevelopmental hierarchies which are influenced by the microenvironment. Emerging evidence also highlights a prominent role for injury responses in steering cellular phenotypes and contributing to tumor heterogeneity. This review highlights how the interplay between injury and neurodevelopmental programs impacts on tumor growth, invasion, and treatment resistance, and discusses potential therapeutic considerations in view of these findings.