tbuckley/cabot-search huggingface dataset:
MANAGEMENT OF THE OLDER PATIENT WITH GLIOBLASTOMA IN THE UK: AN INITIAL REPORT FROM THE HISTO-MOL GBM COLLABORATIVE
Authors: Dr Stephen Robinson, Dr Katherine Ryan, Dr Louisa Black, Dr Sam Forner, Dr Nathaniel Luke Hatton, Dr Rebecca Hatton, Dr Nurjahan Aktar, Mr Haydn Lathangue, Dr David Conkey, Dr Praveen Durage, Mr Paolo de Luna, Dr Pavlos Christodoulou, Dr Timothy Hill, Ms Rachel MacArthur, Dr May Teoh, Dr Adenike Williams, Dr Jennifer Golten, Dr Tasia Aghadiuno, Dr Kohgulakuhan Yogalingam, Dr Jennifer Kahan, Dr Sanjay Dixit, Dr Samir Guglani, Dr Rachel Lewis, Dr Rafael Moleron, Dr Najmus Iqbal, Dr Nick Wadd, Dr Prashanth Bhat, Prof Georgios Giamas, Dr Nektarios Mazarakis, Dr Cressida Lorimer, Dr Edward Chandy, Prof Giles Critchley
Journal: Neuro-Oncology (2024)

Abstract AIMS The management of older (&amp;gt;70 years old) patients with glioblastoma is challenging with signiﬁcant variation in practice. Using the Histo-Mol GBM database we analysed the variation in practice across 11 UK centres. METHOD Biopsy conﬁrmed glioblastoma patients diagnosed between 01/01-31/12/2021 were identiﬁed. Descriptive statistics were used to compare demographic, tumour and treatment characteristics, and the Kaplan-Meier method was used to analyse survival, assessed from surgery date. Differences in treatment between centres were assessed using one way ANOVA. RESULTS In 2021, 81/330 (24.5%) patients with glioblastoma were &amp;gt;70. Compared to younger patients, the older cohort had a greater proportion of males (79.0% vs 59.0%, p&amp;lt;0.001), a worse performance status (66.7% vs 79.5% ECOG PS 0-1, p&amp;lt;0.001), and more likely to have MGMT promoter methylation (30.9% vs 22.9%, p=0.027). Most patients received biopsy only (31/81, 38.3%), followed by subtotal resection (85-94% tumour resection) (26/81, 32.1%), whilst 8/81 (9.9%) underwent debulking, 8/81 near-total resection (95-99% tumour resection), and 8/81 gross total resection, with statistically signiﬁcant variation in resection extent between centres (p=0.031). Adjuvant radiotherapy was used in 56/81 patients (69.1%) with no difference between centres (p=0.220). However, there was a statistically signiﬁcant difference in radiotherapy regime between centres (p=0.041). 6/81 (7.4%) received conventional chemoradiotherapy, 28/81 (34.6%) hypofractionated chemoradiotherapy, 16/81 (19.8%) hypofractionated radiotherapy alone, 2/81 (2.5%) temozolomide alone both with MGMT promoter methylation, and 21/81 (25.9%) received no oncological treatment. Median progression free survival was 5.9 months and median overall survival (OS) was 7.1 months with no difference between centres (p=0.199 and p=0.083 respectively). Median OS was 8.4 months with conventional fractionation chemoradiotherapy, 11.2 months with hypofractionated chemoradiotherapy, 7.3 months with hypofractionated radiotherapy alone, 1.8 months with temozolomide alone, and 2.5 months with no oncological treatment. CONCLUSION We identify variations in the treatment of elderly glioblastoma patients across the UK, although these do not signiﬁcantly impact survival.
IMPROVING THE EﬃCIENCY OF THE NEURO-ONCOLOGY NEW PATIENT CLINIC AT THE ROYAL MARSDEN HOSPITAL
Authors: Dr Cressida Lorimer, Dr Asadullah Anees Khan, Dr Deepthi Yadav, Dr Babusha Kalra, Dr Liam Welsh, Dr Antonia Creak
Journal: Neuro-Oncology (2024)

Abstract AIMS Patients seen for the ﬁrst time in the neuro oncology outpatient unit are typically reviewed by a registrar, then a consultant and a clinical nurse specialist (CNS). This can lead to repetition in history taking and prolonged appointment times. We aimed to improve this by introducing a clerking proforma. METHOD Prospective audit of all new patients seen in clinic over a four month period. The total clinic appointment time was recorded for each patient. A proforma was designed to cover the main domains of presenting symptoms, especially focussing on tumour related symptoms, medications including dexamethasone and antiepileptic use, and ensured the appropriate information was given to the patient about the treatment proposed and driving restrictions. The proforma was introduced in to the clinic after 2 months and results analysed to see if a difference was made in terms of overall patient time in the clinic. Qualitative feedback gathered from the team members involved. RESULTS 10 patients were included prior to the use of the proforma and 9 patients afterwards. Patients presented with a mixture of high and low grade gliomas. Treatment options discussed included chemotherapy, radiotherapy, surveillance and best supportive care. The average time of patient stay in the department prior to the proforma was 107 minutes (range 65 to 165) and after the introduction of the proforma was 91 (range 40 to 110). The proforma was well received by the clinical team, it was felt useful to have a template to structure the new patient consultation, especially for more junior registrars, and the consultants were more conﬁdent that the appropriate information had been given. CONCLUSION Within the conﬁnes of a small sample size, the introduction of a proforma reduced the average new patient consultation time and standardised the clinical information collected.
PROLONGED SURVIVAL IN IDH-WILDTYPE GLIOBLASTOMA: CASE REPORTS, LITERATURE REVIEW AND CURRENT PERSPECTIVES OF MOLECULAR BEHAVIOR
Authors: Mr Ruben Batista, Mr Debasish Hajra, Mr Thaaqib Nazar, Mr Ronan Dardis, Mr Soumya Mukherjee
Journal: Neuro-Oncology (2024)

Abstract AIMS Glioblastoma remains one of the most aggressive primary brain tumours, with a median survival of around 12 months despite advances in treatment. However, rare cases of long-term survival challenge this prognosis. The evaluation of age, tumour location, surgical approach and strategies, adjuvant therapy, and molecular behavior provides valuable prognostic and predictive information in patients with glioblastoma. METHOD We present a case report of two patients diagnosed with wild-type glioblastoma who have survived over 10 years post-primary surgery. A review of epidemiological data, preoperative and postoperative radiological reports, surgical approach, and histology reports were studied. Additionally, we review the current literature to explore current nuances in High-Grade Glioma Wild Type prognosis and potential future directions. Three major medical database engines, PubMed (Medline), Scopus (ELSEVIER), and Cochrane were used to conduct a thorough literature search. RESULTS Both patients underwent maximal safe resection followed by the Stupp Protocol, comprising adjuvant chemotherapy with temozolomide and radiotherapy. Our case report highlights two exceptional cases of prolonged survival in Glioblastoma patients, both under 51 years-old at the moment of diagnosis, early diagnosis with isolated lobar lesions, no compromise of deep white matter, and achieving maximal safe resection and functional independence. Molecular analysis revealed speciﬁc genetic in common, including IDH Wild Type, p53 mutation, retained ATRX expression, TERT mutation, and MGMT promoter methylation, consistent with a favourable prognosis. Moreover, patients without recurrence often exhibit distinct molecular proﬁles, such as MGMT promoter methylation, suggesting a potential subtype associated with prolonged survival. CONCLUSION Our case reports and literature review highlight the possibility of prolonged survival in Glioblastoma patients. The age, tumor location at the time of diagnosis, comprehensive treatment approaches, may contribute to improved outcomes. Molecular proﬁling, particularly assessing genetic mutations and MGMT promoter methylation, holds promise for identifying patients with a higher likelihood of prolonged survival.
VASARI-AUTO: PERFORMANT, EQUITABLE, EﬃCIENT, ECONOMIC, AND SURVIVAL PREDICTIVE FEATURISATION OF GLIOMA MRI
Authors: Dr James Ruﬄe, Ms Samia Mohinta, Dr Kelly Pegoretti Baruteau, Dr Rebekah Rajiah, Ms Faith Lee, Prof Sebastian Brandner, Prof Parashkev Nachev, Dr Harpreet Hyare
Journal: Neuro-Oncology (2024)

Abstract AIMS The VASARI (Visually AcceSAble Rembrandt Images) MRI feature set is a quantitative system designed to standardize glioma imaging descriptions. Though effective, deriving VASARI is time-consuming and therefore seldom used in clinical practice. This is however a problem that performant machine-learning software could plausibly automate. METHOD In 100 patients, two consultant neuroradiologists independently quantiﬁed VASARI features. In parallel, we developed VASARI-auto, an automated VASARI-labelling software applied to both open-source hand-segmented lesion masks and our openly available tumour segmentation model. We quantiﬁed: 1) agreement across neuroradiologists and VASARI-auto; 2) calibration of patient equity; 3) an economic workforce analysis; and 4) ﬁdelity in predicting patient overall survival. Neuroradiologists were blinded to VASARI-auto software development and evaluations, and software developers were blinded to neuroradiologist labelling. RESULTS Segmentation and VASARI-auto were equally performant regardless of age or sex (mean segmentation Dice coeﬃcient 0.947). A modest inter-rater variability between neuroradiologists (mean Cohen’s Kappa 0.49) was comparable between neuroradiologists and VASARI-auto (mean Cohen’s Kappa 0.41), with higher agreement across VASARI-auto methods (mean Cohen’s Kappa 0.94). The time taken for neuroradiologists to derive VASARI features was substantially higher than VASARI-auto (mean time per case 317 vs. 3 seconds, p&amp;lt;0.0001). A hospital workforce analysis of our centre forecast that three years of VASARI glioma featurisation would demand 771 consultant neuroradiologist workforce hours (£40,789) or 8.6 hours of computing time (£3.76 of power) with VASARI-auto. The best-performing survival model utilised VASARI-auto features (R2 0.25), opposed to those derived by consultant neuroradiologists (R2 0.21). CONCLUSION VASARI-auto is a highly eﬃcient automated labelling system for VASARI featurisation with equitable performance regardless of patient age or sex, a favourable economic proﬁle if used as a decision support tool, and with non-inferior ﬁdelity in downstream patient survival prediction. Future work should integrate such tools to enhance patient care.
THE EﬃCACY OF GAMMA KNIFE RADIOSURGERY FOR CYSTIC METASTASIS COMPARED WITH NON-CYSTIC METASTASIS
Authors: Dr Adam Sheriff, Prof Hirokazu Takami, Prof Shota Tanaka, Prof Masashi Nomura, Prof Shunsaku Takayanagi, Prof Hirotaka Hasegawa, Prof Motoyuki Umekawa, Prof Nobuhito Saito
Journal: Neuro-Oncology (2024)

Abstract AIMS Between 20-40% of patients with cancer develop brain metastases (BMets), with metastasis representing the most common type of brain tumour. Cystic metastasis describes a rarer type of BMet characterised by oedematous collections. Stereotactic radiosurgery (SRS) is an effective and minimally invasive method for treating non-cystic BMets but controversy exists regarding its use in cystic BMets. The traditional view that cystic lesions are less responsive to SRS however is not fully evidenced. This investigation aims to elucidate the effectiveness of Gamma Knife (GK) radiosurgery in achieving local control of cystic BMets and enhancing survival versus GK radiosurgery for non-cystic BMets. METHOD Patients who had undergone fractionated GK for either a non-cystic or cystic BMet between 2018 and 2021 were identiﬁed. BMet volume on pre-GK MRI was calculated. Information was additionally collected on BMet location, maximum cyst diameter, if present, the patient’s primary tumour and its control and their performance status at the time of GK. The follow-up of patients is ongoing with survival being calculated using the Kaplan- Meier method and local progression through volumetric analysis of repeat MRI scans. RESULTS 57 patients with 79 cystic BMets were identiﬁed and 67 patients with non-cystic BMets. The most common primary tumour in both the non-cystic and the cystic BMets group was lung, comprising 30% and 23% respectively. The second most common tumour amongst non-cystic BMets was renal (12%) however in the cystic cohort it was breast (9%). The median tumour volume before treatment was 6.2cm3 in the non-cystic group and 12.5cm3 amongst cystic BMets. Median cyst size was 17.4 mm. Karnofsky Performance Status (KFS) was similar across both groups. CONCLUSION By comparing outcomes following GK for cystic and non-cystic metastasis, with the same primary tumours, this study can uncover the eﬃcacy of fractionated GK for cystic lesions and aid the selection of treatments for these patients.
NEURONAL INJURY DRIVES GLIOBLASTOMA INITIATION
Authors: Mr Zan Florjanic Baronik, Dr Melanie Clements, Dr Wenhao Tang, Dr Holly Simpson Ragdale, Ms Rachel Lindsay, Dr Sam Marguerat, Mr Ciaran Hill, Prof Simona Parrinello
Journal: Neuro-Oncology (2024)

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.
MENINGIOMA OEDEMA AND SEIZURES – A META-ANALYSIS
Authors: Dr Matthew Tanti, Dr Sarah Nevitt, Dr Molly Yeo, Dr William Bolton, Mr Paul Chumas, Mr Ryan Mathew, Dr Melissa Maguire
Journal: Neuro-Oncology (2024)

Abstract AIMS Meningiomas are primary intracranial neoplasms. Oedema and seizures can occur in the pre and postoperative period and oedema is commonly cited as a risk factor for seizures. A meta-analysis of eight studies published in 2016 identiﬁed preoperative oedema as a risk factor for preoperative seizures. Our aim is to perform an updated review. The literature base has grown and there are studies presenting data on postoperative seizures. METHOD The meta-analysis protocol is uploaded to INPLASY (DOI: 10.37766/inplasy2023.7.0101). Existing literature from seven databases was collected and Cochrane guidance was followed. Data was analysed using packages within R programming software. Part of this work was presented in draft form at ILAE 2023 and here we present updated work. RESULTS Our search identiﬁed 44 unique studies for meta-analysis. Many studies were biased by subjective oedema measurement or lack of seizure deﬁnition. Preoperative oedema increased the odds of preoperative seizures; odds ratio (OR) 3.41, 95% conﬁdence interval (CI) 3.00 to 3.87, p &amp;lt;.001, studies (k) 24, participants (n) 6,917, low heterogeneity (I2) 0%. There were no subgroup differences by oedema measurement or use of seizure deﬁnition. Preoperative oedema was associated with increased odds of early postoperative seizure (within one week of surgery) but the difference was not signiﬁcant; OR 1.39, CI 0.97-1.99, p =.063, k = 6, n = 2,445, I2 = 0% (low). Preoperative oedema increased the odds of late postoperative seizures; OR 1.95, CI 1.55-2.45, p &amp;lt;.001, k = 7, n = 1,722, I2 = 0% (low). Oedema was associated with seizures following stereotactic radiosurgery in two studies. CONCLUSION Preoperative oedema is associated with seizures prior to and following treatment. While there is a positive association between preoperative oedema and early postoperative seizure it is not statistically signiﬁcant.
IDENTIFYING YB1 AND NPM1 AS PART OF THE MUTANT HISTONE 3 PROTEIN INTERACTOME IN H3 MUTATED PHGG
Authors: Ms Mehar Dhillon, Ms Eleanor Read, Mr Joshua Sulman, Dr Farhana Haque
Journal: Neuro-Oncology (2024)

Abstract AIMS Paediatric high-grade gliomas (pHGG) are the leading cause of childhood cancer deaths, accounting for over 40% of deaths in the UK. pHGG tumours harbour histone H3 mutations, deﬁning 50% of pHGG cases and the major mutations are H3.3K27M and H3.3G34R/V. Our previous proteomic research on H3 intercatomes, identiﬁed unique and common interacting binding partners of H3-G34R and H3-G34V mutant proteins relative to wild type H3 protein. Among these binding proteins we have focused on YB-1 and Nucleophosmin 1 (NPM1). YB-1, is multifunctional transcription factor and a well- characterised oncogenic protein. NPM1 is a molecular chaperone and frequently overexpressed in cancers. Our aim is to analyse the role of YB-1 and NPM1 in H3 mutated pHGG, in order to identify targeted therapeutic options for these diﬃcult to treat tumours. METHOD H3 mutated glioma, H3 wild type pHGG and control cell lines were cultured and then subjected to comparative immunoﬂuorescence microscopy, and western blot analyses to investigate YB-1 and NPM1 expression. RESULTS Results showed statistically signiﬁcant altered protein expression and localisation of YB-1 and NPM1 in H3 mutated pHGG in comparison to wild type and control cells. YB-1 expression was increased in H3 mutated cells and NPM1 showed increased cytoplasmic localization in H3 mutated cells in comparison to H3 WT glioma and control cells. CONCLUSION Results of the study support that YB-1 and NPM1 are important interacting proteins in H3G34-mutated pHGGs and can be explored as potential therapeutic targets in H3 mutated pHGG.
DO NEURO ONCOLOGY PATIENTS FEEL SUﬃCIENTLY SUPPORTED TO MANAGE THEIR SURGICAL WOUNDS AFTER SURGERY?
Authors: Ms Ellie Kostick, Mr Aeron Suarez, Ms Nicola Harding, Ms Sarah Hedges, Ms Pat Sabido, Ms Laura Mullens, Mrs Victoria Hurwitz
Journal: Neuro-Oncology (2024)

Abstract AIMS Establish if neuro oncology patients feel they are suﬃciently well supported to manage their wounds post operatively. Is there any correlation to patient wound care management and developing wound infections. METHOD There was an anecdotal rise in wound infections in the neuro oncology department, which led to the team investigation a cause. This project was looking to see if patients felt they were suﬃciently supported to manage their wounds post operatively. A survey was sent via email to 94 patient’s who had undergone neurosurgery under the neuro oncology team at a London teaching Hospital in December 2023, January 2024, and February 2024. RESULTS There was a response rate of 23.5%. Overall 96% of patients felt able to manage their wound post operatively. 76% of people wished to have the information on wound care at discharge from hospital. 68% advised that they would like to receive information about wound care via printed material and 76% would like verbal instruction with questions. Patients commented that ‘there was a conﬂict of information’, and ‘the information at discharge could have been better’. They would like information on’ how to clean it [the wound]. 3 patients had a suspect infection but did not have treatment, and 1 had a conﬁrmed infection with treatment. CONCLUSION Neuro oncology patients are able to manage their wounds post operatively, but they feel that they would beneﬁt from extra support via written material, and verbal instructions. Future projects may include developing an evidence based post operative wound care information leaﬂet and instructions for wound care. Although in this cohort there was only 1 conﬁrmed infection, further investigation is needed to establish the cause for the apparent increase.
MATHEMATICAL MODELLING OF SURVIVAL IN LOW GRADE GLIOMAS AT MALIGNANT TRANSFORMATION WITH XGBOOST
Authors: Ms Lily Tan, Dr James Ruﬄe, Ms Samia Mohinta, Dr Jeremy Rees, Prof Sebastian Brandner, Prof Parashkev Nachev, Dr Harpeet Hyare
Journal: Neuro-Oncology (2024)

Abstract AIMS To develop non-linear machine learning models using the XGBoost algorithm to predict a continuous (overall survival (OS) and a binary survival outcome (OS &amp;gt; 5 years) using clinical, molecular and genetic, and radiomic data. METHOD Patients with LGGs treated at a single institution (2005-2020) with histology and MRIs at the time of malignant transformation (MT) were retrospectively included in this study. MRIs underwent in-house tumour segmentation pipeline with radiomic feature extraction of whole-tumour, enhancing, non-enhancing and oedema components, and masked disconnectome map components. Patients were split into training and testing sets for the development of the survival models, which were assessed with mean absolute error (MAE) and root mean square error (RMSE) for the prediction of OS; and receiver operating characteristics analysis for the prediction of OS &amp;gt; 5 years. RESULTS Of 553 patients, 415 patients were included in the training set and 138 patients in the testing set. The XGB Regressor model was able to predict overall survival (OS) from the time of malignant transformation (tMRI) with an MAE of 953 days (RMSE: 1163 days). The XGB Classiﬁer model was able to predict the probability of OS &amp;gt; 5 years from tMRI with an accuracy of 64% (sensitivity: 58%, speciﬁcity: 70%). Age, IDH1 mutation, 1p/19q co- deletion, regularity of tumour shape, and disconnectome-related perilesional components were most predictive of survival outcome. CONCLUSION This study has investigated the predictive capabilities of clinical, molecular and genetic, and radiomic data to develop survival analysis models, using XGBoost, to predict OS and OS &amp;gt; 5 years in patients with LGG at tMRI. We corroborate previous ﬁndings that age, 1p/19q co-deletion and IDH1 mutation are positive prognosticators for survival. However, further investigation into the radiomics of the disconnectome, especially of the perilesional oedema compartment, presents an intriguing and novel avenue for survival analysis of patients with LGG.