tbuckley/cabot-search huggingface dataset:
LOCATE-SM PROTOCOL: LOCATION ORIENTED CORTICAL AND SUB-CORTICAL ASSESSMENT FOR THERAPEUTIC EVALUATION- SENSORY-MOTOR TESTING IN AWAKE CRANIOTOMY
Authors: Mrs Elisa Stephenson, Mrs Sara Cooper, Ms Seonaid-Mairi Ewan, Mr William Stephen Bolton, Mr Ryan Mathew
Journal: Neuro-Oncology (2024)

Abstract AIMS Awake craniotomy is a well-established surgical procedure to debulk intracranial tumours in eloquent areas (‘functional hubs’). Intraoperative mapping facilitates maximal safe debulking. Review of current sensory motor assessment tools highlighted the absence of a comprehensive ‘location to function’ protocol. We aimed to develop a new protocol that enables ‘location to function’ sensory-motor task selection in preparation for, and during, awake craniotomy. METHOD A literature review demonstrated multiple different intraoperative strategies exist for the preservation of sensory-motor function in awake craniotomy. Incorporating these with functional neuroanatomy, and consensus agreement in the Tessa Jowell Academy Physiotherapy Awake Craniotomy Working Group and the National Brain Mapping MDT, led to the development of testing strategies aligned with ‘location to function’ task selection. Testing strategies were peer-reviewed by three specialist Neuro-Oncology physiotherapists. RESULTS A protocol (LOCATE-SM) has been developed at Leeds to identify critical cortical and subcortical sensory-motor functions that are aligned with anatomo-functional models. Physiotherapists have used this to select individualised pre-, intra- and postoperative tests depending on tumour location and sensory-motor impairment. Additionally, this facilitates intraoperative mapping of eloquent functional regions that are variably located. Cases using LOCATE-SM are presented. CONCLUSION LOCATE-SM is a new awake sensory-motor testing protocol developed by specialised Neuro-Oncology physiotherapists at a Tessa Jowell Centre of Excellence (Leeds). Current cases demonstrate that it leads to greater consistency between physiotherapists and speciﬁcity in ‘location to function’ sensory-motor task selection. Future work will systematically analyse the outcomes (onco-functional balance) of using this protocol, and validation in other centres.
PATTERNS OF RADIOTHERAPY PRACTICE FOR FUNCTIONING PITUITARY TUMOURS - A SURVEY OF UK CENTRES
Authors: Dr Avinash Pilar, Dr Ruth Ronneberger, Ms Charlotte Tyson, Prof Stephanie Baldeweg, Dr Michael Kosmin
Journal: Neuro-Oncology (2024)

Abstract AIMS Pituitary adenomas are benign tumours that are classiﬁed as functioning or non-functioning based on the production of excess pituitary hormones. Functioning adenomas (FA) typically present as hypersecretory syndromes including acromegaly and Cushing’s disease. In FA, radiotherapy is used when surgery fails to achieve hormone normalisation and/or when medical treatment does not control hormone excess. In the absence of prospective studies that clearly deﬁne the optimal radiotherapy technique in FA, it is expected that there will be variability in practice. A survey of UK neuro-oncology centres was undertaken, aiming to establish the extent of this variability in FA. METHOD A survey was distributed electronically to 20 neuro-oncology departments across the UK. Data were collected on patient numbers, radiotherapy indications, techniques, dosing, and target volume delineation. RESULTS Responses were received from eight centres (40% response rate), treating a total of approximately 32 FA per annum. There was variability in techniques employed to treat FA. While four centres treated most FA with IMRT, two treat most with stereotactic radiosurgery (SRS), and two with fractionated stereotactic radiotherapy (fSRT). The most common dose used for IMRT treatment was 45Gy in 25 fractions (n=7), with 50.4Gy in 28 fractions, 50Gy in 30 fractions and 54Gy in 30 fractions also reported. Use of margins around residual disease (n=5) and inclusion of involved cavernous sinuses and surgical tract (n=3) within clinical target volumes also varied. Most centres (n=7) would agree to a change in target volume delineation practices for the purpose of a clinical trial in FA. CONCLUSION This survey found that there is variability in radiotherapy dosing, technique, and target volume delineation practices for radiotherapy to FA across the UK. All centres but one would accept changes in their practice within the context of a prospective clinical trial of radiotherapy for FA.
THE MOLECULAR HISTORY OF IDH-MUTANT ASTROCYTOMAS WITHOUT ADJUVANT TREATMENT
Authors: Prof Ho Keung Ng, Dr Zhi-Feng Shi, Dr Kay Li
Journal: Neuro-Oncology (2024)

Abstract AIMS Hypermutation and malignant transformation are potential complications arising from temozolomide treatment of IDH-mutant gliomas. However, the natural history of IDH-mutant low-grade gliomas without temozolomide treatment is relatively un-studied. We set out to study the molecular history of paired IDH-mutant astrocytomas without adjuvant treatment in the interim. METHOD We retrieved retrospectively from our hospitals paired tumors from 19 patients with IDH-mutant, 1p19q noncodeleted Grade 2 astrocytomas where no interim adjuvant treatment with either temozolomide or radiotherapy was given between primary and ﬁrst recurrences. Two patients had multiple resected recurrences and radiotherapy but not temozolomide was given before the last specimens were resected. We studied the natural molecular history of these low-grade IDH-mutant astrocytomas without pressure of temozolomide with methylation proﬁling and copy number variation (CNV) analyses, target DNA sequencing, TERTp sequencing, FISH for ALT and selected biomarkers. RESULTS Recurrences were mostly higher grades (15/19 patients) and characterized by new CNVs not present in the primary tumors (17/19 cases). Few novel mutations were identiﬁed in recurrences. Tumors from 17/19 (89.5%) patients showed either CDKN2A homozygous deletion, MYC or PDGFRA ampliﬁcation at recurrences. There was no case of hypermutation. Phylogenetic trees constructed for tumors for the two patients with multiple recurrences showed a conserved evolution pattern. CONCLUSION In summary, our studies demonstrated in contrast to the phenomenon of temozolomide-induced hypermutation, IDH-mutant, 1p19q non-codeleted Grade 2 astrocytomas which were not treated by temozolomide instead acquired new CNVs at tumor recurrences. These ﬁndings improve our understanding of the molecular life history of IDH-mutant astrocytomas.
DESIGN AND SET UP OF A RANDOMISED CONTROLLED TRIAL OF MEDICINAL CANNABINOIDS IN RECURRENT GLIOBLASTOMA - THE ARISTOCRAT TRIAL
Authors: Prof Susan Short, Dr Rhys Mant, Dr Josh Savage, Dr Amit Patel, Prof Lucinda Billingham, Dr Sarah Meade, Mr Peter Buckle, Dr Fiona Collinson, Dr Florien Boele
Journal: Neuro-Oncology (2024)

Abstract AIMS ARISTOCRAT is a unique, randomised, double-blind, placebo-controlled phase II trial of cannabinoids (nabixo- mols) alongside temozolomide in patients with MGMT-methylated recurrent GBM and is open to recruitment in 12 centres across the UK. It was rapidly funded through a crowdfunding campaign organised by The Brain Tumour Charity during the COVID-19 pandemic. METHOD This pragmatic phase II randomised trial was designed and set up by a multi-disciplinary team of co-applicants and trial management group (TMG) members comprising of clinicians, statisticians, trialists, Patient &amp; Public Involvement (PPI), pharmacists and quality of life (QoL) researchers. The protocol randomises on a 2:1 ratio between nabiximols or matched placebo with standard dose temozolomide in patients at ﬁrst recurrence of IDH wild-type GBM. Unique aspects include self-titration of nabiximols based on individual tolerance, and fully blinded randomisation with matched placebo. The primary outcome measure is overall survival time with key secondary outcomes including survival at 6, 12 and 24 months, progression-free survival time, health-related QoL and adverse events. Intermediate assessment of feasibility to conﬁrm safety, compliance and achievability of recruitment will be undertaken after 40 patients are randomised. PPI input has been critical in the trial and patient-facing information design. RESULTS The trial has promoted a high level of patient and public interest, including press coverage. The trial aims to recruit a total of 234 patients over an 18 month period. CONCLUSION ARISTOCRAT will provide unique, robust clinical data on the role of nabiximols (combined with temozolomide) in improving overall survival and the impact on QoL for patients with recurrent GBM and is the ﬁrst of its kind in cancer patients.
RISKS AND OUTCOMES OF STROKE IN PATIENTS WITH PRIMARY BRAIN AND MENINGEAL TUMOURS
Authors: Dr Stuart Innes, Dr Lucia Yin, Dr Gerald T Finnerty
Journal: Neuro-Oncology (2024)

Abstract AIMS People with primary CNS tumours are at increased risk of stroke. However, there is little guidance on stroke management. We investigated the types and timing of stroke in primary brain and meningeal tumours to inform their treatment. METHOD Patient data on stroke aetiology, timing, management and outcomes was collected from electronic medical records at King’s College Hospital between April 2012 to April 2022. A primary brain tumour was deﬁned using the 2021 World Health Organisation Classiﬁcation of Tumours of the Central Nervous System. RESULTS We identiﬁed 244 patients with a brain tumour and a stroke with a total of 317 strokes in the 10-year period (male:female = 48:52; median age, 62 years [IQR 51 – 74]). The most common brain tumours were meningiomas (43%) and glioblastomas (21%). 56% of strokes were ischaemic. Ischaemic strokes were most frequent within 30 days of brain tumour surgery (38%). Haemorrhages were more common in malignant tumours (p=4.7 x10 35% of haemorrhages were intratumoural. Strokes in malignant tumours: occurred closer to diagnosis (p=0.032); caused greater functional loss (mean Modiﬁed Rankin Scale change 2.00 vs 1.17, p 0.001); and had a higher mortality rate (HR 5.87, CI 3.41 - 10.11, p=1.8x10 Recurrent strokes occurred in 64 (26%) patients and were associated with tumour malignancy (p=0.016), radiotherapy (p=0.023) and chemotherapy (p=0.009). CONCLUSION Strokes in malignant brain tumours are more lethal, disabling and often recurrent in patients undergoing chemo and radiotherapy. Clinical trials are needed to improve outcomes of stroke in neuro-oncology patients.
AN ANALYSIS OF THE PATIENT REPORT OUTCOMES OF A JOINT CNS / AHP NEURO-ONCOLOGY CLINIC ON PATIENTS QUALITY OF LIFE
Authors: Dr James Powell, Mrs Cathryn Lewis, Mrs Rhian Burke, Dr Najmus Iqbal, Dr Jillian Maclean, Ms Charlotte John, Mrs Keri Best, Mrs Bethan Moore, Ms Rebecca Davies, Mrs Emma Mackay, Mrs Clare Rogers, Mrs Magdalena Kwiatkowska, Mrs Samantha Tindle
Journal: Neuro-Oncology (2024)

Abstract AIMS Velindre Cancer Centre established a successful model of collaborative working between CNS and AHP services for neuro-oncology patients to holistically support their complex needs throughout treatment. Building on this success, the clinic has introduced a recognised reliable and valid patient reported outcome measure (PROM) to be completed pre and post clinic intervention. This is in addition to the patient reported experience measure that is already established within the pathway. This PROM will enable an analysis of the clinics impact on patients quality of life. METHOD A quantitative methodology will be utilised to enable a objective evaluation of the impact of the clinic on patients quality of life. An EQ-5D-5L PROM is completed with patients prior to their involvement with the clinic enabling an overview of key aspects related to quality of life including mobility, self-care, participation in usual activities, pain and anxiety / depression. Following interventions within the clinic, patient are provided with a post treatment EQ-5D-5L to enable a comparison of these key indicators of quality of life. RESULTS The data will build on the resounding success of collaborative working between CNS and AHP’s in the neurooncology MDT clinic. An analysis of the pre and post data will demonstrate the impact of having access to this unique and integrated way of working, enabling patient access to specialist timely support throughout their treatment. CONCLUSION This innovative model of working is now established in the patient pathway and ﬁndings from patient experience measures have recognised that patients experience of the clinic is extremely highly valued. Findings from this additional dataset will further evidence the impact on patients quality of life. It will add to ﬁndings from a proposed gap analysis to evidence the beneﬁts of developing an outreach service for this patient cohort.
WHICH BRAIN TUMOUR PATIENTS WOULD BENEﬁT FROM SURGERY TO TREAT BOTH THE TUMOUR AND TUMOUR-RELATED EPILEPSY?
Authors: Dr Amber Corrigan, Dr Dorothy Joe, Dr Gerald T Finnerty
Journal: Neuro-Oncology (2024)

Abstract AIMS Poor seizure control is a common problem for brain tumour patients. Epilepsy surgery is considered in patients with seizures not caused by a brain tumour when trials of two anticonvulsants given in therapeutic doses fail. There are no clear guidelines on when epilepsy surgery should be considered for brain tumour patients. Given the high burden on quality of life, preventing recurrent seizures is essential. METHOD Retrospective data collection of patients seen in the Low-Grade Glioma and Joint Neurology-Oncology clinics of a regional Neuro-oncology service between January – June 2023. Data were analysed within STATA 18. RESULTS We identiﬁed 121 patients (61 male, 60 female; age range 20-84 yrs). The majority (93/121) were diagnosed with a low-grade glioma. [GF1] 44 patients had tumour-related epilepsy. Of these, 31/44 (70%) patients presented clinically with seizure(s) and 13/44 (30%) patients had their ﬁrst seizure 3 - 2421 days post diagnosis. All patients were started on anticonvulsant medication, commonly Levetiracetam (70%). Tumour surgery was performed on 28/44 (63%) patients. Recurrent seizures occurred in 22/44 (50%) patients. Seizures were not controlled in 12 (29%) patients after trying two or more anticonvulsants. Four patients were considered for epilepsy surgery. CONCLUSION Recurrent seizures are a common clinical problem in patients with low-grade gliomas. Surgery to treat brain tumour-related epilepsy may be performed as a last option. Brain tumour patients may beneﬁt from earlier consideration of surgery to treat both the epilepsy and the brain tumour.
POSTOPERATIVE VISUAL ﬁELD DEﬁCITS ARE NOT ASSOCIATED WITH REDUCTION IN QUALITY OF LIFE IN GLIOBLASTOMA PATIENTS
Authors: Mr Yizhou Wan, Mr Yonghao Li, Mr Rohit Sinha, Ms Swati Jain, Prof Richard Mair, Mr Robert Morris, Mr Alexis Joannides, Mr Tom Santarius, Prof Stephen Price
Journal: Neuro-Oncology (2024)

Abstract AIMS Preservation of functional integrity is a core goal of glioblastoma surgery. Visual ﬁeld deﬁcits can signiﬁcantly impact quality of life and patient function. Both tumour and surgical effects may affect visual function in these patients. The objective of this Study was to evaluate the effect of visual ﬁeld deﬁcits on HRQoL in the preoperative and early postoperative period (prior to chemoradiotherapy). METHOD 48 patients with glioblastoma received preoperative, early postoperative (withon 1 week) and delayed postoperative testing (6 weeks) for visual function usinga combination of the OCS-Bridge neurocognitive screening tool and formal visual ﬁeld testing. Patients also completed the EORTC QLQ C30 with BN-20 and VFQ-25 visual function questionaires at the same timepoints. Statistical tests were performed using R Statistical Software (v4.1.2; R Core Team 2021). RESULTS The proportion of patients with visual ﬁeld deﬁcits at preoperative, early postoperative and late early postoperative timepoints were 20 (41.7%), 28 (58.3%) and 24 (50%) respectively. Most patients without a preoperative deﬁcit did not have an early 17/20 85% or late postoperative deﬁcit 19/24 79.1%. The proportion of patients with deﬁcits at early and late postoperative timepoints was signiﬁcantly higher in patients with preoperative deﬁcits compared to patients without preoperative deﬁcits, (Chi square p = 0.004) and (p = 0.008) respectively. There was no signiﬁcant differences between HRQoL measures between timepoints or between patients with deﬁcits at any timepoint compared to patients without deﬁcits. CONCLUSION Postoperative visual ﬁeld deﬁcits are related to preoperative tumour-effects rather than surgery. Patients can be counselled that while they do not recover following surgery, it is not associated with signiﬁcant reductions in HRQoL. Patients with preoperative visual ﬁeld deﬁcits may be considered for resection without signiﬁcant worry about the preservation of visual ﬁeld function since these deﬁcits do not recover postoperatively.
SINGLE INSTITUTION RETROSPECTIVE ANALYSIS OF COMPLICATIONS ASSOCIATED WITH SURGICAL DEBULKING OF BRAIN METASTASIS
Authors: Dr Yong Yie Liew, Mr Abhijit Hazra, Mr Siddarth Kannan
Journal: Neuro-Oncology (2024)

Abstract AIMS Surgical resection of brain metastasis is associated with complications, which worsen patient’s quality of life, results in oncological treatment delays and death. Surgical complication data aids decision making, leads to objective risk beneﬁt analysis and informed consent. The aim of this study is to quantify rates, types and risk factors for complications related to surgical debulking of brain metastasis. METHOD Retrospective analysis on adult patients with brain metastasis, who underwent surgical debulking between 2017 and 2023 at Royal Preston Hospital. Data collected included demographics, diagnosis, 30-days post-operative complications, 30-days mortality, 30-days post-operative palliation, primary tumour, Karnofsky-Performance Score (KPS), ﬁrst vs. repeat resection, use of drain and type of suture materials etc. Univariate analysis was carried out using Graphpad software. RESULTS Two-hundred and twenty-seven patients qualiﬁed. The most common primaries were lung (n=93, 41%), breast (n=43, 18.9%), and skin (n=31, 13.7%). The most common complications were Hospital-acquired pneumonia (HAP) (n=27, 11.9%), surgical site infection (SSI) (n=19, 8.4%), wound dehiscence (n=14, 6.2%), thromboembolic events (n=12, 5.3%) and CSF leak (n=8, 3.5%). Thirty days mortality and post-operative palliation (due to surgical complications) were both 3.5% each (n=8). Two-hundred and six (93.2%) had KPS ³70 whilst 15 (6.8%) had KPS &amp;lt; 70 [range 30-60 pre-operatively (median 60)). KPS &amp;lt; 70 was statistically signiﬁcant for post-operative palliation (p=0.01), HAP (0=0.02) and urine infection (p=0.002), but not for 30-day mortality. Twenty-ﬁve (11.1%) patients undergoing repeat resections, experienced higher wound infections (p=0.002). CONCLUSION Surgical debulking is associated with signiﬁcant post-operative complications, with 7% either dying or not receiving any further treatment, 18.1% percent developing serious wound complications (SSI, CSF leak, Wound dehiscence) and 19.4% experiencing signiﬁcant medical complications (HAP/UTI/Thromboembolism). Pre- operative KPS &amp;lt; 70 and repeat resections are associated with statistically increased risk of complications.
NANOPORE-BASED INTRA-OPERATIVE CLASSIﬁCATION OF CENTRAL NERVOUS SYSTEM TUMOURS IN THE NHS
Authors: Dr Simon Deacon, Dr Inswasti Cahyani, Dr Nadine Holmes, Dr Graeme Fox, Mr Satrio Wibowo, Mr Rory Munro, Dr Areeba Patel, Dr Robert Goldspring, Prof Sebastian Brandner, Prof Felix Sahm, Dr Simon Paine, Prof Matthew Loose, Dr Stuart Smith
Journal: Neuro-Oncology (2024)

Abstract AIMS The 2021 WHO classiﬁcation of CNS tumours necessitates the use of molecular testing in order to reach a conﬁdent diagnosis of many tumour types. At present, this is achieved using array-based technology delivered by a centralised model. This approach has inherent delays that mean it is often several weeks before the treating clinical team is informed of diagnosis, delaying the start of adjuvant therapy and causing signiﬁcant distress for patients. As such, there is an urgent need to rethink this pathway and improve time to diagnosis. Nanopore longread sequencing technology has the potential to enable a paradigm shift in diagnostic and therapeutic pathways, offering rapid, comprehensive molecular diagnosis that can be performed in the intra-operative setting. We aimed to test the hypothesis that intra-operative methylation-based classiﬁcation can be performed using nanopore sequencing and thereby expediently inform surgical and oncological decision-making. METHOD Oxford Nanopore Technology (ONT) is a native-strand, long-read sequencing platform that can perform copy- number proﬁling along with parallel single-gene methylation, structural variant, mutational and methylation analyses. Capital and consumable costs are relatively low, and testing can be performed in the local setting on single samples. We have optimised DNA extraction and library preparation for rapid tissue processing. We have developed a robust bioinformatic pipeline which is able to produce intraoperative classiﬁcation within minutes of sequencing and full molecular proﬁling after 24 hours. RESULTS We demonstrate the feasibility of using ONT to deliver intra-operative methylation-based classiﬁcation of CNS tumours in ‘realtime’ within an NHS hospital setting and will discuss the challenges of implementing this testing and the opportunities to inform neuro-oncological practice. CONCLUSION By giving a summary of our novel protocol of rapid DNA extraction, library preparation and bioinformatic analysis, we will show that this approach can revolutionise the diagnosis of brain tumours and has the potential for rapid adoption by non-expert laboratories.
THE UTILITY OF MULTIPARAMETRIC MRI IN REDUCING DIAGNOSTIC UNCERTAINTY FOR PRIMARY CNS LYMPHOMA
Authors: Ms Aimee Goel, Mr Robert Flintham, Dr Ute Pohl, Ms Victoria Wykes, Dr Vijay Sawlani
Journal: Neuro-Oncology (2024)

Abstract AIMS A key limitation in the early treatment initiation in primary central nervous system lymphoma (PCNSL) is the diagnostic delay caused by lack of recognition of a lesion as a possible lymphoma, steroid initiation, and lesion involution, often resulting in inconclusive biopsy. We highlight the importance of multiparametric MRI (MPMRI), which incorporates diffusion weighted imaging (DWI), dynamic susceptibility contrast-enhanced perfusion weighted imaging (DSC-PWI) and proton magnetic resonance spectroscopy (1H-MRS) in addition to standard MRI sequences in resolving diagnostic uncertainty for PCNSL. METHOD We present a consecutive series of 10 patients at our centre with histology-proven PCNSL (speciﬁcally, diffuse large B-cell lymphoma of the CNS) who underwent multiparametric MRI. We retrospectively analyse the qualitative and semi-quantitative parameters and assess their radiological concordance for this diagnosis. RESULTS We note overall low apparent diffusion coeﬃcient on DWI (mean ADCmin of 0.74), high percentage signal recovery on perfusion weighted imaging (mean 170%), a high choline-creatine ratio and a high-grade lipid peak on MRS giving a “twin-tower” appearance. Nine of ten patients had MRMRI ﬁndings concordant for PCNSL, deﬁned as at least 3 of 4 parameters being consistent for PCNSL. CONCLUSION We propose that concordance between these imaging multiparametric modalities could be used as a radiological predictor of PCNSL, reducing diagnostic delays, providing a more accurate biopsy target, and resulting in quicker treatment initiation.