bluuebunny/crossref_metadata_2025_split huggingface dataset:
Brain Tumour Diagnosis and Relationships Among Patients: A Social Science Perspective on Changing Tumour Classification
Authors: Llewellyn Henry , Dulley Louise , Higgs Paul , Louis David , Sampson Elizabeth , Stone Paddy , Thorne Louis 
Published: October 2022

Abstract

AIMS
Peer-to-peer relationships between people with a brain tumour are critical to how they cope with illness. These are often premised on shared diagnoses. However, as molecular genetic/epigenetic markers revise tumour classification, the terms of such relationships could also change. We explore these relationships and the potential repercussions for patients whose diagnoses are revised according to new tumour classification.

METHOD
We draw on two UK-based ethnographic studies of brain tumour care. The first examined how patients navigated complex healthcare systems (2014-2016); the second explored changing classification and personalised medicine (2020-2021). Both involved repeated qualitative interviews with patients, families, clinicians and classification experts, and observations of routine care. Here, we focus on interviews and observations with patients (N=29).

RESULTS
Patients described how peer-to-peer relationships helped them understand their condition, envision their futures, find solidarity, navigate medical decisions, and access non-standard treatments. Many described the importance of finding people who shared their diagnosis. One patient, whose diagnosis was revised to a less aggressive tumour years after being first diagnosed, described how a radical change in prognosis challenged her relationships with peers, and contributed to significant survivor guilt as she outlived them.

CONCLUSION
Our findings confirm the importance of peer-to-peer relationships for patients. They suggest how changing tumour classification could have significant unforeseen social and psychological impacts for patients, including survivor guilt, by changing the nature of such relationships. We speculate that this will become more common in an era of personalised medicine and when breakthroughs in cancer understanding are more rapidly integrated in routine care.
How Can Clinical Teams Support Patients With a Brain Tumour Diagnosis With Sex Relationships and Intimacy?
Authors: Kostick Ellie , La Jessica , Hurwitz Victoria , Hedges Sarah , Robinson Charlotte , Suarez Aeron , Ashkan Keyoumars , Bhangoo Ranjeev , Gullan Richard , Vergani Francesco , Brazil Lucy , Al-Salihi Omar , Swampillai Angela , Chia Kazumi , Cikurel Katia , Joe Dorothy , Finnerty Gerald , Lavrador Jose Pedro 
Published: October 2022

Abstract

AIMS
There is a gap in supporting patients with sexual relationships and intimacy. The aim of this study is to establish if patients with a brain tumour feel they are able to ask questions and concerns about sex, relationships and intimacy following diagnosis; is there an unmet need and how can this be addressed.

METHOD
An anonymous survey was sent to patients known to a neuro-oncology team. Questions were in relation to their experiences of sex relationships and intimacy. Patients were asked if they had concerns about changes in their relationships since their diagnosis. They were also asked for their comments on the subject so we can better understand how as a service we can improve to ensure holistic care.

RESULTS
There are 40 responses. The majority of respondents had concerns about their relationship since diagnosis and that their relationships have changed. 57% were concerned about a physical relationship with a partner/ future partners. 50% agreed their physical relationship had changed. 45% of people agreeing their emotional relationships have changed. 38 out of the 40 people questioned, had not asked their clinical team for advice about sex and relationships. 46% suggested clinicians initiating these conversations.

CONCLUSION
Sex relationships and intimacy are significant for most adult populations, encompassing connection with their loved ones, self esteem and psychological and emotional well-being. With brain tumour diagnosis this part of people’s lives can hugely impacted. Historically clinicians have found this a difficult subject to discuss. Further work is required to understand the barriers initiating this subject
Introducing “Cloudbuster” as 3D Analysis and Quantification Tool of Cellular Glioma Morphologies in 3D Microscopy
Authors: Rohwedder Arndt , Knipp Sabine , Esteves Filomena , Hale Michael , Treanor Darren , Bruning-Richardson Anke 
Published: October 2022

Abstract

AIMS
A faithful representation of real tumour conditions in vivo such as a 3D glioma spheroid in a 3D experimental setting has become highly desirable for brain tumour research as it aids the study of tumour behaviour such as cell invasion and initiation of metastasis. However, data resulting from such studies need to be accurately analysed to correctly assess, for example, inhibitor effects on spheroid morphology and cell migration. To aid 3D data analysis we aimed to develop a reliable system for quantification of observed morphological changes such as number, morphology and size of invasive cells and spheroid extensions.

METHOD
We established a novel workflow that reconstructs a 3D entity from, for example, microtome sectioned glioma spheroids or confocal image z-stacks into pointclouds and subsequent comparison of basic readout parameters. The workflow requires little computational effort. Sliced image stacks are successfully scaled down towards a 1x1x1 ratio at threshold with subsequent edge detection and transformed into a pointcloud and analysed within minutes on a standard workstation /computer, e.g. shared graphics (4x 1.80 GHz CPU, 15 GB RAM).

RESULTS
We were able to validate the usefulness of this workflow using 3D data generated by various means including z-stacks from confocal microscopy and immunohistochemistry sectioning and demonstrate the possibility to accurately characterize inhibitor effects in depth.

CONCLUSION
We developed and validated ‘Cloudbuster’ as a 3D quantification tool to accurately assess structural changes detected in brain tumour cells after drug treatment, resulting in a versatile and adaptable 3D morphology analysis tool.
Brain Tumour Lessons From Alzheimer’s Disease: Beta-Amyloid and SorLA Expression in Glioblastoma
Authors: Jones Lydia , Jones Vicky , Shaw Lisa , Stasik Izabela , Smith Christopher 
Published: October 2022

Abstract

AIMS
Exploring how two proteins strongly associated with Alzheimer’s disease are expressed in glioma. Amyloid beta (Aβ) is a peptide cleaved from amyloid precursor protein (APP) that is shuttled around the cell by sorting-related receptor with A-type repeats (SorLA). Low expression of SorLA has been linked to increased risk of Alzheimer’s disease as APP processing shifts towards production of the plaque-forming Aβ42 rather than the more benign Aβ40.

METHOD
Expression of Aβ40, Aβ42 and SorLA was determined in immortalised cell lines (grade 4 glioblastoma U87MG, grade 2 astrocytoma 1321N1, foetal astrocytes SVGp12), glioblastoma patient-derived cells (PD301, PD304) and normal human astrocytes through western blotting or immunocytochemistry.

RESULTS
SorLA was present in all cells. Relative optical density was more than 60-fold higher for U87MG glioblastoma cells and approximately 10-fold higher for 1321N1 astrocytoma cells than SVGp12 cells. Similarly, SorLA had a significantly higher expression (p&lt;0.01) in patient derived cells than normal human astrocytes. High expression of SorLA was accompanied by lower Aβ42 in patient derived cells compared to normal human astrocytes. Expression of Aβ40 was similar across patient derived cells and normal human astrocytes.

CONCLUSION
These data suggest that SorLA is retained in glioblastoma and remains functional to drive APP processing away from Aβ42 production. Future work will determine how high SorLA expression contributes to the increased motility and invasiveness seen in glioblastoma cells by transfecting siRNA to knock down SorLA.
The Two-Week-Wait Referral Pathway: Not Fit for Purpose
Authors: Moosa Almira , Rees Jeremy 
Published: October 2022

Abstract

AIMS
The two-week-wait (2WW) referral pathway was set up by the Department of Health to improve early diagnosis and overall survival of cancer. Brain tumours, however, present with non-specific neurological symptoms. As such, this study set out to evaluate the efficacy of the 2WW pathway in detecting brain cancer in patients referred by primary care.

METHOD
Data from 217 patients referred via the 2WW pathway from January to September 2021 were extracted retrospectively, using the electronic health record system within the University College London NHS Foundation Trust. Details of the diagnoses, imaging results, and follow-up treatments were analysed.

RESULTS
Of the 217 patients referred with a suspected brain tumour, 0 patients received a new diagnosis of brain cancer. However, 4 cases of benign tumours were newly diagnosed through the 2WW pathway, with an additional 17 cases of benign tumours being referred for further management, having been detected on previous external imaging. 9 cases of known malignant brain tumours were referred for on-going management, having been treated previously elsewhere.

CONCLUSION
The 2WW pathway does not detect new cases of brain cancer. It is rather being used as a means of rapid referral of patients in primary care with benign tumours or previously identified brain cancer. This study therefore suggests that the initial aspiration of detecting brain cancer earlier via this pathway has not been fulfilled, but it is a useful tool for GPs to refer patients with brain tumours into Neuro-oncology services.
Redefining a Rare CNS Tumour Through Targeted Genetic Sequencing
Authors: Abuhusain Hazem , Bagga Veejay 
Published: October 2022

Abstract

AIMS
Isolated cerebellar vermis lesions in adults is a rare location and entity with few literature case reports detailing gangliogliomas and gangliocytomas. Using targeted genetic sequencing, traditional histological diagnosis can be refined further, with a clear impact on prognosis as well as possible genetic counselling implications.

METHOD
A single case of cerebellar vermis lesion, identified incidentally through imaging of a neck nodule, with subtle features of ataxia and mild impairment of initiation of speech. Sub-total resection of lesion underwent standard histopathological work-up, followed by targeted genetic sequencing to obtain an integrated diagnosis.

RESULTS
Histological assessment identified atypical ganglion cells labelled with Synaptophysin on immunohistochemistry. Features closely resembled dysplastic cerebellar gangliocytoma (Lhermitte-Duclos Disease). Further targeted sequencing showed no evidence of IDH1, IDH2, TERT promoter, or histone mutation, however, BRAF mutation was present, supporting an alternate diagnosis of ganglioglioma.

CONCLUSION
Precision medicine is facilitated with advanced diagnostic techniques. This redefines categorisation of some CNS tumours, particularly rare entities. Techniques are especially valuable to individual patient management as they can have a direct impact on aspects of clinical work-up, prognosis, follow-up, and in some cases, genetic counselling.
First Line Treatment of Adult Glioblastoma Patients in England 2103-2018 from the GlioCova Project
Authors: Le Calvez Kerlann , Mauricaite Radvile , Williams Matt 
Published: October 2022

Abstract

AIMS
The Gliocova dataset uses linked English national cancer data on all 51,775 adult primary brain tumour patients diagnosed between 2013-2018. Here we present detailed analysis of first-line treatments of adult glioblastoma (GBM) patients.

METHOD
We identified all adults patients diagnosed with a GBM. We focused on the first line of treatment and we defined ‘maximal’ first-line treatment as surgical resection followed by chemo-radiotherapy with 59-60 Gy and with at least one cycle of adjuvant chemotherapy Temozolomide.

RESULTS
15,294 patients were diagnosed with a glioblastoma (60% male) with a median age of 66. 79% of patients received some treatment, with younger patients more likely to be treated (&gt;90%, 18 - 59; &lt; 30%, &gt; 80). 54% underwent debulking surgery; 23%, biopsy. 14% received ‘maximal’ treatment and 21%, none. Patients who had no treatment had a median survival of 2 months whereas patients who received ‘maximal’ treatment had a median survival of 16 months.

CONCLUSION
Most adult patients with a GBM in England have a histological diagnosis, and some oncological treatment. However, only 14% receive ‘maximal’ treatment. Of the 3222 patients who received none, some of these may have had purely private treatment; however, our dataset includes any private sector work undertaken in NHS hospitals. Survival remains poor, but outcomes in those receiving maximal treatment match those from clinical trials. However, most patients do not receive maximal treatment, and so the easiest route to improving outcomes may be optimise delivery of treatment in the 65% of patients who receive sub-maximal treatment. More information on https://blogs.imperial.ac.uk/gliocova
Deep Learning for Tumour Segmentation with Missing Data
Authors: Ruﬄe James , Mohinta Samia , Gray Robert , Hyare Harpreet , Nachev Parashkev 
Published: October 2022

Abstract

AIMS
Brain tumour segmentation remains a challenging task, complicated by the marked heterogeneity of imaging appearances and their distribution across multiple modalities: FLAIR, T1-weighted, T2-weighted, and contrast-enhanced T1-weighted sequences (T1CE). But the use of all four imaging sequences is not always possible. The causes for this are legion, with common examples including corruption by image artefacts and acquisition constraints, such as those imposed in pre-operative stealth studies. We therefore aimed to quantify how well tumour segmentation models perform with incomplete imaging data.

METHOD
We developed a collection of 30 state-of-the-art deep learning tumour segmentation models, nnU-Net-derived, and deployed them across all possible combinations of imaging modalities, trained, and tested with five-fold cross-validation on the 2021 BraTS-RSNA glioma population of 1251 patients, with additional out-of-sample comparison to neuroradiologist hand-labelled lesions from our own centre.

RESULTS
Regardless of imaging available, models largely performed well. The best models with varying degrees of missingness were as follows: single sequence available - FLAIR (Dice 0.938); two sequences available - FLAIR + T1CE (Dice 0.943) and three sequences available – FLAIR + T1CE + T2 (Dice 0.945). In comparison, a model with complete data (FLAIR + T1 + T1CE + T2) achieved a similar Dice coefficient of 0.945.

CONCLUSION
Tumour segmentation models with missing sequences – common in clinical practice - still delineate lesions well, often with comparable performance to when all data is available. This provides opportunity for quantitative imaging in patients and clinical situations wherein full MRI acquisitions are not possible.
Lynch/Turcot Syndrome and Sporadic Mismatch Repair Deficient High-Grade Gliomas – A Case Series
Authors: Briggs Mayen , Bruty Jonathan , O’Donovan Dominic , Liu Hongxiang , Tischkowitz Marc , Tarpey Patrick , Hewer Ekkehard , Giger Olivier 
Published: October 2022

Abstract

AIMS
The DNA mismatch repair (MMR) system is critical for genomic stability correcting errors generated during DNA replication with germline pathogenic variants (PVs) causing Lynch syndrome. Although acquired MMR deficiency is associated with temozolomide resistance, the incidence in treatment naïve tumours is unknown and not routinely screened for. Here we present three MMR deficient gliomas and describe their comprehensive molecular profile.

METHOD
Thirteen gliomas; 9/34 that had undergone sequencing of 50 cancer-associated genes and found to have frameshift/multiple point PVs, indicative of defective MMR, and four MSI-high tumours, identified following microsatellite analysis for 1p/19q co-deletion as part of routine care, were selected for analysis. MMR expression was then assessed by immunohistochemistry. Seven tumours showed loss of one or more MMR proteins and were molecularly characterised using PCR-based Promega MSI analysis and NGS-based Illumina TruSight500 panel.

RESULTS
Pathogenic variants in MMR genes and hypermutated phenotypes (TMB &gt; 10mutations/Mb) were identified in three cases. One individual harboured an additional POLE PV resulting in an ultra-hypermutated phenotype (&gt;100mutations/Mb). Two MMR PVs were germline, leading to a new diagnosis of Lynch syndrome. Only one of three tumours was found to be MSI-high using the Promega MSI analysis whilst all three were identified as MSI-high using TruSight500 MSI calling algorithms.

CONCLUSION
We describe the comprehensive molecular profile of seven treatment naïve gliomas, three being MMR deficient. We show TruSight500 to be more sensitive and reliable for detecting MSI compared to Promega. Given the implications, this additional analysis should be considered as part of the molecular report on all gliomas.
Extent of MGMT Promoter Methylation Modifies the Effect of Temozolomide on Overall Survival in Patients with Glioblastoma: A Regional Cohort Study
Authors: Poon Michael T C , Keni Shivank , Vimalan Vineeth , Ip Chak , Smith Colin , Erridge Sara , Weir Christopher , Brennan Paul 
Published: October 2022

Abstract

AIMS
MGMT methylation in glioblastoma predicts response to temozolomide but dichotomizing methylation status may mask the true prognostic value of quantitative MGMT methylation. This study evaluated whether extent of MGMT methylation interacts with the effect of temozolomide on overall survival.

METHOD
We included consecutive glioblastoma patients aged ≥16 years diagnosed (April 2012–May 2020) at a neuro-oncology center. All patients had quantitative MGMT methylation measured using pyrosequencing. Those with MGMT methylated tumors were stratified into high and low methylation groups based on a cut-off using Youden index on 2-year survival. Our accelerated failure time survival models included extent of MGMT methylation, age, postoperative Karnofsky performance score, extent of resection, temozolomide regimen, and radiotherapy.

RESULTS
There were 414 patients. Optimal cut-off point using Youden index was 25.9% MGMT methylation. The number of patients in the unmethylated, low and high methylation groups was 223 (53.9%), 81 (19.6%), and 110 (26.6%), respectively. In the adjusted model, high (hazard ratio [HR] 0.60, 95% confidence intervals [CI] 0.46– 0.79, P=0.005) and low (HR 0.67, 95% CI 0.50–0.89, P&lt;0.001) methylation groups had better survival compared to unmethylated group. There was no evidence for interaction between MGMT methylation and completed temozolomide regimen (interaction term for low methylation P=0.097; high methylation P=0.071). This suggests no strong effect of MGMT status on survival in patients completing temozolomide regimen. In patients not completing the temozolomide regimen, higher MGMT methylation predicted better survival (interaction terms P&lt;0.001).

CONCLUSION
Quantitative MGMT methylation may provide additional prognostic value. This is important when assessing clinical and research therapies.
Exploring the Role of Specialist Physiotherapy in Awake Craniotomy Surgery for the Neuro-Oncology Patient
Authors: Jones Amy , Price Sally , Lavrador Jose Pedro , Gullan Richard , Vergani Francesco , Bhangoo Ranjeev , Rajwani Kapil , Ashkan Keyoumars , Mirallave-pescador@nhs.net Ana 
Published: October 2022

Abstract

AIMS
To describe the methods used to assess and monitor motor function during awake craniotomy surgery for tumour resection.

METHOD
A service review was carried out over 10 months. Patients with highly motor eloquent lesions – invasion of primary motor cortex or fronto-parietal connections involved in motor cognition – were included. Clinical notes were reviewed and summarised using descriptive analysis. Dexterity and grip strength were measured using 9-hole peg test and handheld dynameter pre/intra and post-operatively. Patient occupation/interests were reported to guide bespoke assessments to trial intra-operatively.

RESULTS
From April 2021 to January 2022, 13 patients (mean age 39.7 years, 4 female:10 male, 9 low grade:5 high grade gliomas) were included. Mean score 9-hole peg test 22.2sec pre-operatively, 30.6sec post-operatively; handheld dynameter 26.7kg pre-operatively, 18.4kg post-operatively. At discharge 5 of 7 impaired patients demonstrated motor improvement. For motor coordination, motor tasks used frequently included repetitive finger tapping, open/closed hand. Bespoke tasks included texting/writing, playing instruments, and computer games. Movement was closely monitored and verbal feedback given to the neurosurgeons throughout. With video analysis movement comparisons were made.

CONCLUSION
The role of physiotherapy in awake surgery is evolving to provide movement analysis for complex motor tasks such as upper limb sequencing and dexterity. A combination of standard and bespoke assessments have been trialled and their feasibility within surgery tested. A post-operative deterioration of motor function (power and cognition) is expected after surgery for highly eloquent motor gliomas. However, intraoperative motor assessment for motor cognition allows function preservation and potentiates its recovery.
Cardiovascular Events After Primary Malignant and Non-Malignant Brain Tumour Diagnosis: A Population Matched Cohort Study in Wales (United Kingdom)
Authors: Poon Michael T C , Jin Kai , Brennan Paul , Figueroa Jonine , Sudlow Cathie 
Published: October 2022

Abstract

AIMS
It is uncertain whether the elevated cardiovascular diseases (CVD) risks in patients with brain tumours is due to differences in the distribution of risk factors. We compared CVD risks among patients with a primary brain tumour to a matched general population cohort.

METHOD
Using data from the Secured Anonymised Information Linkage (SAIL) Databank in Wales, we identified adults aged ≥18 years with a diagnosis of brain tumour identified in the cancer registry between 2000-2014, and a matched cohort (case-to-control ratio 1:5) by age, sex and primary care provider from the general population. Outcomes included fatal and non-fatal major vascular events and venous thromboembolism (VTE). We used multivariable Cox models adjusted for clinical risk factors to compare risks.

RESULTS
There were 2,869 and 3,931 people diagnosed with malignant and non-malignant brain tumours, respectively, in Wales. They were matched to 33,785 controls. Within the first year of tumour diagnosis, malignant tumour was associated with VTE (hazard ratio [HR] 21.58, 95% confidence interval 16.12-28.88) and stroke (HR 3.32, 2.44-4.53). People with malignant tumour surviving one year had higher risks of VTE (HR 2.20, 1.52-3.18) and stroke (HR 1.45, 1.00-2.10) compared to their matched controls. Individuals with non-malignant tumours had higher risks of VTE (HR 3.72, 2.73-5.06), stroke (HR 4.06, 3.35-4.93) and aortic and peripheral arterial disease (HR 2.09, 1.26-3.48) within the first year of diagnosis compared with their controls.

CONCLUSION
The elevated risks of CVD suggest risk reduction a potential strategy to improve life quality and survival in people with malignant and non-malignant brain tumour.