bluuebunny/crossref_metadata_2025_split huggingface dataset:
DUAL PET IMAGING OF NEOPLASTIC AND INflAMMATORY BIOMARKERS IN HIGH GRADE GLIOMA
Authors: Alfaifi Bandar , Jackson Alan , Hinz Rainer , Lewis Daniel , Coope David 
Published: September 2023

Abstract

AIMS
To characterize spatial distributions of 18kDa translocator protein (TSPO) and amino acid uptake as measured through dynamic [11C] (R)-PK11195 and [11C]-methionine PET in high-grade glioma.

METHOD
Twelve patients with newly diagnosed high-grade glioma underwent dual PET studies. [11C] (R)-PK11195 binding potential (BPND) maps were generated using simplified reference tissue model with grey-matter cerebellar time- activity-curve as tissue input-function. [11C]-methionine uptake was calculated as tumour-to-background ratio (TBR). Volumes of interest (VOIs) were defined on T1W post-contrast MRI as contrast-enhancing (CE) tumour and a ‘peritumoural’ region 5mm from the CE edge. Voxel-wise comparison of the tracers used Pearson’s correlation coeffcient. VOIs were furthermore subdivided into higher/lower TSPO (BPND &gt; 0.17) and higher/lower methionine (TBR &gt; 1.7).

RESULTS
Within the CE, voxel-wise comparison showed a strong correlation (r &gt; 0.7) in eight subjects, moderate correlation (r &gt; 0.5) in three subjects and weak correlation (r &lt; 0.5) in one subject. Volume (mm3) with high BPND/high TBR accounted for 62±29% whereas high BPND/low TBR accounted for 13±16%. Within the peritumoral area, there was a small reduction in the proportion of subjects in the strong correlation group (6/12) but the pro- portion of voxels with higher TSPO binding and lower methionine uptake was substantially greater (35±16%).

CONCLUSIONS
Within high-grade glioma, there is a strong overall correlation between TSPO expression and amino acid uptake. However, in the peritumoural region there are areas of elevated TSPO expression without increased methionine uptake which could represent an inflammatory component or a discrete neoplastic cell population that may not be adequately defined with standard imaging biomarkers.
BRAIN TUMOUR GENETIC NETWORK SIGNATURES SUPERIORLY FORECAST SURVIVAL
Authors: Ruffle James , Mohinta Samia , Pombo Guilherme , Gray Robert , Kopanitsa Valeriya , Lee Faith , Brandner Sebastian , Hyare Harpreet , Nachev Parashkev 
Published: September 2023

Abstract

AIMS
Gliomas typically exhibit a spectrum of genetic mutations, reflecting multiple, potentially complex interactions across distinct molecular pathways. Predicting disease evolution and prescribing individually optimal treatment plausibly requires statistical models complex enough to capture the intricate genetic structure underpinning oncogenesis.

METHOD
Here we formalize this task as the discovery of distinct patterns of connectivity within network representations of the interactions between genetic loci. Evaluating multi-institutional clinical, genetic, and outcome data from 4023 consecutive patients over a 14-year period, we employ Bayesian stochastic block modelling to reveal a hierarchical network structure of tumour genetic interactions spanning glioblastoma, oligodendroglioma, and astrocytoma.

RESULTS
We show that this structure not only identifies diagnosis but predicts patient survival with greater fidelity than the latest WHO tumour classification or linear models of genetic features. For example, a diagnosis of IDH- wildtype glioblastoma yielded median survivals varying from 289 days in patients with the signature of marked EGFR amplification, MGMT methylation, and histone mutations, to 425 days in those with the signature of TERT mutations, histone, and EGFR wild-types, and variable MGMT methylation.

CONCLUSIONS
Our findings illuminate the complex dependence between features across the genetic landscape of brain tumours and show network analysis reveals distinct signatures of survival with better prognostic fidelity than current gold standard diagnostic categories, paving the way for personalised prognostication.
NHS BRAIN CANCER HEALTHCARE AND RESEARCH: DOES IT MATTER WHERE YOU ARE TREATED?
Authors: Huskens Nicky , Goetz Camille , Bushby Katie 
Published: September 2023

Abstract

AIMS
The Tessa Jowell Centre of Excellence designation initiative recognizes and awards neuro-oncology centres for excellence in patient treatment, care and research.

METHOD
Twenty-eight NHS centres were assessed through an extensive application form, virtual site visits and patient feedback. Applications were reviewed against a set of standards established through an iterative process in- volving expert specialists in brain cancer treatment and care.

RESULTS
Many pockets of excellence and innovations were found across the entire patient pathway. Centres demonstrated consistencies in service provision, common challenges threatening service development and sustainability, as well as areas of significant variations. Patients are most likely to experience variations in genetic testing of their tumour samples, access to clinical studies and the extensiveness of nurse and allied health professional- led care and support they receive. To date, 17 centres have been awarded Excellence status and all applicant centres have obtained support through the Tessa Jowell Academy to develop services and innovate.

CONCLUSIONS
Based on the findings, patients being treated for brain cancer in any UK centre will be able to obtain an effective standard of care, delivered by a motivated team. There are however areas of striking variation, with disparities in the design, quality and extent of the treatment and care pathway. Service development and addressing gaps in treatment and care will require a tailored approach at both a hospital and national level. In 2023/24, a new application round will open for all UK centres to re-apply to be assessed.
TRANSFORMING BRAIN CANCER TREATMENT, CARE AND RESEARCH: A CASE STUDY OF A SPECIALISED NATIONAL DIGITAL LEARNING AND NETWORKING PLATFORM FOR NHS HEALTH PROFESSIONALS
Authors: Huskens Nicky , Burton Olivia , Goetz Camille , Bushby Katie 
Published: September 2023

Abstract

AIMS
The aim of this case study is to highlight the outcomes of a specialized digital learning platform, the Tessa Jowell Academy, to share excellence and jointly tackle challenges in brain cancer treatment, research and care. The free platform is co-designed with the professional community to address unmet needs and offers members features such as virtual courses, a clinical trial finder and a peer-to-peer learning service.

METHOD
Performance data has been collected over the last 12 months from: online member surveys and platform data (workshop registrations, member registrations, member logins, resource downloads, video views, certificate downloads, feature requests, clinical trial updates and national network sign-ups).

RESULTS
The platform has over 800 member registrations from 29 NHS hospitals from a range of disciplines. There have been: 42 peers matched through the platform, 19 clinical trials added, 4 national networks set-up and 35 workshops delivered to 1200 attendees live and on-demand. Common themes from member feedback include increased learning and networking opportunities, increased specialist support, improved confidence in MDT participation and increased knowledge of other sub-specialties.

CONCLUSIONS
It is well evidenced that specialized knowledge sharing between centres can contribute to better outcomes, improved patient satisfaction and access to research for rare diseases. This case study highlights the national demand and potential benefits of a specialized, national digital learning platform for NHS professionals working in brain cancer. As the platform grows, the impact will continue to be measured on a national level.
PLASMA PROTEOMICS AND MACHINE LEARNING FOR NOVEL BIOMARKER DISCOVERY IN ADULT MALIGNANT GLIOMA
Authors: Pedersen Henriette , Elbæk Kirstine Juul , Vandborg Michael Wodstrup , Lim Yi Chieh , Azam Aleena , Pedersen Sarah Skovlunde Hornshøj , Skjøth-Rasmussen Jane , Schoof Erwin , Hamerlik Petra 
Published: September 2023

Abstract

AIMS
Plasma is a valuable source for identifying non-invasive biomarkers, and when combined with an examination of the highly dynamic proteome, it has the potential to lead to the identification of novel biomarkers in glioma. The aim of this study was to uncover plasma-based protein biomarkers for adult malignant glioma.

METHOD
Mass spectrometry-based proteomics with tandem mass tag (TMT) labelling of plasma from healthy individuals and adult malignant gliomas was performed. A differential abundance analysis was carried out to identify proteins that were deregulated in primary gliomas compared to healthy individuals. Machine learning was employed to identify a diagnostic biomarker panel.

RESULTS
When comparing plasma from healthy individuals to that of primary gliomas, several high and low abundant proteins were found to be deregulated. To improve the accuracy and ability of biomarkers to detect malignant gliomas, machine learning was employed and led to a development of a classifier, which performed with high accuracy, specificity, and sensitivity.

CONCLUSIONS
The discovery of a plasma-based protein classifier, once validated, may facilitate an earlier diagnosis of glioma patients, and thereby reduce time-to-treatment.
PCV VS. LOMUSTINE FOR PATIENTS WITH RECURRENT GLIOBLASTOMA
Authors: Fofanah Isata , Pigott Thomas , Mansell Julie , Flatley Michael , Hatfield Paul , Bhaumik Suchandana , Short Susan , Murray Louise 
Published: September 2023

Abstract

AIMS
Almost all patients with glioblastoma relapse after initial treatment. At relapse, chemotherapy using multi-agent PCV (Procarbazine, Lomustine and Vincristine) or single agent Lomustine is often employed. Lomustine is an oral agent, and therefore spares patients from additional hospital visits for intravenous vincristine and removes the need for dietary restrictions while taking procarbazine, and so would be an attractive option, especially if there was no difference in survival compared to PCV. There are currently no data regarding whether PCV or Lomustine is superior. This project examines survival in patients treated with PCV or Lomustine for recurrent glioblastoma.

METHOD
A retrospective study was performed including patients treated at Leeds Cancer Centre between January 2015 and December 2019. Patients had a histological diagnosis of glioblastoma and received (chemo)radiotherapy at initial presentation. PCV or Lomustine was used at recurrence. Factors predictive of overall survival (OS) were investigated.

RESULTS
116 patients were included (66 received PCV, 50 received Lomustine). Performance status (PS) was 0, 1 and 2/3 in 22, 59 and 35, respectively. Median OS from first PCV or lomustine was 5.7 months (95% confidence interval: 5.1-6.3). The median number of cycles was 2 for both PCV and Lomustine with 115/116 (99%) discontinuing treatment due to disease progression. On univariate analysis, PS and type of chemotherapy were statistically significant. On multivariate analysis, only PS remained significant.

CONCLUSIONS
After adjusting for PS, there was no statistically significant difference in OS for patients treated with PCV or Lomustine. This finding has treatment implications and requires validation in a larger cohort.
RADIOGENOMICS FOR IMMUNOTHERAPY IN GLIOBLASTOMA
Authors: Ghimire Prajwal , Karami Golestan , Modat Marc , Booth Thomas 
Published: September 2023

Abstract

AIMS
Immunotherapy is an effective precision medicine treatment for several cancers. Obtaining imaging signatures of the underlying genome (radiogenomics) in glioblastoma patients, has the potential to identify immune biomarkers pre-operatively and allow personalized neo-adjuvant treatment. The increased use of whole genome sequencing data, and the developments in bioinformatics and machine learning provide the opportunity for such developments. Therefore, we performed a systematic review of radiogenomic biomarkers for immunotherapy in glioblastoma to identify current and potential targets for immunotherapy.

METHOD
A systematic review was performed following PRISMA guidelines on the databases of PubMed, Medline and Embase. QUADAS 2 questionnaire was utilized for quality assessment. Qualitative analysis was performed. Insuffcient data prevented meta-analysis. PROSPERO: CRD42022340968

RESULTS
Five articles were included, and all articles were retrospective studies. Biomarkers identified from MRI im- ages included apparent diffusion coeffcient (ADC) values, relative cerebral blood flow (rCBV) values and radiomic features that correlated with genomic markers from tumour cells and immune cells (tumour associated macrophages (TAMs), T cells and antigen presenting cells. Risk of Bias and applicability concerns were raised by QUADAS quality assessment.

CONCLUSIONS
Radiogenomic immune biomarkers are likely to provide early treatment options to patients with glioblastoma and will help improve quality of life of patients. There is a paucity of prospective studies identifying these diagnostic biomarkers, and interpretation is limited due to high risk of bias and poor generalisability . Targeted immunotherapy based on these biomarkers has the potential to allow individualised neo-adjuvant precision treatment options in clinical trials, plausibly leading to enhanced overall survival of these patients.
CLIC1 ION CHANNELS AS BIOELECTRIC TARGETS FOR TTFIELDS IN PAEDIATRIC HIGH-GRADE GLIOMA
Authors: Griffn Michaela , Smith Paul , Khan Raheela , Smith Stuart 
Published: September 2023

Abstract

AIMS
Develop and validate a comprehensive understanding of CLIC1 and its prognostic significance, coupled with a functional analysis in pHGG cells.
To develop electrical and pharmacological methods of manipulating CLIC1 for combination with TTFields

METHOD
Chloride Intracellular Channel (CLIC) channel expression patterns were identified via RNA sequencing of in- house patient tissues. siRNA depletion of CLIC1 and CLIC4 was assessed using functional assays, alone and in combination with TTFields and or CLIC inhibitor. Whole transcriptome gene expression analysis (Human Clairom™ Array) of pGBM cells treated with TTFields was carried out. Whole cell and cell attached patch clamp protocols were used to assess ion channel activity in pHGG.

RESULTS
CLIC1 deficiency was associated with increased overall survival(p=&lt;0.003). siRNA depletion propagates a re- duction in the proliferation, migration and invasion of pHGG cells, associated with cell cycle arrest. CLIC1 deficiency exacerbated the effect of TTFields, reducing clonogenic and proliferative capabilities. Combination of metformin and TTFields increased the sensitivity of cells to TTFields. Whole transcriptome gene expression analysis found that cells treated with TTFields exhibited a down-regulation in CLIC1 compared to untreated cells, with tolerance to long-term TTFields treatment being associated with recovery of CLIC1 expression.

CONCLUSIONS
These data provide rationale that genetic, electrical, and pharmacological manipulation of CLIC1 can reduce the capacity of childhood brain tumours to proliferate and invade. TTFields treatment results in a dysregulation of CLIC channel expression and function, and combination with CLIC inhibitions demonstrates a synergistic effect. CLIC channels may be a suitable target for combination therapy to enhance the treatment effcacy of TTFields.
GRAPHENE NANOMATERIAL REPROGRAMMING OF IMMUNE CELLS TO UNLOCK THE EffCACY OF IMMUNOTHERAPY IN GLIOBLASTOMA
Authors: Kisby Thomas , Stylianou Maria , Kostarelos Kostas 
Published: September 2023

Abstract

AIMS
Immunotherapy has substantiated its promise and achieved striking clinical effcacy in at least a subset of patients in several cancer types. However, in patients with glioblastoma multiforme (GBM), immunotherapies have lacked effcacy as a consequence of the highly immunosuppressive “cold” tumour microenvironment. Small, thin graphene oxide (GO) nanosheets possess notable pharmacokinetic properties in GBM including deep translocation throughout the whole tumour volume and selective internalization by tumour associated macrophages and microglia (TAMMs) following local administration. The current study aimed to investigate whether this selective nanomaterial-TAMM interaction could be exploited to reprogram the immune- microenvironment of GBM.

METHOD
GO nanosheets were non-covalently complexed with a TLR7/8 agonist to form a stable immunomodulatory nanosystem (imodGO) which was tested in primary macrophages in vitro, and an orthotopic syngeneic GBM model in vivo.

RESULTS
ImodGO enhanced the polarization of macrophages toward a pro-inflammatory M1-like phenotype in vitro without disrupting their phagocytic or cytokine producing capacity. A single intratumoral administration of the same nanocomplex in an intracranial GL261 model was also effective in increasing M1-like TAMMs (CD86+, MHCII+, TNFα+) while decreasing immunosuppressive M2-like TAMMs (Ym1+, Arg1+) which resulted in a wider reprogramming of the brain tumour immune-microenvironment. Repeat imodGO administration was able to significantly inhibit tumour progression highlighting the therapeutic potential of this nanomaterial enabled immunomodulatory strategy.

CONCLUSIONS
Based on these results, imodGO has emerged as a novel strategy to ameliorate the immunosuppressive char- acter of GBM. Further work is warranted to assess whether imodGO could enhance the effcacy of systemic immunotherapies used in combination.
REVIEW OF THE INTRODUCTION OF WHOLE GENOME SEQUENCING AS NHS STANDARD OF CARE FOR BRAIN TUMOUR PATIENTS AT QUEEN ELIZABETH HOSPITAL BIRMINGHAM, UK
Authors: Wykes Victoria , Hyatt Meena , Goel Aimee , Parikh Shefali , Berki Fred , Cole Naomi , Freeth Sarah , Garratt William , Goddard claire , Pohl Ute , Nagaraju Santosh , Chowdhury Yasir , O’Hallaran Phillip , Petrik Vladimir , Ughratdar Ismail , Zisakis Athanasios , Benghiat Helen , Meade Sara , Sanghera Paul , Glover Kate , Hughes Lowri , Vafadar Natasha , Wallis Yvonne , Raghavan Manoj , Watts Colin 
Published: September 2023

Abstract

AIMS
Describe delays in the NHS pathway from initial consent for whole genome sequencing (WGS) to delivery of the final WGS report (WGS-R) to the treating oncologist.
Review number of patients with mutations that inform, diagnosis, prognosis or treatment.

METHOD
Prospective audit of time to key stages along WGS pathway and review of final WGS-R.

RESULTS
WGS pathway and process:
Data snapshot at 24/02/2023 showed 96 patients consented for WGS: 12/96 awaiting surgery; 41/96 awaiting GTAB discussion; 1/96 WGS sample used for histopathological diagnosis, 1/96 ineligible.
41/96 WGS results discussed at a GTAB meeting; 39/44 with complete WGS-R sent to the treating oncologist, including discussion at the local neuro-oncology multi-disciplinary team meeting.
Median time from consent to final WGS-R was 225 days (range 145-567).
WGS results:
4 patients with glioblastoma (GBM) have RB1 variant, associated with improved progression-free and overall survival (Dono et al 2021).
10 patients had clinically actionable mutations with recommended trials or compassionate-use drugs. 1/10 patient with GBM and High Tumour Mutational Burden who completed standard of care (SOC) treatment has commenced anti-PD1 immunotherapy (Nivolumab; Goodman et al 2017). 5/10 patients are currently on SOC treatment, 3/10 had deteriorated and 1/10 were deceased at time of WGS-R.
Excellent concordance of WGS data with SOC genetic/immunohistochemistry testing.
No germline mutations identified.

CONCLUSIONS
Nearly a third of patients had genetic variants that may have the potential to inform future clinical management. Further investment in the WGS pathway is required to deliver timely results to allow application of precision medicine for brain cancer patients.
ADENOSINE TO INOSINE RNA EDITING ASSOCIATED TUMOUR MICROENVIRONMENT AS A THERAPEUTIC TARGET IN GLIOBLASTOMA
Authors: Chen Sean Chun-Chang 
Published: September 2023

Abstract

AIMS
Glioblastoma (GBM) remains incurable because of the high level of intratumor heterogeneity and the poor understanding of its complex genetics. We recently identified adenosine to inosine (A-to-I) RNA editing as a sex- specific prognostic factor in GBM. However, the underlying mechanism remains unclear. We sought to identify RNA editing-associated molecular effectors and assess their prognosis potential.

METHOD
We analyzed RNA-Seq data of 196 primary IDH wild-type GBMs from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) cohorts. Genome-wide A-to-I RNA editing events were characterized and GBM tumours were split into two subtypes based on RNA editing signatures (high- and low-editing). Differential expression and tumour microenvironment analyses between the two subtypes were performed to identify molecular effectors. Survival impact of these effectors was determined using Cox proportional hazards model.

RESULTS
Genes more highly expressed in the high-editing subtype were enriched in immune-related pathways, while those more highly expressed in the low-editing subtype were enriched in cell proliferation and stemness path- ways. Consistent with differential expression analysis, high-editing GBMs exhibited higher infiltration levels of macrophages, monocytes and dendritic cells. Intriguingly, increased cell proliferation and elevated infiltration of dendritic cells were associated with poorer survival in men only, whereas enhanced CSF1 (colony stimulating factor 1) response and elevated infiltration of monocytes and Th1 cells conferred poorer survival outcomes in women only.

CONCLUSIONS
Our study suggests sex-specific impact of A-to-I RNA editing in the pathogenesis of glioblastoma, highlighting the importance of developing sex-specific treatments and opening a new avenue for the design of novel therapeutic targets.
MICROLENS - A DESIGN-CENTRED APPROACH TO AI IN HEALTHCARE
Authors: Pakzad-Shahabi Lillie , Mauricaite Radvile , PPI ICL_ICHT Neuro-oncology , Williams Matthew 
Published: September 2023

Abstract

AIMS
MicroLens aims to co-develop tools and functions that enable patients & caregivers to view and understand their own images.

METHOD
We used an explicit design-led approach, foregrounding user needs. Over 7 months we used a series of 4 meetings, written reports and online questionnaires capturing the views of 20 staff, patient and caregiver participants (55% patients & caregivers; primary & metastatic brain tumours) to explore feasibility and requirements for an AI-enhanced online medical image viewing tool.

RESULTS
There were two distinct patterns of preferred usage: smartphone-based “snapshot” approach vs. online plat- form with detailed review of all images. Participants wanted to use it as a “scan photo album” and said help in understanding the scans would be useful, but the desired level of technical performance was relatively low: patients and caregivers would mostly be happy with labelling of common simple structures and sides, rather than detailed annotation. Further benefits and concerns raised were ability to
• share with family members who could not attend hospital appointments.
• review their scans outside of an appointment.
• better understand images.
• Use tools to assist in the interpretation reducing staff workload
• image-share causing more work for staff

CONCLUSIONS
Patients, caregivers and staff all expressed a clear view that an AI-enhanced online tool to allow patients to view and understand their images would be useful. However, there were significantly different use cases between different patients, and the level of functionality that patients & caregivers expressed a need for was substantially simpler than that originally envisaged. We are currently implementing a prototype.