bluuebunny/crossref_metadata_2025_split huggingface dataset:
Seizure Semiology Over Time in Adult Diffuse Glioma
Authors: Carstairs Claire , Pandey Anmol , Moulder Zachary , Kosela Monika , Rees Jeremy 
Published: October 2022

Abstract

AIMS
Patients with gliomas often present with generalised seizures, but subsequently develop focal seizures on treatment. The occurrence of a single generalised seizure at onset precludes the return of a driving licence, even if a patient continues to have only focal aware seizures. We investigated seizure semiology over time, to determine how many patients with ongoing seizures may be safe to drive.

METHOD
We analysed clinical data of patients with histologically-confirmed IDH-mutant diffuse gliomas, diagnosed between 2004-2015. Seizures were classified as: 1 – focal / 2 - generalised; A – aware / B – unaware; M – motor / N – non-motor. Seizure type at diagnosis and last follow-up was recorded.

RESULTS
189 patients were identified, of whom 140 presented with seizures (74%). 115 of these patients had a full data set. 59 (51%) presented with generalised seizures. 10% had only a single seizure at presentation, 55 % had further seizures then became seizure-free and 35% continued to have seizures at last follow-up. Of the 40 patients who continued to have seizures, 7 (17.5%) had 1AN, 16 (40%) had 1AM, 1 (2.5%) had 1BN and 5 (12.5%) had 1BM. 11 (27.5%) had generalised seizures. Of the 7 patients with 1AN seizures at last follow-up, 4 initially presented with a generalised seizure, 1 with 1AN, 1 with 1AM and 1 with 1BM.

CONCLUSION
Almost two thirds of patients became seizure-free and, of those that continued to have seizures, 57.5% developed only focal aware seizures. Current driving regulations may be unduly restrictive for patients with gliomas.
The Identification and Validation of Plasma Membrane Proteins as Potential Therapeutic Targets for Histone H3 Mutant Paediatric High-Grade Gliomas
Authors: Snary Anya , Haque Farhana , Pickering James , Rahman Ruman , Grundy Richard , Layfield Robert 
Published: October 2022

Abstract

AIMS
Paediatric high-grade gliomas (pHGG) are the leading cause of cancer-related death in children. Histone H3.3 mutations are an important hallmark of pHGG, but for which their underlying oncogenic mechanisms are incompletely understood. This research aims to identify potential molecular effectors in these tumours that may be therapeutically effective.

METHOD
To assess potential molecular effectors, we employed proteomic profiling using LC-MS/MS and determined plasma membrane proteins of the surfactome that are differentially expressed on the surface of H3.3 mutant (G34R, G34V), compared to H3.3-wildtype human glioma cells in culture.

RESULTS
Profiling of plasma membrane-enriched fractions identified 34 membrane proteins exclusively detected from H3 G34V mutant cells compared to H3 wild-type cells, and 10 membrane proteins exclusively detected from H3 G34R mutant cells, with 39 membrane proteins shared between both H3 G34R/V genotypes. One of these shared membrane proteins, GLUT1 (glucose transporter) has very recently been reported to be over-expressed and linked to tumour phenotypes in mouse glioma cells manipulated to carry the most common DIPG-associated H3.3-K27M mutation [Miya et al. Neuro-Oncology Advances 2021]. Here, we explore the functional significance of GLUT1 differential expression in H3.3 mutant (G34R, G34V) human glioma cells.
Glioma Espionage From Longitudinal CSF Proteomics
Authors: Riviere-Cazaux Cecile , Burns Terry 
Published: October 2022

Abstract

AIMS
Rapid, detailed feedback is needed to understand the individualized biological impacts of novel glioma therapies. We are performing glioma biomarker discovery by serial cerebrospinal fluid (CSF) sampling from Ommaya reservoirs to determine how the CSF proteome can reveal early longitudinal intelligence regarding glioma status, biology, and therapeutic response.

METHOD
Global proteomic analysis of CSF was performed on the Somalogic platform – an aptamer-based technology for highly sensitive and specific analysis of over 7,000 proteins. Discovery analysis comprised of the top-500 ranked proteins in CSF from seven patients with high-grade gliomas (HGG) versus non-glioma controls. The top-500 HGG proteins were then preliminarily filtered to include only proteins that met two additional criteria of decrease with resection and increase with recurrence in individual paired patient samples.

RESULTS
Proteomic enrichment analysis revealed a conserved HGG CSF proteomic signature defined by 79 proteins, including ones known to be over-expressed in solid tumor malignancies, such as retinoblastoma binding protein 4, heat shock protein 90, and sorcin. The HGG proteomic signature was consistently enriched in an independent validation cohort consisting of 13 gliomas diverse in primary versus recurrent status, subtype, and grade, when compared to control CSF samples. Encouragingly, proteins in the HGG signature decreased in the two patients for whom CSF was collected prior to and after resection (both at POD16 and POD18) with decreased tumor burden.

CONCLUSION
Our data demonstrate the ability to gain detailed, individualized insights regarding glioma biology, tumor burden, and evolution through global CSF proteomics acquired from longitudinal access to gliomas via Ommaya reservoirs.
Newly Diagnosed Brain Tumours: When Is a Staging CT Required?
Authors: El-Sayed Ali Ahmad Mahmoud , Doherty John Anthony , Konteas Anastasios Benjamin , Varasteh Amir Ali , Iqbal Noorulain , Vupputuri Hemanth , Brodbelt Andrew 
Published: October 2022

Abstract

AIMS
Newly diagnosed brain lesions (NBL) on imaging can be either primary or secondary in nature. Of these, only secondary brain lesions routinely require a staging CT chest, abdomen, and pelvis (CTCAP). But owing to lack of clear guidelines, all NBLs usually receive a staging investigation. This leads to over investigation of primary brain tumors. We sought to identify predictors of secondary brain lesions using CT head alone to guide the selection of patients for a CTCAP.

METHOD
Patients with NBLs referred to a tertiary Neurosurgical centre were reviewed. For protocol creation, data was collected from patients referred between July to December 2020, potential predictor variables were identified. Potential candidate protocols identified were assessed in a protocol-testing stage using data from a different set of patients. Sensitivity, specificity, and area under the curve (AUC) values were computed for each protocol.

RESULTS
The protocol-creation stage included 222 patients. Multivariate logistic regression analysis identified candidate protocols. This identified the most sensitive predictors of metastatic disease as : a previous history of cancer, multiple lesions, lesion size &lt;4cm, and infratentorial location. A final protocol identified was found to have a sensitivity of 99.1% (AUC 0.704).

CONCLUSION
The use of the above protocol derived from this study would reduce unnecessary CTCAPs by 37.5-40% overall. Patients who do not fulfil at least one of the above said criteria on the first assessment should not have a CTCAP initially. This protocol reduces the financial and time costs from unnecessary CTCAPs as well as reduces patient exposure to radiation and contrast.
Patient and Service User Representation in Language Assessments on an Awake Craniotomy Pathway
Authors: Smith Georgette , Ughratdar Ismail , Wykes Victoria , Dawson Camilla 
Published: October 2022

Abstract

AIMS
Awake craniotomy (AC) with language mapping facilitates maximal safe intracranial tumour resection whilst preserving neurological function [1], and is associated with increased postoperative patient satisfaction and quality of life [2, 3]. We examine patients’ preoperative language assessment scores, alongside cultural and sociodemographic information to consider the impact on surgical planning and patient outcomes.

METHOD
A service evaluation of assessment tools was undertaken using clinical note audit and clinician reflections. Retrospective data collection from 48 patients assessed for AC with language mapping included language assessment scores, cultural and sociodemographic data, and surgical plan for awake or asleep tumour resection.

RESULTS
Analysis suggests language assessment scores may be influenced by a range of patient factors outside of the lesion location and its associated language deficits, including native language, age, ethnicity and religion.

CONCLUSION
Assessment scores influence a patient’s suitability for AC with language mapping and subsequent morbidity and mortality outcomes. Culture and sociodemographic background are integral to daily language use, and can therefore be expected to influence scores on language assessment tasks. This evaluation highlights the necessity for diversity of language use to be reflected in assessment tools used within an AC pathway.
REFERENCES
1. Hervey-Jumper, S.L. and M.S. Berger, Maximizing safe resection of low- and high-grade glioma. JNO, 2016.
2. Wahab, S.S., P.L. Grundy, and C. Weidmann, Patient experience and satisfaction with awake craniotomy for brain tumours. BJNS, 2011.
3. Coello, A.F., et al., Selection of intraoperative tasks for awake mapping based on relationships between tumor location and functional networks: A review. JNS, 2013.
Working Together to Accelerate the Preclinical to Clinical Translation of Drug Delivery Systems for Children’s Brain Tumours
Authors: Campbell Emma , Aquilina Kristian , Dandapani Madhumita , Walker David , Rahman Ruman 
Published: October 2022

Abstract

AIMS
Several techniques, such as intra-cerebrospinal fluid chemotherapy, ultrasound-mediated blood-brain barrier disruption, convection enhanced delivery, polymer delivery systems, electric field therapy, and intra-arterial and intra-nasal chemotherapy, have the potential to transform the treatment of brain tumours in children. However, there have been very few clinical trials to evaluate these. We aim to address challenges in the pre-clinical to clinical research pathway for CNS drug delivery systems in order to increase the number of clinical trials in this area.

METHOD
In 2021, the CBTDDC (Children’s Brain Tumour Drug Delivery Consortium) and the ITCC (Innovative Therapies for Children with Cancer) brain tumour group established a Clinical Trials Working Group comprising international researchers and clinicians to address this issue.

RESULTS
This partnership highlighted the main challenges as: (1) a lack of specific funding for prototype development and/or scale-up for clinical trials; (2) difficulties in navigating the regulatory landscape; (3) lack of accurate preclinical models; and (4) increased need for multi-centric working. In response to this, we ran a workshop on ‘Clinical Trial Readiness’, attended by around 50 delegates (comprising clinicians, researchers, trial regulatory experts, policy makers, and representatives from funding organisations, brain tumour charities and industry).

CONCLUSION
We have now established speciality-specific working groups with the aim of producing recommendations around the use of preclinical models and drug delivery techniques according to brain tumour type. We have also created a ‘Roadmap’ document for preclinical to clinical translation, which will be freely shared with the neuro-oncology research community.
Surgery on a Primary Cranial Vault Lymphoma
Authors: de la Fuente Pablo , Rajwani Kapil , Sistiaga Iñigo , Lavrador Jose Pedro 
Published: October 2022

Abstract

AIMS
Unique cranial involvement in Lymphomas is extraordinary and when it occurs, it is usually accompanied by systemic involvement. The role of the surgery in these cases is still unclear.

METHOD
Case report of a 72-year-old female with a primary cranial vault lymphoma with primary surgical management at time of recurrence.

RESULTS
72-year-old female, with a background of treated breast cancer and ischemic heart, presented with a right parieto-occipital lytic bone lesion with a soft tissue mass with a diagnosis of Non-Hodgkin’s Lymphoma Type B, compatible with follicular lymphoma, with no other symptoms Systemic involvement was ruled out in PET CT bone marrow biopsy. First-line chemotherapy was precluded due to the cardiotoxicity, and she was started on Rituximab-Bendamustine and radiotherapy. PET-CT one year later shows local progression with lytic destruction. The MRI showed an imprint on the brain and a lesion in intimate contact with the superior longitudinal sinus. As an apparently localized lesion and the patient could not receive the optimal chemotherapy treatment, a craniectomy was proposed. Fifteen months after surgery the patient is free of disease on PET CT.

CONCLUSION
Primary cranial lymphoma is an unusual entity which precludes clear algorithms. The primary treatment is the chemotherapy, nonetheless, If the patient cannot receive the optimal treatment due to his background or in the presence of recurrent disease with limited treatment options, surgery should be considered if technically plausible and adequate to patient’s performance status.
Targeting Replication Stress for Glioma Stem Cell Specific Cytotoxicity
Authors: Clough Emily , Strathdee Karen , Carruthers Ross 
Published: October 2022

Abstract

AIMS
Glioma stem cells (GSC) show high levels of DNA replication stress and exhibit abnormal S phase in comparison to differentiated, non GSC tumour cells. We investigated the DNA replication phenotypes of GSC and mechanism of GSC specific cytotoxicity following DNA replication stress response inhibition with combined ATR/PARP inhibition (CAiPi).

METHOD
Paired GSC enriched (‘GSC’) and GSC deplete differentiated (‘bulk’) populations were cultured from resected GBM specimens and maintained in neurobasal media with growth factors or serum containing media respectively. Cell viability, neurosphere and clonogenic assays were used to assess cytotoxicity whilst DNA replication was interrogated utilising immunofluorescent repair foci, flow cytometry and DNA fibre assay. CAiPi consisted of VE821 (ATRi) with Olaparib (PARPi).

RESULTS
GSC show reduced DNA replication rates and alterations in cell cycle profile and demonstrate extreme sensitivity to CAiPi. CAiPi resulted in significantly elevated levels of 53BP1 nuclear bodies in GSC indicating genomic under- replication, however did not preferentially reduce fork speed compared to non-GSC. Analysis of replication fork structures revealed an increase in new origin firing in GSC dependent upon PARP trapping. GSC cytotoxicity was reduced by roscovitine induced inhibition of origin firing, suggesting an important role of dysregulated origin firing in CAiPi response. CAiPi is also potently radiosensitising by clonogenic assay.

CONCLUSION
Taken together these data suggest that GSC are vulnerable to dysregulation of origin firing which results in under-replication of their genome and reliance upon G1 cell cycle resolution of DNA damage. We propose that CAiPi is an attractive therapeutic strategy for translation to the clinic.
Improving the Odds - Long Term Survivors of Glioblastoma Multiforme (GBM)
Authors: Akbar Palwasha Khan , Lord Hannah 
Published: October 2022

Abstract

AIMS
To review the data of patients in NHS Tayside who survived &gt;24 months from a diagnosis of GBM, identifying trends in: (i) fixed demographic features; (ii) genetic mutations; (iii) treatment pathways.

METHOD
A retrospective case note review of patients with a new diagnosis of GBM 2015-2020, identifying those with &gt;2 year survival. Data analysed: demographics (gender, age), mutations (IDH1, MGMT), and treatment (surgical, chemotherapy/radiotherapy).

RESULTS
84 patients identified. 18 survived &gt;24 months (2 year survival rate of 21.4%). Median survival = 31 months (range 24-110 months); 18 patients: M:F ratio = 1.6:1; Median age at diagnosis 54.5 (range 34-72 years); 13 methylated MGMT, 2 unmethylated (3 unknown); 2 mutated IDH1, 10 wildtype (6 unknown); 16 maximum surgical resection; 17 chemoradiation and adjuvant chemotherapy; 17 received radiation dose of 60Gy in 30#, 1 received 40Gy in 15#; 11 had disease progression requiring further treatment; 5 had no progression, 2 progressed but did not have further treatment.

CONCLUSION
In Stupp data a 2 year survival of 26.5% was reached. In our real world cohort, a 2 year survival of 21.4% is satisfactory. MGMT methylation was common, but not exclusively the case. Only 2 were IDH1 mutated, possibly reflecting the frequency of occurrence in the GBM population, but demonstrating that it is not a prerequisite for improved survival. Younger age, and maximal surgical resection followed by chemoradiation and adjuvant chemotherapy are associated with improved prognosis. Recognising our dataset is small, we recommend further studies using a larger cohort to improve understanding of better outcomes in this patient group.
The Impact of Molecular Analysis on Patient Waiting Time: A Neurosurgical Audit
Authors: Maducolil Jeremy Easow , Mustafa Mohammad Arish , Hayes Wallis , Williams Amanda , Pal Piyali , Rathi Nitika , Brodbelt Andrew 
Published: October 2022

Abstract

AIMS
The 2021 WHO classification includes molecular characterizations to a much greater degree. Molecular markers play an important role in deciding treatment choice and predicting prognosis. Molecular markers are often performed in separate laboratories. This has led to concerns about the amount of time taken to get further molecular markers and the delay in diagnosis. Therefore our aim was to determine the waiting time for molecular markers to be returned from the lab following surgery.

METHOD
We retrospectively collected data for patients who had molecular analysis conducted in 2020 for gliomas at The Walton Centre, Liverpool. Descriptive statistics were conducted using SPSS V27.0.

RESULTS
182 patients were included. 130 patients waited &lt;4 weeks, 46 patients &gt;4 weeks, and 6 patients &gt;8 weeks for molecular marker results. The median waiting time was 21 days (range: 11-219, IQR: 17.00-31.00). For patients who waited &gt;4 weeks and &gt;8 weeks, there were 7 WHO Grade I, 7 Grade II, 2 Grade III, and 26 Grade IV tumours. The median time taken between surgery and treatment to begin was 15 working days (range: 7-86, IQR: 12.00- 25.00). M-array took the longest time to return with a median of 63.5 days (range: 48-93, IQR: 60.00-80.00). Following which was NGS results which took a median of 32 days (range: 21-219, IQR: 27.00-40.00)

CONCLUSION
Most patients received their results in less than 4 weeks, however nearly a third had a waiting time of greater than 4 weeks. Reasons for delays need to be explored further to allow for quicker intervention from the MDT.
COVID-19 Pandemic Neuro-Oncology Consultation Settings: Ensuring Services Address Patient Preferences
Authors: Galante Joao , Ben-Joseph Aaron , Forner Samantha , Kennaird Elaine , Durve Meeta , Glendenning Jennifer 
Published: October 2022

Abstract

Aims
The Covid-19 pandemic expanded the use of virtual consultations (telephone (T) or video (V)). Moving forward, Neuro-Oncology consultation settings require tailoring to optimally meet patient needs. This project aimed to evaluate patient perceptions of consultation settings to optimise service planning and ongoing incorporation of T and V options for patients with high grade brain tumours.

METHOD
From February 2022, patient perceptions on consultation settings were prospectively sought on follow-up/on- treatment appointments in Kent Oncology Centre. The peer-reviewed anonymised survey explored rationale for consultation setting, travelling (time, distance and arrangements) , satisfaction with appointment parameters (amount/ clarity of information, patient perception of support, assessment of symptoms and ability to ask questions) and setting preferences moving forward.

RESULTS
The majority of consultations were F2F, 1/3 had teleconsultations. 2/5 of patients were given a choice of consultation setting. Reason for teleconsultation included geographical distance, longer journey time, consultant decision, disability, work and active Covid-19 infection. All settings recorded good levels of satisfaction, however the majority (&gt;2/3) would recommend F2F appointments to others for scan results, pre-chemotherapy/on-radiotherapy checks, specialist nurse reviews and end of treatment reviews.

CONCLUSION
Despite reassuring levels of satisfaction for both F2F and non-F2F appointments, F2F setting remains preferred regardless of the aim of the consultation. For a selected number of patients, teleconsultation has advantages due to geographical constraints, however the option of F2F consultations remains important and patients should be involved in these decisions.
10-Year Institutional Retrospective Case Series of WHO Grade II Gliomas and Correlation of Incidence of Seizures, Isocitrate Dehydrogenase No. 1 (IDH-1) Mutation and Lobar Location (2010-2020)
Authors: Lammy Simon , Bridgman Elsie , Johnson Hannah , Taylor Aaron , Grivas Athanasios 
Published: October 2022

Abstract

AIMS OBJECTIVES
To assess the correlation in World Health Organisation (WHO) Grade II gliomas of IDH-1 mutation, lobar location and seizures

DESIGN
10-year retrospective case series

SUBJECTS
Histopathological WHO Grade II gliomas

METHODS
We searched case notes in NHS Greater Glasgow & Clyde and Scottish National PACS.

RESULTS
84 patients underwent tissue diagnosis. Mean age 42rs (range: 21-77yrs]). Seizures (NB: pre-2017 International League against Epilepsy classification [ILAE]) occurred in 71% (52% generalised, 37% partial and 11% mixed). 31% had ongoing seizures postoperatively. 38% had headache (50% had headache and seizures). 21% had a focal neurological deficit (FND) (61% had a FND and seizure). Seizure, as an isolated pre-operative symptom occurred in 48% patients compared to isolated headache in 10% and isolated FND in 4%. Overall, 58% of lesions and 60% of seizures were frontal. Histologically, 60% were astrocytomas and 40% oligodendrogliomas (49% of astrocytomas and 71% of oligodendrogliomas arose from the frontal lobe). IDH-1 mutation occurred in 80% (75% had seizures) and 66% were frontal.

CONCLUSION
This confirms a correlation between IDH-1, incidence of seizures and frontal lesions (p = &lt;0.05)
REFERENCES
Zhong et al. IDH1/2 Mutation is Associated with Seizure as an Initial Symptom in Low-Grade Glioma. Epilepsy Res. 2015 109:100-105
An Audit of Serial Stereotactic Biopsies at the WCFT Between 2018-2021
Authors: Gilder Connor , Pal Piyali 
Published: October 2022

Abstract

AIMS
(1) To assess how often serial stereotactic brain biopsies of gliomas perform at Walton Centre between 20018 and 2021 allow clinically requisite molecular results, within the expected turnaround times. (2)Assess reasons for delay or not obtaining molecular results.

METHOD
All data obtained from LIMS (TDHC) and electronic patient records (eP2) at the Walton Centre Foundation Trust, and analysed in MS Excel. High grade glioma cases explored in detail.

RESULTS
Of 61 cases included, 45 were gliomas. 37 (61%) were HGGs i.e. GBMs or AAs. All requested molecular data could be obtained on 74% GBMs and 40% of AAs. One Oligodendroglioma remained ungraded. All the 4 DMGs could be issued final histological diagnosis based on immunohistochemistry and required no extra molecular tests. All requested molecular data could be obtained in 71% of LGG cases. MGMT results were obtained in 89% of GBM cases. NGS results were obtained in 57% of GBM cases. The average turnaround time from date of biopsy to authorised report 13 – 97 days, with a mean of 26 days.

CONCLUSION
(1) The majority of GBM cases yielded all requested molecular results. (2) Sample size was a limiting factor in obtaining molecular results. (3) Turnaround times have been compounded by failed molecular tests, ultimately affecting patient waiting times in HGGs. (4) Histological grading by mitotic index is not possible on small biopsy fragments. (5) If viable tumour cells are present, immunohistochemical molecular markers have proved valuable.