tbuckley/cabot-search huggingface dataset:
ROR1 MRNA EXPRESSION IN GLIOMA - A NOVEL PROGNOSTIC BIOMARKER
Authors: Dr Daniel Madani, Dr Laveniya Satgunaseelan, Ms Jessica El-Hayek, Prof Brindha Shivalingam, Prof Caroline Ford
Journal: Neuro-Oncology (2024)

Abstract AIMS Glioblastoma is the most common and aggressive primary brain tumour in adults. Despite maximal surgical resection followed by concomitant chemo-/radiotherapy, the three-year survival remains less than 5%. Receptor tyrosine kinase-like orphan receptor 1 (ROR1) overexpression is associated with poor prognosis in several cancers. ROR1 therapeutics are in Phase I/II clinical trials making it an exciting novel target with translational potential to explore for glioblastoma treatment. The aim of this study was to examine the association between ROR1 mRNA expression and overall survival (OS), by applying the WHO 2021 classiﬁcation of transcriptomic glioma datasets. METHOD Clinical, histological, and molecular data were extracted from four independent glioma datasets (TCGA, CGGA, Rembrandt, and Gravendeel) via the GlioVis portal and analysed using the WHO 2021 classiﬁcation. Only conﬁrmed cases of astrocytoma, oligodendroglioma, or glioblastoma, and ROR1 mRNA expression data were included (2,216 cases). Kaplan-Meier survival curves were produced for OS with low/high grade glioma versus ROR1 mRNA expression. Log-rank (Mantel-Cox) multivariate regression was applied to analyse the effect of selected covariates on OS and ROR1 mRNA expression. RESULTS We observed a signiﬁcant decrease in median OS in patients with high-ROR1 mRNA expression when compared to the low-ROR1 mRNA expression cohort (20 and 70 months, respectively). High-grade gliomas represented the highest ROR1 mRNA expression across the consortium, resulting in a poor median OS of 16 months. CONCLUSION This study represents the ﬁrst report of an association between OS and the oncogenic role of ROR1 in glioma, a targetable cell surface marker for novel putative treatment in glioblastoma.
UNDERSTANDING THE MANAGEMENT OF MALIGNANT GLIOMAS DURING COVID-19 PANDEMIC IN A HIGH VOLUME TERTIARY GOVERNMENT HOSPITAL IN THE PHILIPPINES
Authors: Dr Francis James Gatdula
Journal: Neuro-Oncology (2024)

Abstract AIMS Malignant glioma is a common primary brain tumor with a great burden of disease. When COVID-19 set in, it became a challenge to manage an already diﬃcult treatment process in low-resource-setting centers. Despite this, conventional recommendations and standard treatment protocols are followed. However, outcomes were perceived to deviate from the convention, hence the reason for this study which is to understand the nature of outcomes in the management of malignant gliomas during the COVID-19 pandemic in Southern Philippines Medical Center (SPMC), the largest government tertiary hospital in the Philippines. METHOD A retrospective chart review of nine clinically and histologically diagnosed cases of malignant gliomas admitted in SPMC between April 2020 to September 2021 was performed. The clinical presentations, image correlation, and outcomes were listed. Then, classiﬁed as desirable, undesirable but acceptable, or unacceptable based on factors identiﬁed. Qualitative analysis by deduction including outcomes determining possible modiﬁcations in treatment of future cases was done. RESULTS Of the nine cases, one was listed as desirable, one with unacceptable outcome due to management complications, and the rest were labeled as undesirable but acceptable either because of advanced disease or poor KPS score. Three major factors were determined: the roles of pre-hospital and initial treatment delays, the decision for surgical treatment, and the COVID-19 pandemic. CONCLUSION The shift in the outcomes of malignant gliomas during COVID-19 shows the management challenge in low resource centers. There is an increase in highly malignant cases with guarded prognosis due to lack of education, support, and resources in terms of early diagnosis, treatment, and post-surgical care. This was aggravated by the restrictions imposed by the pandemic and ﬁnancial crisis, especially for patients below the poverty line. Delays in management show a signiﬁcant inﬂuence on prognosis regardless of treatment. As such, possible modiﬁcations in the current treatment algorithm are hereby recommended.
ANALYSING THE RATE OF RECURRENCE AND LEPTOMENINGEAL DISEASE IN POSTERIOR FOSSA BRAIN METASTASES FOLLOWING POSTOPERATIVE RADIOTHERAPY- SINGLE CENTRE EXPERIENCE
Authors: Dr Farida Hegazy, Dr Helen Wong, Mrs Michelle Forshaw, Dr Chloe May, Dr Aditya Shenoy, Dr Shaveta Mehta
Journal: Neuro-Oncology (2024)

Abstract AIMS The management of posterior fossa brain metastases is complex and necessitates a multidisciplinary approach involving neurosurgeons and oncologists. Post-operative radiotherapy (PORT) to surgical cavity has demonstrated positive oncologic outcomes as well as preserving cognitive function when compared to conventional whole brain radiation therapy. However, larger post-operative volumes in posterior fossa and greater target volume uncertainty due to presence of pseudomeningocele may result in an increased risk of local recurrence (LR) and leptomeningeal disease (LMD). The aim of this retrospective single centre study was to determine the rates of LR and LMD in patients with posterior fossa metastases who underwent PORT to surgical cavity. METHOD Retrospective analysis of data of patient who underwent PORT in between 2017-2022, for posterior fossa brain metastases at our centre. Clinical, imaging and radiotherapy data was collected from electronic medical records. Statistical analysis was performed using SPSS Statistics version 28.0.1. RESULTS We identiﬁed 42 patients meeting the study criteria. The median age of the patients was 60.5 years. 71.4% of patients were females, while 28.6% were males. 52.4% of patients had pseudomeningocoele on their radiotherapy planning scans. The median time gap between the date of surgery and initiation of radiotherapy was 34.5 days. 20 out of 42 (47.6%) patients had local recurrence of a posterior fossa brain metastasis and 7 out of 42 (16.7%) patients developed LMD. Out of 7 patients with LMD, 4 patients had pseudomeningocoele present at the time of PORT. The timing of radiotherapy after surgery (≤4 weeks or &amp;gt;4 weeks) showed no statistically signiﬁcant impact on LR (p-value: 0.413, log-rank test). CONCLUSION The risk of LR remains high despite PORT. This study highlights the challenges in management of posterior fossa metastases. High LR and LMD rates underscore the need for improved treatment strategies.
ORTHOPTIST LED VISUAL ﬁELD MONITORING DURING AWAKE CRANIOTOMY OF LOW GRADE GLIOMA: A UK TERTIARY CENTRE EXPERIENCE
Authors: Mrs Danielle Guy, Mr John Goodden, Mr Paul Chumas, Ms Rebecca Chave-Cox, Mr Ryan Mathew
Journal: Neuro-Oncology (2024)

Abstract AIMS To describe orthoptist led monitoring of visual function during awake craniotomy for low grade glioma and to retrospectively review visual ﬁeld outcomes comparing to published results. METHOD Intraoperative visual ﬁeld monitoring was performed by the same advanced orthoptist, performing ﬁelds to confrontation as well as monitoring for observed visual phenomena. Goldman visual ﬁelds were performed pre-operatively and approx. 6 weeks post operatively. Results compared to published outcomes. RESULTS 26 awake procedures were attended with 2 being repeat surgeries therefore 28 surgical episodes. Testing was abandoned for 6 (inability to wake suﬃciently, inability to cope with the awake procedure or change in diagnosis from low to high grade). Results were retrospectively reviewed over a ﬁve year period from 2019 to 2024. Post operative visual ﬁelds were found to be unaltered or only mild superior dipping (not precluding driving) in 18 patients, loss of ﬁeld to a quadrantiopia negating driving requirements in 2, 2 patients with quadrantiopia pre and post op unchanged. CONCLUSION Visual ﬁeld assessment during awake craniotomy can give surgeons additional conﬁdence to continue the resection. Utilisation of an Orthoptist with minimal equipment as well as no alteration to the surgical positioning has demonstrated comparable visual outcomes to those published. The authors would recommend that other centres consider utilization of specialised allied health professionals to assess and monitor eloquent function during awake procedures; such as orthoptists for visual function.
LONG-TERM SURVIVAL OF TANYCYTIC EPENDYMOMA OF LATERAL VENTRICLE WITH ADJACENT FRONTAL LOBE INVASION: CASE REPORT AND LITERATURE REVIEW
Authors: Mr Ruben Batista, Mr Ronan Dardis, Mr Ian Edwards, Mr Debasish Hajra
Journal: Neuro-Oncology (2024)

Abstract AIMS Tanycytic ependymoma (TE) of lateral ventricle is a rare variant of ependymoma often challenging to diagnose due to its distinctive histological features and similarity to other central nervous system neoplasms. This report presents a case of TE in a 48 years-old lady with 20 years of long-term survival and provides a comprehensive review of the literature to elucidate the clinical, radiological, and pathological characteristics of this entity. METHOD A 48-year-old woman presented with a left lateral ventricular tumor invading the left frontal lobe and pericallosal region, subsequently diagnosed as TE after stereotactic biopsy followed by radical radiotherapy. Epidemiological features, preoperative and postoperative radiological surveillance, and functional performance after adjuvant radiotherapy were reviewed. Additionally, we review the current literature to explore current perspective of TE. Three major medical database engines, PubMed (Medline), Scopus (ELSEVIER), and Cochrane were used to conduct a thorough literature search. RESULTS The patient exhibited notable neurological improvement following stereotactic biopsy and radical radiotherapy, with long-term surveillance demonstrating stability and reduction in tumor size over a 20-year period. Our literature review underscores the rarity of TE and its diagnostic challenges, emphasizing the importance of histopathological examination and immunohistochemical analysis for accurate diagnosis. TE exhibit unique ultrastructural features, requiring meticulous examination for proper classiﬁcation. Additionally, we discuss the implications of TE’s histological resemblance to other intramedullary tumors and its potential impact on therapeutic decisions. CONCLUSION Tanycytic ependymomas pose diagnostic dilemmas due to their morphological overlap with other CNS tumors. However, heightened awareness among clinicians and pathologists is crucial for accurate identiﬁcation and appropriate management. Further research into the molecular mechanisms underlying TE is warranted to enhance diagnostic precision and reﬁne treatment strategies, ultimately improving patient outcomes.
METABOLOMIC PROﬁLING OF ASTROCYTE-GLIOBLASTOMA CELL INTERACTION IN A POSTOPERATIVE TUMOUR MICROENVIRONMENT MODEL
Authors: Ms Une Kontrimaite, Dr Phoebe McCrorie, Mr Harry Porter, Dr Stuart Smith, Dr Dong-Hyun Kim, Dr Ruman Rahman
Journal: Neuro-Oncology (2024)

Abstract AIMS Despite multimodal treatment, 9/10 patients diagnosed with isocitrate dehydrogenase wild-type glioblastoma experience tumour recurrence within 5 years. Poor prognosis is in considerable part attributed to the ability of cancer cells to inﬁltrate healthy brain. We hypothesise that metabolic changes underpinning cellular crosstalk between astrocytes and glioblastoma invasive margin cells within a physiologically representative in-vitro tumour microenvironment, may reveal therapeutic targets to prevent or delay glioblastoma recurrence. An initial study aimed to establish baseline metabolomic proﬁles for glioblastoma invasive margin cells and healthy human frontal lobe astrocytes. METHOD We used human frontal lobe astrocytes (n=6) and transgenic glioblastoma invasive margin cells tagged with eGFP (n=18) to extract cellular metabolites using biphasic extraction method (methanol:water:chloroform). Liquid Chromatography – Mass Spectrometry (LC-MS) with a ZIC-pHILIC column, coupled to an Orbitrap Mass Spectrometer (Q-Exactive Orbitrap) was used to identify metabolites. Both multivariate and univariate statistical analyses were used to investigate signiﬁcant alterations observed in the metabolic data. RESULTS The study uncovered distinct metabolic proﬁles differentiating glioblastoma invasive margin cells from astrocytes. Signiﬁcant alterations were identiﬁed in the alanine, aspartate, and glutamate metabolism pathway, which is required for amino acid synthesis and neurotransmitter balance. Other metabolic pathways include glycine, serine, and threonine metabolism as well as glycerophospholipid metabolism. These preliminary ﬁndings lay the groundwork for further exploration into the cellular interactions in a postoperative tumour microenvironment model and elucidate mechanisms that may contribute to tumour recurrence. CONCLUSION Understanding the interactions between cancerous cells and astrocytes is crucial for developing new therapeutic approaches. Our subsequent research will integrate an advanced tumorsphere model composed of a scaffold combining PEGDA hydrogel and an extracellular matrix derived from a decellularized human autopsy brain. This model aims to replicate the postoperative tumour microenvironment more accurately to investigate astrocyte-glioblastoma cell interactions associated with tumour recurrence.
HAS THE INITIATION OF A FORMAL PATHWAY FOR TUMOUR TISSUE COLLECTION IN NEURO ONCOLOGY PATIENTS LED TO AN INCREASE IN PATIENT’S HAVING WHOLE GENOME SEQUENCING (WGS), AND HOW WILL THIS IMPACT ONCOLOGY MANAGEMENT IN THE FUTURE?
Authors: Mr Aeron Suarez, Mrs Victoria Hurwitz, Ms Ellie Kostick, Ms Laura Mullens, Mrs Jessica La, Mrs Charlotte Robinson, Mrs Sarah Hedges, Ms Nicola Harding, Ms Pat Sabido, Ms Kazumi Chia, Mr Jahard Aliaga-Arias, Mr Ross Laxton, Ms Kelly Eggleton, Prof Safa Al-Sarraj, Dr Zita Reisz, Mr Istvan Bodi
Journal: Neuro-Oncology (2024)

Abstract AIMS To change the standard of care for collection of glial tumour tissue at a London teaching hospital. This would enable WGS on the tumour tissue, and give patients access to further clinical trials. METHOD The previous standard of care was for brain tumour pathology samples to be stored in paraﬃn. This was not suitable for WGS or for many clinical trials; the tumour samples needed to be sent to the lab as fresh tissue. The introduction of a genomics clinical nurse specialist meant that relationships were built between the surgical team, pathology teams and ward teams. There was a teaching by one of the neurosurgical team to the theatre staff. Genomics CNS led training for the nursing team. Adults started having WGS in May 2023 but many patient’s still had tissue incorrectly stored and could not have the sequencing performed. There was an introduction of a formal pathway in theatre created by one of the neurosurgeons in Dec 2023. RESULTS From May 2023 - November 2023, 58% adult glioma patients had WGS. Since December 2023 - current (March 2023) and the introduction of the formal pathways, 71% had WGS. CONCLUSION A formal pathway has now changed the standard of care for collecting tissue. There is still not 100% compliance, and this remains multifactorial. However the introduction of a formal pathway has now increased the percentage of eligible patients receiving WGS. This positive outcome has now led to discussions about freezing the fresh glioma tissue to allow glioma patient’s wider access to clinical trials which they would previously not have had access to.
IMPACT OF DNA METHYLATION PROﬁLING IN REﬁNING MENINGIOMA RECURRENCE RISK STRATIﬁCATION AND CLINICAL FOLLOW UP
Authors: Mr Ali Bakhsh, Prof Sebastian Brandner, Prof Ian Scott, Prof Michael Jenkinson, Dr Nitika Rathi
Journal: Neuro-Oncology (2024)

Abstract AIMS To assess clinical impact of the additive information gained from Integrated Meningioma Risk Score on the risk of meningioma recurrence. METHOD DNA methylation (Illumina EPIC Array) analysis was performed on all recurrent meningioma tumours, primary tumours CNS5 WHO grade 2, 3 and grade 1 with unusual morphological features from Dec 2021 to Jan 2024. DNA methylation analysis was performed, and data ﬁles were processed on the DKFZ Heidelberg Classiﬁer v12.5/6 (molecularneuropathology.org). The output from the classiﬁer including methylation class combined with WHO Grade and chromosomal loss (1p, 6q,14q) was used to produce an integrated meningioma risk score for recurrence. RESULTS 70 meningioma cases were proﬁled. This included 68 cranial meningiomas, ((WHO grade 1, n=19; recurrences=7), (grade 2, n=47; recurrences =9), (grade 3 n=2; recurrences=1)) and 2 spinal meningiomas (grade 1 n=1, grade2 n=1). 3 tumours were excluded due to poor calibration scores. Of the 67 cases the diagnosis was revised in 1 case following DNA methylation analysis due to presence of CDKN2A/B loss. Molecular-morphologic integrated risk score was calculated for all 67 cases. In 10% of overall patients the predicted risk of meningioma recurrence was increased to either intermediate or high, whilst 32% had the risk lowered mainly from intermediate to low. Interestingly, 1 patient who underwent a gross total resection of a WHO Grade 2 meningioma, experienced recurrence with the integrated meningioma risk score indicating low risk of recurrence, which is contrary to the clinical aggressiveness of the tumour. CONCLUSION Meningioma integrated risk stratiﬁcation by DNA methylation proﬁling has shown concordance of integrated risk score with WHO Grade in 58% of cases. In 42% of cases the predicted risk was altered when compared to the WHO Grade alone. These results need to be further validated with long term data on patient outcomes.
ABNORMAL CORTICAL EXCITABILITY IS ASSOCIATED WITH DECREASED OVERALL SURVIVAL IN PATIENTS WITH GLIOBLASTOMA
Authors: Mr Jose Lavrador, Ms Ana Mirallave Pescador, Ms Sabina Patel, Dr Qusai Al Banna, Mr Kapil Rajwani, Mr Francesco Marchi, Mr Ali Elhag, Mr Alba Diaz Baamonde, Mr Jose Mosquera, Prof Keyoumars Ashkan, Mr Ranjeev Bhangoo, Mr Francesco Vergani
Journal: Neuro-Oncology (2024)

Abstract AIMS Navigated transcranial magnetic stimulation (nTMS) is a well-established technique for motor cortex mapping and assessing motor tract integrity in patients with brain tumours. Pre-surgical nTMS mapping in patients with glioma has shown an altered interhemispheric excitability that correlates well with WHO grade. The aim of this study is to correlate the preoperative nTMS ﬁndings with overall survival (OS) in patients with motor-eloquent brain tumours operated at our institution. METHOD We conducted a retrospective cohort study using electronic patient records to search for all patients with a motor-eloquent brain tumour resected between 2017 and 2023. We included all adult patients (&amp;gt;18 years) with pre-operative nTMS mapping and a tissue diagnosis. Two nTMS measures of cortical excitability were assessed; cortical excitability score (CES) and the intraM1 excitability score (IMES). Our outcome measure was OS. RESULTS 160 patients fulﬁlled the inclusion criteria (mean age 48.34 years). The commonest tumour histology was glioblastoma (n=51; 32%). Among patients with diffuse gliomas, IDH was mutated in 59% patients and MGMT was methylated in 61%. Majority of patients (62.5%) underwent gross total resection. Resting motor thresholds (RMTs) for both upper and lower limbs between the tumour and healthy side were not signiﬁcantly different. Interhemispheric RMT ratio in the upper limbs was abnormal in 60.93% patients and in the LLs was abnormal in 57.14%. A higher CES was related to lower overall survival (p=0.04). A subgroup analysis showed this was particularly the case among patients with a diagnosis of Glioblastoma (p=0.015). When adjusted for cofounding factors EOR, MGMT methylation and age, both CES and IMES were inversely related to OS (p=0.002). CONCLUSION A higher CES and IMES is related with poor overall survival in patients with Glioblastoma even when other cofounding factors affecting OS are considered. This information can be used when counselling patients and planning surgical approach to motor-eloquent tumours.
NOVEL HETEROCYCLIC COMPOUNDS AS KINASE INHIBITORS WITH ANTICANCER ACTIVITY IN MEDULLOBLASTOMA
Authors: Prof Rafael Roesler, Ms Isadora Serraglio Fortes, Dr Marcela Lopes, Dr André Brunetto, Dr Caroline Brunetto de Farias, Dr Mariane Jaeger, Mr Bruno Toson, Prof Saulo de Andrade
Journal: Neuro-Oncology (2024)

Abstract AIMS Medulloblastoma is the most common malignant brain tumor of childhood. Protein kinases are often overexpressed and constitute targets for the development of novel molecularly-targeted therapies in brain tumors. Here, we report the synthesis of new derivatives with kinase inhibitory activity and their anticancer activity in an early screening in medulloblastoma cells. METHOD The synthesis route was performed through six steps using a proper amino acid as starting material. The inhibitory activity of the ﬁnal derivatives on the protein kinase was measured by ﬂuorescence. Cultured DAOY medulloblastoma cells were used to examine anticancer activity. RESULTS The compounds display potent inhibitory activity on viability of DAOY medulloblastoma cells. The more promising derivative shows IC50 in the μM range in inhibiting the targeted protein kinase. CONCLUSION Further optimization of compounds in this series is currently being carried out. The encouraging preliminary results have revealed potential novel strategies for inhibiting kinase activity for the treatment of medulloblastoma.
MAPPING GLIOMAS: A RADIOGRAPHIC AND SPATIAL ANALYSIS ACCORDING TO THE 2021 WHO CLASSIﬁCATION
Authors: Mr Yonghao Li, Mr Yizhou Wan, Prof Stephen Price
Journal: Neuro-Oncology (2024)

Abstract AIMS The spatial positioning of gliomas within the brain signiﬁcantly inﬂuences prognosis, potentially mirroring the genetic landscape of their precursor cells. Furthermore, the association between glioma subtypes and their spatial distribution underscores a complex interplay that may illuminate underlying pathogenetic mechanisms. This study explores the intricate relationship between the location of gliomas and their classiﬁcation according to the 2021 WHO guidelines, aiming to unravel the spatial and genetic nuances that deﬁne glioma heterogeneity. METHOD In this study, preoperative anatomical MRI data from 242 glioma patients were meticulously analyzed to elucidate spatial distribution patterns in relation to tumor genetics. The imaging data underwent registration to the MNI-152 standard brain space, facilitating uniform analysis. Subsequent tumor segmentation and division of the brain into 84 distinct subregions allowed for a detailed examination of tumor locations. A statistical analysis was conducted to explore the stereospeciﬁc frequency of glioma occurrence across these subregions, correlating ﬁndings with tumor grade and pivotal genetic markers, including MGMT promoter methylation, IDH1 mutation, 1p/19q co-deletion, and CDKN2A/B homozygous deletion. RESULTS We developed 21 distinct tumor frequency atlases based on subtypes (Glioblastoma, Oligodendroglioma, Astrocytoma), biomarker status (IDH, 1p19q, MGMT, CDKN2A/B), and grade (2, 3, 4). Employing probability vectors for statistical analysis revealed a signiﬁcant correlation among different subtypes, locations and overall survival. Furthermore, we used a Visualization tool to build a 3D heatmap for each tumor subtype, more intuitively illustrating spatial correlations. CONCLUSION Our study underscores the prognostic value of tumor location and its correlation with glioma subtypes and patient outcomes, suggesting a potential pathway to personalized treatments. Future efforts will focus on incorporating multi-omics data into spatial radiographic analyses.