bluuebunny/crossref_metadata_2025 huggingface dataset:
PROLONGED SURVIVAL IN IDH-WILDTYPE GLIOBLASTOMA: CASE REPORTS, LITERATURE REVIEW AND CURRENT PERSPECTIVES OF MOLECULAR BEHAVIOR
Authors: Batista Mr Ruben , Hajra Mr Debasish , Nazar Mr Thaaqib , Dardis Mr Ronan , Mukherjee Mr Soumya
Published: October 2024

AIMS

Glioblastoma remains one of the most aggressive primary brain tumours, with a median survival of around 12 months despite advances in treatment. However, rare cases of long-term survival challenge this prognosis. The evaluation of age, tumour location, surgical approach and strategies, adjuvant therapy, and molecular behavior provides valuable prognostic and predictive information in patients with glioblastoma.

METHOD

We present a case report of two patients diagnosed with wild-type glioblastoma who have survived over 10 years post-primary surgery. A review of epidemiological data, preoperative and postoperative radiological reports, surgical approach, and histology reports were studied. Additionally, we review the current literature to explore current nuances in High-Grade Glioma Wild Type prognosis and potential future directions. Three major medical database engines, PubMed (Medline), Scopus (ELSEVIER), and Cochrane were used to conduct a thorough literature search.

RESULTS

Both patients underwent maximal safe resection followed by the Stupp Protocol, comprising adjuvant chemotherapy with temozolomide and radiotherapy. Our case report highlights two exceptional cases of prolonged survival in Glioblastoma patients, both under 51 years-old at the moment of diagnosis, early diagnosis with isolated lobar lesions, no compromise of deep white matter, and achieving maximal safe resection and functional independence. Molecular analysis revealed speciﬁc genetic in common, including IDH Wild Type, p53 mutation, retained ATRX expression, TERT mutation, and MGMT promoter methylation, consistent with a favourable prognosis. Moreover, patients without recurrence often exhibit distinct molecular proﬁles, such as MGMT promoter methylation, suggesting a potential subtype associated with prolonged survival.

CONCLUSION

Our case reports and literature review highlight the possibility of prolonged survival in Glioblastoma patients. The age, tumor location at the time of diagnosis, comprehensive treatment approaches, may contribute to improved outcomes. Molecular proﬁling, particularly assessing genetic mutations and MGMT promoter methylation, holds promise for identifying patients with a higher likelihood of prolonged survival.
ABNORMAL CORTICAL EXCITABILITY IS ASSOCIATED WITH DECREASED OVERALL SURVIVAL IN PATIENTS WITH GLIOBLASTOMA
Authors: Lavrador Mr Jose , Pescador Ms Ana Mirallave , Patel Ms Sabina , Banna Dr Qusai Al , Rajwani Mr Kapil , Marchi Mr Francesco , Elhag Mr Ali , Baamonde Mr Alba Diaz , Mosquera Mr Jose , Ashkan Prof Keyoumars , Bhangoo Mr Ranjeev , Vergani Mr Francesco
Published: October 2024

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 (>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.
ORTHOPTIST LED VISUAL ﬁELD MONITORING DURING AWAKE CRANIOTOMY OF LOW GRADE GLIOMA: A UK TERTIARY CENTRE EXPERIENCE
Authors: Guy Mrs Danielle , Goodden Mr John , Chumas Mr Paul , Chave-Cox Ms Rebecca , Mathew Mr Ryan
Published: October 2024

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.
AN ANALYSIS OF THE PATIENT REPORT OUTCOMES OF A JOINT CNS / AHP NEURO-ONCOLOGY CLINIC ON PATIENTS QUALITY OF LIFE
Authors: Powell Dr James , Lewis Mrs Cathryn , Burke Mrs Rhian , Iqbal Dr Najmus , Maclean Dr Jillian , John Ms Charlotte , Best Mrs Keri , Moore Mrs Bethan , Davies Ms Rebecca , Mackay Mrs Emma , Rogers Mrs Clare , Kwiatkowska Mrs Magdalena , Tindle Mrs Samantha
Published: October 2024

AIMS

Velindre Cancer Centre established a successful model of collaborative working between CNS and AHP services for neuro-oncology patients to holistically support their complex needs throughout treatment. Building on this success, the clinic has introduced a recognised reliable and valid patient reported outcome measure (PROM) to be completed pre and post clinic intervention. This is in addition to the patient reported experience measure that is already established within the pathway. This PROM will enable an analysis of the clinics impact on patients quality of life.

METHOD

A quantitative methodology will be utilised to enable a objective evaluation of the impact of the clinic on patients quality of life. An EQ-5D-5L PROM is completed with patients prior to their involvement with the clinic enabling an overview of key aspects related to quality of life including mobility, self-care, participation in usual activities, pain and anxiety / depression. Following interventions within the clinic, patient are provided with a post treatment EQ-5D-5L to enable a comparison of these key indicators of quality of life.

RESULTS

The data will build on the resounding success of collaborative working between CNS and AHP’s in the neurooncology MDT clinic. An analysis of the pre and post data will demonstrate the impact of having access to this unique and integrated way of working, enabling patient access to specialist timely support throughout their treatment.

CONCLUSION

This innovative model of working is now established in the patient pathway and ﬁndings from patient experience measures have recognised that patients experience of the clinic is extremely highly valued. Findings from this additional dataset will further evidence the impact on patients quality of life. It will add to ﬁndings from a proposed gap analysis to evidence the beneﬁts of developing an outreach service for this patient cohort.
RISKS AND OUTCOMES OF STROKE IN PATIENTS WITH PRIMARY BRAIN AND MENINGEAL TUMOURS
Authors: Innes Dr Stuart , Yin Dr Lucia , Finnerty Dr Gerald T
Published: October 2024

AIMS

People with primary CNS tumours are at increased risk of stroke. However, there is little guidance on stroke management. We investigated the types and timing of stroke in primary brain and meningeal tumours to inform their treatment.

METHOD

Patient data on stroke aetiology, timing, management and outcomes was collected from electronic medical records at King’s College Hospital between April 2012 to April 2022. A primary brain tumour was deﬁned using the 2021 World Health Organisation Classiﬁcation of Tumours of the Central Nervous System.

RESULTS

We identiﬁed 244 patients with a brain tumour and a stroke with a total of 317 strokes in the 10-year period (male:female = 48:52; median age, 62 years [IQR 51 – 74]). The most common brain tumours were meningiomas (43%) and glioblastomas (21%). 56% of strokes were ischaemic. Ischaemic strokes were most frequent within 30 days of brain tumour surgery (38%). Haemorrhages were more common in malignant tumours (p=4.7 x10 35% of haemorrhages were intratumoural. Strokes in malignant tumours: occurred closer to diagnosis (p=0.032); caused greater functional loss (mean Modiﬁed Rankin Scale change 2.00 vs 1.17, p 0.001); and had a higher mortality rate (HR 5.87, CI 3.41 - 10.11, p=1.8x10 Recurrent strokes occurred in 64 (26%) patients and were associated with tumour malignancy (p=0.016), radiotherapy (p=0.023) and chemotherapy (p=0.009).

CONCLUSION

Strokes in malignant brain tumours are more lethal, disabling and often recurrent in patients undergoing chemo and radiotherapy. Clinical trials are needed to improve outcomes of stroke in neuro-oncology patients.
DEXAMETHASONE WEAN POST CRANIOTOMY FOR MENINGIOMA- A CASE STUDY
Authors: Mullens Ms Laura , Hurwitz Mrs Victoria , Hedges Mrs Sarah , Kostick Ms Ellie , Suarez Mr Aeron , Sabido Ms Pat , Harding Ms Nicola , Lavrador Mr Jose , Ashkan Prof Keyoumars , Vergani Mr Francesco , Cikurel Mrs Katia , Gullan Mr Richard
Published: October 2024

AIMS

Case review/analysis of dexamethasone wean post craniotomy for meningioma. To identify any quality of life issues experienced during the wean, how and why steroid wean was adjusted and any impact steroid use had on serum cortisol level causing adrenal insuﬃciency.

METHOD

Review of documentation to identify steroid related side effects, how and when this impacted on the patient’s quality of life. Collection of data; steroid doses, length of time on steroids (pre-surgery and post-surgery), serum cortisol result. Clinical choices regarding dose/timings of dexamethasone reviewed and compared to literature.

RESULTS

Delays/changes with theatre dates, capacity, neurological symptoms on presentation led this individual to a four month pre-surgical dose of dexamethasone which led to weight gain, pre-diabetes and insomnia. Quality of life pre and post-surgically affected by steroid use namely mental health, employment and social belonging. This case study conﬁrms adrenal insuﬃciency was precipitated by the prolonged pre-surgical use of dexamethasone. Clinical nurse specialists are integral in adjusting steroid dose to manage neurological recovery and safely wean steroids to zero as well as identifying adrenal insuﬃciency.

CONCLUSION

Data collection from a large sample size is required to conﬁrm how many patients coming through the neurooncology surgical pathway have conﬁrmed adrenal insuﬃciency post neurosurgery secondary to Dexamethasone. Once data is collected guidance on how to manage a safe post surgical steroid wean and minimise impact of quality of life can be formalised.
LONG-TERM SURVIVAL OF TANYCYTIC EPENDYMOMA OF LATERAL VENTRICLE WITH ADJACENT FRONTAL LOBE INVASION: CASE REPORT AND LITERATURE REVIEW
Authors: Batista Mr Ruben , Dardis Mr Ronan , Edwards Mr Ian , Hajra Mr Debasish
Published: October 2024

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.
IDENTIFYING YB1 AND NPM1 AS PART OF THE MUTANT HISTONE 3 PROTEIN INTERACTOME IN H3 MUTATED PHGG
Authors: Dhillon Ms Mehar , Read Ms Eleanor , Sulman Mr Joshua , Haque Dr Farhana
Published: October 2024

AIMS

Paediatric high-grade gliomas (pHGG) are the leading cause of childhood cancer deaths, accounting for over 40% of deaths in the UK. pHGG tumours harbour histone H3 mutations, deﬁning 50% of pHGG cases and the major mutations are H3.3K27M and H3.3G34R/V. Our previous proteomic research on H3 intercatomes, identiﬁed unique and common interacting binding partners of H3-G34R and H3-G34V mutant proteins relative to wild type H3 protein. Among these binding proteins we have focused on YB-1 and Nucleophosmin 1 (NPM1). YB-1, is multifunctional transcription factor and a well- characterised oncogenic protein. NPM1 is a molecular chaperone and frequently overexpressed in cancers. Our aim is to analyse the role of YB-1 and NPM1 in H3 mutated pHGG, in order to identify targeted therapeutic options for these diﬃcult to treat tumours.

METHOD

H3 mutated glioma, H3 wild type pHGG and control cell lines were cultured and then subjected to comparative immunoﬂuorescence microscopy, and western blot analyses to investigate YB-1 and NPM1 expression.

RESULTS

Results showed statistically signiﬁcant altered protein expression and localisation of YB-1 and NPM1 in H3 mutated pHGG in comparison to wild type and control cells. YB-1 expression was increased in H3 mutated cells and NPM1 showed increased cytoplasmic localization in H3 mutated cells in comparison to H3 WT glioma and control cells.

CONCLUSION

Results of the study support that YB-1 and NPM1 are important interacting proteins in H3G34-mutated pHGGs and can be explored as potential therapeutic targets in H3 mutated pHGG.
INVESTIGATING CUDC-101 EFFECT AND MECHANISM OF ACTION AGAINST GLIOBLASTOMA IN VITRO
Authors: Chandler Ms Rebecca , Alder Dr Jane , Mathews Dr Roshini , Stasik Dr Izabela
Published: October 2024

AIMS

Glioblastoma (GB) has complex pathophysiology, diﬃcult treatment and resultant poor prognosis. Its median survival rate is approximately 15 months. The aggressive nature of GB results in rapid disease progression in 60-70% patients often within 12 weeks. Limited treatment options include maximal safe surgical resection, followed by radiotherapy and temozolomide (TMZ). The blood brain barrier restricts chemotherapeutic entry and increases dosage leading to increased side effects and decreased treatment tolerance. Furthermore, signiﬁcant disease heterogeneity means reoccurrence is expected in most cases, for which there are no standard treatment routes. This coupled with ineﬃcient treatment with temozolomide (TMZ) due to the blood brain barrier, highlights the requirement for novel treatments.

METHOD

Histone deacetylases (HDAC) and endothelial growth factor receptor (EGFR) are mutated and upregulated in GB allowing tumour inﬁltration and proliferation. CUDC-101 is known to target both HDAC and EGFR in other cancers making it a promising therapeutic to trial in GB. Cell viability of U251, T98G and U87MG human cells was measured post-CUDC-101 administration at 24, 48 and 72hrs. SVGp19 embryonic non-cancerous human glial cells were used as a control to establish CUDC-101 preliminary speciﬁcity. Targeting another major hallmark of GB, wound healing assays were performed to assess CUDC-101 capacity to inhibit migration. In addition to this, long-term cellular resistance was investigated through clonogenic assays. Western blotting was then used to identify non-/treated expression levels of activated EGFR and acetylated histone H3. Expression levels in non/-treated cells were then visualised with ﬂuorescent microscopy. In addition, ﬂow cytometry was utilised to observe cell cycle changes.

RESULTS

Overall, results indicate CUDC-101 has a dose-dependent effect on cell viability (long-term and short-term) and migration. Additionally, ﬂuorescent images show treatment does increase histone acetylation and decrease total EGFR.

CONCLUSION

Future work will solidify these datasets and show changes in activated EGFR and acetylated histone H3 using western blotting.
SUPERSOFT SPONGE-LIKE CRYOGEL AS AN IMPLANT TO TREAT GLIOBLASTOMA
Authors: Wang Mr Yu , Le Joncour Dr Vadim , Laakkonen Prof Pirjo , Newland Dr Ben
Published: October 2024

AIMS

Create cylindrical cryogels with well-deﬁned size. Investigate clemastine drug loading capicaty and drug release patterns. Investigate in vitro and in vivo safety and antitumor eﬃcacy.

METHOD

A 3D printed template was designed and printed to make cylindrical shape cryogels. The morphology of cryogels was characterized by bright ﬁeld photos, SEM, FTIR and confocal microscopy photos. The mechanical property was evaluated by uniaxial compression tests. The orthotropic glioblastoma tumor model was established by engrafting BT12 human glioblastoma stem cells intracerebrally into immunocompromised nude mice. The tumor was surgically removed after two weeks and the cryogel was implanted into the resection cavity. Animals were euthanized after two weeks, and their brains were collected for the immunohistochemistry.

RESULTS

Cylindrical cryogels were prepared to exactly ﬁt the biopsy resection cavity in the mouse glioblastoma tumor resected model. The macropore structure in the cryogel was observed under confocal microscopy. Young’s modulus of the cryogel was only 1.6 kPa. The loading capacity of clemastine in one cryogel was more than 100 μg. Clemastine could be sustained released for around a week. In vitro cell viability studies showed that empty cryogels were not toxic to the tumor cells and drug loaded cryogels killed the tumor cells in a time and concentration dependent manner. In vivo studies further conﬁrmed that cryogels could be safely implanted into the brain. Although the implantation of clemastine loaded cryogels did not prevent the growth of the primary tumor, it reduced the amount of invasion tumor cells compared with the mice only resected the tumor.

CONCLUSION

Cryogels were easily created by the 3D printed templates. The soft material avoided mechanical mismatch with the brain tissue. The cryogel did not show any toxicity in in vitro and in vivo studies, which indicated it would be a promising material to be implanted into the brain.
NANOPORE-BASED INTRA-OPERATIVE CLASSIﬁCATION OF CENTRAL NERVOUS SYSTEM TUMOURS IN THE NHS
Authors: Deacon Dr Simon , Cahyani Dr Inswasti , Holmes Dr Nadine , Fox Dr Graeme , Wibowo Mr Satrio , Munro Mr Rory , Patel Dr Areeba , Goldspring Dr Robert , Brandner Prof Sebastian , Sahm Prof Felix , Paine Dr Simon , Loose Prof Matthew , Smith Dr Stuart
Published: October 2024

AIMS

The 2021 WHO classiﬁcation of CNS tumours necessitates the use of molecular testing in order to reach a conﬁdent diagnosis of many tumour types. At present, this is achieved using array-based technology delivered by a centralised model. This approach has inherent delays that mean it is often several weeks before the treating clinical team is informed of diagnosis, delaying the start of adjuvant therapy and causing signiﬁcant distress for patients. As such, there is an urgent need to rethink this pathway and improve time to diagnosis. Nanopore longread sequencing technology has the potential to enable a paradigm shift in diagnostic and therapeutic pathways, offering rapid, comprehensive molecular diagnosis that can be performed in the intra-operative setting. We aimed to test the hypothesis that intra-operative methylation-based classiﬁcation can be performed using nanopore sequencing and thereby expediently inform surgical and oncological decision-making.

METHOD

Oxford Nanopore Technology (ONT) is a native-strand, long-read sequencing platform that can perform copy- number proﬁling along with parallel single-gene methylation, structural variant, mutational and methylation analyses. Capital and consumable costs are relatively low, and testing can be performed in the local setting on single samples. We have optimised DNA extraction and library preparation for rapid tissue processing. We have developed a robust bioinformatic pipeline which is able to produce intraoperative classiﬁcation within minutes of sequencing and full molecular proﬁling after 24 hours.

RESULTS

We demonstrate the feasibility of using ONT to deliver intra-operative methylation-based classiﬁcation of CNS tumours in ‘realtime’ within an NHS hospital setting and will discuss the challenges of implementing this testing and the opportunities to inform neuro-oncological practice.

CONCLUSION

By giving a summary of our novel protocol of rapid DNA extraction, library preparation and bioinformatic analysis, we will show that this approach can revolutionise the diagnosis of brain tumours and has the potential for rapid adoption by non-expert laboratories.
IMPROVING THE EﬃCIENCY OF THE NEURO-ONCOLOGY NEW PATIENT CLINIC AT THE ROYAL MARSDEN HOSPITAL
Authors: Lorimer Dr Cressida , Khan Dr Asadullah Anees , Yadav Dr Deepthi , Kalra Dr Babusha , Welsh Dr Liam , Creak Dr Antonia
Published: October 2024

AIMS

Patients seen for the ﬁrst time in the neuro oncology outpatient unit are typically reviewed by a registrar, then a consultant and a clinical nurse specialist (CNS). This can lead to repetition in history taking and prolonged appointment times. We aimed to improve this by introducing a clerking proforma.

METHOD

Prospective audit of all new patients seen in clinic over a four month period. The total clinic appointment time was recorded for each patient. A proforma was designed to cover the main domains of presenting symptoms, especially focussing on tumour related symptoms, medications including dexamethasone and antiepileptic use, and ensured the appropriate information was given to the patient about the treatment proposed and driving restrictions. The proforma was introduced in to the clinic after 2 months and results analysed to see if a difference was made in terms of overall patient time in the clinic. Qualitative feedback gathered from the team members involved.

RESULTS

10 patients were included prior to the use of the proforma and 9 patients afterwards. Patients presented with a mixture of high and low grade gliomas. Treatment options discussed included chemotherapy, radiotherapy, surveillance and best supportive care. The average time of patient stay in the department prior to the proforma was 107 minutes (range 65 to 165) and after the introduction of the proforma was 91 (range 40 to 110). The proforma was well received by the clinical team, it was felt useful to have a template to structure the new patient consultation, especially for more junior registrars, and the consultants were more conﬁdent that the appropriate information had been given.

CONCLUSION

Within the conﬁnes of a small sample size, the introduction of a proforma reduced the average new patient consultation time and standardised the clinical information collected.
WHICH BRAIN TUMOUR PATIENTS WOULD BENEﬁT FROM SURGERY TO TREAT BOTH THE TUMOUR AND TUMOUR-RELATED EPILEPSY?
Authors: Corrigan Dr Amber , Joe Dr Dorothy , Finnerty Dr Gerald T
Published: October 2024

AIMS

Poor seizure control is a common problem for brain tumour patients. Epilepsy surgery is considered in patients with seizures not caused by a brain tumour when trials of two anticonvulsants given in therapeutic doses fail. There are no clear guidelines on when epilepsy surgery should be considered for brain tumour patients. Given the high burden on quality of life, preventing recurrent seizures is essential.

METHOD

Retrospective data collection of patients seen in the Low-Grade Glioma and Joint Neurology-Oncology clinics of a regional Neuro-oncology service between January – June 2023. Data were analysed within STATA 18.

RESULTS

We identiﬁed 121 patients (61 male, 60 female; age range 20-84 yrs). The majority (93/121) were diagnosed with a low-grade glioma. [GF1] 44 patients had tumour-related epilepsy. Of these, 31/44 (70%) patients presented clinically with seizure(s) and 13/44 (30%) patients had their ﬁrst seizure 3 - 2421 days post diagnosis. All patients were started on anticonvulsant medication, commonly Levetiracetam (70%). Tumour surgery was performed on 28/44 (63%) patients. Recurrent seizures occurred in 22/44 (50%) patients. Seizures were not controlled in 12 (29%) patients after trying two or more anticonvulsants. Four patients were considered for epilepsy surgery.

CONCLUSION

Recurrent seizures are a common clinical problem in patients with low-grade gliomas. Surgery to treat brain tumour-related epilepsy may be performed as a last option. Brain tumour patients may beneﬁt from earlier consideration of surgery to treat both the epilepsy and the brain tumour.
EXPLORING MOLECULAR LINKS IN BRAIN TUMOUR BIOPSY TISSUES AND ALZHEIMER’S DISEASE
Authors: Montalbo Ms Kristy , Stasik Dr Izabela , Bakker Dr Emyr , Smith Dr Christopher George Severin
Published: October 2024

AIMS

Generate and identify putative targets in the SORL1-network by mining online databases. Analyse 21 FFPE human brain tumour biopsy tissues through transcriptome sequencing performed by CeGaT (Tübingen, Germany) to explore differentially expressed genes. These biopsy samples are from consenting patients in association with Brain Tumour North West (BTNW) and the Royal Preston Hospital.

METHOD

Group comparisons are performed with the control and cancerous sample groups (low-grade glioma staying low, low-grade glioma becoming high and high-grade staying high). Further analysis involves comparing section and resection from the same patient for each cancer tissue group. Samples are explored on four different bioinformatic levels and sequenced on the Illumina platform. In Level 1 the data is demultiplexed and trimmed and in Level 2 trimmed reads are additionally mapped. Level 3 provides insights into the cell’s metabolic state and Level 4 performs several group comparisons.

RESULTS

Gain insights into differentially expressed genes’ presence in biopsy tissues from different stages of brain cancer, expression levels and links to clinical characteristics. Bioinformatic analysis provides data on quality control of the starting material, library preparation, sequencing parameters, and the Q30 value of the sequencing.

CONCLUSION

The analysis demonstrates molecular links in the SORL1-network in tissue from section and resection from a patient cohort to better understand disease recurrent and progression. Prospective bioinformatic work would explore interactions between signiﬁcant targets identiﬁed to create a curated network that could predict druggable targets in gliomas.
GENES ENCODING CELL SURFACE RECEPTORS AS NOVEL PROGNOSIS BIOMARKERS IN BRAIN TUMORS
Authors: Roesler Prof Rafael , Bark Dr Samir , Badalotti Dr Rafael , Buffon Dr Viviane , Dalmolin Mr Matheus , Fernandes Prof Marcelo , Malafaia Prof Osvaldo , Isolan Dr Gustavo
Published: October 2024

AIMS

A number of cell surface receptors that bind growth factors, neurotransmitters, and hormones are known to inﬂuence cancer initiation and progression. For example, CD114 (also called GCSFR or CSFR), which is encoded by the CSF3R gene, is a receptor for the granulocyte colony stimulating factor (GCSF) and a marker of cancer stem cells expressed in various cancer types. Also, the γ-aminobutyric acid (GABA) type A (GABAA) receptor for the inhibitory neurotransmitter GABA is proposed to play a role in brain cancer. Here, we report how the mRNA expression levels of CSF3R, the gene that encodes CD114, and genes encoding subunits of the GABAA receptor, are related to prognosis of brain tumor patients assessed by overall survival (OS).

METHOD

Data were obtained from brain tumor datasets, mainly the French and The Cancer Genome Atlas (TCGA) datasets for gliomas and the Cavalli dataset for medulloblastoma. Gene expression was analyzed using the R2 Genomics Analysis and Visualization Platform. OS was calculated using the Kaplan-Meier estimate.

RESULTS

Levels of CSF3R⁄CD114 transcripts are higher in different types of gliomas, namely astrocytoma, pilocytic astrocytoma, and glioblastoma (GBM), in comparison to non-tumoral neural tissue. Higher expression of CSF3R in gliomas is associated with poorer outcome indicated by a shorter OS. Genes for GABAA receptor subunits associated with OS in gliomas include GABRA2, GABRA3, GABRG1, GABRG2, and GABRB3. Higher GABRA5 expression was associated with shorter patient OS in Group 3 and Group 4 medulloblastoma.

CONCLUSION

These ﬁndings indicate that gene expression levels of CSF3R and GABAA receptor subunits are potential biomarkers of poorer prognosis in patients with brain tumors.
MGMT METHYLATION AND ITS PROGNOSTIC SIGNIﬁCANCE IN INOPERABLE IDH WILDTYPE GLIOBLASTOMA: A SIX-YEAR REVIEW AT A TERTIARY NEURO-ONCOLOGY CENTER
Authors: Ghimire Dr Prajwal , Ashkan Prof Keyoumars , Lavrador Mr Jose , Vergani Mr Francesco , Bhangoo Mr Ranjeev
Published: October 2024

AIMS

IDH wild-type glioblastoma has the worst prognosis among glioma patients. The methylation of the O6- Methylguanine-DNA Methyltransferase (MGMT) gene is a valid biomarker for predicting response to therapy with alkylating agents and, independently, prognosis. Patients undergoing biopsy only without subsequent treatment have poor prognosis. We aimed to study the survival impact of MGMT methylation in this subset of patients.

METHOD

We collected six-year retrospective (2017-2023) data at a tertiary neuro-oncology center for patients undergoing biopsy as the only surgical procedure for an unresectable IDH wildtype glioblastoma. Data was collected from patient records including neuro-oncology MDT documentation. Patients were grouped into four categories according to different types of treatment received after biopsy (biopsy only, Biopsy + chemotherapy(CT), biopsy + radiotherapy(RT), biopsy + complete/incomplete STUPP, biopsy + STUPP + 2nd Line). Analysis was performed in python and R statistical software. Survival analysis was performed with Kaplan-Meier Analysis in python.

RESULTS

166 glioblastoma IDH wildtype patients were included in the study with mean age of 62.5 years (M: F = 1.5: 1). 50% (n=83) patients had unmethylated MGMT status (0-5%), 29.5% (n=49) patients had methylated MGMT status (>15%) and 19.2% (n=32) patients had borderline methylated MGMT status (5-15%). 21%(n=35) patients did not receive any treatment post biopsy,, 6.6% (n=11) received CT only, 15% (n=25) RT only, 27% (n= 45) complete/incomplete STUPP therapy, whereas 13.2% (n=22) received STUPP therapy along with second line treatment. In biopsy only group, there was no notable difference in survival outcomes among the different methylation statuses. For biopsy and any-other-form-of-treatment groups showed a distinct trend of better survival compared to the borderline or unmethylated groups. Overall, methylated patients had better survival as compared to unmethylated or borderline groups.

CONCLUSION

Methylated MGMT status is a predictor for better overall survival in unresectable IDH wildtype glioblastoma patients undergoing biopsy and treatment.
The Weight of Nutrition on Post-Resection Oncologic Morbidity and Mortality: A Systematic Review and Meta-Analysis of Nutritional Indices
Authors: Pierce Katherine , Gaskins Jeremy , Martin II Robert C G
Published: October 2024

Context

Nutritional status is a critical factor in the selection of patients for solid tumor resection. A variety of indices have been developed to quantify nutritional status, and they have differing degrees of predictive power for various postoperative outcomes.

Objective

This study aimed to comprehensively evaluate the predictive ability of commonly used nutritional indices in relation to postoperative complications (POCs), recurrence-free survival (RFS), and OS.

Data Sources

We performed a systematic review of 14 established nutritional indices from January 2015 to July 2022:

Data Extraction

The primary end point was OS, while the secondary end points were POCs and RFS. A subsequent meta-analysis was performed to further assess the predictive ability of these indices for OS based on general index type, primary tumor site, and the patient’s index status.

Data Analysis

In this evaluation, 38 articles reporting data on 23 970 patients were analyzed, focusing on 14 nutritional indices. The indices were categorized into phenotypic, metabolic, immunologic, and combined types. Patients within the cut-off range of any index were predicted to have lower OS (hazard ratio [HR] 2.14, 95% CI 1.84–2.49, P < .01). Lower gastrointestinal (GI) and “other” sites were less predictive than upper GI primary tumors (HR 1.63, HR 1.82, and HR 2.54, respectively; all with P < .01). Phenotypic indices were less predictive than combined indices (HR 1.73 vs HR 2.47, P < .01). Within the combined category, there was no significant difference in the predictive ability of Prognostic Nutritional Index (PNI) vs Geriatric Nutritional Risk Index (GNRI) vs Controlling Nutritional Index (CONUT) (HR 2.63 vs HR 2.42 vs HR 2.07, P = .07).

Conclusion

The predictive efficacy of a nutritional index was found to be highly dependent on the index type, the primary tumor site, and the outcome of interest. In the context of upper GI resections, nutritional status appeared to be more of a significant predictor of OS, compared with cases involving lower GI and hepatic malignancies. Indices that integrate phenotypic, metabolic, and immunologic patient factors potentially offer greater clinical utility in forecasting OS.
Multi-Stage Evolution of the Oceanic Lithosphere beneath Heard Island, Southern Indian Ocean
Authors: Abersteiner Adam , Beier Christoph , Genske Felix , Berndt Jasper , Kamenetsky Maya , Goemann Karsten , Nekrylov Nikolai , Kamenetsky Vadim S
Published: October 2024

The Kerguelen Plateau is the second biggest submarine large igneous province (LIP) on Earth, however, the nature of the lithospheric mantle source underlying it remains poorly constrained. In this contribution, we provide novel insights into the oceanic lithospheric mantle underlying Heard Island (southern Indian Ocean), which represents the most recent and active phase of volcanic activity (<1 Ma) in the Kerguelen Plateau. We present petrographic and geochemical data for a suite of spinel-bearing harzburgite xenoliths hosted in basanite lavas and provide detailed constraints for distinguishing in situ mantle metasomatism from post-entrapment modification of the xenoliths following interaction with the host magma. We demonstrate that the xenolith mineral compositions and textures preserve a complex multistage history of different modal and cryptic transformations that occurred in the mantle due to: i) high degrees of partial melting that produced highly refractory whole-rock Mg# (Mg# = (Mg + Fe)/Mg × 100; 88–92), major element (FeO/MgO = 0.17) and mineral compositions (e.g. highly forsteritic olivine; Fo = (Mg + Fe)/Mg × 100; 91–92 mol %); ii) solid-state re-equilibration reactions during decompression that caused exsolution of clinopyroxene and Cr-spinel from xenolith orthopyroxene to form symplectite intergrowths; iii) cryptic metasomatism affecting the composition of xenolith clinopyroxene (i.e. enrichment in Na, Th, U and light rare earth elements, and depletion in Rb, Nb, Zr, Hf and Ti) due to interaction with carbonatitic melts in the mantle. Mantle fragments, entrapped by ascending basanite magmas as xenoliths were further modified by reactions with the host magma. This resulted in the partial dissolution of mantle orthopyroxene and replacement by newly formed and compositionally distinct assemblages of clinopyroxene (Mg# 87–91), olivine (Fo: 81–88 mol %) and Cr-spinel (i.e. ‘wehrlitisation’ of the xenoliths). This study highlights the utility of combining petrography and mineral chemistry to decipher the complex and sometimes overprinting and masking effects that different processes (e.g. melting events, metasomatism) exert on the lithospheric mantle, as well as constrain the processes that modify the xenoliths during transport towards the surface.
Transcriptome analysis reveals role of transcription factor WRKY70 in early N-hydroxy-pipecolic acid signaling
Authors: Foret Jessica , Kim Jung-Gun , Sattely Elizabeth S , Mudgett Mary Beth
Published: October 2024

N-Hydroxy-pipecolic acid (NHP) is a mobile metabolite essential for inducing and amplifying systemic acquired resistance (SAR) following a pathogen attack. Early phases of NHP signaling leading to immunity have remained elusive. Here, we report the early transcriptional changes mediated by NHP and the role salicylic acid (SA) plays during this response in Arabidopsis (Arabidopsis thaliana). We show that distinct waves of expression within minutes to hours of NHP treatment include increased expression of WRKY transcription factor genes as the primary transcriptional response, followed by the induction of WRKY-regulated defense genes as the secondary response. Most genes induced by NHP within minutes were SA dependent, whereas those induced within hours were SA independent. These data suggest that NHP induces the primary transcriptional response under basal levels of SA and that new SA biosynthesis via ISOCHORISMATE SYNTHASE 1/SA-INDUCTION DEFICIENT 2 is dispensable for inducing the secondary transcriptional response. We demonstrate that WRKY70 is required for the induced expression of a set of genes defining some of the secondary transcriptional response, SAR protection, and NHP-dependent enhancement of reactive oxygen species production in response to flagellin treatment. Our study highlights the key genes and pathways defining early NHP responses and the role of WRKY70 in regulating NHP-dependent transcription.
Survey of potential fungal antagonists of coffee leaf rust (Hemileia vastatrix) on Coffea arabica in Hawai‘i, USA
Authors: Keith Lisa
Published: October 2024

Hemileia vastatrix, causal agent of coffee leaf rust (CLR), is an aggressive, economically devastating pathogen of coffee plants worldwide. Coffee leaf rust was discovered in Hawai‘i in 2020 and quickly spread throughout the state. Hawai‘i’s coffee industry, produced commercially on six islands by over 1,470 growers on more than 10,000 acres, is conservatively valued at $100M per year. Conventional fungicides have played a major role in the suppression of CLR, but due to a recent shift toward eco-friendly farming practices, additional novel, effective, and sustainable strategies for CLR control are needed. Naturally occurring fungal antagonists could be well-positioned to meet this demand; however, these fungi need to be isolated and tested for efficacy to identify organisms with potential. In this study, a survey of fungi associated with CLR lesions in three districts of Hawai‘i Island was conducted. Coffee leaves infected with CLR were collected from 22 locations and over 600 lesions co-infected with fungi were plated on selective media. DNA was extracted from purified isolates and the internal transcribed spacer region (ITS) was sequenced and analyzed by BLASTn. In total, 194 isolates comprising 50 taxa were recovered. Several of the genera are known antagonists of Hemileia vastatrix or other plant pathogens. The identification of potential CLR antagonists and their use by coffee farmers as part of an integrated pest management plan will be discussed.
Adjuvant Therapy after Esophagectomy for Esophageal Cancer: Who Needs It?: Multi-institution Worldwide Observational Study
Authors: Raja Siva , Rice Thomas W. , Lu Min , Semple Marie E. , Toth Andrew J. , Blackstone Eugene H. , Murthy Sudish C. , Ahmad Usman , McNamara Michael , Ishwaran Hemant ,   for the Worldwide Esophageal Cancer Collaboration Investigators
Published: October 2024

Objective:

Based on current practice guidelines, we hypothesized that most patients with esophageal cancer, particularly those with locally advanced cancer, would benefit from adjuvant therapy after esophagectomy versus esophagectomy alone. We sought to obtain a granular estimate of patient-level risk-adjusted survival for each therapeutic option by cancer histopathology and stage.

Background:

Although esophagectomy alone is now an uncommon therapy for treating locally advanced esophageal cancer, the value of adjuvant therapy after esophagectomy is unknown.

Methods:

From 1970 to 2014, 22,123 consecutive patients from 33 centers on 6 continents (Worldwide Esophageal Cancer Collaboration) were diagnosed with biopsy-proven adenocarcinoma (n = 7526) or squamous cell carcinoma (n = 5625), of whom 10,873 received esophagectomy alone and 2278 additional adjuvant therapy. Random forests for survival and virtual-twin analyses were performed for all-cause mortality.

Results:

For adenocarcinoma, adjuvant therapy was beneficial only in pT4NanyM0 cancers (6–8 month survival benefit) and in pTanyN3M0 cancers (4–8 month benefit); a survival decrement was observed in pT1-3N0M0 cancers, with no effect on TanyN1-2M0 cancers. In squamous cell carcinoma, there was a 4 to 21 month survival benefit for pT3-4N0M0 cancers and a 4 to 15 month survival benefit for pT2-4N1-3M0 cancers.

Conclusions:

Adjuvant therapy after esophagectomy appears to benefit most patients with node-positive squamous cell carcinoma, but for adenocarcinoma, its value is limited to deep cancers and to those with substantial nodal burden. Future studies of the role of adjuvant therapies should treat these 2 cancers differently, with guidelines reflecting the histopathologic-appropriate survival value of adjuvant therapy.
Morphological and Clinical Aspects of Pott’s Disease in Ancient Human Remains
Authors: Papa Veronica , Varotto Elena , Vaccarezza Mauro , Galassi Francesco M.
Published: October 2024

Study Design.

The present study is a scoping review of the literature on Pott’s disease in ancient human remains.

Objective.

Comprehending the origin and history of Pott’s disease is relevant to assessing this pathological condition from an evolutionary perspective.

Summary of Background Data.

Tuberculosis (TB) is an ancient pulmonary disease that remains the leading cause of death from a single infectious agent, rating above HIV/AIDS. The disease typically affects the lungs but can also target other anatomical sites. Of those, the most common and characteristic are the skeletal changes involving the spine, such as in Pott’s disease. Spinal tuberculosis accounts for approximately half of all cases of musculoskeletal tuberculosis. It can lead to loss of function in the lower limbs due to damage to the spinal column. Nevertheless, its origin and evolution are still not fully understood and need further investigation.

Methods.

The authors investigated the published studies on Pott’s disease in ancient human remains, intending to survey the literature, map the evidence and identify gaps and future perspectives on TB in paleopathology. The search strategy was conducted between September 2021 and March 2023 using keywords including the terms “Pott disease” OR “tuberculosis” AND “skeletal remains” in PubMed Biomed Central, Scopus, and Google Scholar search engines and biomedical databases. Five hundred and three records were initially identified, and 66 studies were finally included and assessed for qualitative analysis. Finally, the included records were analyzed in terms of non-narrative data, including the type of publication, country of excavation, dating of the sample, the number of human remains, and their details. Furthermore, the type of bone lesion was indicated as well as the diagnostic method if detailed.

Results.

Among articles identified, most were classified as original articles, and were published between 2011 and 2020. Close to 77% of the records reported excavation in Europe and the Near middle east. Included studies considered a total of 3388 human remains, mostly excavated in archaeological sites and necropolis. Interestingly, the reported prevalence was higher among young males and adults.

Conclusions.

Although most of the findings are consistent with the literature, since the majority of the human remains were from Europe and the Near Middle East, more research is necessary in other sectors of the world. The suggestion of a male predominance needs to be confirmed and questions about the possible pathognomic role of rib lesions as well Serpes endocranica symmetrica (SES) represent further areas of research that need to be explored.