bluuebunny/crossref_metadata_2025_split huggingface dataset:
END OF LIFE CARE IN BRAIN TUMOUR PATIENTS: DEMOGRAPHICS AND PREFERENCES
Authors: Mauricaite Radvile , Calvez Kerlann Le , Droney Joanne , Williams Matthew 
Published: September 2023

Abstract

AIMS
We used a regional NHS Electronic Palliative Care Coordination System (Coordinate My Care) to understand patient preferences and priorities for care at end-of-life. We present data on patient demographics and preferences and factors influencing the location of death in a primary brain tumour patient cohort.

METHOD
We identified all primary brain tumour patients from NW and SW London on the system. We examined patient demographics and compared the recorded preferred place of death (PPD) with the actual place and explored how patient demographics differ according to this.

RESULTS
Our dataset contains 1437 patients. 55% were male and 53% were 65 or older. 1222 (85%) were deceased. Of patients that had a recorded preference (N=987), 30 (3.0%) had hospital recorded as one of their two PPDs. Of those with a recorded place of death (N=864), 10.5% died in hospital. 24.8% had an unknown actual or PPD. Of those with a recorded preferred and actual place of death , 83.6% died in PPD. Patients who died at their preferred location had lower overall survival and were more likely to have stayed in a care home. A higher percentage of men compared to females died in a location other than their PPD.

CONCLUSIONS
Here we present preliminary analysis of patient provided data and their preferences for end-of-life care. We will triangulate these data end-of-life care data from Gliocova project, where we have data on over 50,000 brain tumour patients, to get a more in depth understanding of the patient care in the last months of life.
LOW-GRADE GLIOMAS IN OLDER PATIENTS: A MATCHED PROPENSITY-SCORING ANALYSIS TO DETERMINE SEIZURE OUTCOMES AND PROGNOSIS
Authors: Lee Jing Xian , Waqar Mueez , Younis Michael , Maye Helen , Bailey Matthew , D’urso Pietro , Coope David , Youshani Amir Saam , Karabatsou Konstantina 
Published: September 2023

Abstract

AIMS
Low-grade gliomas (LGG) are associated with significant morbidity and age is assumed to be a negative prognostic factor. The aim of this study was to compare outcomes between older patients with LGGs and a matched cohort of younger patients.

METHOD
Retrospective review of WHO grade II LGGs from 2009-2022. Propensity-score matching (1:3 matching) was used to compare older (≥65 years old) and matched younger controls (&lt;65 years old). The two groups were matched by age, gender, presenting seizures, Karnofsky performance status, location, extent of resection, use of awake neurosurgical monitoring, histology subtype and post-operative chemoradiotherapy. Survival analysis was performed using Kaplan-Meier survival curves and log-rank test.

RESULTS
40 patients were included - 10 older and 30 young. The median age was 70.0 and 48.5 years, respectively, with no differences in other demographic variables. Following resection, the older group had a shorter seizure-free period (median 2.5 vs. 10.9 months) and worse 1-year seizure-free rates (25.0% vs. 50.0%). Other outcomes were also worse in the older group including a shorter overall survival (median 95.0 vs. 117.0 months) and shorter progression-free survival (median 24.0 vs. 61.0 months).

CONCLUSIONS
In this novel study, we present the first matched analysis to evaluate outcomes in older patients with LGGs. We report worse seizure outcomes, overall survival and progression-free survival in these patients. Larger longitudinal multicentre studies will more accurately assess post-operative seizure-control and prognostic outcomes in between these groups.
A SINGLE CENTRE 10-YEAR EXPERIENCE WITH GAMMA KNIFE STEREOTACTIC RADIOSURGERY FOR CEREBRAL METASTASES
Authors: Crispi Vassili , Reveendran Dharsshini , Hatfield Paul , Mathew Ryan 
Published: September 2023

Abstract

AIMS
An estimated 20-40% of patients with metastatic cancer will have brain metastases, whose management depends on multiple factors. Stereotactic radiosurgery (SRS) is increasingly preferred to whole brain radio- therapy (WBRT), since it delivers a precise, high-dose of radiation to individual metastases.
This study evaluated the 10-year experience of SRS at the Leeds Gamma Knife Centre.

METHOD
This is a retrospective, observational study of patients undergoing SRS between 2010 and 2020. Data on primary tumour, Karnofsky Performance Status (KPS), previous treatment for brain metastases, intracranial disease burden, oral steroid therapy, and toxicity were recorded. Follow-up was undertaken for a minimum of 6 months with regular MRI brain.

RESULTS
3,940 intracranial metastases in 1,113 patients (478 male) were treated with SRS. Lung (48.2%) and breast (15%) were the most common primary tumours. Median survival was 10 months. Using multivariate analysis, primary diagnosis (p&lt;0.001), KPS (p&lt;0.001), number of lesions (p=0.005) and total tumour volume (p=0.012) were the most statistically significant predictors of survival.
At follow-up, 375 (33.7%) patients had new brain metastases. Median time to new metastases was 6 months, and 195 (17.5%) patients underwent further SRS with a median time to repeat SRS of 7 months.
Side effects following SRS were usually very mild, primarily including short-term fatigue (28.8%). Steroid dose also dropped significantly after SRS(p&lt;0.001).

CONCLUSIONS
This 10-year analysis of SRS in brain metastases demonstrated a statistically significant association of survival with pre-treatment predictors, including primary diagnosis, KPS, intracranial disease burden. SRS provides minimal side effects with an associated significant decrease in steroid use following treatment.
DEfiNING SPATIAL HETEROGENEITY OF A NOVEL LIVING BIOBANK OF POST-SURGICAL RESIDUAL GLIOBLASTOMA TO DEVELOP STRATEGIES FOR TARGETED THERAPY
Authors: McGarrity-Cottrell Connor , Myers Katie , Dunning Mark , Bagga Veejay , Sinna Saurabh , Al-Tamimi Yahia , Rominiyi Ola , Collis Spencer 
Published: September 2023

Abstract

AIMS
Glioblastoma is the most common cancer arising within the brain accounting for &gt;2,000 deaths/year in the UK. Current standard-of-care therapy consists of maximal safe surgical resection followed by radiochemotherapy which activates the cellular DNA damage response (DDR). However, disease prognosis remains poor (median OS ~12-15 months). This stagnation in the development and clinical translation of novel therapeutics is largely attributed to extensive inter- and intra-tumoral heterogeneity and resistant glioma stem cell (GSC) niches. Traditionally, primary ex vivo and in vivo models of glioblastoma have been generated from the resected tumour mass potentially omitting the post-surgical residual tumour cells that give rise to disease recurrence and morbidity.

METHOD
Multiple parallel primary ex vivo GSC cell models were generated from anatomically discrete regions of en-bloc partial lobectomy glioblastoma specimens to produce 3D models of resected (tumour “core”) and typically residual (distal invasive tumour “edge”) GSC niches. These models were characterised using an array of biomolecular techniques and 3D based assays.

RESULTS
Preliminary RNA-seq analyses revealed largely divergent transcriptional landscapes for resected vs residual GSCs and protein expression/immunofluorescence analyses also identified key differences in GSC and DDR ex- pression, and subsequent cellular responses to current standard-of-care radio-chemotherapy regimens.

CONCLUSIONS
These data reveal phenotypic relationships between GSC “stemness” and DDR activity, therefore highlighting the potential clinical relevance of our novel parallel resected and residual ex vivo glioblastoma models. Characterisation of further models from within our 3D GSC biobank will also aid evaluation of novel therapeutics capable of targeting post-surgical GSC subpopulations leading to improved disease outcomes.
SIMVASTATIN INHIBITS MEDULLOBLASTOMA CELL MIGRATION VIA TARGETING THE MEVALONATE PATHWAY
Authors: Comer Charley , Michod David , Niklison-Chirou Maria Victoria 
Published: September 2023

Abstract

AIMS
Medulloblastoma (MB) is the most common malignant paediatric brain tumour. Arising in the cerebellum, MBs consist of four subgroups: Wingless (WNT), Sonic Hedgehog (SHH), Group 3 (G3) and Group 4 (G4), each with unique molecular and genetic features and clinical outcomes. G3 and G4 are the most aggressive, with a high tendency to metastasise, but are the least characterized. Current treatment for MB is surgical resection, radiation and chemotherapy, associated with high morbidity and adverse side effects. Therefore, more targeted and less toxic therapies are needed to improve quality of life for survivors. Cancer cells can enhance lipid metabolism through upregulation of the mevalonate pathway (MVP). Aberrant activity of MVP in tumour cells has been widely reported. Previous studies have shown statins can decrease mortality in colorectal, breast and lung cancer patients, and even decrease metastasis of osteosarcoma. Notably, simvastatin can penetrate the blood-brain barrier. This study aims to utilise statins as a potential novel therapy for MB metastasis.

METHOD
In silico gene expression analysis was performed to evaluate expression of enzymes involved in MVP in MB, validated through immunocytochemistry and RT-PCR in SHH, G3 and G4 cell lines. Further study analysed the anti-cancer and anti-metastatic potential of simvastatin using both 2D and 3D cell culture methods.

RESULTS
Results show that in 2D and 3D cell culture, simvastatin is capable of decreasing migration of MB cells in vitro.

CONCLUSIONS
Our work demonstrates that simvastatin has the capacity to decrease MB cell invasion, therefore making it an appealing novel therapy option for MB tumours.
AUTOMATIC DETECTION OF FACIAL LOCATIONS TO MEASURE FACIAL ASYMMETRY AFTER PAEDIATRIC RADIOTHERAPY
Authors: Dronne Clea , Durrant Helena , Davey Angela , Henderson Edward , Osorio Eliana Vasquez , Aznar Marianne 
Published: September 2023

Abstract

AIMS
Children receiving radiotherapy for head and neck tumours, such as Head and Neck Rhabdomyosarcoma (HN- RMS), often experience facial asymmetry later in life. Here, we present a convolutional neural network (CNN) that will enable the automatic detection of facial anatomical landmarks on MR images taken during follow-up examinations. This model will facilitate quantitative tracking of facial asymmetry, thus revealing the centres of growth that are most affected by radiation, with the ultimate goal of defining precise dose tolerance levels.

METHOD
A dataset of 61 paediatric MRI images was used to train separate models that infer the locations of four facial landmarks. These locations had previously been manually labelled by two independent observers. Before training, the images were normalised and registered to optimise model performance. The model was judged to be of acceptable accuracy if the distances between the observed landmark (gold-standard location) and the location predicted by the trained models were smaller than the inter-observer distances of each facial landmark.

RESULTS
The model predicted landmarks which were closer to the gold-standard location than the inter-observer locations. In detail:
• Optic chiasm: 0.81 ± 0.45 mm (inter-observer 1.49 mm).
• Nasion: 0.70 ± 0.62 mm (inter-observer 3.24 mm).
• Left Ectoconchion: 1.22 ± 0.44 mm (inter-observer 3.58 mm).
• Right Ectoconchion: 0.80 ± 0.82 mm (inter-observer 4.04 mm).

CONCLUSIONS
This research shows promising potential for a CNN to accurately locate head and neck landmarks in paediatric MRI images. This tool can label craniofacial landmarks in large clinical datasets quicker and more accurately than can be achieved through manual techniques.
IDENTIFYING ROLE OF YB1 AND NPM1 AS PART OF HISTONE 3 MUTANT PROTEIN INTERACTOME, IN H3 MUTATED PHGG
Authors: Cambampaty Tarak , Barrow Lucy , Layfield Robert , Haque Farhana 
Published: September 2023

Abstract

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. Studies show prominent mutations as being H3.3K27M and H3.3G34R/V.
Our previous research has identified unique and common interacting binding partners of H3-G34R and H3-G34V mutant proteins. Among these we have focused on YB-1 and Nucleophosmin (NPM1). YB-1 is multifunctional transcription factor and a well-known oncogenic protein. NPM1 is a molecular chaperone and frequently over- expressed in cancer as well. Our aim is to analyse the role of YB-1 and NPM1 in H3 mutated pHGG, in order to identify targeted therapeutic option for these diffcult to treat tumours.

METHOD
Further data analyses of mass spectrometric proteomic data were performed. Subsequently, H3 mutated glioma cell lines, and control H3 wild type pHGG cells were cultured and then subjected to proteomic analyses. A comparative immunofluorescence and microscopy, and western blot analyses were performed to investigate the role of YB-1 and NPM-1.

RESULTS
Results verified the proteomic data and further showed altered protein expression of YB-1 and altered localization of protein NPM1 in H3 mutated pHGG.

CONCLUSIONS
Results of the study support that YB-1 and NPM1 are important interacting proteins in H3G34-mutated pHGGs and can be explored as therapeutic targets in H3 mutated pHGG.
RECOVER REALITY FEASIBILITY TRIAL: INVESTIGATING THE FEASIBILITY OF IMMERSIVE TECHNOLOGIES TO ENHANCE NEUROREHABILITATION EDUCATION AFTER NEUROSURGERY FOR BRAIN CANCER
Authors: Bolton William , Sinha Rohit , Adebola Oluwaseyi , Stephenson Elisa , Cooper Sara , Ewan Seonaid , Mathew Ryan 
Published: September 2023

Abstract

AIMS
Neurorehabilitation is fundamental to better outcomes for those recovering from neurosurgery for brain cancer. Access to this essential therapy is limited by resource shortages and unfulfilled therapy needs lead to longer hospital stays. Immersive technologies such as virtual reality (VR) could be used to augment neurorehabilitation in a self-directed, safe, virtual environment. The aim of this study is to demonstrate the feasibility of a VR rehabilitation programme in an acute neurosurgical inpatient environment to augment neurorehabilitation.

METHOD
A single group, feasibility study was conducted in a tertiary UK neurosurgical department. Patients aged 16 and over who had undergone a neurosurgical intervention for brain tumours were eligible. Participants were offered a VR session at least once per day for the first 14 days post-surgery/injury or until discharge, whichever comes first, with reasons for non-engagement collected. Primary outcomes were feasibility outcomes, and secondary outcomes included rehabilitation engagement and length of stay.

RESULTS
Data collection is ongoing. At submission we have n=6 participants who used the VR. A seventh participant who was screened for inclusion declined, citing anxiety over causing headaches as the reason. All six participants used the VR on either post operative day 2 or day 3. Although offered VR on the immediate day after surgery, participants declined due to nausea or pain.

CONCLUSIONS
If this present study demonstrates feasibility of using VR in patients after neurosurgery for brain cancer, a randomised clinical effectiveness study with health-economics analysis will follow to inform widespread adoption into practice.
FISH-BASED INVESTIGATION OF CDKN2A AND IFNA14 IN GLIOBLASTOMA
Authors: Shboul Sofian Al , Boyle Shelagh , Singh Ashita , Saleh Tareq , AlRjoub Moath , Karsaneh Ola Abu Al , Mryyian Amel , Dawoud Rand , Gul Sinem , baker Shaden Abu , Ball Kathryn , Hupp Ted , Brennan Paul 
Published: September 2023

Abstract

AIMS
Glioblastoma (GBM) tumours have a dismal prognosis despite aggressive anticancer therapy. Deletion of CDKN2A is among the most common genetic changes in GBM (~50%) and has been strongly associated with worse prognosis. Next generation DNA sequencing had shown that deletion of IFNA genes (located proximal to CDKN2A) is also a major genetic event in GBM (~25%). Clinical Identification of in vivo state of these two genes might facilitate improved individualized therapeutics.

METHOD
Glioma tissue microarray consisting of 45 samples was used to assess the co-deletion of CDKN2A and IFNA14 genes simultaneously, using a novel three-color fluorescence in situ hybridization (FISH) probe. We examined the correlation between CDKN2A and p16INK4a protein expression detected using immunohistochemistry (IHC).

RESULTS
FISH analysis showed that 44% of the primary GBMs harboured homozygous deletions of both CDKN2a and INFA14. By contrast, all grade II and III gliomas, had either wild-type or amplified CDKN2A and INFA14. All samples that showed CDKN2A homozygous deletion (n=11) were negative for p16INK4a staining, while 20 cores that were positive for p16INK4a expression did not harbour CDKN2A deletion. Survival curves of primary GBMs suggested that both the co-deletion of CDKN2A/INFA14 and negative p16INK4a expression were associated with shorter survival time.

CONCLUSIONS
Our FISH/IHC analyses indicate a strong correlation between CDKN2A and p16INK4a protein expression in grade III/II glioma, suggesting that amplification of CDKN2A might act as a gatekeeper to reduce the incidence of grade
IV. Our data also highlight the high frequency of CDKN2A/INFA14 co-deletion in GBM tumours that might together impact on survival time.
FOCAL MANAGEMENT OF BRAIN METASTASES IN SMALL CELL LUNG CANCER: A SYSTEMATIC REVIEW
Authors: Wong Claudia Dols , Chandy Edward , Critchley Giles , Robinson Stephen David 
Published: September 2023

Abstract

AIMS
Small cell lung cancer (SCLC) brain metastases (BM) are common at both presentation and relapse. Historically, BM are managed with whole brain radiotherapy (WBRT) +/- chemotherapy. However, WBRT is associated with significant cognitive impairment, and so interest in the focal management of BM (encompassing stereotactic radiosurgery (SRS) and surgery) is increasing. We systematically reviewed the current literature regarding focal BM management.

METHOD
A systematic literature search of PubMed, Embase, and CENTRAL databases and clinicaltrials.gov was conducted to obtain published articles, abstracts, and ongoing studies regarding focal management of SCLC BM. Exclusion criteria included publication before 2005 and publication in a non-English language. Additional papers were added by reviewing citations of relevant papers.

RESULTS
Following initial review of 15,420 records, we identified 67 articles eligible for inclusion. 24 were published before 2015 and 44 published 2015-2023. 8 related to surgical BM treatment: case studies (n=6), retrospective cohort studies (n=2). 60 articles were identified regarding SRS: abstracts (n=13), case studies (n=5), retrospective cohort studies (n=14), retrospective case series (n=20), prospective trials (n=8). These papers have been further divided by topic: upfront SRS (n=23), salvage SRS (n=19) and WBRT with SRS boost (n=3). There are several ongoing trials (n=8) investigating outcomes in SRS for SCLC BM, both alone and when compared with WBRT.

CONCLUSIONS
Focal treatments for SCLC BM are being used more frequently. However, randomised trial evidence for their safety and effectiveness are still pending.
Indoximod-based chemo-immunotherapy for pediatric brain tumors: A first-in-children phase I trial
Authors: Johnson Theodore S , MacDonald Tobey J , Pacholczyk Rafal , Aguilera Dolly , Al-Basheer Ahmad , Bajaj Manish , Bandopadhayay Pratiti , Berrong Zuzana , Bouffet Eric , Castellino Robert C , Dorris Kathleen , Eaton Bree R , Esiashvili Natia , Fangusaro Jason R , Foreman Nicholas , Fridlyand Diana , Giller Cole , Heger Ian M , Huang Chenbin , Kadom Nadja , Kennedy Eugene P , Manoharan Neevika , Martin William , McDonough Colleen , Parker Rebecca S , Ramaswamy Vijay , Ring Eric , Rojiani Amyn , Sadek Ramses F , Satpathy Sarthak , Schniederjan Matthew , Smith Amy , Smith Christopher , Thomas Beena E , Vaizer Rachel , Yeo Kee Kiat , Bhasin Manoj K , Munn David H 
Published: September 2023

Abstract

Background
Recurrent brain tumors are the leading cause of cancer death in children. Indoleamine 2,3-dioxygenase (IDO) is a targetable metabolic checkpoint that, in preclinical models, inhibits anti-tumor immunity following chemotherapy.

Methods
We conducted a phase I trial (NCT02502708) of the oral IDO-pathway inhibitor indoximod in children with recurrent brain tumors or newly diagnosed diffuse intrinsic pontine glioma (DIPG). Separate dose-finding arms were performed for indoximod in combination with oral temozolomide (200 mg/m2/day x 5 days in 28-day cycles), or with palliative conformal radiation. Blood samples were collected at baseline and monthly for single-cell RNA-sequencing with paired single-cell T cell receptor sequencing.

Results
Eighty-one patients were treated with indoximod-based combination therapy. Median follow-up was 52 months (range 39–77 months). Maximum tolerated dose was not reached, and the pediatric dose of indoximod was determined as 19.2 mg/kg/dose, twice daily. Median overall survival was 13.3 months (n = 68, range 0.2–62.7) for all patients with recurrent disease and 14.4 months (n = 13, range 4.7–29.7) for DIPG. The subset of n = 26 patients who showed evidence of objective response (even a partial or mixed response) had over 3-fold longer median OS (25.2 months, range 5.4–61.9, p = 0.006) compared to n = 37 nonresponders (7.3 months, range 0.2–62.7). Four patients remain free of active disease longer than 36 months. Single-cell sequencing confirmed emergence of new circulating CD8 T cell clonotypes with late effector phenotype.

Conclusions
Indoximod was well tolerated and could be safely combined with chemotherapy and radiation. Encouraging preliminary evidence of efficacy supports advancing to Phase II/III trials for pediatric brain tumors.
Using Developmental Evaluation to Support Adaptive Strategies
Authors: Coffman Julia , Beer Tanya , Stid Daniel , Armstrong Kathy 
Published: September 2023

Abstract
Developmental evaluation is well suited for emergent strategies that are tackling problems rooted in complex systems. This chapter describes the use of developmental evaluation during the initial years of a complex philanthropic initiative focused on strengthening US democracy and its institutions—especially Congress—in a time of political polarization. Because the initiative reflected a different way of thinking about foundation strategy that was emergent and systems-focused, an innovative evaluation and learning approach was used to support ongoing decision-making and adaptation. The chapter, authored by and written from the perspective of both strategists and evaluators, describes the methods used, how the evaluation informed strategy, and reflections and lessons on the developmental evaluation experience and approach.
Process and Implementation Evaluation Methods
Authors: Rogers Patricia J. , Woolcock Michael 
Published: September 2023

Abstract
Beyond assessing whether or not interventions have achieved their stated goals, evaluations can also provide greater understanding—in real time and at completion—about how, where, for whom, over what time frame, and which aspects of an intervention may (or may not) have succeeded, and where improvements might be sought. Implementation evaluations help identify where breakdowns in the delivery system may have occurred and spaces wherein frontline implementers were able to find innovative solutions to local (“binding constraint”) problems. Process and implementation evaluations serve the vital purpose of jointly promoting accountability and learning, and provide discipline to internal procedures for promoting partnerships, innovation, and improvement. In this chapter, the authors describe six different types of process and implementation evaluations and describe their respective strengths and weaknesses in various contexts. As part of collective efforts to enhance the effectiveness of all classes of interventions, impact and process evaluations should be regarded as necessary complements.