bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiparametric 18F-Choline PET/MR in childhood and teenage-young adult gliomas: assessment of suspected disease progression
Authors: Ferrazzoli Valentina , Shankar Ananth , V Cockle Julia , Tang Christine , Bomanji Francesco Fraioli Jamshed , Hyare Harpreet 
Published: October 2019

Abstract

Aim
Evaluation of post-treatment glioma burden remains a significant challenge in childhood, Teenage and Young Adults (TYA). Although amino acid PET impacts on glioma imaging, 18fluoro-Choline Positron Emission Tomography (ChoPET) is more widely available. The aim was to evaluate the utility of ChoPET/MRI for suspected disease progression in childhood and TYA gliomas.

Methods
27 consecutive patients with suspected glioma disease progression were evaluated with ChoPET/MR and 59 scans included. Relative cerebral blood volume (rCBV), ADC and SUVmax in enhancing (enh), non-enhancing (ne) tumour volumes and normal appearing white matter (wm) were calculated (rCBVenh, rCBVne, rCBVwm, ADCenh, ADCne, ADCwm, SUVenh, SUVne, SUVwm). Blinded nuclear medicine and neuroradiologist scored the images on tumour probability (1:unlikely-5:definitely). Receiver Operating Characteristic (ROC) analysis considering as gold standard histopathology or clinical follow-up was performed.

Results
Combined ChoPET/MR accuracy was 100% for residual tumour, conventional MR accuracy was 96.3% (91.7% <14years, 100% ≥15years) and ChoPET accuracy was 73.1% (66.7% <14years, 80.0% ≥15 years). Lack ack of agreement in 9/27 with ChoPET superior to MR in 1 case. Tumour component analysis demonstrated significantly higher SUVenh and SUVne than SUVwm (SUVenh: p<0.001,SUVne: p=0.003) equivalent to ADC (ADCenh, ADCnenh: p<0.001) and rCBV (rCBVenh, rCBVnenh: p<0,001).

Conclusions
Combined ChoPET/MR has 100% accuracy in TYA gliomas with suspected disease progression. ChoPET is able to detect enhancing and non-enhancing tumour but it is more reliable for evaluating enhancing disease >15 years. In selected cases where MRI is equivocal, a quantitative multi-modality ChoPET/MR better defines both enhancing and non-enhancing tumour for improved assessment of childhood and TYA gliomas.
Predicting meningioma recurrence using spectrochemical analysis of tissues and subsequent predictive computational algorithms
Authors: Lilo Taha , Morais Camilo , Ashton Kate , Pardilho Ana , Dawson Timothy , Gurusinghe Nihal , Davis Charles , Martin Frank 
Published: October 2019

Abstract

Introduction
Meningioma recurrence remains a clinical dilemma. This has a significant clinical and huge financial implication. Hence, the search for predictors for meningioma recurrence has become an increasingly urgent research topic in recent years.

Objective
Using spectrochemical analytical methods such as attenuated total reflection Fourier-transform infrared (ATR-FTIR) and Raman spectroscopy, our primary objective is to compare the spectral fingerprint signature of WHO grade I meningioma vs. WHO grade I meningioma that recurred. Secondary objectives compare WHO grade I meningioma vs. WHO grade II meningioma and WHO grade II meningioma vs. WHO grade I meningioma recurrence.

Materials and Methods
Our selection criteria included convexity meningioma only restricted to Simpson grade I & II only and WHO grade I & grade II only with a minimum 5 years follow up. We obtained tissue from tumour blocks retrieved from the tissue bank. These were sectioned onto slides and de-waxed prior to ATR-FTIR or Raman spectrochemical analysis. Derived spectral datasets were then explored for discriminating features using computational algorithms in the IRootLab toolbox within MATLAB; this allowed for classification and feature extraction.

Results
After analysing the data using various classification algorithms with cross-validation to avoid over-fitting of the spectral data, we can readily and blindly segregate those meningioma samples that recurred from those that did not recur in the follow-up timeframe. The forward feature extraction classification algorithms generated results that exhibited excellent sensitivity and specificity, especially with spectra obtained following ATR-FTIR spectroscopy. Our secondary objectives remain to be fully developed.
Characterisation of the invasive tumour niche using astrocyte-glioblastoma organoids and decellularised human brain
Authors: Diksin Mohammed , Rowlinson Jonathan , Kondrashov Alexandar , Denning Chris , Hughes Jamie , Constantin-Teodo Tim , Cui Wei , Gell Chris , Onion David , Croxall Nicola , Smith Stuart , Rahman Ruman 
Published: October 2019

Abstract
Glioblastoma therapeutic challenges are in considerable part due to myriad survival adaptations and mechanisms, which allow malignant cells to repurpose signalling pathways within discreet microenvironments. These Darwinian adaptations facilitate invasion into brain parenchyma and perivascular space or promote evasion from repressive factors that represent anti-cancer defence mechanisms.
We hypothesised that pre-clinical modelling of glioma invasion by recapitulating early events occurring immediately after surgery at the glioblastoma invasive margin, could reveal the cross-talk between malignant cells and the surrounding healthy astrocytes, which facilitates tumour recurrence.
We first generated transgenic H1-derived neural stem cells using CRISPR/Cas9-mediated knock-in of the YFP reporter gene under the control of the GFAP promoter. Reproducible ultrahigh-throughput AggreWells™ (19,200 micro-wells per 24-well plate) were used to create astrocyte-glioblastoma organoids, which we term ‘Gliomasphere Matrices’. YFP-labelled astrocytes were co-cultured with 10 treatment-naïve patient-derived cell lines isolated from the 5-aminolevulinic (5ALA)-determined glioblastoma invasive margin. Co-cultures were seeded upon on a sequentially constructed, time-of-flight secondary ion mass spectrometry (ToF-SIMS)-characterised 3D scaffold, composed of decellularised human brain extract with defined PEGDA hydrogel.
YFP-astrocytes were purified from each of the 10 Gliomasphere Matrices using fluorescence-activated cell sorting (FACS) after 6- and 10-days co-culture. RNAseq profiling to address both putative astrocytic reprogramming by invasive glioblastoma cells and gene expression changes intrinsic to tumour cells will be discussed in relation to RNAseq data from patient-derived 5ALA FACS-purified glioblastoma invasive margin tissue.
This novel multi-faceted model offers a unique opportunity to recapitulate early molecular cross-talk which facilitates glioblastoma recurrence and may be utilised for high-throughput drug screening.
CRISPR/Cas9 gene editing of brain cancer stem cells using lipid-based nano-delivery
Authors: Rouatbi Nadia , Mun Lim Yau , Grant Vivien , Miguel Costa Pedro , Pollard Steven M , Wang Julie Tzu-Wen , Al-Jamal Khuloud T 
Published: October 2019

Abstract
Despite advances in cancer therapy glioblastoma (GBM) remains one of the deadliest brain tumours. Effective therapy is restricted by the presence of multiple resistance mechanisms. Physical barriers such as the blood-brain barrier limit the brain delivery of therapeutic compounds. In addition, the presence of a subset of GBM-stem-like cells (GSCs), characterized by radio/chemoresistance, and the intratumor heterogeneity impede standard therapies from being effective. New therapeutic approaches are urgently needed. Given its high specificity, CRISPR/Cas9-mediated genome editing provides new prospects for novel therapeutic targets. While promising, in vivo application of CRISPR/Cas9 is currently hampered by poor pharmacokinetics and limited ability to cross biological membranes.
The present research is designed to utilise stable nucleic acid lipid nanoparticles (SNALPs) for in vivo delivery of CRISPR/Cas9 to GSC by disrupting the epidermal growth factor receptor variant III (EGFRvIII), a GBM associated mutation, responsible for tumour cell proliferation, angiogenesis and invasion. Near Infrared fluorescence labelling and live optical imaging confirmed SNALPs uptake in GSC tumours implanted intracranially in mice after intravenous injection. Higher uptake of SNALPs in tumourous tissues compared to healthy brain tissues was further confirmed by ex vivo imaging and flow cytometry. EGFRvIII-specific sgRNA has been designed and validated in GSCs using commercial transfection regents. Studies are underway to load CRISPR/Cas9 mRNA/gRNA into SNALPs to test their in vitro gene editing efficacy. Successful in vivo delivery of CRISPR/Cas9 will represent a promising approach for identifying GBM therapeutic targets in vivo which in the long-run can be applied for GBM treatment.
Low grade glioma patients: how does this patient group perceive their quality of life prior to surgical or oncological interventions?
Authors: Robinson Charlotte , Pedro Lavrador Jose , Gullan Richard , Brazil Lucy , Swampillai Angela , Al’Salihi Omar , Bhangoo Ranj , Vergani Francesco , Hurwitz Vicky , La Jess , Mullens Laura , Ford Liz , Mcewan Maria , Ashkan Keyoumars 
Published: October 2019

Abstract

Introduction
Literature analysing how patients with a provisional low-grade glioma perceive their own quality of life prior to any surgical or oncological intervention is scarce. This patient group are often highly functioning individuals, able to lead ordinary lives which stresses that their management must be carefully considered in a holistic sense. Low grade gliomas represent 5 % of brain tumours and they are typically of a younger cohort who will be less equipped to manage the uncertainties a diagnosis like this brings.

Methods
Prospective single centre cohort study over 14 months where 56 patients completed the EORTC QLQ – BN 20 and 30 prior to initial consultation in the dedicated low grade glioma clinic.

Results
54% of patients did not feel ‘limited in doing work or other daily activities’ but of those who were affected to some degree, 21% of women felt ‘very much affected’ compared to 3% of men. 78% of patients expressed to a degree some ‘uncertainty about the future’ and this was shown to be a common theme among all age groups which reflects the huge burden of anxiety this patient group faces regardless of age.

Conclusion
Data demonstrated a variety of quality of life scores that are not particular to a certain age group/gender which reinforces the importance of individual assessment as assumptions of patients in a particular category cannot be made. By assessing quality of life, clinical management is improved as a more in-depth assessment is facilitated on an individual basis and patient experience is enhanced.
New trial of convection enhanced drug delivery (CED) in DIPG- applying the SIOPe DIPG survival prediction model for power calculation.
Authors: Szychot Elwira , Collins Peter , Cassidy Hannah , Desai Mohammed , Hyare Harpreet , Shankar Ananth , Gill Steven , van Vuurden Dannis , Veldhuijzen van Zanten Sophie , Walker David 
Published: October 2019

Abstract

Background
In diffuse intrinsic pontine glioma (DIPG) drug resistance is in part due to inadequate penetration of blood-brain barrier (BBB) by systemically administered drugs. Convection-enhanced drug delivery (CED) techniques have been established to bypass BBB. Trial design to measure efficacy requires evidence to justify power calculation.

Aims
To apply SIOPe DIPG registry survival prediction tool to pilot cohort of children with DIPG treated with CED of carboplatin and sodium valproate.

Methods
Case note and imaging review of 9 children with typical DIPG on imaging who were treated on compassionate basis with CED intra-tumoural infusions of carboplatin (0.12 mg/ml) and sodium valproate (14.4 mg/ml), after radiotherapy (n=9) and chemotherapy (n=4). Each had Renishaw device placed with 4 micro-catheters located within tumour mass. Up to 8 treatment cycles of CED infusions delivered through 2 pairs of catheters on 2 days to encompass pontine tumour volume. Survival prediction was performed using clinical criteria: age, sex, duration of symptoms, prior chemotherapy; and radiological criteria: absence of distant metastases; disease involving more than 50% of, and confined to, pons, ring enhancement at diagnosis.

Results
Cases were categorized as intermediate or high-risk using SIOPe risk scoring with predicted median overall survival (OS) of 9.7, and 7.0 months, respectively. Four patients, categorized as high-risk, had median overall survival (OS) of 14.2 months. Five children, categorized as standard-risk, had median OS of 16.0 months.

Conclusions
Results justify a phase 2 trial of CED carboplatin and sodium valproate powered to detect at least 4-month prolongation of survival.
Using surgical and oncology workload to plan brain tumour trial recruitment in England
Authors: Le Calvez Kerlann , Treasure Peter , Williams Matt 
Published: October 2019

Abstract

Introduction
Access to clinical trials is a common request for patients with brain tumours. However, opening clinical trials requires additional work per centre opened. We have previously shown that surgical and oncology workload varies between centres, and fluctuates over time. There is a trade-off between offering access to clinical trials and increasing costs associated with opening trials in centres that treat few patients.

Methods
We used two separate datasets from England covering 3 years – one for neurosurgical workload and one for radiotherapy. We only included adult patients and calculated cumulative proportions of the malignant primary brain tumour population (C71) by number of centres. We investigated stability by checking how many patients would have to be added/ removed from a centre to change their rank.

Results
There were 7061 surgical and 5060 radiotherapy patients. To capture 25% of patients, we would need to open trials in 4 surgical/5 radiotherapy centres; for 50%, 9 surgical/ 13 radiotherapy centres; for 75%, 16 surgical/ 24 radiotherapy centres. Centre rank was fluid: adding 16 surgical/9 radiotherapy patients would change the rank of a centre.

Discussion
These are the first data to allow for rational planning of trials in brain tumour patients. We have shown that we can reach 75% of the brain tumour population by opening trials in ~50% of surgical and radiotherapy centres. Centre rank alters over year, so we should be cautious about being too prescriptive. Nonetheless, these data should allow some rational planning of trial centre inclusion.
Early effects of surgery and radiotherapy on activity levels in patients with brain tumours: preliminary data from the BrainWear trial
Authors: Dadhania Seem , Wei Wang James , Yu Boyu , Saleem Waqar , Blake Catherine , Shahabi Lillie , Williams Matthew 
Published: October 2019

Abstract

Background
BrainWear is a phase II observational clinical trial which collects data on patient activity levels, fatigue, Quality of Life (QoL) and imaging in patients with brain tumours

Methods
Newly diagnosed patients were offered wrist worn accelerometers (Axivity AX3) to be worn continuously throughout their treatment (surgery, chemoradiotherapy or radiotherapy) to monitor physical activity. We collected standardised measures of QoL, fatigue, MRI imaging data and disease progression. Here, we report early results on activity data 5 days before and after treatment.

Results
Of 23 patients recruited, we report complete pre and post treatment data in 4 patients (2 HGG, 2 metastatic) who underwent craniotomy (2), fractionated radiotherapy (1) and SRS (1). Both craniotomy patients experienced an immediate 60 – 70% reduction in activity, and were successfully discharged at day 2 post-op even though their activity was still significantly reduced. Both patients recovered another 10% in their activity levels following discharge. Radiotherapy patients experienced no early change within 5 days of starting treatment.

Conclusion
As expected craniotomy results in much larger changes in activity levels than SRS and radical radiotherapy. Activity levels recover post craniotomy, but this takes > 5 days.
Using wearable activity monitors in brain tumour patients is feasible, although there are multiple practical problems. Interpreting such data will require consideration of inpatient vs. outpatient settings.
Patient Reported Experience Measures in navigated Transcranial Magnetic Stimulation
Authors: Patel Sabina , Lavrador José , Ghimire Prajwal , Gullan Richard , Ashkan Keyoumars , Bhangoo Ranjeev , Vergani Francesco 
Published: October 2019

Abstract

Introduction
Navigated Transcranial Magnetic Stimulation (nTMS) is a non-invasive adjunct used in surgical planning for lesions in eloquent brain. However, its patient tolerability and effect on their overall healthcare experience is still unknown. To our knowledge, there is no other literature available evaluating patient experience with nTMS.

Methods
A single-institution prospective cohort study carried out between February 2018 and December 2018 at King’s College Hospital. All patients were supplied with a PREMs-TMS questionnaire to evaluate the different domains of the nTMS experience.

Results
Feedback was obtained from 50 patients. 26% of patients underwent motor mapping (MM), whilst 74% underwent both motor and language mapping (MLM). The former group reported a better overall experience (p=0.020). The mean exam duration was 103.3±5.1 min (MM 85.8±6.1 min; MLM 106.9±5.9 min). The whole experience of nTMS received positive feedback (94%), particularly with confidence in the staff (95%). Unsurprisingly, the exam domain received a poorer rating (70% as good) with significant anxiety and pain reported in 26% and 24% of patients respectively. None of the studied variables influenced the way patients rated the overall experience of nTMS (p>0.05).

Conclusions
nTMS is a non-invasive investigative tool, which allows patients to better understand their condition and symptoms related to their lesion. Serial assessment and feedback using a PREM tool, can only improve and enhance this experience. Departmental collaboration may be useful in comparing patient experience with nTMS in different centres.
Improving multidisciplinary communication during awake craniotomy: First use of a novel robotic exoscope
Authors: Anzak Anam , Alamri Alex , Doke Thomas , McKenna Grainne , Elsmore Andrew , Paraskevopoulos Dimitri , McKintosh Edward 
Published: October 2019

Abstract

Background
Awake craniotomies require exceptional intra-operative communication between the multidisciplinary team. This is difficult with traditional operating microscopes, where the operative field cannot be visualised by all parties. The Synaptive Modus V is a hands-free, robotic, extracorporeal telescope (exoscope), allowing images to be viewed on multiple large monitors. The Royal London Hospital is the first United Kingdom installation of this device and the first unit in Europe to apply it to awake craniotomies for low-grade glioma.

Methods
Two consecutive patients with low grade glioma underwent awake craniotomy using the Modus V. Qualitative feedback (semi-structured interview) was received from the MDT including surgeons, occupational/ speech and language/ physio-therapists, neurophysiologists, anaesthetists and scrub team. Optimal device positioning is described.

Results
Both female patients (38 and 52 years old) underwent surgery between December 2018 and February 2019. Lesions were located in right perisylvian and posterior inferior frontal gyrus locations respectively.
Surgical resection was satisfactory. Patient 1 developed a wrist-drop intra-operatively. Patient 2 had transient mild word finding difficulties. Surgeons reported easier surgical flow with hands-free positioning, larger working area and improved ergonomics. Adapting to non-stereoscopic vision increased operating times. Multi-disciplinary team members reported an better communication with the operating surgeon during patient assessment and a more involved educational experience.

Conclusion
Hands-free exoscopes may provide improved surgical flow and efficiency for awake craniotomy whilst simultaneously improving multidisciplinary communication and education. There is an, as yet, unidentified learning curve for its use that requires learning curve data generation.
Brain mapping for lesions in primary motor cortex: integrated surgical approach
Authors: Lavrador José , Ghimire Prajwal , Brogna Christian , Furlanetti Luciano , Patel Sabina , Gullan Richard , Ashkan Keyoumars , Bhangoo Ranjeev , Vergani Francesco 
Published: October 2019

Abstract

Background
Lesions within the corticospinal tract (CST) represent significant surgical challenge with a delicate functional trade-off that should be integrated in the overall patient-centred treatment plan.

Methods
Patients with lesions within the CST with preoperative cortical and subcortical mapping (nTMS and tractography), intraoperative mapping and intraoperative provisional histological information (smear +- 5-ALA) were included. This independently acquired information was integrated in a decision-making process model to determine the intraoperative extent of resection.

Results
10 patients (6 patients with metastatic precentral tumour; 1 patient with Grade III and 2 patients with grade IV gliomas; 1 patient with precentral vascular malformation) were included in the study. Majority of the patient had pre-operative motor deficit (60%). 50% patients underwent gross total resection and 40% patients underwent near total resection of the lesions. In only one patient, no surgical resection was possible after both pre-operative and intraoperative mapping. 70% of patients remained stable postoperatively and 20% improved from previous motor weakness.

Conclusion
The independently acquired anatomical (anatomical MRI) and functional (nTMS and tractography) in patients with CST lesions provide a more accurate guide for resection. The inclusion of the histological information (smear +- 5-ALA) further allows the surgical team to balance the potential functional risks within the global treatment plan. Therefore, the patient is kept at the centre of the informed decision making process.
Grade III meningioma: 10 year single centre case series
Authors: Mcgrath Hari , Lavrador Jose , Christodoulides Ioannis , Ghimire Prajwal , Gullan Richard , Bhangoo Ranjeev , Ashkan Keyoumars , Vergani Francesco 
Published: October 2019

Abstract

Rationale
WHO Grade 3 meningiomas are a rare, malignant subtype of meningioma. Few controlled case series detailing its treatment and follow-up are to be found in the literature.

Methods
Retrospective cohort study of patients treated in a single neuro-oncology centre in the period between September 2008 and March 2019 with an initial diagnosis of WHO Grade 3 meningioma. Demographic and clinical data has been collected from the available medical records.

Results
9 patients were included in this series: 2 had convexity, 2 sphenoid wing, 2 parafalcine, 1 parasagittal with a further 3 multiple locations and 1 patient with parietal convexity meningioma. 3 tumours displayed rhabdoid features, whilst 4 displayed papillary features and a further 2 displayed epithelial structures. All patients underwent surgical intervention: 5 patients had a subtotal resection with 3 having total resection. 3/4 of reported Simpson Grading was grade 2, whilst the remaining 1/4 was grade 1. The extent of resection for 1 patient was uncertain. Post surgically, 6 received adjuvant radiotherapy, 2 had no further treatment and 1 received gamma knife therapy. No patient received chemotherapy. 5 patients saw no tumour recurrence at follow up appointments (mean 50 months). Within 2 years of their respective surgical interventions, 4 patients died due to tumour recurrence and associated complications (3 patients).

Conclusion
To establish a uniform approach to treatment of patients with WHO Grade 3 meningiomas is challenging. Management involves a patient-centred approach based on multidisciplinary meeting decisions. Multicentre registries may allow further conclusions.