During 2006–2021, Canada had 55 laboratory-confirmed outbreaks of foodborne botulism, involving 67 cases. The mean annual incidence was 0.01 case/100,000 population. Foodborne botulism in Indigenous ...communities accounted for 46% of all cases, which is down from 85% of all cases during 1990–2005. Among all cases, 52% were caused by botulinum neurotoxin type E, but types A (24%), B (16%), F (3%), and AB (1%) also occurred; 3% were caused by undetermined serotypes. Four outbreaks resulted from commercial products, including a 2006 international outbreak caused by carrot juice. Hospital data indicated that 78% of patients were transferred to special care units and 70% required mechanical ventilation; 7 deaths were reported. Botulinum neurotoxin type A was associated with much longer hospital stays and more time spent in special care than types B or E. Foodborne botulism often is misdiagnosed. Increased clinician awareness can improve diagnosis, which can aid epidemiologic investigations and patient treatment.
Abstract
Aims
Every year, the Queen Elizabeth Hospital Birmingham (QEHB) neuro-oncology team review over 2000 individuals with brain tumour. Patient and public involvement (PPI) has been fragmented ...to date. Initially we invited two patient advocates and a core group of allied health professionals to meet virtually to discuss development of a local PPI group, its aims, specific goals, and timescales to maintain momentum. In March 2021 we launched “BERTI: Brain tumour Education and Research paTient and public Involvement group, West Midlands”. Our inaugural meeting will be virtual in April 2021 and will be followed by three meetings per year.
Method
We developed information leaflets to promote the BERTI initiative. A membership form has been developed to record baseline information (non-clinical) e.g. contact details, which tumour type the individual is interested in, which aspect of BERTI they are interested in (Education, Research or Clinical service development). Patient advocates have reviewed all patient and public facing forms. All forms have been checked by Information Governance at QEHB to ensure General Data Protection Regulation compliant. Contact details and non-clinical data will be stored in a password protected database on a NHS computer network. Information to ensure members can unsubscribe from this group is easy to find and will be done immediately. A BERTI email account has been set up with a core group of professionals having access who are all fully trained in data protection and have GDPR certification. We will produce an annual BERTI newsletter.
Results
BERTI is a group for people affected by brain tumours in any way. We include patients, friends and family, health professionals and researchers who are committed to improving the care of people with a brain tumour. It is run between the QEHB and University of Birmingham (UoB).
BERTI provides a forum to meet other people affected by brain tumours and
- Share experiences;
- Understand the condition better;
- Work with clinical staff and researchers to improve clinical care and facilitate research for people living with brain tumours.
We will meet three times per year, virtually at the moment but face to face once Covid restrictions ease. We will have a formal talks explaining certain aspects of brain tumour or research initiatives. Throughout, there will be dedicated time set aside for group discussions to promote a genuine two-way dialogue between health-care/research professionals and individuals affected by brain tumour.
Conclusion
The PPI group will be allowed to evolve rather than start out too prescriptive. It will capitalise on its strengths and skills of its composite members. There are no set models rather principles that will provide the foundations for a group which is supported to fulfil their specific purpose.
The views of the PPI group will be presented at the quarterly Neuro-Oncology Multi-disciplinary team business meetings to provide a forum to discuss issues. We aim to foster a PPI friendly environment, deliver real engagement and involvement across the group.
Abstract
Aims
There are approximately four thousand neuro-oncology procedures in the UK per annum. Many of these result in tissue and biofluid specimens that are surplus to diagnostic requirement and ...can be collected as standard of clinical care. However, developing technologies and treatments for precision medicine require access to a range of individualised biospecimens paired with deep clinical phenotyping data. Here, we present Brain Surgical Tissue for Advanced Tumour Models (BRAINSTAT) programme, an infrastructure that has been established between Queen Elizabeth Hospital, Birmingham and the University of Birmingham, to collect, structure and store these resources and also maximise their value for research over the long-term. Using this approach our aim is to provide high-quality, annotated resources to help develop novel treatments for patients with brain tumours.
Method
BRAINSTAT infrastructure allows:
Prospective consent
Biospecimens, including tumour tissue (brain and other primary in the case of metastasis), cyst fluid, dura, skin, CSF, blood (matched “germ-line” and for circulating cell free tumour DNA analysis), urine and saliva can be collected. Consent for long term follow-up, is either via clinic or NHS digital. More limited consent for non-oncological neurosurgical cohorts (e.g. epilepsy or vascular) and healthy volunteers allow healthy access-tissue and biofluids to be collected.
B. Rapid transfer of fresh surgical tissue samples:
Strong collaborative links and close physical proximity between operating theatre and laboratory allows rapid transfer of biospecimens minimising transit time.
C. Standardised annotation across disciplines
The RedCAP database system allows granular control over data-access, and each specialist research team is provided access only to the sub-sections relevant to them. All users must have Good Clinical Practice certification and GDPR training, prior to access of the BRAINSTAT database.
Results
Between 25/11/2019-16/03/2020 and 27/07/2020-16/11/2020, 65 patients were consented for BRAINSTAT at the weekly neurosurgical oncology clinic. (Recruitment gaps due to the SARS-COVID 19 pandemic). Pathological diagnosis of surplus tissue collected included: 37 high grade glioma, 3 low grade glioma and 16 brain metastasis including: (6 lung, 6 breast, 2 colorectal, 1 oesophageal, 1 endometrial). Meningioma (5 WHO I; 1 WHO III) 1 patient undergoing anterior temporal lobectomy for hippocampal sclerosis contributed access tissue from the lateral neocortex. 1 patient had a non- neoplastic, non-diagnostic sample. All patients had matched “germ-line” blood samples.
Median time from resection to arrival in the laboratory was 10 minutes (range 4-31). Standardised operating protocols to optimise this have been developed.
Glioblastoma and breast-brain metastasis tumourspheres and cerebral organoids are currently being validated.
Conclusion
Despite the challenges of the pandemic we have established a viable tissue pipeline from neurosurgical operating theatre to our university laboratories. We are developing clinically annotated human brain tumour cell lines, stem cells and 3D organoid models, principally for commonly encountered brain tumours such as glioma and metastasis.
The research sets the foundation for a multitude of downstream applications including:
- Building more complex organoid cultures e.g. by including other cell types such as healthy brain cells and endothelial cells allowing future experiments to more accurately model tumour growth.
- Developing high-throughput, patient-specific drug screens of novel drugs and drug combinations using these 3D tumour models aiming to more effectively treat tumour proliferation and spread. These patient avatars will help inform and test more “stratified” personal medical treatments and will provide opportunities to allow earlier intervention with the aim of improving survival, coupled with a better quality of life.
Abstract
Aims
Magnetic resonance imaging (MRI) is a valuable tool for non-invasive diagnosis of paediatric brain tumours. The rarity of the disease dictates multi-centre studies and imaging ...biomarkers that are robust to protocol variability. We investigated diffusion tensor MRI (DT-MRI), combined with machine learning, as an aid to diagnosis and evaluated the robustness of the imaging metrics.
Method
A multi-centre cohort of 52 clinical DT-MRI scans (20 medulloblastomas (MB), 21 pilocytic astrocytomas (PA), 11 ependymomas (EP)) were analysed retrospectively. Histograms for regions of solid tumour for fractional anisotropy (FA), mean diffusivity (MD), pure anisotropic diffusion (q) and pure isotropic diffusion (p) were compared to assess diagnostic capability. Linear discriminate analysis (LDA) was used for classification and validated using leave-one-out-cross-validation (LOOCV).
Results
Histogram medians for FA, MD, q and p were all different between tumor groups (P<.0001, Kruskal Wallis test). Median MD, p and q values were highest in PA, then EP and lowest in MB (P<.0001, Pairwise Wilcox test). FA median was higher for EP than PA (P=.004) with no significant difference between EP and MB (P=.591). ROC analysis showed that median MD, q and p perform best as a diagnostic marker (AUC= 0.92 to 0.99). LOOCV showed an overall accuracy of the LDA classification, ranging between 67% - 87%. FA values were highly dependent on protocol parameters, whereas pure anisotropic diffusion, q, was not.
Conclusion
DT-MRI metrics from multi-centre acquisitions can classify paediatric brain tumours. FA is the least robust metric to protocol variability and q provides the most robust quantification of anisotropic behaviour.
Abstract
Aims
Circulating tumour DNA (ctDNA), shed from solid cancers in to the plasma, represents an exciting analyte for diagnosis and monitoring of disease in cancer patients. However, its use in ...glioma brain cancer patients represents a challenge, due to reduced permeability of the blood brain barrier.
This pilot study sought to investigate the practical aspects and clinical utility of using cell-free DNA (cfDNA) in glioma tests in a NHS diagnostic laboratory. Firstly, we investigated the potential of ctDNA as a proxy for the brain cancer biopsy; where cfDNA analysis was compared to the paired FFPE brain specimen for relevant glioma genetic biomarkers. Secondly, ctDNA constitutes a portion of the overall cfDNA and there is evidence cfDNA metrics per se may also be of value as prognostic tools and surrogates of tumour burden. Additionally, we investigated a potential role for cfDNA metrics in prognostic impact; linking cfDNA concentrations to clinical outcome measures.
Method
10ml peripheral blood was collected in specialist preservative tubes and cfDNA isolated using an extraction kit (Qiagen MinElute ccfDNA kit). cfDNA concentration and purity was assessed using chip-based automated electrophoresis.
Where relevant (12/39 cases), cfDNA samples were run though laboratory tests of IDH variant detection, 1p19q co-deletion assessment and MGMT promoter methylation analysis. Results were compared with ‘standard of care’ brain biopsy tests.
A potential correlate of cfDNA concentration and clinical outcomes data were assessed in a sub-cohort of glioblastoma patients (n=32). The cohort was divided in to 2 groups – high cfDNA vs. low cfDNA - based on whether a subject’s extracted sample cfDNA concentration fell above or below the mean. Comparison of overall survival in months between subjects was checked for normal distribution using the Shapiro-Wilk t-test. The test of equity of survival distributions for the high cfDNA vs. low cfDNA was then analysed as a Kaplan-Meier curve.
Results
The protocol delivered cfDNA of high purity, averaging 91%, within the plasma nucleic acid fraction, however the cfDNA concentrations (mean ≈1ng µl-1) fell below the conventional limit of detection of the laboratory tests. In spite of the low concentration, cfDNA samples did generate test PCR amplicon; however results reflected the germline DNA profile rather than the new somatic changes of the tumour. The cfDNA analysis did not pick up the tumour biomarkers seen in the paired tumour biopsy sample.
In a second part of the study, cfDNA concentrations for the glioblastoma cohort were assessed in the context of their clinical outcomes data. The data showed a correlate where high cfDNA concentration in the extracted sample was independently associated with inferior outcome in terms of overall survival, with Log Rank significance p=0.014 (Figure 1).
Conclusion
The cfDNA yields from a 10ml blood sample were consistently too low to meet the limit of detection requirements of the standard laboratory neuropathology genetic tests and glioma tumour profile could not be picked up against the germline background. Thus, in spite of the considerable advantages to glioma plasma molecular testing, using cfDNA as a proxy for a brain biopsy would currently not be possible in our routine diagnostic environment.
However, within the limitations of the pilot project testing strategy, the data showed an interesting correlate where high cfDNA concentration was independently associated with inferior outcome in terms of overall survival for glioblastoma patients. Given the simplicity of obtaining this quantifiable metric, there are grounds for further investigations as to its utility; not only with survival outcomes, but also potential correlation with the clinical assessment of tumour burden, blood brain barrier integrity and disease pseudoprogression.
Abstract
Aims
Signs and symptoms that develop in people with brain tumours are often attributed to their tumour. The prevalence and management of functional neurological symptoms in brain tumour ...patients have received little attention. This is surprising because functional neurological symptoms complicate management greatly and misdiagnosis can lead to inappropriate treatment and iatrogenic side-effects. Therefore, we investigated the presentation, diagnosis and management of functional neurological disorders (FND) in patients who had a brain or meningeal tumour.
Method
A retrospective case review was performed from 2017 - 2021 to identify adult brain tumour patients who developed a functional neurological disorder that caused significant disability necessitating expedited investigations. All patients attended a regional neuro-oncology centre. We recorded type of brain tumour and diagnostic investigations. The onset of functional symptoms was divided into three time windows: before tumour diagnosis, after diagnosis and before treatment or after tumour treatment. A neuropsychological review looked for evidence of previous adverse life events. Therapeutic interventions for functional neurological disorder and their outcomes were documented. The case review was combined with a systematic review of the literature to identify the published presentations of functional neurological disorder in the adult brain tumour population. MEDLINE, EMBASE and PsycINFO databases were searched for studies published between January 1980 and February 2021.
Results
Six patients (5 female, 1 male) were identified from the case review with a median age of 41 (range 29 - 56) years old. Four patients had non-epileptic attack disorder, which was diagnosed with videotelemetry of habitual attacks. One patient had a functional hemiparesis with normal central motor conduction time. One patient had a functional speech disorder with normal EEG. Half of these patients had functional neurological symptoms prior to surgery/oncological treatment. Five patients (83%) were referred for further neuropsychiatric or psychological evaluation. A history of significant psychological trauma prior to the brain tumour diagnosis was elicited in four (66%) patients.
Conclusion
Patients with either a brain or meningeal tumour may develop functional neurological symptoms. Our findings suggest the possibility that diagnosis of a brain tumour may precipitate a debilitating functional neurological disorder. The neurobiological basis for functional neurological disorders is being actively investigated. There are suggestions in the literature that some brain diseases increase the risk of developing a functional neurological disorder. Further work is needed to determine whether this is true for patients with brain tumours. Increased awareness of functional neurological disorders will improve management. Withdrawal of unnecessary treatment, such as anticonvulsant drugs, reduces the risk of iatrogenic side effects. Initiation of multi-disciplinary care pathways, e.g. physiotherapy, speech and language therapy and psychological treatments, promotes recovery. Collectively, these interventions improve our patients’ quality of life.
Abstract
Aims
Key governing guidelines recognise that the holistic and complex needs of neuro-oncology patients are best served by a cohesive multidisciplinary team (MDT). Achieving a joint Clinical ...Nurse Specialist (CNS) and Allied Healthcare Professional (AHP) clinic (including Speech and Language Therapy, Physiotherapy, Dietetics and Occupational Therapy) for neuro-oncology patients has been a longstanding vision at Velindre Cancer Centre (VCC) in Cardiff. A successful funding application to Welsh Government in July 2020 allowed the establishment of a virtual “one stop shop” clinic with CNS and AHPs available along the care trajectory to improve patient and carer quality of life. The project reports on whether this innovative clinic model successfully achieved the desired coordinated, anticipatory and holistic care.
Method
The project utilised service improvement methodology principles with aims inherent within quarterly timeframes. This included robust data collection on patient attendances and interventions, improving patient education and self-management and wide patient, care and staff engagement by means of questionnaires and semi-structured interviews. The mixed methods approach yielded rich quantitative and qualitative data.
Results
The data demonstrates an increasing demand for the joint neuro-oncology clinic indicating that additional resources may be required. From triangulation of patient, carer and wider team engagement the key benefits were perceived to be having accessibility to the team in a convenient way, the provision of support and timely information and the overall perception of enhanced holistic care.
Conclusion
The data demonstrates the huge successes of the joint neuro-oncology clinic so far, including improvements to patient and carer quality of life, wider VCC benefits and cost saves. The persuasive case was presented to Welsh Government, and ongoing endorsement has been achieved for the next financial year.
Abstract
Aims
Glioblastoma (GBM) is currently an incurable malignancy with a very poor prognosis for the majority of patients. Many patients undergo debulking surgery, radiotherapy and chemotherapy ...however therapeutic options are limited, and this can lead to patients sourcing their own treatments. There is some evidence that cannabinoids have the effect of inhibiting GBM tumour growth through a variety of pathways, some of which include CB2 cannabinoid receptor pathway activation. We undertook a patient questionnaire to understand what alternative therapies patients are accessing and why, with a focus on cannabinoid use.
Method
We undertook a prospective observational questionnaire based qualitative study of 50 … consecutive patients undergoing treatment for glioblastoma at our centre.
Results
43 patients responded to our questionnaire. 33% of patients were taking some kind of supplementary therapy with 25% taking cannabis derivatives, mainly CBD oil. There were no clear discriminators amongst our cohort including age or sex when considering the likelihood of taking cannabis derivatives. 6 out of 11 (55%) patients taking cannabis derivatives reported some positive effects with improved sleep and general wellbeing being most commonly reported. Patients reported spending between £10-£300 per month with an average of £42 per month. Cannabis products were obtained via the internet or from friends.
Conclusion
This small cohort of patients indicates that a significant proportion of glioblastoma patients investigate and use alternative therapies, in particular cannabis oil. NICE guidance for clinicians simply notes there is insufficient evidence to support the use of cannabis oil in the treatment of this disease. Given the publicity and interest in the utility of cannabis oil to treat cancers this leaves patients to research the use of these agents without access to robust clinical data to guide their use or indeed to conclude they are not beneficial. The accessing of these compounds, potentially by a sizeable number of patients, leaves them vulnerable to unregulated perhaps unscrupulous drug sources. This small study has further highlighted the unmet need for information and guidance on supplementary treatments for glioma patients and this poses a challenge to all those treating this group of patients to answer a question our patients are clearly wanting answered.
Abstract
Aims
There is limited evidence on cerebrovascular risks in glioblastoma and meningioma patients. We aimed to compare cerebrovascular risks of these patients with the general population.
...Method
We used population-based routine healthcare and administrative data linkage in this matched cohort study. Cases were adult glioblastoma and meningioma patients diagnosed in Wales 2000-2014 identified in the cancer registry. Controls from cancer-free general population were matched to cases (5:1 ratio) on age (±5 years), sex and GP practice. Factors included in multivariable models were age, sex, index of multiple deprivation, hypertension, diabetes, high cholesterol, history of cardiovascular disease, and medications for cardiovascular diseases. Outcomes were fatal and non-fatal haemorrhagic and ischaemic stroke. We used flexible parametric models adjusting for confounders to calculate the hazard ratios (HR).
Results
Final analytic population was 16,921 participants, of which 1,340 had glioblastoma and 1,498 had meningioma. The median follow-up time was 0.5 year for glioblastoma patients, 4.9 years for meningioma patients, and 6.6 years for controls. The number of haemorrhage and ischaemic stroke was 154 and 374 in the glioblastoma matched cohort, respectively, and 180 and 569 in the meningioma matched cohort, respectively. The adjusted HRs for haemorrhagic and ischaemic stroke were 3.74 (95%CI 1.87-6.57) and 5.62 (95%CI 2.56-10.42) in glioblastoma patients, respectively, and were 2.42 (95%CI 1.58-3.52) and 1.86 (95%CI 1.54-2.23) in meningioma patients compared with their controls.
Conclusion
Glioblastoma and meningioma patients had higher cerebrovascular risks; these risks were even higher for glioblastoma patients. Further assessment of these potentially modifiable risks may improve survivorship.
PDF
