Using surgical and oncology workload to plan brain tumour trial recruitment in England

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.

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Qualitative study: patients’ and parents’ views on brain tumour MRIs

Archives of Disease in Childhood ◽

10.1136/archdischild-2019-317306 ◽

2019 ◽

pp. archdischild-2019-317306 ◽

Cited By ~ 1

Author(s):

Natalie Tyldesley-Marshall ◽

Sheila Greenfield ◽

Susan Neilson ◽

Martin English ◽

Jenny Adamski ◽

...

Keyword(s):

Young People ◽

Brain Tumour ◽

No Value ◽

Brain Tumours ◽

Emotional Responses ◽

Working Relationships ◽

Structured Interviews ◽

Children And Young People ◽

Parent Preferences ◽

Over Time

BackgroundMRI is essential to the clinical management of children and young people with brain tumours. Advances in technology have made images more complicated to interpret, yet more easily available digitally. It is common practice to show these to patients and families, but how they emotionally respond to, understand and value, seeing brain tumour MRIs has not been formally studied.MethodsQualitative semi-structured interviews were undertaken with 14 families (8 patients, 15 parents) purposively sampled from paediatric patients (0 to 18 years) attending a large UK children’s hospital for treatment or monitoring of a brain tumour. Transcripts were analysed thematically using the Framework Method.ResultsFour themes were identified: Receiving results (waiting for results, getting results back, preferences to see images), Emotional responses to MRIs, Understanding of images (what they can show, what they cannot show, confusion) and Value of MRIs (aesthetics, aiding understanding, contextualised knowledge/emotional benefits, enhanced control, enhanced working relationships, no value). All families found value in seeing MRIs, including reassurance, hope, improved understanding and enhanced feeling of control over the condition. However emotional responses varied enormously.ConclusionsClinical teams should always explain MRIs after ‘framing’ the information. This should minimise participant confusion around meaning, periodically evident even after many years. Patient and parent preferences for being shown MRIs varied, and often changed over time, therefore clinicians should identify, record and update these preferences. Time between scanning and receiving the result was stressful causing ‘scanxiety’, but most prioritised accuracy over speed of receiving results.

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Missed opportunities for diagnosing brain tumours in primary care: a qualitative study of patient experiences

British Journal of General Practice ◽

10.3399/bjgp19x701861 ◽

2019 ◽

Vol 69 (681) ◽

pp. e224-e235 ◽

Cited By ~ 5

Author(s):

Fiona M Walter ◽

Clarissa Penfold ◽

Alexis Joannides ◽

Smiji Saji ◽

Margaret Johnson ◽

...

Keyword(s):

Qualitative Study ◽

Brain Tumour ◽

Brain Tumours ◽

Help Seeking ◽

Patient Experiences ◽

Missed Opportunities ◽

North West ◽

Primary Brain Tumour ◽

Symptom Appraisal ◽

Poor Outcomes

BackgroundBrain tumours are uncommon, and have extremely poor outcomes. Patients and GPs may find it difficult to recognise early symptoms because they are often non-specific and more likely due to other conditions.AimTo explore patients’ experiences of symptom appraisal, help seeking, and routes to diagnosis.Design and settingQualitative study set in the East and North West of England.MethodIn-depth interviews with adult patients recently diagnosed with a primary brain tumour and their family members were analysed thematically, using the Model of Pathways to Treatment as a conceptual framework.ResultsInterviews were carried out with 39 patients. Few participants (n = 7; 18%) presented as an emergency without having had a previous GP consultation; most had had one (n = 15; 38%), two (n = 9; 23%), or more (n = 8; 21%) GP consultations. Participants experienced multiple subtle ‘changes’ rather than ‘symptoms’, often noticed by others rather than the patient, which frequently led to loss of interest or less ability to engage with daily living activities. The most common changes were in cognition (speaking, writing, comprehension, memory, concentration, and multitasking), sleep, and other ‘head feelings’ such as dizziness. Not all patients experienced a seizure, and few seizures were experienced ‘out of the blue’. Quality of communication in GP consultations played a key role in patients’ subsequent symptom appraisal and the timing of their decision to re-consult.ConclusionMultiple subtle changes and frequent GP visits often precede brain tumour diagnosis, giving possible diagnostic opportunities for GPs. Refined community symptom awareness and GP guidance could enable more direct pathways to diagnosis, and potentially improve patient experiences and outcomes.

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Brain tumours repurpose endogenous neuron to microglia signalling mechanisms to promote their own proliferation

eLife ◽

10.7554/elife.46912 ◽

2019 ◽

Vol 8 ◽

Cited By ~ 4

Author(s):

Kelda Chia ◽

Marcus Keatinge ◽

Julie Mazzolini ◽

Dirk Sieger

Keyword(s):

Brain Tumour ◽

Brain Tumours ◽

Atp Release ◽

Live Imaging ◽

Tumour Cells ◽

Cellular Interactions ◽

Neoplastic Cells ◽

Highly Active ◽

The Brain

Previously we described direct cellular interactions between microglia and AKT1+ brain tumour cells in zebrafish (Chia et al., 2018). However, it was unclear how these interactions were initiated: it was also not clear if they had an impact on the growth of tumour cells. Here, we show that neoplastic cells hijack mechanisms that are usually employed to direct microglial processes towards highly active neurons and injuries in the brain. We show that AKT1+ cells possess dynamically regulated high intracellular Ca2+ levels. Using a combination of live imaging, genetic and pharmacological tools, we show that these Ca2+ transients stimulate ATP-mediated interactions with microglia. Interfering with Ca2+ levels, inhibiting ATP release and CRISPR-mediated mutation of the p2ry12 locus abolishes these interactions. Finally, we show that reducing the number of microglial interactions significantly impairs the proliferation of neoplastic AKT1 cells. In conclusion, neoplastic cells repurpose the endogenous neuron to microglia signalling mechanism via P2ry12 activation to promote their own proliferation.

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EPCT-08. TRIAL WORKING GROUPS FOR PAEDIATRIC BRAIN TUMOURS

Neuro-Oncology ◽

10.1093/neuonc/noab090.194 ◽

2021 ◽

Vol 23 (Supplement_1) ◽

pp. i48-i48

Author(s):

Ruman Rahman ◽

David Walker ◽

Emma Campbell ◽

Kristian Aquilina

Keyword(s):

Drug Delivery ◽

Clinical Trials ◽

Brain Tumour ◽

Brain Tumours ◽

International Workshop ◽

Convection Enhanced Delivery ◽

Children With Cancer ◽

Cns Drug Delivery ◽

Working Groups ◽

Paediatric Brain Tumours

Abstract Introduction Brain tumours are the biggest cancer killer in children and young adults. Several recent developments have the potential to change the treatment of brain tumours in children. These include ultrasound-mediated blood-brain barrier disruption, convection enhanced delivery, polymer delivery systems and electric field therapy, as well as intra-arterial, intra-CSF and intra-nasal chemotherapy. To date, there have been very few clinical trials to evaluate any of these. The science and technology underlying these developments is not traditionally embedded within the standard paediatric neuro-oncology network. In addition, custom-built hardware, novel surgical procedures and, in some cases, the testing and licensing of implantable devices, add difficulty at the regulatory level. Methods The authors participated in an international workshop funded by the charity Children with Cancer UK in 2016, where different experimental techniques aimed at optimising CNS drug delivery were discussed. Following this workshop and two subsequent workshops run by the CBTDDC (Children’s Brain Tumour Drug Delivery Consortium) in 2018 and 2020, the CBTDDC and the recently developed ITCC (Innovative Therapies for Children with Cancer) brain tumour group started working together to set up a new initiative. This aims to develop CNS-delivery-focused trial working groups for paediatric brain tumours. Results We have assembled a prestigious steering group, comprising international researchers and clinicians with expertise in diverse aspects of translational and clinical research in CNS drug delivery. At our first group meeting in March, participants will discuss the most effective ways of translating the emerging drug delivery modalities into clinical trials. Prioritised actions will be taken forward and the group will reconvene to discuss developments and next steps at a workshop in the Autumn. Conclusion We present this abstract to the SNO Paediatric conference to raise awareness of this initiative with the large number of relevant stakeholders who will be attending the event.

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Trial working groups for paediatric brain tumours

Neuro-Oncology ◽

10.1093/neuonc/noab195.020 ◽

2021 ◽

Vol 23 (Supplement_4) ◽

pp. iv9-iv9

Author(s):

Kristian Aquilina ◽

Ruman Rahman ◽

David Walker ◽

Emma Campbell

Keyword(s):

Drug Delivery ◽

Clinical Trials ◽

Brain Tumour ◽

Brain Tumours ◽

Delivery Systems ◽

Children With Cancer ◽

Cns Drug Delivery ◽

Oncology Research ◽

Steering Group ◽

Paediatric Brain Tumours

Abstract Aims Children's brain tumours are the biggest cancer killer in children and young adults. Several recent developments have the potential to change the treatment of brain tumours in children. These include intra-CSF chemotherapy, ultrasound-mediated blood-brain barrier disruption, convection enhanced delivery, polymer delivery systems and electric field therapy, as well as intra-arterial and intra-nasal chemotherapy. To date, there have been very few clinical trials to evaluate any of these. The science and technology underlying these developments is not traditionally embedded within the standard paediatric neuro-oncology network. In addition, custom-built hardware, novel surgical procedures and, in some cases, the testing and licensing of implantable devices, add difficulty at the regulatory level. Method The authors participated in an international workshop funded by the charity Children with Cancer UK in 2016, where different experimental techniques aimed at optimising CNS drug delivery were discussed. Following this workshop and two subsequent workshops run by the CBTDDC (Children’s Brain Tumour Drug Delivery Consortium) in 2018 and 2020, the CBTDDC and the recently developed ITCC (Innovative Therapies for Children with Cancer) brain tumour group started working together to set up a new initiative. Called the ‘Clinical Trials Working Group for Central Nervous System Drug Delivery’, this aims to accelerate clinical trials to assess the safety and effectiveness of drug delivery devices for the treatment of paediatric brain tumours. On March 1st, 2021, CBTDDC with guest chair, Mr Kristian Aquilina (Consultant Paediatric Neurosurgeon at Great Ormond Street Hospital), hosted the first virtual meeting of this group. Results We have assembled a prestigious steering group, comprising international researchers and clinicians with expertise in diverse aspects of translational and clinical research in CNS drug delivery. At our first group meeting on March 1st, 2021, 38 leading brain tumour research scientists and clinicians from the UK, EU and US tackled the challenges head-on, with commitment and a driving passion to identify and move forwards with the most effective ways of translating drug delivery modalities into clinical trials. Attendees were split into three break-out sessions based on distinct drug delivery systems, and lots of insightful comments were collated. Conclusion The ideas generated during the 1st March meeting will help form the basis of a CBTDDC ‘Clinical Trials’ workshop in the autumn of 2021. In particular, there was an agreed consensus that a key objective will be the creation of a ‘Roadmap’ document for pre-clinical to clinical translation which would be shared with the paediatric neuro-oncology research community. CBTDDC look forward to working with steering group as we act on their recommendations to address the current challenges faced by translational drug delivery research. We present this abstract to the BNOS Annual 2021 Meeting to raise awareness of this initiative with the large number of relevant stakeholders who will be attending the event.

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Are patients with brain tumours being given timely DVLA advice?

Neuro-Oncology ◽

10.1093/neuonc/noab195.005 ◽

2021 ◽

Vol 23 (Supplement_4) ◽

pp. iv2-iv3

Author(s):

Shumail Mahmood ◽

Yazan Hendi ◽

Hasan Zeb ◽

Yasir A Chowdhury ◽

Ismail Ughratdar

Keyword(s):

Brain Tumour ◽

Secondary Care ◽

Brain Tumours ◽

Tertiary Care ◽

Queen Elizabeth Hospital ◽

The Public ◽

Primary Brain Tumour ◽

The Uk ◽

New Diagnosis

Abstract Aims Over 11,000 patients are diagnosed with a primary brain tumour annually in the UK, with many more being diagnosed with a secondary brain tumour. UK law stipulates that all individuals with a brain tumour must inform the Driver and Vehicle Licensing Agency (DVLA) and may be required to surrender their driving license depending on their specific tumour and symptoms. Despite this guidance, we found that patients continue to arrive at the neuro-oncology clinic without the correct DVLA advice being given. This can potentially lead to patients with brain tumours continuing to drive on the public highway, which poses a severe hazard as the risk of seizures could endanger the public. This retrospective study looks to review what information was provided to patients with brain tumours upon initial diagnosis and determine the adequacy of this; ultimately aiming to improve the quality of information given to future neuro-oncology patients. Method A structured questionnaire was designed, asking patients who have been treated for a brain tumour at the Queen Elizabeth Hospital in Birmingham about any information they received about driving when they were first diagnosed. The questionnaire comprised of 11 questions designed to gather an understanding of what information was given to patients about driving. The study secured local audit approval. 75 patients identified from the weekly neuro-oncology MDT list were contacted. All patients included in this audit were required to stop driving and inform the DVLA about their condition as per the DVLA guidelines. Their responses were collated and analysed. Using this data, we determined if there were inadequacies in the information that was given to these patients about driving, and how this process may be improved in the future. Results 60 patients (80%) possessed driving licenses when first diagnosed and 17% of these (n=10) were not told to stop driving; 8 of whom were diagnosed in primary/secondary care. 39 patients (65%) were first diagnosed in primary/secondary care, however, only 21% of these (n=8) were told to stop driving by primary/secondary care consultants. The remaining 31 patients (81%) were only told to stop driving after referral to tertiary care, by consultant neurosurgeons at the Queen Elizabeth Hospital. Conversely, of the 12 patients first diagnosed at the Queen Elizabeth Hospital, 85% were told to stop driving at diagnosis, suggesting a notable difference in informing patients between primary/secondary care and tertiary care. Patients also commented on the quality of the information received, as 10 individuals (21%) mentioned needing more information about getting their license back, and 5 individuals (11%) mentioning being given conflicting or incorrect information from different members of the MDT. Conclusion The results show that in practice, there are inconsistencies about mandatory DVLA advice which should be clearly provided to patients with a new diagnosis of a brain tumour. Only 78% of patients were told to stop driving at diagnosis, suggesting that the remainder could be liable to continue driving despite their diagnosis. Furthermore, many patients diagnosed in primary/secondary care are not being told to stop driving until after referral to tertiary care which can take weeks, causing delays in them being given this information, which can pose risks to themselves and the public. These delays may be alleviated by giving patients a simplified resource when they are first diagnosed which clearly explains the driving rules. We therefore propose developing a one-page resource based on DVLA guidance and distributing this to patients and referring healthcare professionals at first diagnosis. A subsequent re-audit can evaluate if this intervention improves the current situation.

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Know the symptoms: diagnosing a brain tumour early is key

British Journal of Child Health ◽

10.12968/chhe.2021.2.1.10 ◽

2021 ◽

Vol 2 (1) ◽

pp. 10-11

Author(s):

Sarah Lindsell

Keyword(s):

Brain Tumour ◽

Brain Tumours ◽

Healthcare Professionals ◽

Signs And Symptoms ◽

Childhood Brain Tumours ◽

Early Signs ◽

The Uk ◽

The Brain

Everyone has a role to play in reducing diagnosis times for childhood brain tumours, the biggest cancer killer of children and adults under 40 years old in the UK. The Brain Tumour Charity's HeadSmart campaign aims to inform parents and healthcare professionals about the key early signs and symptoms of brain tumours.

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P14.45 The incidence of major subtypes of primary brain tumours in adults in England 1995–2017

Neuro-Oncology ◽

10.1093/neuonc/noab180.160 ◽

2021 ◽

Vol 23 (Supplement_2) ◽

pp. ii46-ii47

Author(s):

H Wanis

Keyword(s):

Brain Tumour ◽

Brain Tumours ◽

Incidence Rates ◽

Diagnostic Tools ◽

Cancer Registration ◽

Molecular Testing ◽

Malignant Tumours ◽

Primary Brain Tumours ◽

Primary Brain Tumour ◽

European Standard Population

Abstract BACKGROUND Primary brain tumours are a complex heterogenous group of benign and malignant tumours. Reports on their occurrence in the English population by sex, age, and morphological subtype and on their incidence are currently not available. Using data from the National Cancer Registration and Analysis Service (NCRAS), the incidence of adult primary brain tumour by major subtypes in England will be described. METHODS Data on all adult English patients diagnosed with primary brain tumour between 1995 and 2017, excluding spinal, endocrinal and other CNS tumours, were extracted from NCRAS. Incidence rates were standardised to the 2013 European Standard Population. Results are presented by sex, age, and morphological subtype. RESULTS Between 1995 and 2017, a total of 133,669 cases of adult primary brain tumour were registered in England. Glioblastoma was the most frequent tumour subtype (31.8%), followed by meningioma (27.3%). The age-standardised incidence for glioblastoma increased from 3.27 per 100,000 population per year in 1995 to 7.34 in men in 2013 and from 2.00 to 4.45 in women. Meningioma incidence also increased from 1.89 to 3.41 per 100,000 in men and from 3.40 to 7.46 in women. The incidence of other astrocytic and unclassified brain tumours declined between 1995 and 2007 and remained stable thereafter. CONCLUSION Part of the increase in the incidence of major subtypes of brain tumours in England could be explained by advances in clinical practice including the adoption of new diagnostic tools, classifications and molecular testing, and improved cancer registration practices.

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MP006: Review of clinical presentation and trajectory of patients with a diagnosis of primary brain tumour in a pediatric tertiary centre

CJEM ◽

10.1017/cem.2016.147 ◽

2016 ◽

Vol 18 (S1) ◽

pp. S68-S68

Author(s):

J. Abou-Diab ◽

S. Gouin ◽

I. Bouhout ◽

A. Carret

Keyword(s):

Brain Tumour ◽

Brain Tumours ◽

Clinical Presentation ◽

Age Groups ◽

Nausea And Vomiting ◽

Primary Brain Tumour ◽

Clinical Presentations ◽

The Mean ◽

Mean Time ◽

Symptoms And Signs

Introduction: Recognition of life-threatening conditions, such as brain tumours, remains a challenge among pediatric patients. Few studies have described the implication of initial presentation, clinical evolution and healthcare system factors in diagnosis delay of brain tumours in children. We aimed to determine the clinical presentation patterns and health care trajectory of children with a diagnosis of primary brain tumour. Methods: A retrospective chart review in a pediatric university-affiliated hospital was conducted. Participants were all patients less than 18 years of age diagnosed with a brain tumour by neuroimaging between Jan 2003 and Dec 2014. Data were extracted from an institutional tumour registry and medical records. Results: From the registry, 288 patients were identified. The mean age at time of diagnosis was 7.44 ± 0.29 years. Most tumours were infra-tentorial (55%) and had astrocytic origin (29%). The majority (35%) had consulted only once prior to diagnosis, while 14% had consulted at least 4 times prior to diagnosis. The mean time between the onset of symptoms and diagnosis was 147 ± 19 days. The mean time between symptoms onset and first consultation was 84 ± 14 days. The most frequent symptoms and signs at onset and diagnosis were respectively: headache (44% vs 59%, p<0.01), nausea and vomiting (31% vs 58%, p<0.01) and abnormalities of gait (10% vs 32%, p<0.01). 129 patients (45%) were diagnosed in an Emergency Department (ED). Symptoms and signs that differed significantly for those diagnosed in an ED were: headache (71% vs 42%, p<0.01), nausea and vomiting (73 % vs 32%, p<0.01), lethargy (26% vs 9%, p<0.01), weight loss (15% vs 3%, p<0.01), irritability (9% vs 0%, p<0.01) and endocrine abnormality (2% vs 8%, p=0.02). Clinical presentations of infants up to one year of age (14%) differed from other age groups. They presented mostly with growth abnormality (46%), macrocephaly (40%), irritability (40%), development abnormalities (18%) and sun-setting eyes sign (10%). Conclusion: In this large comprehensive cohort, we have found that the diagnosis of primary brain tumours is most frequently made in the ED. Different clinical presentations have been identified and varied between different settings of diagnosis and different age groups.

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Proton therapy for brain tumours in the area of evidence-based medicine

British Journal of Radiology ◽

10.1259/bjr.20190237 ◽

2020 ◽

Vol 93 (1107) ◽

pp. 20190237 ◽

Cited By ~ 2

Author(s):

Damien C Weber ◽

Pei S Lim ◽

Sebastien Tran ◽

Marc Walser ◽

Alessandra Bolsi ◽

...

Keyword(s):

Brain Tumour ◽

Proton Therapy ◽

Brain Tumours ◽

Organs At Risk ◽

The United States ◽

Quality Data ◽

Cancer Management ◽

Randomized Design ◽

Prospective Trials ◽

The Brain

Proton therapy (PT) has been administered for many years to a number of cancers, including brain tumours. Due to their remarkable physical properties, delivering their radiation to a very precise brain volume with no exit dose, protons are particularly appropriate for these tumours. The decrease of the brain integral dose may translate with a diminution of neuro-cognitive toxicity and increase of quality of life, particularly so in children. The brain tumour patient’s access to PT will be substantially increased in the future, with many new facilities being planned or currently constructed in Europe, Asia and the United States. Although approximately 150’000 patients have been treated with PT, no level I evidence has been demonstrated for this treatment. As such, it is this necessary to generate high-quality data and some new prospective trials will include protons or will be activated to compare photons to protons in a randomized design. PT comes however with an additional cost factor that may contribute to the ever-growing health’s expenditure allocated to cancer management. These additional costs and financial toxicity will have to be analysed in the light of a more conformal radiation delivery, non-target brain irradiation and lack of potential for dose escalation when compared to photons. The latter is due to the radiosensitivity of organs at risk in vicinity of the brain tumour, that photons cannot spare optimally. Consequentially, radiation-induced toxicities and tumour recurrences, which are cost-intensive, may decrease with PT resulting in an optimized photon/proton financial ratio in the end. Advances in knowledge: This review details the indication of brain tumors for proton therapy and give a list of the open prospective trials for these challenging tumors.

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