NCRI Brain and CNS CSG: supportive and palliative care January 2018: Issue 2
Welcome to our New Year Cracker of a newsletter... Our raison d’etre Improved quality of life improves outcomes for patients & caregivers living with a brain tumour. How we spent 2017... a year of gaining traction. Looking back at the newsletter published 12 months ago, the distance of travel has been significant. Back then the sub group strategy was in our heads, but the membership of the group was evolving and whilst we knew the direction of travel, we were missing
some key navigators on the journey. Charting our direction of travel for the next three years has taken priority and with a clear road map ahead we have made considerable progress. Priorities align with the main Brain and CNS CSG Strategy and include:
Long term aims Quality trials & studies in neurooncology: develop a system that will improve the number and quality of clinical trials in Living with and Beyond Cancer (LW&BC) and Screening, Prevention and Early Diagnosis (SPED) of brain & CNS tumours
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Grantsmanship in neurooncology: support grant submissions fulfilling NCRI brain S&PC criteria (Table 1) in priority areas for clinical research
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Building relationships in neurooncology: with governmental, professional, clinical and patient public involvement (PPI) communities to work collaboratively in the promotion of clinical studies in LW&BC and SPED
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earlier referral to palliative care services, interventions to help carers cope, fatigue management, and extent of resection on survival.
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Building patient and caregiver accrual in neuro-oncology: increase patient/caregiver opportunity for involvement in clinical trials and studies in supportive and palliative care and quality of life.
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So who are the new team members? We’re delighted to welcome aboard Prof Richard Neal (Prof Primary Care Oncology). Professor Neal leads research around the interface of primary care and cancer, especially around the diagnosis of cancer in general practice. He chairs the Primary Care Clinical Study Group of the National Cancer Research Institute and is based in Leeds. Prof Robert Hills (Lead for Clinical Cancer Research Methodology) joins us from Cardiff. Professor Hills has experience in Statistics and Trial Methodology. He is a translational statistician working in the integration of clinical trials and laboratory studies and is a statistician and grantholder for the UK NCRI portfolio of randomised trials. And to complete the team we have Professor Jon Evans from Glasgow. Professor Evans is Programme Director for the MSc in Clinical Neuropsychology. His research interests include the assessment and rehabilitation of disorders of memory, attention and executive functioning, the application of new technology in cognitive rehabilitation and the treatment of mood disorder in the context of brain injury.
What has gained ground? Since 2015 NCRI brain CSG Supportive & Palliative Care Subgroup has held Incubator Days on six priority questions – lifestyle factors, earlier diagnosis,
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Incubator Days have also been held on Seizure Prophylaxis in Glioma and Cerebellar Cognitive Affective Syndrome.
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Cochrane Priority Reviews are underway for reviews in lifestyle factors, second GBM recurrence, interventions to help carers cope, fatigue management, and extent of resection on survival.
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Cochrane Complex Reviews are planned following a successful NIHR Cochrane Systematic Review Programme Grant in interval scanning, earlier diagnosis, earlier referral to palliative care services, molecular subtyping, long term effects of surgery and/or radiotherapy.
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Funding applications have been submitted to NIHR or charity funders on lifestyle factors, earlier referral to palliative care services, interventions to help carers cope, fatigue management, and extent of resection on survival.
Successful applications include: NIHR HTA 16/31/136 – SPRINGSeizure Prophylaxis IN Glioma (Multi-Centre RCT)
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NIHR Cochrane Systematic Review Programme Grant 16/114/18 (NCRI/Cochrane): 8 Complex Systematic Reviews
Applications submitted/ in development: Palliative Care Supportive Care Master Protocol – Prof Robert Hills/Dr Anthony Byrne – Cardiff University (NCRI Haematology Oncology CSG)
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Improving support for family caregivers in neuro-oncology – Dr Florien Boele – Acad. Fellow in Neuro-Psychology, Leeds University
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NOCTURN (Neuro-Oncology Clinical Trials UK Research Network) website has developed out of the Neuro-Oncology JLA Website. Its purpose is twofold: 1. To act as a resource for neurooncology clinical researchers to obtain all the latest NIHR/ CRUK/Wellcome/MRC funding sources and resources that assist application for clinical research funding 2. To inform the community about the top 10 JLA questions and help that NCRI brain CSG can give. Its community led and is a place where carers, patients and healthcare professionals can come together to discuss various neurooncology topics, such as the JLA PSP and top ten priorities, research and funding. The site invites engagement through discussion threads – anyone can join in.
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TBTC Grant – BT LIFE “Brain Tumours – Lifestyle Intervention and Fatigue Evaluation – a multicentre feasibility RCT (see below).
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Industry Sponsored: (Vitaflo International Ltd) – A randomised pilot study of Ketogenic Diet (The KEATING trial). A randomised feasibility trial (NCT03075514)
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BTR Grant – Effect of Ketogenic Diet on tumour growth – prospective study
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NCRI Brain and CNS CSG: supportive and palliative care news: January 2018
Robin Grant, group chair.
Table 1
NCRI brain CSG advice & support We have been thinking of criteria for NCRI brain S&PC subgroup advice and support. This is still to be formalised but in general, the Supportive & Palliative Care Subgroup is happy to look at any studies that are considered within our remit (Symptoms Control and Quality of Life). Some funders submission forms ask if there has been external feedback. We are particularly interested in research that fits into one or more of the following:
A. Selection Criteria
a. James Lind Alliance NeuroOncology Priority Setting Partnership areas. b. Other important clinical studies for brain or spinal cord tumour patients not covered by the JLA – e.g. brain metastases, meningioma, spinal cord compression, neurological cancer symptoms research, e.g. neuropathy or neurorehabilitation. c. Intervention trials with a PICO format clinical trial design d. Prospective clinical studies examining areas such as early diagnosis, symptom control or other supportive and palliative complex interventions e. Clinical studies, where appropriate, should demonstrate mixed methodological approaches, multi-centre involvement and multi-specialty involvement f. Evidence of structured patient and public engagement g. Where there has been a grant awarded by competitive application and
B. The study has a ISRCTN registration number
If you are not sure whether your study fits easily into these groups, then contact us (email) and we can always advise. If selected as a NCRI supported study, it will be appear as a study on our research portfolio.
Studies reviewed by NCRI brain S&PC subgroup 2016 KEATING study – Keto-genic diet (Pilot RCT study) – Liverpool
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Early diagnosis of primary brain tumour prospective study – Edinburgh & Bristol/Exeter
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Review Criteria for the NCRI Brain CSG Supportive and Palliative Care Subgroup: The purpose of this review is to identify the suitability of the study proposal for adoption onto the Brain CSG portfolio. It is not primarily a scientific review – which will occur at institutional and funder levels. Q1. Does the proposed study address an area/s of importance defined by the JLA Neuro-Oncology Priority Setting Partnership?
Please tick all that apply: (insert list here)
Q2. If the answer to Q1 is no, does the study address an area of importance defined by current national strategic developments or a current national call for evidence?
Yes No
Yes/No
If so, please state which: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Q3. Does the study question duplicate work already being undertaken elsewhere on the CSG portfolio?
Yes/No
Q4. Does the study question duplicate work already being undertaken outside the UK? If yes, is it appropriate to replicate the study question in a UK context?
Yes/No
Q5. Is the study population appropriately defined and relevant to UK practice?
Yes/No
Q6. Is the study intervention appropriately defined and applicable in UK practice?
Yes/No
Q7. Is there evidence of structured patient and public involvement?
Yes/No
Q8. Is there evidence of appropriate study team skill ix in the areas of:
multi-methods approaches
Yes/No
multi-professional involvement?
Yes/No
multi-centre involvement
Yes/No
Q9. This is not a scientific review. However if you have significant concerns regarding trial design or methods please summarise below (insert comment box)
Score: (1 point for each, or weighted) NCRI Brain and CNS CSG: supportive and palliative care news: January 2018
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BT-LIFE
Fatigue is highly prevalent among patients with a primary brain tumour (PBT), with reports of fatigue ranging between 40–70%. As well as being extremely common, fatigue can also markedly reduce quality of life. Previous pharmacological methods to reduce fatigue in PBT have been largely unsuccessful. A growing body of literature on non-drug interventions aimed at managing fatigue offers an opportunity for patients to regain control and improve their quality of life. However, to date, little research has been directed toward non-drug interventions for fatigue in patients with PBT. BT-LIFE is a multi-centre Randomised Controlled Trial aimed at addressing the feasibility of implementing two forms of non-drug intervention in adults with fatigue and PBT. It is a three-arm trial. Participants in the first arm will receive a ten-week programme of personally-tailored Health Coaching, working on small patient-centred goals surrounding their lifestyle. Those in the second arm will receive an additional ‘Patient Activation’ coaching intervention aimed at boosting their knowledge and skills to manage Health Coaching. The third arm is a control arm in which patients will receive standard care. The research team will assess the feasibility of implementing these non-drug interventions in fatigued PBT patients. The study is on-track to open by May 2018. Acceptable completion, together with patient views raised in a parallel qualitative interview sub-study, will guide a full future randomised control trial of non-drug interventions for fatigue in PBT. The BT-LIFE team has recently appointed a Research Assistant – say hello! Will Hewins. Research Assistant BT-LIFE. “I have always loved research and BT-LIFE is giving me an excellent opportunity to develop my clinical research experience whilst integrating with a team of neurooncology symptom specialists. I am particularly looking forward to being part of a team doing meaningful research aimed at assisting the lives of an inspiring patient group.” BT-LIFE:
Brain Tumours, Lifestyle Interventions and Fatigue Evaluation
Centres:
Edinburgh Glasgow Manchester
Funder:
The Brain Tumour Charity
Trials Unit:
Scottish Clinical Trials Research Unit
Chief Investigator:
brainstrust has launched its fabulous fatigue resource which has already had to go to reprint due it’s popularity. We know that one of the most frequent and distressing problems described by people living with a brain tumour is fatigue. But brain tumour fatigue is different. It occurs with emotion, cognitive and behavioural problems and can be due to neurological dysfunction, treatments, mood disturbances and supportive medications. My Fatigue Book is really important as it enables patients and caregivers living with a brain tumour to understand what is meant by fatigue and to self-manage brain cancer related fatigue so that they: Understand and evaluate their fatigue
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Learn a new pace of living
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Take steps to mitigate the impact of fatigue
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Make the most of what they can do, rather than what they can’t.
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To find out mor e about our wor k, call: 01983 292 email: hello@br 405, ainstrust.org.uk, visit: www.bra or follow us on: instrust.org.u twitter.com/brai k and faceboo nstrust k.com/brainstru st My fatigue book – A resource to help you understa and own fatig ue, edition 1, pub nd, manage lished by brain due for review strust Septemb September 2020 er 2017, .
Dr. Ally Rooney Edinburgh Centre for Neuro-Oncology
Registered charitab le trust, brainstr is a registered charity in England ust and Wales (1114634), and Scotland (SC044 642). September 2017.
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fatigue book A resource to he understand, m lp you anage and own fatigue
© brainstrust
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Edition 1: Sept
igue Resource-Cov
Ally Rooney, CI. 4
And whilst we’re on the subject of fatigue...
NCRI Brain and CNS CSG: supportive and palliative care news: January 2018
er-PRINT.indd
ember 2017
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07/09/2017
08:10
What else has gathered momentum?
Ketogenic diet
Trial development continues and there is now a clear plan for it. The plan is to have two parallel cohorts (high grade glioma treated with chemo-rad and low grade glioma). Each has a non-randomised part, followed by a randomised part, which will be modified ketogenic diet vs. standard diet. The trial will measure ketosis, psychological aspects, translational measures. Matthew Williams, Imperial.
Incubator Day: Does earlier diagnosis of patients with brain tumours improve outcomes? This is one of the JLA top ten questions for clinical research in neuro-oncology. Some presentations are quick (e.g. progressive focal unilateral weakness, dysphasia/confusion) while others are slow (headache +/– personality or cognitive or memory). In an Incubator Day held on 8th December 2017, several primary care specialists, neurologists, and researchers interested in the area met to discuss potential proposals for clinical research. The NCRI Early Diagnosis Group was supported by members of the Leeds Clinical Trials Unit, Health Economists, Research Design Service members, patients and charity representatives. A potential randomised study of patients with “headache suspicious of cancer” to different pathways to care (direct access to imaging versus referral to a neurologist) with clinical and health economic endpoints was discussed but it was considered too early for such a study and the clinical endpoints need to be better considered. A prospective multi-centre study of “headache suspicious of cancer” looking at the red flag features in the history, the value of a simple fast screening test of cognition (semantic verbal fluency test) and other features prior to imaging, will be developed – led by Dr. Robin Grant (Neurology, Edinburgh); Prof Richard Neal (Primary Care, Leeds) and Prof Leone Risdale
(Prof Neurology and General Practice, Kings College, London). Other Centres involved will include Cambridge and Sheffield. Further work is planned studying the value of integrating Optometry into the GP referral pathway where the GP is uncertain whether or not the there is papilloedema or visual field defect. This will form the basis of a further Incubator Day in the spring of 2018. Finally, the value and potential of data linkage between existing databases including the CPES database, NCRAS database and Primary Care Databases will be discussed further between Dr. Sally Vernon (PHE/NCRAS), Prof Yoav Ben-Shlomo, (Epidemiology Bristol) Dr. Fiona Walter (Primary Care, Cambridge), Dr. Helen Bulbeck (brainstrust). The day was supported by a Conference Grant from The Brain Tumour Charity and the meeting was preceded by a meeting of researchers currently working on two TBTC Early Diagnosis Grant Project Grants. Robin Grant, group chair.
Headache Suspicious of Cancer: Point of Care Conference 17 November 2017 On behalf of the subgroup, Helen presented ‘headache suspicious of brain tumour – identifying the best pathway to diagnosis’ in 7 minutes to a group of friendly Dragons at this Point of Care workshop. Point of Care Trials (PoCTs) are interventional trials in which patients are randomised to two or more standard care options and some or all of the patient outcome data is collected from NHS data sources (NHSD, PHE, hospital electronic patient records etc). Although there are a few trials, which are using this approach, there aren’t that many and we are trying to promote this type of methodology as part of Cluster F’s Medical Informatics and Data Linkage cross-cutting theme. Cluster F, is the catchy name for the NIHR CRN group that deals with research studies in Cancer or Dental Health or Surgery, although this PoCT workshop included other diseases. Prof Sir Alex Markham and Matt Seymour chaired the meeting, with 30 attendees from a wide range of clinical specialties. The morning session gave an overview of the advantages and challenges of doing PoCTs and a couple of examples of current trials being undertaken was shared. NIHR CRN also invited attendees to submit ideas for future trials (ours was one) and these were reviewed in the afternoon, along a Dragon’s Den style. Helen Bulbeck, sub group secretariat and brainstrust.
NCRI Brain and CNS CSG: supportive and palliative care news: January 2018
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SPRING (Seizure PRophylaxis IN Glioma)
This NIHR HTA funded study is due to start in the Spring of 2018. The study will be coordinated through the Scottish Clinical Trials Research Unit (SCRTU) in Edinburgh, which is part of Cancer Clinical Trials Unit Scotland (CaCTUS) with accreditation from the UK Clinical Research Collaboration (UKCRC). The study will recruit over 3 years with a years follow-up and will see over 800 patients with brain tumours who do not have epilepsy randomised to either prophylactic Levetiracetam or to no Anti-Epileptic Drug prior to first brain surgery. This will be the first RCT examining the potential seizure reduction benefits, or harms, of the newer generation AED most commonly prescribed in brain tumour patients. It will be the largest RCT examining prophylactic AED and is a collaboration between neurosurgeons, neurologists, oncologists, health economists and a cancer trials unit in a supportive care RCT. Epilepsy endpoints form the basis for Primary and Secondary endpoints but Oncological endpoints of Progression Free Survival and Overall Survival will also be recorded.
CRUK Centres of Excellence
In 2014, CRUK launched its research strategy, which highlighted an ambition to see three in four cancer patients survive their disease for ten or more years by 2014. Within that ambition was the recognition that not all cancers have benefitted from progress in the last forty years, and four of these ‘hard-to-treat’ cancers were highlighted as priority areas: brain tumours, lung cancer, oesophageal cancer and pancreatic cancer. A real problem in the UK brain tumour research community is research capacity. Put simply, there aren’t enough people in the field, and this is a problem across all career levels and across all stages of the translational pipeline. And researchers that are already in the field don’t have the right tools they need to study the disease in detail, because things like mouse models or cell lines that faithfully mimic the human disease simply don’t exist. And while there are undoubtedly great collaborative efforts between some researchers, there’s plenty of scope to knit the community together even more tightly – bringing for example – basic biologists closer to their clinical colleagues, and having the adult and paediatric communities exchanging expertise and ideas. CRUK’s Centres of Excellence model aims to tackle these three issues.
Robin Grant, group chair.
It’s first Centre of Excellence – a lung cancer-focussed partnership between researchers in Manchester and London has led to a stunning uplift in the number of scientists working in lung cancer. And with outstanding leadership at the helm afforded by Professors Caroline Dive and Charlie Swanton, the Centre has established itself as a real hub for innovative lung cancer research. Moreover, through a programme of conferences, workshops and summer schools, the Centre successfully engages with lung cancer scientists across the UK and beyond. CRUK recently invited UK host institutions to apply for up to £3m to become a CRUK Brain Tumour Centre of Excellence; the charity hopes to fund two Centres. Similar to the lung model, the funds will support infrastructure; equipment, recruitment, technical support staff and training, and the Centres of Excellence will have to show a real commitment to building capacity through recruitment and/or training. Moreover, applications will need to demonstrate how the Centre will develop a suite of tools and resources that will be made freely available to spark downstream research. And they’ll be expected to assume a position of leadership within the UK brain tumour research community through networking and engagement. CRUK will be announcing its Brain Tumour Centres of Excellence early in 2018. Safia Danovi, research funding manager CRUK.
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NCRI Brain and CNS CSG: supportive and palliative care news: January 2018
Living With and Beyond Cancer Priority Setting Partnership
In 2017 NCRI launched the Living With and Beyond Cancer Priority Setting Partnership to identify research priorities that matter most to people affected by cancer and health and social care professionals (www.ncri.org.uk/jla). This important project reached a milestone in November with the closing of its UK-wide survey to gather unanswered questions. The survey received responses from nearly 1,500 people – those affected by cancer and health and social care professionals who asked a total of 3471 questions. A representative profile of patients across ages, patient pathway, cancer types, living with
metastatic and secondary cancers and a range of professionals including medical staff, nursing staff, allied health professionals, and social care professionals as well as many carers responded to the survey. 1.3% of the patient respondents had been first diagnosed with brain cancer and 5.5% of carers have looked after people first diagnosed with brain cancer.
The Steering Group is currently analysing the questions. From initial analysis, the questions cover a wide range of living with and beyond cancer topics. There will be a second survey to prioritise these questions in early 2018 and we hope to identify the priorities for living with and beyond cancer research by mid2018. The priorities will be promoted to many research organisations and relevant funders in the UK. Please share this project with your communities, organisation, colleagues, friends and family. Make sure you sign up to our mailing list at www.ncri.org.uk/jla/get-involvedand-contacts/ to hear about the next steps and the final priorities. Feng Li, NCRI programme manager.
Get Data Out: New, routinely accessible brain tumour data to help people understand the impact of the disease brainstrust and Public Health England have been working on a project which will see the regular release of new brain tumour data. This data will help us all to understand the impact of brain tumours at a population level. This work will see regular publication of anonymised data on: Brain Tumour Incidence
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Survival
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Brain tumour treatment
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Routes to diagnosis
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This is the vanguard to a wider piece of work to establish ways of producing anonymised data on rarer cancers. With the systems now established, and patient anonymity guaranteed the stage is set for unprecedented access to data on rarer cancers. The policy context for this piece of work is also significant. The All Party Parliamentary Group (APPG) on Cancer published its inquiry ‘Progress of the England Cancer Strategy: Delivering outcomes by 2020?’. Amongst concerns raised
in the inquiry is that the APPG is “calling for NHS England and Public Health England to increase data transparency by making more of it available to the public” and that ‘this must include rare and less common cancers, all aspects of the patient pathway, and national and local data.” The ‘Get Data Out’ project is a step in the right direction. Of course there is much yet to be done. This initial release of data marks a watershed as Public Health England is able to ensure safe and secure policies, processes and procedures are in place that meet the requirements of the law and best practice to ensure that patient data (your data) is shared in a way that does not compromise anonymity.
However, data on its own does not tell a story. We (brainstrust and the SPC sub group) will be working to bring meaningful narrative to this data, with the support of clinical, patient and public health partners in the coming weeks, months and years. We will also be working to make the data visually engaging, accessible and meaningful to the general pubic. The future is bright as we look forward to the next stages of this work which will build on solid foundations to ensure that Public Health England releases more brain tumour data that is interesting and useful to the community. This will move the conversation on from traditional measures that focus on incidence and survival and help us Continued on page 8...
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to evidence at a whole population level the struggle, nationwide, to ensure that there is parity of care and that life is as good as it can be when you have a brain tumour in the family. We are delighted to have been able to support Public Health England in this work. See the data here: https://www.cancerdata.nhs. uk/standardoutput Early analysis of this data bears some significant headlines for our community 1. Until now we have had oceans of data but only a few puddles with any meaning. What this has done is brought nuance and story to the headline figures. For example – incidence data. We have known that there are just over 9000 PBT
diagnosed every year. What we didn’t know (but we do now) is that there is a J curve (incidence in under 5s and the elderly is higher) and that this is unusual in other cancers. 2. This work adds colour too to other datasets e.g. early diagnosis. We know that the routes to diagnosis for a brain tumour mean that, nationally, 58% of patients will present through A and E. What we now understand is that this tends to be the case in the very old and the very young. GP referral is also common. This will bring weight to early diagnosis work that is being led by the NCRI supportive and palliative care subgroup, which is looking at identifying the best pathway for earlier diagnosis of brain tumour presenting with
headache, through direct access to cerebral scanning. 3. Treatment – what this data does is focus the mind. What has happened which means that 5–9 year olds receiving RT has dropped from 43% in 2013 to 27% in 2014? 4. 10% of people with a non malignant tumour do not survive one year. 450 people are dying within the year, and most of the people who don’t survive the year die within three months of diagnosis. 5. We can see that groups of people (30–49 yr olds and 50–69 year olds) have similar treatment but have a big gap in outcomes. Helen Bulbeck, sub group secretariat and brainstrust.
The year ahead... what does it look like?
More incubator days planned in Posterior Fossa Syndrome, Early Diagnosis (optometry), Palliative Care (day 2), Late Effects, Second Recurrence, Interventions for caregivers (day 2).
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2 March
NCRI brain metastases workshop
London
7 March
NCRI supportive and palliative care CSG
London
8 and 9 March
British Psycho-Oncology Society Conference
Southampton
19 March
Royal College of Radiology Brain Tumour Day
Leeds
19 April
NCRI Brain and CNS CSG
20 April
NCRI supportive and palliative care CSG
1 to 3 May
CRUK has planned its inaugural Brain Tumour Conference which aims to unite the brightest minds in cancer research to discuss and debate some of the greatest issues in the field. The multidisciplinary programme combines expertise from across the breadth of brain tumour research, together with insights from allied disciplines, to spark new opportunities for collaborative research.
4 to 6 July
BNOS
NCRI Brain and CNS CSG: supportive and palliative care news: January 2018
Winchester