Written evidence from Cancer Research UK (BTR0003)

Cancer Research UK is the world’s leading cancer charity dedicated to saving lives through research. We’re the only cancer charity fighting all 200 types of cancer. Our pioneering work has been at the heart of the progress that has seen survival rates double in the last 40 years. We receive no government funding for our research.

In our Research Strategy, launched in May 2014, we recognised that some cancer types including brain have extremely poor survival rates and we committed to dramatically increase our research effort to accelerate progress. We welcome the opportunity to provide written evidence to the Petitions Select Committee during their inquiry into funding for research into brain tumours.

Contents

1. Incidence, mortality and survival
2. Comparison with other cancer types
3. Classification of brain tumours – use of data for statistics
4. About Cancer Research UK – break down of research spend
5. Cancer Research UK – Research Strategy
6. Barriers to research
7. Routes to diagnosis of brain tumours

1. Incidence, mortality and survival

Incidence

•         Around 9,700 people were diagnosed with a brain, other Central Nervous System (CNS) or intracranial tumour in 2012 in the UK, that’s 27 people every day.

•         Around 350 children under the age of 15 in the UK are diagnosed with a brain, other CNS or intracranial tumour in Britain each year. These are the second most common group of cancers diagnosed in children, accounting for more than a quarter (26%) of all children’s cancers.

•         Brain, other CNS and intracranial tumours account for 3% of all new cases of cancer.

•         Brain, other CNS and intracranial tumours are the ninth most common cancer in the UK (2012).[1]

•         The 20 most common cancers in the UK in 2012 are:

•         There are presently no reliable data on the incidence of secondary brain, other CNS and intracranial cancers (which have spread to the brain from other parts of the body). Estimates suggest that secondary brain, other CNS and intracranial cancers occur in at least 6% of all cancer patients, but this varies by the site of the primary cancer.

Europe & World incidence statements 

• Brain and other CNS cancer are the 17th most common cancer type worldwide, with more than 256,000 new cases diagnosed in 2012 (2% of the total). Incidence rates for brain and other CNS cancer are highest in Northern Europe and lowest in Western Africa, but this partly reflects varying data quality worldwide.

Mortality

•         Around 5,200 people died from a brain, other CNS or intracranial tumour in 2012 in the UK, that’s 14 people every day.

•         Brain, other CNS and intracranial tumours are the most common cause of children's cancer death. More than a quarter of brain, other CNS and intracranial tumour deaths are in people aged under 60.

Survival

•         Around 3 in 20 (14%) people diagnosed with brain cancer in England and Wales survive their disease for ten years or more (2010-11).

•         Around a fifth (19%) of people diagnosed with brain cancer in England and Wales survive their disease for five years or more (2010-11).

•         4 in 10 (40%) people diagnosed with brain cancer in England and Wales survive their disease for one year or more (2010-11).

•         Brain cancer survival is improving and has doubled in the last 40 years in the UK.

2. Comparison with other cancer types

• The percentage increase and decrease in the 20 most common male cancers in the UK over the last decade

• The percentage increase and decrease in the 20 most common female cancers in the UK over the last decade

• Improvement in 10 year survival in England and Wales from 1971 to 2011.

3. Brain tumour classification- use of data for statistics

Brain tumours are classified according to different systems by different organisations. There are substantial differences between the groups categorising brain, other CNS and intracranial tumours so these figures should be interpreted with caution.

The most important difference is if non-malignant brain tumours are included in the definition. Non-malignant tumours are usually not life threatening but even ‘benign’ tumours can invade surrounding tissue to some degree, and can be fatal, depending on their location and size and this is particularly true for brain tumours.

The figures only include tumours which have arisen in the brain, other CNS or intracranial region (i.e. only primary tumours). This tumour group is sometimes called simply ‘brain tumours’, but where we give 'brain tumours' figures they include ‘brain, other CNS and intracranial tumours’ unless otherwise specified.

4. About Cancer Research UK (CRUK)- breakdown of research spend

We spent £464 million on our work this year. This includes all of the pioneering research we agreed to fund in 2014/15, as well as our policy and information work – for example supporting GPs, our Cancer Awareness Roadshow and campaigns to keep cancer at the top of the political agenda. Our contribution to building The Francis Crick Institute is also included in this amount.

Within this figure we spent £341 million on life-saving research in 2014/15. This figure includes £35 million on clinical trials, £27 million on research into new drugs, and £13 million on research into possible causes of cancer, helping people to reduce their risk.  £116 million was spent on research underpinning all cancer types. 

Research spend on brain

The NCRI reported that we spent £4.77m on brain tumour research last year.  The figure in our 2014/15 annual report was £9m. These figures differs because of how spend is calculated. We include a % added to each disease site to account for non –site specific research that’s extrapolated across them all.

We do not set a figure on how much we will spend in a particular tumour type. The amount we spend on each type varies from year to year as new research projects start and finish. We always aim to fund the best quality research with the greatest potential to bring benefits to people affected by all types of cancer. As per our Strategy we aim to fund research into cancers of unmet need (such as brain) as a priority, where the research proposal is of the best quality.

5. Cancer Research UK - Research Strategy

Aims

CRUK’s strategic ambition is to improve survival rates from cancer from two in four to three in four by 2034[2]. A key part of this ambition is our focus on four cancers of unmet need, namely brain, lung, oesophageal and pancreas. We are focusing on these tumour types as there has been little improvement in survival rates over the last 20 years. In addition, there is a low base of researchers investigating these tumour types, which is highlighted in the low levels of funding relative to their incidence and mortality rates. Our ambition is to increase our investment two to three fold in these tumour types over the next five years to strengthen long-term research capacity.

Progress and opportunities

Published in May 2014 the implementation of our research strategy is still in its early days but we are focusing on how to engage with the research community to understand what the key research questions are in brain tumours and how we might address them.

In 2014, to develop our approach to increasing research capacity in brain tumours, CRUK convened a group of leading UK and international brain tumour researchers and UK research funders (Brain Tumour Charity and Brain Tumour Research). This workshop was focused on understanding the barriers to progress in adult and paediatric brain tumours and spanned basic, translational and clinical research. From this, major barriers were identified in research leadership, training and networking of existing researchers (outlined below).  We are planning to hold a further workshop in the New Year, which will have international representation to explore the key research questions. We will use this to drive further work to try to bring together teams to tackle these questions. 

We have recruited Richard Gilbertson to Cambridge[3] - he is a world leader in paediatric brain tumours. He will lead the CRUK centre in Cambridge and we are engaging with him around how to progress our work in brain tumours.

Improving the quality and quantity of research into this area is a key organisational priority for CRUK. Building a sustainable, high-quality research base will take time, but we see this as the best approach to making progress. Within this we will look to build from the top down, through recruitment and development of research leaders and from the bottom up, through research training.

In brain, there is an increasing focus on basic research in metabolism and epigenetics that can be applied to brain tumour research - in these areas we are thinking about how we can bring together the right teams to align the basic research better with clinical questions in brain tumours.

To do this, we will:

• Make targeted investments aimed at building leadership, training and facilitating better networking
• Work with the research community to encourage new, high-quality proposals to grow the share of competitive funding for these cancers over time
• Increase focus on these cancers within our Institutes and Centres
• Prioritise high-quality applications for funding within our committees
• Collaborate with other cancer-specific charities

To address the key research questions and barriers presented below we will:

• Develop mechanisms to bring scientists from related disciplines to research brain tumours – these include, but are not limited to, neurosciences, developmental biology and imaging sciences.
• CRUK supports a broad portfolio of basic research to understand the fundamental biological processes in cancer, which will be directly applicable to brain tumours. What we currently lack is a cohort of basic researchers who use brain tumours as their experimental model system. As a result we will look to create opportunities for basic researchers to apply their research in a brain tumour specific context.
• There is a need for research infrastructure to support high quality longitudinal sample collection linked to defined clinical questions. The collection of clinically annotated samples has the potential to provide the research community with vital tools to investigate the biology of brain tumours and the development of novel therapeutic targets. It would also aide the development of novel biomarkers that could be used clinically to inform disease progression, drug resistance and prediction of response to therapy. CRUK has Centre Network Accelerator Awards that could provide the infrastructure to support brain tumour research.
• There is a need to develop more effective therapeutic strategies that do not rely on drugs being able to cross the blood brain barrier. There is an opportunity to consider how to engage with engineers and physical scientists to develop novel drug delivery mechanisms that do not rely on small molecules crossing the blood brain barrier.

In terms of other activity, we are highlighting the cancers of unmet need across our funding streams and are prioritising applications for funding in our committees (where they are of sufficiently high quality). We have also sponsored a session at the National Cancer Research Institute (NCRI) conference this year.

6. Barriers to research

Issues with brain tumour research:

There are a significant number of barriers to research into brain tumours, these include:

• Multiple disease types and rarity of disease – Brain tumours are not a single disease and there are differences between paediatric and adult diseases. Given overall incidence rates, this makes each brain tumour subtype a rare disease.
• Clinical trials in rare diseases – Rare diseases present significant research challenges, from basic biology through translational research to clinical trials. A challenge in clinical trials is the need for sufficient patient numbers to be able to demonstrate the impact of the therapeutic approach. With rare diseases, this not only limits the number of studies that can be undertaken but also necessitates collaborative multinational studies.

• Sample collection – There are difficulties in obtaining high quality samples during surgery, which include access to tumour site and the potential to impact on the patient’s quality of life. Access to research nurse support is vital to collect and process samples collected during surgery.
• Longitudinal sample collection – In most cases, brain tumour patients do not undergo surgery or biopsy at disease recurrence. This limits the opportunity to understand the biology disease progression and to develop therapeutic approaches to treat recurrent disease. 
• Model systems – Currently very few high quality preclinical models exist that recapitulate the human disease. The lack of preclinical model systems impacts on both basic understanding of disease and additionally on the level of confidence to take new therapeutics into trials. Many therapeutics that demonstrate therapeutic response in preclinical models have failed in clinical trials, which limits confidence that they accurately model the human disease.
• Blood brain barrier – There are many similarities between the biology of brain tumours and other tumour types; however, in brain tumours the blood brain barrier impacts on the development of novel therapeutic approaches. Most drugs are designed to be excluded by the central nervous system and therefore don't cross the blood brain barrier, which limits the efficacy of new therapeutic strategies.
• Limited funding for PhDs and post-docs – Retention of high quality researchers in the field is also a challenge, with many researchers moving to related disciplines (e.g. neurosciences/ other tumour types) where there is a perception that there is more funding available.

Clinical Research Governance

• The UK is one of the best places in the world to conduct clinical research but in the past regulatory hurdles have slowed progress. We welcome the Government’s creation and support for the Health Research Authority (HRA).
• The HRA is working to improve the regulation and governance system of the UK by providing a streamlined application and authorisation process. We wish to see continued support for this work which will ultimately support the recruitment of brain cancer patients to trials.
• We are concerned that NHS England are not providing clear leadership on the importance of research in the NHS. The lack of research strategy has meant that commissioners and providers have not been clear on how to support research, this has resulted in delays to trials taking place and some sites not opening trials at all.

Data

• Patient data is crucial to our understanding of the causes and treatments for brain cancers. Delays in researchers being able to access data are leading to hold ups in clinical trial set ups and understanding of brain tumours.
• In the past we have had significant concerns about the Health and Social Care Information Centre’s (HSCIC) governance processes for data release. Researchers reported problems with data release, as well as poor communication from HSCIC on the progress of applications.
• We welcome commitments from HSCIC to make significant changes to their processes. We have initial reports that communication is improving and HSCIC are clearer on what is required from them as a result of the changes implemented so far. We are still waiting to see how these changes have affected.
• Overall we need better public understanding of the role of data in healthcare and research.

7. Routes to diagnosis of brain tumours

People who are diagnosed with brain cancer via emergency presentation have worse relative survival.  In 2006, 64% of those diagnosed with a brain tumour were diagnosed by emergency presentation. In 2013, 53% were diagnosed by emergency presentation. This suggests there has been a decrease in the number of people who are diagnosed by emergency presentation, which is positive progress when it comes to improving the diagnosis of brain cancer.

The job of a GP is an extremely difficult one – the average GP will see fewer than 8 new cases of cancer per year, and most of these will be more common cancers. It is therefore vital that GPs have the appropriate tools at their disposal to make their job easier.

The new cancer strategy[4] highlights the importance of early diagnosis efforts, especially with regards to brain cancer:

To a large extent, approaches to improve early diagnosis focus on cancer in its broadest sense. These initiatives could support expedited diagnosis across a large number of cancer types. However, there are some cancers where some specific factors are at play. One such area is brain tumours in children, where a disproportionate number present through emergency routes51. We need to understand better why this is the case, so that we can tailor initiatives accordingly. It may be there are some specific symptom patterns that parents of young children should be alert to. In this case, these could be communicated in a similar way as symptoms of meningitis, since the incidence rates are similar. Public Health England and NHS England should evaluate data from the HeadSmart programme to determine what factors influence late diagnosis of brain tumours in children and whether tailored initiatives would be appropriate.

We support the recommendations of the Independent Cancer Taskforce and are calling for it to be funded and implemented in full.

Recently updated NICE guidelines on referral for suspected cancer[5] aim to give GPs more flexibility to refer patients in order to help diagnose cancers earlier:

• Symptom thresholds lowered; any that have a three in 100 chance (or more) of being caused by cancer are now included;

• For children and young adults, that threshold has been lowered even further;
• Guidance organised by signs and symptoms is now available, a format that much better reflects how patients present to primary care;
• GPs recommended to refer patients directly for tests, such as CT scans and endoscopies, for a number of symptoms. This should support more comprehensive rollout of direct access nationally;
• “Very urgent” referrals now recommended for some symptoms, where a patient should be seen within 48 hours;
• Specific recommendations on safety netting patients are now included.

Largely Cancer Research UK supports the introduction of these updated referral guidelines, although there may be some areas where they need adjustment for particular symptoms or cancer types. We are working to ensure these guidelines are disseminated and widely used.

It is also imperative that in addition to supporting GPs with their referral, there needs to be increased access to diagnostic tests. In some cases this should occur through direct access, which NHS England should mandate for GPs by the end of 2015[6] . Direct access for brain MRI was included in ‘Improving Outcomes: A Strategy for Cancer’ four years ago and is not yet uniformly available across England.

Existing diagnostic services must have adequate capacity (through staffing and equipment) to deliver timely diagnostic services: our recent report on diagnostic imaging capacity found that:

• Staff shortages are the biggest barrier for units in managing the rising demand for the imaging services, and staff shortfalls are likely to increase.
• Many imaging departments are working with aging imaging equipment and the UK has a very low number of CT and MRI scanners compared to other similar countries.
• Most imaging units do not have the time or headspace to plan how demand will be met, how gaps in the workforce will be filled, or how the aging equipment will be replaced.

We therefore need more detail on the recent welcome announcement from the Department of Health on the additional £300m per year investment in diagnostics.

It is also important that diagnostic services are supported to innovate (such as through the Accelerate, Coordinate and Evaluate (ACE) programme, where multi-disciplinary diagnostic centres are being piloted), in order to find new solutions – this is especially important for the vague or unclear symptoms which may be associated with brain cancer. 

November 2015