Tag Archive for: Cancer

Landmark ‘Pill-On-A-Thread’ cancer screening trial welcomes first participants

Cytosponge device

A pivotal clinical trial of a ‘pill-on-a-thread’ test, which will decide if it becomes a new screening programme for oesophageal cancer, has welcomed its first participant.

The BEST4 Screening trial will find out if the capsule sponge test could be used to screen people with heartburn for Barrett’s oesophagus – a condition that can lead to oesophageal cancer.

The trial is backed by £6.4 million of funding from Cancer Research UK and the National Institute for Health and Care Research (NIHR).

The capsule sponge test takes ten minutes to do and can be done by a nurse – making it much faster and less expensive than endoscopy. The trial will find out if the capsule sponge test can reduce the need for cancer treatments and prevent deaths from oesophageal cancer. The trial showcases UK science and innovation and is the last step in a series of clinical trials to see if the capsule sponge test could be offered in the cancer screening programmes of the 4 UK nations.

Over the next three years, the trial will recruit 120,000 people who regularly take medication for heartburn – the most common symptom for Barrett’s oesophagus. Barrett’s oesophagus is a precursor condition to oesophageal cancer, where cells in the food pipe start to grow abnormally.

Invitations to join the trial will be sent by text message from NHSResearch to encourage as many eligible people as possible to take part in England. Participants will be asked to join Heartburn Health, a new platform to take part in clinical trials in heartburn-linked cancers like BEST4 Screening. Mobile screening vans will be rolled out across England to deliver the tests as part of the trial.

There are around 9,300 new cases of oesophageal cancer in the UK every year, according to analysis from Cancer Research UK*. Oesophageal cancer is the seventh most common cause of cancer death in the UK, with around 22 deaths a day from the disease**.

The capsule sponge starts off as a small, coated pill attached to a thread. When a patient swallows the pill and it reaches the stomach, the coating dissolves and the sponge inside it expands to the size of a 50p coin. The sponge collects cells from the oesophagus as it is gently pulled out from the stomach by a nurse or GP. The cells are sent for testing for two proteins called Trefoil Factor 3 (TFF3), which is only found in Barrett’s oesophagus, and altered p53 protein, which identifies cells which are starting to grow out of control and become oesophageal cancer.

The trial follows decades of research by Professor Rebecca Fitzgerald and a team of scientists, clinicians and nurses at the Early Cancer Institute, University of Cambridge and Cancer Research UK Cambridge Centre, who invented and refined the capsule sponge test. The early trials were supported by the NIHR Cambridge BRC and carried out at the NIHR Cambridge Clinical Research Facility.

The future Cambridge Cancer Research Hospital will bring together clinical and research expertise, including Professor Fitzgerald’s work, under one roof. It will enable the development and discovery of more non-invasive devices like the capsule sponge, to detect cancer earlier, and save more lives.

Cancer Research UK has funded several successful clinical trials to demonstrate that the test is safe and accurate, which have been designed and run by the Cancer Research UK Cancer Prevention Trials Unit at Queen Mary, University of London. A previous clinical trial, BEST3, showed that the capsule sponge test picks up 10 times more cases of Barrett’s oesophagus in people with chronic heartburn, compared to routine GP care.

The test is faster, less invasive and far less expensive than endoscopy, which is currently used to diagnose Barrett’s oesophagus and oesophageal cancer. The test has been piloted in health services in England, Scotland and Northern Ireland for patients who are currently on waiting lists for endoscopy, because they have long-term heartburn or have been diagnosed with Barrett’s oesophagus. To date, over 24,000 capsule sponge tests have been performed in pilot programmes, helping to reduce diagnostic backlogs in endoscopy and NHS pathology.

Paul Anderson (59), a stock controller from St Neots, pictured left, is one of the first participants to join the BEST4 Screening trial in Cambridgeshire. Paul said: “I first experienced acid reflux 10 years ago and I was referred for endoscopy to get it checked out. I’ve been on medication for heartburn ever since to manage it.

“I’d never been on a clinical trial before, but when the invitation came for this one, I felt I had to sign up as the acid reflux had flared back up again. I’m hoping that it may give me some more insight into my chronic heartburn, as well as helping people who may have similar concerns about their health. I’m hopeful that playing my small part in this worthy cause will help others to get checked out earlier.”

Director of the Early Cancer Institute at the University of Cambridge, inventor of the capsule sponge test and co-principal investigator of the BEST4 trials, Professor Rebecca Fitzgerald, pictured right, said: “The capsule sponge is changing how we detect Barrett’s oesophagus and oesophageal cancer. Catching it earlier can save lives by reducing the need for chemotherapy and surgery to remove the oesophagus.

“The BEST4 Screening trial is the pinnacle of many years of painstaking research, which has demonstrated that the capsule sponge can reliably identify Barrett’s oesophagus. Thousands of people have already benefited in trials and pilot programmes, and now we’re taking the test to the next level to see if we could offer this to everyone with heartburn.

“The BEST4 Screening trial could fundamentally transform the lives of people affected by oesophageal cancer by providing the crucial evidence needed to make it a viable screening programme, rolled out to every part of the UK.”

Director of the Cancer Research UK Cancer Prevention Trials Unit at Queen Mary University of London and co-principal investigator of the BEST4 trials, Professor Peter Sasieni, said: “Most people with Barrett’s oesophagus have heartburn, but most people with heartburn don’t have Barrett’s oesophagus. We have already shown that the capsule sponge can reliably identify people with Barrett’s oesophagus. Now we need to show that using it in a targeted screening programme can help prevent oesophageal cancer and reduce deaths from this disease.

“The BEST4 Screening trial will involve over a hundred thousand people joining across the UK. It is a huge undertaking which will take many years, but it is important that we find out whether a new routine screening programme really will prevent cancers and save lives.”

Scientific Director for NIHR Programmes, Professor Danny McAuley, said: “The capsule sponge is an innovative device that has already shown great potential to prevent deaths from oesophageal cancer.

“It’s a great milestone to see the first patient recruited on this pioneering NIHR and CRUK funded trial which in future we hope can lead to routine screening for this deadly disease.

“Thousands of people are needed to join this trial, and we encourage people to sign up as participants. This important research will help benefit patients, and inform those who plan and deliver NHS services of how best to test for the disease.”

Chief Executive of Cancer Research UK, Michelle Mitchell, said: “Around 59% of all oesophageal cancer cases are preventable. Yet endoscopy, the gold standard for diagnosing and treating this cancer, is labour-intensive and not practical for a population screening programme.

“Backed by funding from Cancer Research UK, the capsule sponge has become one of the most exciting early detection tools to emerge in recent years. It’s a remarkable invention by Professor Fitzgerald and her team, and previous trials have shown how powerful it can be in identifying cancer earlier.

“Cancer Research UK is proud to be supporting this landmark clinical trial, bringing the capsule sponge test into the community and offering it to a much wider group of patients. After many decades of research, we’re on the cusp of transforming oesophageal cancer diagnosis forever.”

Minister for Public Health and Prevention, Andrew Gwynne, said: “This trial is a shining example of how we can harness the power of technology to improve patient experience and speed up diagnosis.

“This innovation has the potential to allow us to perform lifesaving screenings quicker and cheaper, freeing up vital NHS resources.

“As part of our 10 Year Health Plan to radically reform our broken NHS, we are committed to fighting cancer on all fronts, and ensuring patients have access to cutting edge, government-funded research.”

The BEST4 Screening trial is open to men over the age of 55 and women over the age of 65 who are currently taking medication for chronic heartburn. The Endosign test used in the trial is manufactured by Cyted Health, who also carry out the pathology tests on samples obtained by the capsule sponge.

More information about how to join the trial can be found at BEST4 or by contacting cuh.best4.trial@nhs.net.

You can also sign up to the NIHR’s Be Part of Research service to take part in clinical research. Simply answer a few questions about yourself and the conditions you’re interested in to be matched to studies happening in locations near you.

Study highlights increased risk of second cancers among breast cancer survivors



Socioeconomic deprivation linked to greater risk of second cancers among breast cancer survivors

Survivors of breast cancer are at significantly higher risk of developing second cancers, including endometrial and ovarian cancer for women and prostate cancer for men, according to new research studying data from almost 600,000 NHS England patients.

For the first time, the research has shown that this risk is higher in people living in areas of greater socioeconomic deprivation.

Breast cancer is the most commonly diagnosed cancer in the UK. Around 56,000 people in the UK are diagnosed each year, the vast majority (over 99%) of whom are women. Improvements in earlier diagnosis and in treatments mean that five year survival rates have been increasing over time, reaching 87% by 2017 in England.

People who survive breast cancer are at risk of second primary cancer, but until now the exact risk has been unclear. Previously published research suggested that women and men who survive breast cancer are at a 24 and 27% greater risk of a non-breast second primary cancer than the wider population respectively. There have been also suggestions that second primary cancer risks differ by the age at breast cancer diagnosis.

To provide more accurate estimates, a team led by researchers at the University of Cambridge analysed data from over 580,000 female and over 3,500 male breast cancer survivors diagnosed between 1995 and 2019 using the National Cancer Registration Dataset. The results of their analysis are published today in Lancet Regional Health – Europe.

First author Isaac Allen from the Department of Public Health and Primary Care at the University of Cambridge said: “It’s important for us to understand to what extent having one type of cancer puts you at risk of a second cancer at a different site. The female and male breast cancer survivors whose data we studied were at increased risk of a number of second cancers. Knowing this can help inform conversations with their consultants to look out for signs of potential new cancers.”

The researchers found significantly increased risks of cancer in the contralateral (that is, opposite) breast and non-breast second primary cancers for both genders compared to the wider population. The greatest increases in risks were for second cancer of the contralateral breast, and for endometrium and prostate cancer in females and males, respectively.

Females who survived breast cancer were at double the risk of contralateral breast cancer compared to the general population and at 87% greater risk of endometrial cancer, 58% greater risk of myeloid leukaemia and 25% greater risk of ovarian cancer.

Age of diagnosis was important, too – females diagnosed with breast cancer under the age of 50 were 86% more likely to develop a second primary cancer compared to the general population of the same age, whereas women diagnosed after age 50 were at a 17% increased risk. One potential explanation is that a larger number of younger breast cancer survivors carry genetic mutations that increase risk for multiple cancers. For example, women with germline BRCA1 and BRCA2 mutations are at increased risk of contralateral breast cancer, ovarian and pancreatic cancer.

Females from the most socioeconomically deprived backgrounds were at 46% greater risk of a second primary cancer compared to the general population, whereas those from the least deprived backgrounds were at 16% greater risk. These differences were primarily driven by non-breast cancer risks, particularly for lung, kidney, head and neck, bladder, oesophageal and stomach cancers. This may be because smoking, obesity, and alcohol consumption – established risk factors for these cancers – are more common among more deprived groups.

Allen, a PhD student at Clare Hall College, added: “This is further evidence of the health inequalities that people from more deprived backgrounds experience. We need to fully understand why they are at greater risk of second cancers so that we can intervene and reduce this risk.”

Male breast cancer survivors were 55 times more likely than the general male population to develop contralateral breast cancer – though cases were still very rare. They were 58% more likely to develop prostate cancer.

Professor Antonis Antoniou from the Department of Public Health and Primary Care at the University of Cambridge, the study’s senior author, said: “This is the largest study to date to look at the risk in breast cancer survivors of developing a second cancer. We were able to carry this out and calculate more accurate estimates because of the outstanding data sets available to researchers through the NHS.”

The research was funded by Cancer Research UK with support from the National Institute for Health and Care Research Cambridge Biomedical Research Centre.

Reference

Allen, I, et al. Risks of second primary cancers among 584,965 female and male breast cancer survivors in England: a 25-year retrospective cohort study. Lancet Regional Health – Europe; 25 April 2024: DOI: 10.1016/j.lanepe.2024.100903

Paediatric cancers: a researcher’s quest to find answers

Clinician, researcher, teacher, mother: it’s exhausting just listing the many hats that paediatric consultant oncologist Dr Aditi Vedi wears.

But we interviewed Aditi not to find out how she ended up in Cambridge UK, 12,000 miles away from her home in Sydney, nor how she raised three young children while working on her PhD (although these are also fascinating!)

Instead we wanted to find out more about her two main research projects that NIHR Cambridge BRC is funding.

It started with a question that Aditi asked herself: What does chemotherapy do to stem cells?

Aditi explained: “We know that children who have chemotherapy are at increased risk of leukaemia, diabetes, metabolic disease and heart disease in the future.

“But just recently, in the space of a year, two children who had received chemotherapy for other reasons were back in hospital because they had developed leukaemia.

“I looked in the scientific literature and, although rare, there are reported cases of this happening and no one really understands why.

“That got me thinking, can I build on what I know about stem cell behaviour from my PhD and look at what chemotherapy does to those stem cells in children?”

In her PhD, Aditi looked at how genetic mutations affect blood stem cell development in adult leukaemia patients.

She found that the gene mutation DNM3TA blocks the production of healthy blood stem cells in adult patients, which then predisposes them to leukaemia.

Now working in paediatric oncology, Aditi decided to build on her knowledge of stem cell behaviour to see how they behave in children with all types of cancer who have received chemotherapy.

That led to the research project on therapy-related AML in children, , in which Aditi will study the effects of gene mutations in blood stem cells from children who developed leukaemia after getting chemotherapy for another cancer. This is in collaboration with Dr Alex Thompson from Nottingham University and is part-funded by the NIHR Cambridge BRC and the Little Princess Trust.

At the same time that Aditi was setting up this trial, she was working on another to investigate making whole genome sequencing (WGS) faster. If successful, this trial has the potential to change clinical practice in England.

Aditi said: “WGS has changed clinical practice for many paediatric cancers, and the NHS has now commissioned this test for all children and young adults up to 25 with cancer or relapsed cancer.

“But it can take up to three months to get the results back. And for aggressive cancers like leukaemia or metastatic disease that’s often too late – and doctors have to make clinical decisions before the data’s back.”

So Aditi is working with current NHS WGS supplier Illumina on a trial to develop a pipeline to deliver WGS data in 24-48 hours.

The Ultrafast WGS study has already recruited 11 patients, and preliminary results are so promising that Aditi has applied for more funding from a number of organisations including Addenbrooke’s Charitable Trust and the Rosetrees Trust to expand the study to 100 patients, whom she hopes to recruit throughout 2024.

Aditi explained: “This is achievable, especially if we include another site and several other hospitals have approached me about joining the study, including Great Ormond Street Hospital who are already very proactive about recruiting patients into WGS.

“If we can get to 100 patients then that would hopefully provide enough data to clearly demonstrate that not only is it feasible but superior to the current NHS pipeline.

“And it could replace not just the WGS pipeline but also other tests including DNA and RNA sequencing, that the NHS currently pays for separately as needed.

“It may work out cheaper to run the single new test rather than up to five smaller tests.”

While the sequencing is the most expensive part of the trial, the funding from NIHR Cambridge BRC covers staff time, including the appointment of a genomics nurse and dedicated research time for Aditi and the geneticists involved.

Next steps

Both projects are expected to take about three to four years. After that, Aditi plans to undertake more discovery and translational science: “My passion lies in acute myeloid leukaemia (AML), which is less common than lymphoid leukaemia in children, but much more aggressive, and which hasn’t really had any major new treatments over the last two decades.

“I’d like to work with other scientists to look at how AML develops in children, and how we can target its weaknesses with newer medications.

“Research is so rewarding, it gives me a purpose for what I do in the clinic, to look for the answers to the questions that directly relate to my patients.

“That’s amazing.”

Professor Charlotte Coles receives top honour from Royal College of Radiologists

Congratulations to NIHR Cambridge BRC cancer researcher Professor Charlotte Coles, CRUK RadNet Cambridge lead, on being awarded the Gold Medal by the Royal College of Radiologists.

The Gold Medal is the highest honour that the College can give to a Fellow (radiologist or clinical oncologist) for important work that benefits patients.

Charlotte, who is Professor of Breast Cancer Clinical Oncology and NIHR Research Professor at the University of Cambridge, and Honorary Consultant in Clinical Oncology at Addenbrooke’s Hospital, leads practice-changing research on the best way to deliver radiotherapy treatment to breast cancer patients.

Her research aims to provide breast cancer patients with the best chance of cure with least side effects by personalising radiation techniques based on risk of recurrence.

Charlotte’s work has influenced international hypofractionation policy and she is Chair of the Lancet Breast Cancer Commission, an international multidisciplinary team aiming to influence global policy and improve the lives of people at risk of, and living with, breast cancer.

She leads CRUK RadNet Cambridge, one of seven centres of excellence across the UK pioneering new radiotherapy technologies and techniques to provide better radiotherapy treatments for patients with fewer side effects.

On receiving the Gold Medal at a ceremony at Central Hall Westminster last week, she said: “I feel very honoured and privileged to receive this award on behalf of collaborative patient-centred research in breast cancer and radiation therapy research.”

Major funding for Cambridge will help find new cancer treatments

Clinicians and scientists in Cambridge have today (23 January 2023) welcomed news that the search for new cancer treatments in the city is to receive a major funding investment of around £3 million, providing future hope for people diagnosed with the disease.

Cambridge’s Experimental Cancer Medicine Centre (ECMC) will receive the cash injection over the next five years to help doctors and scientists find the cancer interventions of the future for both adults and children.

The funding has been made possible by a partnership between Cancer Research UK, the National Institute for Health and Care Research (NIHR) and the Little Princess Trust specifically for children’s cancers.

Cambridge is part of a network of 17 ECMCs across the UK, funded by Cancer Research UK, that deliver clinical trials of promising new treatments and work in conjunction with local NHS facilities to provide access to cutting-edge cancer treatments. Testing these treatments helps to establish new ways of detecting and monitoring the disease, and to evaluate how it responds to the treatment.

Since 2012, Cambridge’s ECMC has contributed to the diagnosis and treatment of thousands of people with cancer or at risk of developing cancer in over 230 clinical trials conducted at Cambridge University Hospitals NHS Foundation Trust and supported by the NIHR Cambridge BRC.

The funding will allow new, experimental treatments – including immunotherapies – for a wide variety of cancers to be developed as well as improve existing treatments.

Cambridge ECMC lead Dr Bristi Basu said: “We are delighted that Cambridge has secured this funding.

“It clearly demonstrates recognition of our research excellence in experimental cancer medicine and is a credit to all our research teams working in alliance with our patient and public involvement group, and our academic and industrial partners.

“Clinical trials are crucial to new and improved treatments becoming adopted as standard treatments by the NHS, and this funding will allow us to advance how we can diagnose and treat cancer effectively.

“Over the next five years, we’ll continue to champion experimental medicine studies for patient benefit, across the spectrum of early to advanced disease, supporting translation of basic research to patient-facing trials, so impacting people with cancer in Cambridge and beyond.

“The new Cambridge Cancer Research Hospital opening in 2026/27 will enable even greater ambition in our plans.”

One in two people in the UK will be diagnosed with cancer within our lifetimes*, so finding new effective treatments is vital.

Cancer Research UK has been integral in aiding the discovery of many new cancer treatments such as the drug tamoxifen, for which Cancer Research UK funded phase four clinical trials to validate it as an effective treatment for breast cancer.

Tamoxifen is now a mainstay treatment for people with oestrogen receptor positive breast cancer and appears on the World Health Organisation’s list of essential drugs for the disease.

As a result of tamoxifen, nearly two thirds of people diagnosed with breast cancer this decade are predicted to survive their disease for 20 years or more.

Executive Director of Research and Innovation for Cancer Research UK, Dr Iain Foulkes, said: “We are proud to be supporting an expansion of our successful ECMC network, bringing together vast medical and scientific expertise to translate the latest scientific discoveries from the lab into the clinic.

“The ECMC network is delivering the cancer treatments of the future, bringing new hope to people affected by cancer. The trials taking place today will give the next generation the best possible chance of beating cancer.

“The adult and paediatric ECMC networks will offer clinical trials for many different types of cancer. Researchers will be working to find new treatments and tackle the unique challenges presented by cancers in children and young people. Working with our partners, this new funding will bring hope for more effective, personalised therapies for everyone affected by cancer.”

Chief Executive of the NIHR, Professor Lucy Chappell, said: “The ECMC network is a vital strategic investment in the UK’s cancer research community, bringing together top scientists and clinicians to tackle some of the biggest scientific challenges in cancer and improve outcomes for patients.

“Through this route, we enable more people to join trials that could help them. The ECMC network will give access to brand new experimental treatments for patients, including children and young people, paving the way for these treatments to be used in the clinic one day. This is a crucial part of NIHR’s work and enables more people to join trials that might help them. We are proud to be partnering with Cancer Research UK and the Little Princess Trust in funding this network.

“The UK has considerable strengths in cancer research. We will continue to back life-saving research for the thousands of adult and children patients affected by cancer every year.”

Minister of State for Health, Helen Whately, said: “A cancer diagnosis can be devastating, but the earlier the diagnosis, the better the chance to treat it and beat it. We are already picking up more cancers early by screening, but we can do even better.

“This partnership between Cancer Research UK, the National Institute for Health and Care Research and the Little Princess Trust will fund innovative trials that could lead to new life-saving treatments.

“Every life lost to cancer is devastating and I’m pleased that across the country people will be given renewed hope – especially children and young people – that we can beat this awful disease.”

Cambridge researchers develop safe, affordable device for prostate cancer diagnosis

A new medical device developed at Addenbrooke’s and supported by the NIHR Cambridge BRC and NIHR Cambridge Clinical Research Facility aims to reduce the risk of infection in prostate patients – and save time and money.

The device – called the Cambridge Prostate Biopsy Device (CamPROBE) – has been developed by urology specialist Professor Vincent Gnanapragasam and his team at Cambridge University Hospitals and Cambridge University.

Traditionally, prostate patients have had transrectal biopsies, where a sample of tissue is removed from the prostate using a thin needle that is inserted through the rectum and into the prostate.

This carries a significant risk of side effects, including urinary infections and severe sepsis -and medical and professional bodies now advocate using instead the transperineal route, which is the space between the legs and under the scrotum.

The CamPROBE uses the transperinal route – making it safer for patients. It’s also cost-effective and simple to use – the procedure can be carried out in outpatients under local anaesthetic.

Urology consultant Professor Gnanapragasam (pictured below) said: “In trials cancer detection rates were equivalent to other means of biopsy.

“Procedure times were short and only low amounts of local anaesthetic were required, yet low pain scores were reported by patients.

Vincent Gnanapragasam

“More than 85% of patients said they would recommend the CamPROBE procedure as a method of having a prostate biopsy done.”

The CamPROBE aims to make the lives of patients better through a simple and low pain approach of prostate cancer detection, hopefully benefitting the millions of men who have prostate biopsies every year.

A licensing agreement for CamPROBE has been agreed with product development company JEB Technologies.

Research reveals how genetic mutations cause kidney cancer

Researchers at the University of Cambridge have shown that genetic mutations associated with kidney cancer rely on factors that regulate normal kidney cells in order to develop into cancer cells.

The study suggests that similar mechanisms could explain why cancer mutations cause specific types of cancer to develop.

Inherited genetic variants and mutations that are randomly acquired during the lifetime of an individual can lead to the development of cancer. But different mutations tend to cause different types of cancer.

While this cancer-specificity of mutations has been clear for decades, exactly why mutations can lead to the formation of tumours in some tissues but not others has remained poorly understood.

All tissues have specific functions that are ultimately dependent on the instructions encoded by the genome. These instructions are read by a group of proteins called transcription factors that recognise specific DNA sequences and ensure that the right regions of the genome are active in each cell. This mechanism allows the same genome to control the functions of diverse cell types with vastly different characteristics.

In this study, published in the journal Nature, the researchers tested whether the transcription factors that control tissue-specific functions of normal kidney cells were also required for the growth of kidney cancers.

They used a combination of advanced genomic tools, experimental cancer models and analysis of large human data sets.

The results show that the ability of kidney cancer-associated genetic alterations to promote tumour formation was dependent on transcription factors that are specifically active in normal kidney cells.

When kidney-specific transcription factors were inactivated experimentally, the cancer mutations were no longer capable of activating genes that are important for tumour growth.

Senior author Dr Sakari Vanharanta said: “Our results provide some insight into the molecular mechanisms that dictate the cancer type-specificity of mutations.

“Genetic alterations that cause kidney cancer rely on factors that under normal conditions regulate specific functions of healthy kidney cells. If these factors are not present, as they are not in most other cell types, the process that eventually leads to cancer formation does not proceed.”

Large genetic alterations commonly observed in advanced, metastatic kidney cancer cells also relied on kidney-specific transcription factors for their cancer-promoting effect.

The common genetic variant characterised in this study is carried by the majority of individuals of European descent and it increases the risk of kidney cancer. Overall, the molecular mechanisms described in this work are likely to be important for a large proportion of kidney cancers.

Professor Grant Stewart, study co-author and co-lead of the CRUK Cambridge Centre Urological Malignancies Programme, said: “[This] paves the way to new thinking on how to develop new treatments for kidney cancer and even prevent it from developing in the first place.

“These same mechanisms might also be at play in other cancer types, making this study highly relevant across all cancers”.

Funding boost for ‘sponge on a string’ trial

Millions of pounds in funding has been announced for a trial that could pave the way for a ‘sponge on a string’ test to be established as a routine screening programme to detect Barrett’s oesophagus – a condition that can lead to oesophageal cancer.

Cancer Research UK and the National Institute for Health and Care Research (NIHR) are providing £6.4 million for testing of the Cytosponge-TFF3 pioneered by Professor Rebecca Fitzgerald and her team at the University of Cambridge.

The Cytosponge was created in Cambridge by Professor Fitzgerald back in 2001. Early trials were supported by the NIHR Cambridge BRC and NIHR Cambridge Clinical Research Facility, making sure the device was safe and accurate in detecting Barrett’s oesophagus.

Further studies then showed the Cytosponge detected 10 times more cases of Barrett’s oesophagus compared with routine GP care*.

The new trial, BEST4, will now explore if the Cytosponge can prevent deaths from oesophageal cancer when offered as a screening test to people on long-term medication for heartburn – one of the most common Barret’s oesophagus symptoms.

Researchers will also investigate if the Cytosponge, coupled with additional lab biomarker tests, can be used to monitor people already diagnosed with Barrett’s oesophagus instead of endoscopy, an invasive hospital procedure for which there is a major backlog caused by the pandemic.

It is anticipated the trial team will begin setting up sites in autumn, with 120,000 patients to take part over 14 years. Those involved will be randomised to different groups and a third of those will receive the Cytosponge, a quick and simple test that can be carried out by a GP.

Professor Fitzgerald will lead the trial alongside Professor Peter Sasieni and his team from King’s College London.

Professor Rebecca Fitzgerald

Professor Fitzgerald, pictured right, said: “The BEST4 trial is an exciting opportunity to take our work on the Cytosponge-TFF3 to the next level and see whether this test not only detects more cases, but also saves lives from cancer of the oesophagus. It will be a big piece of work, but it’s timely given the push from the NHS leadership, the Life Sciences Industrial Strategy and Cancer Research UK to detect cancers earlier in order to improve outcomes for patients.”

The Cytosponge begins as a pill on a string. It is swallowed by a patient and when it reaches the stomach the coating dissolves. This allows the pill to expand into a small sponge, about the size of a 50p coin. The sponge is pulled back out of the stomach by a nurse. As the sponge comes up it collects cells from the oesophagus for lab analysis.

Dr Iain Foulkes, executive director of research and innovation for Cancer Research UK, said: “Cancer Research UK is celebrating 120 years of life-saving discoveries this year and we’re really pleased to be funding what will hopefully be the final trial before this pioneering development is established as a screening device to detect Barrett’s oesophagus.

“There are 9,200 people diagnosed with oesophageal cancer in the UK every year and the Cytosponge will mean they can benefit from kinder treatment options if their cancer is caught at a much earlier stage, hopefully helping to boost survival rates at the same time.”

Using the Cytosponge during the pandemic

During the height of the pandemic patients were not being seen for routine gastroscopy. It was decided to rapidly implement use of the Cytosponge test because it has a low aerosol generation and needs only one person to carry out the procedure.

Irene Debiram-Beecham led on the implementation and at the Royal College of Nursing’s annual Nursing Awards she was highly commended in the Excellence in Cancer Research Nursing Award category. The award is sponsored by Cancer Research UK and the only one in the UK to recognise research nurses working on cancer trials and studies.

Irene, principal research nurse for the Cambridge ACED Clinic, said: “As part of this initiative, I provided a new robust training programme for nurses, clinicians and health care professionals across the UK. Having developed a system to sign them off as competent to carry out the procedure, I also provided a 24-hour support service for my colleagues if they had any questions.

“As a research nurse, it makes me proud to see something I’ve been working on for many years has finally made it into clinical practice.”

* Fitzgerald, R. C., et al. A pragmatic randomised, controlled trial of an offer of Cytosponge-TFF3 test compared with usual care to identify Barrett’s oesophagus in primary care. The Lancet, 2020

Adapted from CRUK press release

Children with cancer benefit from whole genome sequencing

More than 100 children with cancer from across the East of England have had their tumours tested by whole genome sequencing at Addenbrookes Hospital and supported by the NIHR Cambridge BRC, to help improve their diagnosis and treatment.

In cancer, Whole Genome Sequencing looks at the ‘whole genome’ or entire genomic (DNA) profile of a patient as well as the cancer.

For children with cancer, scientists look for differences, known as ‘variants’ or ‘mutations’, in the DNA from their tumour compared with their blood. This helps doctors and scientists give a far more detailed and personalised diagnosis, in some cases providing clues to the most effective treatments for each patient. Data from the first 36 children, who consented to the test as part of the national 100,000 Genome Project cohort, has now been published in the British Journal of Cancer.

The published findings, also shared at the 2021 National Cancer Research Institute (NCRI) Festival, described 23 different solid tumour types, and revealed several potentially important variants. In a number of cases, the information either refined or changed the children’s diagnosis, revealed new information about the children’s prognoses, showed hereditary causes, or revealed treatments that might not otherwise have been considered.

A further 65 patients across the region have had their whole genomes read since the test was made routinely available through the NHS Genomic Medicine Service at the start of 2021. Early review of the data and outcomes shows that these results continue to demonstrate the value of centralised WGS for children with cancer.

Aubrey, from Bedfordshire, was diagnosed with cancer in January 2021 when she was only 16 months old. However, as the actual type of Aubrey’s cancer was not certain from standard testing, her parents Anna and Paul agreed to a WGS test for Aubrey.

Aubrey with her dad and Professor Matt Murray

Anna, Aubrey’s mother said: “The test gave us a confirmed diagnosis for Aubrey after other tests had narrowed it down to one of two potential types of cancer. The result meant that the clinicians could be more confident as to the best treatment to use.

“Whist we still have a challenging journey with Aubrey’s diagnosis and treatment, we were relieved to know that she did not have cancer that was inherited, and hence we did not have to worry that it could affect our son or other members of the family as well.

Professor Matthew Murray

Professor Matthew Murray, Honorary Consultant Paediatric Oncologist, Cambridge University Hospitals, pictured left, said: “Seeing 100 children with cancer benefit from WGS is a milestone. Overall, as a result of these tests, we’ve been able to confirm or refine the diagnosis for many of the children, identify and in some cases start new and beneficial treatment, and importantly in others have a clearer idea of the likely course of a patient’s cancer.”

Following referral, the NHS pathway allows patients and family to meet the clinical team at CUH to discuss the next steps.

Once consent to WGS had been obtained, a sample of tumour (usually taken from a previous procedure) is sent alongside a blood sample via the NHS East Genomic Laboratory Hub (NHS East GLH) to the company Illumina – located a few miles away from CUH. Samples are then sequenced at Illumina and results sent back for discussion at a meeting with the patient’s clinical team as well as expert scientists from the NHS East GLH to decide on best patient management.

This data has been released to coincide with the publication of the results from the patients enrolled in the 100,000 genome project in the British Journal of Cancer.

The research was supported by the NIHR Cambridge Biomedical Research Centre.

Adapted from CUH press release

Personalised blood test can detect persistent lung cancer

Patients who are at a higher risk of their lung cancer returning can be identified by a personalised blood test that is performed after treatment, according to researchers at the University of Cambridge. 

Scientists at the Cancer Research UK Cambridge Institute and supported by the NIHR Cambridge BRC, used a personalised blood test for patients, which is a type of liquid biopsy that can pick up tiny fragments of DNA that are released into the blood as tumours grow. This DNA, called circulating tumour DNA (ctDNA), can reveal the state of the tumour, its location and potentially its weaknesses, which could be used to select the best treatments. 

The results from the Lung Cancer Circulating Tumour DNA (LUCID-DNA) study, funded by Cancer Research UK, have been published today (Thursday 17th March) in the Annals of Oncology.

Many patients who are treated for early-stage non-small cell lung cancer can be cured with either surgery, radiotherapy or sometimes (chemo)radiotherapy. 

After treatment, lung cancer patients are carefully followed up with tests including CT scans to find out if the treatment has removed the tumour, but scans won’t pick up tiny quantities of cancer cells known as minimal residual disease (MRD) which could still regrow into further tumours. 

By finding signs that lung cancer cells might still be present and active after treatment, using methods such as liquid biopsy, doctors might be able make better choices about treating patients, aiming to improve the chances of survival for patients who are at higher risk while reducing side effects for patients who are at a lower risk group.  

The LUCID-DNA study aimed to find out if circulating DNA can be detected in early stage lung cancers. It used a liquid biopsy, called RaDaR™, which analyses up to 48 different mutations that are unique to each patient’s tumour. 

RaDaR™ was developed by Inivata, a biotech company co-founded by Dr Nitzan Rosenfeld, and is based on technologies developed initially by his lab at the Cancer Research UK Cambridge Institute.

Dr Nitzan Rosenfeld, group leader at the Cancer Research UK Cambridge Institute, Chief Scientific Officer of Inivata and co-lead author of the study, said:  

“If cancer cells remain in the body after treatment a tumour can regrow. If that happens, it is a big setback for patients and the doctors treating them.

“Liquid biopsy can be used to detect tiny amounts of residual cancer after treatment, flagging those patients who have signs that their tumour may not have been eradicated completely with treatment. We’re hoping that this technology could help doctors decide when additional rounds of treatment are needed, and could save lives.”

To find out if liquid biopsy could find lung cancer patients with MRD, the LUCID-DNA study team enrolled 88 patients who were treated at Royal Papworth Hospital and Addenbrooke’s Hospital for early stage** non-small cell lung cancer (NSCLC). NSCLC accounts for over 85% of all lung cancer cases. 

The research team extracted DNA from tumour samples provided by the patients and sequenced the DNA to find combinations of mutations unique to each patient’s lung cancer. Using this genetic “fingerprint”, Inivata created a blood test which was personalised to the patient’s tumour. 

The liquid biopsies were then used to detect tumour DNA in blood samples collected before treatment, and for up to 9 months after treatment. The researchers found that patients who had tumour DNA present between two weeks and four months after treatment were much more likely to have their lung cancer come back or to die from it. 

Professor Robert Rintoul, Professor of Thoracic Oncology at the University of Cambridge, Honorary Respiratory Physician at Royal Papworth Hospital and co-lead author of the study, commented:

“We need to study these liquid biopsies further to find the best ways to deploy them, but these results clearly show that they can potentially be an effective tool to help decide which patients need further treatment.

“Being able to offer patients personalised monitoring and treatment will ultimately save more lives and help us to beat cancer sooner.”

Lung cancer is the third most common type of cancer in the UK. Every year, around 48,500 people are diagnosed with lung cancer*** and every year around 35,100 people die from the disease in the UK****.

Aart Alders participated in the Lung Cancer Circulating Tumour DNA (LUCID-DNA) observational clinical study at Royal Papworth Hospital following his lung cancer surgery.  

“I was first diagnosed with an early-stage lung cancer about five years ago and underwent a surgical operation to remove it,” he said. “Although some people need further treatment with chemotherapy, I have been very fortunate and my original lung cancer has not returned.

“I was very pleased to be able to help with the LUCID-DNA research study. By trying to develop a blood test to help doctors predict whether a lung cancer might come back or not, we will increase the chance of curing more people.”

Michelle Mitchell, Chief Executive of Cancer Research UK, said: “Lung cancer is one of the biggest killers in the UK. The earlier it is caught, the more likely it is to be treated successfully. 

“Detecting signs of cancer before or after treatment without the need for invasive surgery has huge potential for both patients and doctors. 

“I look forward to seeing more research that will develop liquid biopsy further, which will ultimately make it much easier for doctors to offer treatment that best matches the patient’s needs, increasing their chance of survival.” 

Adapted from CRUK press release

Notes:

** The proportion of patients taking part in the study by stage of lung cancer at diagnosis was 48.9% at stage I, 28.4% at stage II and 22.7% at stage III.

*** Based on the annual average number of new cases of lung cancer in the UK between 2016 and 2018, available from https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/lung-cancer#heading-Zero (accessed 10/03/22).

**** Based on the annual average number of deaths from lung cancer in the UK between 2016 and 2018, available from https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/lung-cancer#heading-One (accessed 10/03/22).  

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