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Take a look at a selection of our recent media coverage:

HLA-II heterozygosity associated with reduced lung cancer risk in smokers

5th March 2024

Population-level immunogenetic variation is a factor underlying lung cancer risk in current and former smokers, a large study has found.

Researchers used genetic and clinical data from two large-scale population cohorts – UK Biobank and FinnGen – together with multi-modal genomic analyses of non-malignant and lung tumour samples to evaluate the effect of human leukocyte antigen (HLA) heterozygosity on lung cancer risk.

The analysis found heterozygosity at the HLA class II (HLA-II) loci was associated with reduced risk of lung cancer over more than a decade of follow-up, study authors wrote in the journal Science

Of note, HLA-II heterozygosity was associated with reduced risk of lung cancer in both current and former smokers, but not never-smokers.

This suggested that smoking-derived antigens might augment the immune response to early neoplastic disease, they wrote.

In contrast, HLA-II homozygosity conferred substantial lifetime risk of disease (13.9% for current smokers in the UK Biobank cohort) and was independent of known clinical and genetic risk factors.

Co-senior author Dr Diego Chowell, assistant professor of oncological sciences, and immunology and immunotherapy at the Icahn School of Medicine at Mount Sinai in New York, which led the study in collaboration with the University of Helsinki and Massachusetts General Hospital, said the findings challenged conventional thinking by demonstrating that immune genetics, specifically HLA-II heterozygosity, played a significant role in lung cancer risk, especially among smokers.

Dr Chowell said: ‘Further, when we added polygenic risk scores – which is a measure of genetic predisposition based on multiple genes – to the analysis, it increased the lifetime risk of lung cancer, specifically in smokers who have identical versions of the HLA-II genes.’

Understanding HLAs and cancer risk

HLAs are cell surface molecules that recognise antigenic peptides and present them to T-cells to initiate an immune response.

In lung cancer, genetic variation in the HLA locus was known to be linked to tumour evolution and treatment outcomes, but it was unclear whether HLA polymorphisms reduced lung cancer risk, the researchers explained.

This study was designed to test the heterozygote advantage hypothesis, which is a foundational principle of the evolution of the HLA system and of HLA-mediated protection against disease.

‘According to this hypothesis, individuals heterozygous at HLA are afforded greater protection against disease because they present more antigens for T-cell recognition through their two different HLA allomorphs than do homozygous individuals and consequently clear infected or neoplastic cells more efficiently,’ the researchers wrote.

The data underscored the role of immunosurveillance in protecting against lung cancer, the researchers said.

‘The association of HLA-II heterozygosity with reduced risk of lung cancer implies that genetic variation in immune-surveillance is a feature of cancer susceptibility, together with environmental exposures, hereditary risk and DNA replication errors,’ they said.

The findings broadened the understanding of the role the host immune system played in cancer risk and might motivate the incorporation of immunogenetics into lung cancer screening programmes, the study authors concluded.

‘A greater understanding of immunogenetic determinants of cancer risk, including genetic variation in HLA and other immune genes and pathways commonly associated with autoimmune and infectious diseases, may foster the development of improved strategies for cancer prevention,’ they wrote.

The findings suggested that current or former smokers homozygous at HLA-II could be considered at an earlier age for low-dose computed tomographic (LDCT) screening, which might reduce lung cancer mortality.

Whether the combination of genotype-driven risk assessment and LDCT reduced lung cancer mortality compared with either method alone should be comprehensively investigated in a future prospective clinical trial, they said.

Are blood tests, robotics and AI the secrets to earlier lung cancer diagnosis?

4th January 2024

With the results of the lung cancer screening SUMMIT study expected imminently, Helen Gilbert caught up with consultant respiratory physician Dr Neal Navani to discuss this research, promising new innovations in lung cancer diagnostics and what they might mean for the future of lung cancer care.

As Cancer Research UK’s Lung Cancer Centre of Excellence, University College London and University College London Hospital (UCLH) have been at the forefront of lung cancer innovations, pioneering diagnostic modalities such as endobronchial ultrasound.

This diagnostic focus is particularly pertinent as lung cancer is Europe’s biggest cancer killer, with 380,000 deaths across the continent in 2020 – a fifth of all cancer deaths.

In England, more than 60% of lung cancer patients are diagnosed at either stage three or four, and this late diagnosis is a frustration for Dr Neal Navani, lead consultant respiratory physician for lung cancer services at UCLH, as he says cure rates can be as high as 80-90% for patients whose small, early-stage lung cancer is detected.

Dr Navani, who is also the clinical lead of the UK National Lung Cancer Audit and clinical director for the Centre for Cancer Outcomes at the North Central London Cancer Alliance, has long been involved in pioneering research at UCLH to improve early detection and diagnosis.

And recent projects suggest there are further innovations on the horizon that have the potential to improve patient outcomes.

The SUMMIT study

In May 2023, the largest lung cancer screening study of its kind in the UK drew to a close.

The four-and-a-half-year SUMMIT study was a collaboration between researchers from UCLH, University College London (UCL), the National Institute for Health Research, UCLH Biomedical Research Centre and GRAIL – a US healthcare company focused on the early detection of cancer.

Their aim was to identify lung cancer early among at-risk Londoners and support the development of a new blood test for the early detection of lung and multiple cancer types.

More than 13,000 people aged 55-77 from north and east London who had a significant smoking history were offered a blood test and a low-dose CT scan of their lungs. They were followed up at three months or immediately if a cause for concern was identified.

Dr Navani describes the research – results of which are expected imminently – as ‘a really fantastic, rich data set on which we can look to answer a lot of questions about detecting cancer early’.

He is particularly interested in developing a model that incorporates PET-CT scans to predict malignancy in screen-detected lung nodules. Often these appear like freckles on the lung, which may or may not be cancerous.

The challenge, he says, is working out whether they are malignant or benign, and currently this is done using a risk calculator developed in 2005.

It involves an injection of radioactive sugar before a PET-CT scan to see whether the nodule – or anything else for that matter – takes up the sugar. This then correlates with the risk of malignancy.

However, Dr Navani describes the current tool, which was developed in 2005, as out of date and prone to underestimating the risk of cancer in lung nodules.

Updated lung cancer risk and diagnosis tools

Data from the SUMMIT trial are set to be used to develop and test a new risk calculator that takes into account more than 10 factors including family history, smoking and the size and appearance of nodules. It aims to accurately predict the chance of a nodule being cancerous.

‘We’re able to see whether sugar is taken up by that nodule in the lung – the idea being that small cancers use up more sugar than nodules that are not due to cancer,’ Dr Navani says.

‘Data for that work are being collected and developed. We’re pulling together data through other trials doing a similar thing and hopefully we’ll be able to clarify the role of PET-CT scanning for nodules in the next two years.’

The risk calculator will be compared against the existing model as well as others that do not include PET-CT scanning.

If found to be more accurate, the potential benefits are numerous and may include fewer patient investigations at lower cost, earlier treatment and reduced anxiety for those called in, Dr Navani explains.

UCL researchers are also using blood samples from the SUMMIT study to evaluate a blood test that can diagnose tumours earlier and detect 50 types of cancer, including lung cancer, with high accuracy.

Developed by GRAIL and an international team of researchers co-led by UCL, the test looks for tell-tale chemical changes to bits of genetic code – cell-free DNA – that leak from tumours into the bloodstream.

It was developed using artificial intelligence (AI) after researchers fed data on methylation patterns from the blood samples of thousands of cancer patients into a machine learning algorithm. It is said to identify many types of cancer, including bowel, ovarian and pancreatic, and can diagnose in which tissue the cancer originated with 96% accuracy.

Revolutionary robotics

But the potential of technology in bolstering cancer diagnosis doesn’t stop at AI. Another promising area of innovation is robotics.

Dr Navani is intrigued by the potential of this kind of diagnostic ability, and he is aware of robotic techniques that will be ‘the subject of research over the next year or two’.

He says: ‘We need to understand the cost effectiveness of robotic diagnosis of lung nodules. It’s potentially exciting.’

Earlier this year NHS clinicians at the Royal Brompton and St Bartholomew’s Hospital in London began a clinical study trialling a robotic-assisted bronchoscopy system.

Each hospital site is aiming to recruit around 50 patients with small lung nodules located in areas that are challenging to reach via traditional bronchoscopy.

The system combines software, robotic assistance and a flexible catheter with a camera to create a 3D roadmap of the lungs – much like a car’s sat-nav.

Doctors are directed to deep and hard-to-reach areas in each of the 18 segments of the lung, with the aim of removing tissue samples for biopsy with greater precision and accuracy.

The benefits of diagnosing a lung nodule accurately with a tiny camera could ‘open up a world of possibilities in terms of drug delivery, or ablation [to destroy cancerous nodules] in a controlled and accurate way,’ says Dr Navani. ‘I think in the next five to 10 years we’re going to see novel diagnosis and treatment options for our patients with early-stage lung cancer in particular.’

Endobronchial ultrasound

Another key development Dr Navani anticipates is the continued and increasing importance of collaboration, particularly when it comes to technology.

Endobronchial ultrasound (EBUS), one of the biggest innovations in respiratory medicine over the last 15 years, evolved from endoscopic ultrasound used in other clinical areas.

EBUS was trialled in the early 2000s by the UCLH research team, of which Dr Navani was a leading player, and uses a bronchoscope with a light, camera and integral ultrasound scanner to produce a detailed image inside the chest.

It enables doctors to take targeted needle biopsies of any enlarged lymph nodes and suspicious lesions while avoiding areas such as blood vessels.

Prior to this, patients at-risk of lung conditions required incisions to the chest under general anaesthetic, resulting in hospital stays and the possibility of complications or even death.

The arrival of EBUS in clinical practice in 2007 meant the diagnostic procedure could be performed on outpatients in under 30 minutes, with patients able to leave just one or two hours later.

‘It’s a very safe technique [and] in the last 10-15 years it’s really become a mainstay of diagnosis in respiratory medicine,’ Dr Navani acknowledges. ‘It started off very slowly but now in the UK there are 140 centres that are doing this technique and it’s been adopted globally for diagnosing lung conditions.’

Dr Navani believes the adaption of tools and techniques used in other clinical fields will continue to play a pivotal role in the advancement of lung cancer diagnostics and treatment. He points out, for example, that tumour ablation, which is used to treat lung and liver cancer, is now happening at a research stage for pancreatic cancer.

And this collaboration doesn’t just extend across clinical specialities. Imaging and information providers, including the likes of Fujifilm, also serve a vital purpose by providing increasingly innovative imaging solutions.

In June 2023, NHS England announced the national rollout of a targeted lung cancer screening programme to help detect cancer sooner and speed up diagnosis.

The rollout followed a successful pilot phase in which lung cancer scanning trucks carrying out on-the-spot chest scans operated from convenient locations such as football stadiums, supermarket car parks and town centres.

In September, NHS England announced that more than one million people had been invited for a lung cancer check via the scheme and almost 2,400 cancers had been caught – an impressive 76% of which were diagnosed at stage one or two.

‘That’s going to hopefully need innovative imaging solutions, particularly low-dose scanners, and I think we need to work with industry in terms of the use of artificial intelligence to help with the reporting of those scans,’ Dr Navani says.

Innovative diagnostic imaging techniques are certainly in development, and Dr Navani sees huge potential in new technologies for treating patients, too.

‘In terms of delivering novel therapies, in the future there may be a role for delivering drugs directly into the lungs, the pleural space or endobronchially, lymph nodes, or primary lung lesions,’ he says.

Addressing unmet needs in lung cancer

Dr Navani describes working in a hospital that is attached to a world-class university as ‘fantastic’ because it grants access to ‘extraordinary expertise’ spanning science, sociology, data science, computer science and engineering.

‘The research into lung cancer at UCL is really incredibly broad and, dare I say it, world leading, right the way through the basic science, biology and understanding how cancer develops and spreads and changes over time… to understanding the societal impact, equality and equity of care,’ he says.

According to Dr Navani, there appears to be a big difference in the outcomes of lung cancer patients based on socio-economic status.

‘We’ve really tried to address this in the National Cancer Audit, but it remains a significant challenge,’ he says. “A lot of this comes down to local resources… access to healthcare, equality and subsequent diagnosis and treatment in a timely fashion.’

Another major unmet need, Dr Navani says, is the 15% of patients with lung cancer who have never smoked and it’s here that ‘urgent research is needed’.

‘Given the high burden of lung cancer care, that’s a significant number of people – if you consider [non-smoking-related lung cancer] as a cancer in its own right it would be the seventh most common cause of cancer death,’ he says.

‘We’re really starting to get to grips with lung cancer in smokers but we are still at the early stages of understanding why people who’ve never smoked develop lung cancer. It would be important to predict who these people might be so that we can identify them at an earlier stage so hopefully their outcome will be better.’

Looking to the future

The most pressing issue facing the NHS is limited resources, according to Dr Navani.

‘We simply don’t have enough scanners, radiologists, or space to do bronchoscopies,’ he states. ‘We’ve talked a lot about innovation but actually the most important thing that can be done to improve lung cancer care is for each hospital and primary care setting to have the appropriate resources to deliver what we know is already appropriate care, to drive out inequalities and drive everybody up to the best possible standards.’

While the future of funding for lung cancer care in the UK remains in flux, one thing is for certain: the research, expertise and drive to support the early diagnosis of patients remains, and Dr Navani’s commitment to supporting patients through innovative routes is stronger than ever.

Lung cancer screening could be ‘game changer’ in Scotland, Wales and Northern Ireland

19th December 2023

The UK’s devolved nations could detect greater numbers of lung cancer cases with improved screening programmes, new analyses by Cancer Research UK have found as the charity calls for governments to ’urgently implement’ such programmes.

Lung cancer is the leading cause of cancer death in England, Scotland, Wales and Northern Ireland and smokers and former smokers aged 55-74 are at greatest risk.

In November 2022, the National Screening Committee (NSC) recommended that everyone in this group be screened but, to date, only England has initiated a screening programme on this advice.

Almost 900,000 people were invited for checks during the pilot stages in England. Of the 200,000 scans carried out, more than 2,000 people were detected as having lung cancer, and 76% of those were identified at an earlier stage (stage 1 or 2) compared to 29% identified outside of the pilot programme in 2019.

Nationwide lung cancer screening could be a ‘game changer’

Cancer Research UK’s latest analyses suggests that equivalent lung cancer screening programmes in the devolved nations could diagnose around 4,000 more lung cancer patients in Scotland at an early stage over the next decade, as well as 2,400 more people in Wales and 1,400 in Northern Ireland.

If just 50% of eligible people took part in screening, earlier lung cancer diagnosis could save 2,300 lives in Scotland, 1,000 lives in Wales and 600 lives in Northern Ireland over the next 10 years, Cancer Research UK said.

Professor David Weller, professor of general practice at the University of Edinburgh, believes a nationwide screening programme ’has the potential to be a game changer when it comes to reducing the burden of lung cancer in Scotland’.

He said: ’For too long, lung cancer has been perceived as a disease you can’t do anything about, but we know that diagnosis at an early stage really can make a difference.

’Major trials of targeted lung cancer screening show significant reductions in mortality from lung cancer. Pilot studies in the UK and internationally consistently show people being diagnosed with lung cancer at an earlier stage.’

In Scotland, a pilot project called LUNGSCOT – of which Professor Weller is the principal investigator – is exploring the challenges for local lung cancer screening. It is running in Lothian with funding released for Grampian, Greater Glasgow and Clyde, and the Highlands and Islands.

A pilot is also running in Cwm Taf Morgannwg in Wales, where charities including Cancer Research UK are running a public petition in the hopes of raising the issue in the Senedd.

In Northern Ireland, there are no plans or pilots to report due to the lack of a Northern Irish Executive following the 2022 elections. That said, authors of the Northern Ireland Cancer Strategy 2022-2032 have said they intend to implement all NSC recommendations.

Debbie King, Cancer Research UK’s senior external affairs manager in the devolved nations, said: ’Lung screening matters because it means more people can be diagnosed at an earlier stage, when treatment is more likely to be successful.

’A fully-funded national targeted lung cancer screening programme in Northern Ireland, Scotland and Wales is a real chance to reduce the toll of this disease.

’There have been big improvements in how we diagnose and treat other forms of cancer, but long-term lung cancer survival in the UK isn’t much higher than it was 50 years ago. This is unacceptable when evidence shows that earlier diagnosis through targeted lung cancer screening can potentially help thousands of people live longer healthier lives.’

Cancer manifesto launched

These latest analyses were published shortly after Cancer Research UK released its manifesto for reducing cancer deaths by 20,000 a year by 2040.

While overall cancer deaths have halved over the last 50 years, progress is at risk of stalling in the UK, the charity said.

As part of the manifesto, Cancer Research UK has called on the next UK Government to address variation in treatment across different geographical areas, which includes optimising cancer screening programmes and accelerating the roll-out of the lung cancer screening programme in England.

On the manifesto, former national cancer director at the Department of Health and chair of the National Screening Committee, Professor Sir Mike Richards, said: ’Cancer outcomes in the UK are lagging behind comparable countries like Denmark. We need consistent funding and long-term strategies to make the UK the best in the world for cancer survival.’

First robotic-assisted lung biopsy performed at UK hospital to aid early diagnosis

8th August 2023

A robotic-assisted bronchoscopy system is being used in the UK for the first time in a move that could help to transform the early diagnosis of suspected lung cancer by improving precision and speed when taking tissue biopsies of lung nodules.

NHS clinicians at the Royal Brompton Hospital and St Bartholomew’s Hospital are participating in a clinical study to determine if the Ion Endoluminal System (Ion), which was developed by the robotic-assisted surgery company Intuitive, could benefit patients and the NHS.

Each hospital site will aim to recruit around 50 patients with small lung nodules located in areas that are challenging to reach via traditional bronchoscopy.

Ion uses unique shape-sensing technology and robotic assistance to allow clinicians access to deep and hard-to-reach areas in each of the 18 segments of the lung. This means tissue samples can be removed for biopsy with greater precision and accuracy.

During a procedure with the Ion system, a physician inserts the Ion, fully articulating the catheter into the patient’s lung via the mouth and throat through an endotracheal tube, which may have fewer complications than biopsy approaches that use a needle inserted from outside the body.

Transforming early diagnosis

Kelvin Lau (pictured), consultant thoracic surgeon for St Bartholomew’s Hospital, said’The UK is leading the world in rolling out a national lung cancer screening programme. However, only some of the lung nodules identified during screening are cancerous and need treatment. Current biopsy techniques carry risk and are not always accurate, and many patients end up waiting for a repeat scan. The uncertainty of the wait causes anxiety and could allow a cancer to grow and spread.

’With this shape-sensing robotic technology, I have the precision and stability to lock onto a very small lung nodule and obtain an accurate biopsy quickly and safely. This could transform early diagnosis and treatment, reduce the need for repeat scans and treat lung cancer earlier.’

Also commenting on the ’transformative’ technology, Professor Pallav Shah, consultant respiratory physician based at Royal Brompton Hospital, added: ’We know that an earlier diagnosis of lung cancer leads to significantly improved outcomes for our patients. When we see patients with cancerous lung nodules of more than 30mm, their five year survival rate is around 68%, but if we are able to detect these nodules at a smaller size, when they are less than 10mm in size, we are looking at a 92% survival rate.’

There are already over 400 Ion systems installed in US hospitals, and Intuitive continues to explore its applications in other countries including in the UK, across Europe and beyond.

Tiny robot represents possible novel approach for less invasive lung cancer detection and treatment

3rd August 2023

The use of magnetic tentacles offer a novel therapeutic and targeted approach for minimally invasive lung cancer detection and treatment, according to researchers from the University of Leeds.

The researchers developed a tiny, magnetically operated robot that is capable of travelling deep into the lungs and able to detect and treat the first signs of cancer. Their approach makes use of a 2.4 mm diameter, ultra-soft, patient-specific magnetic catheter – or tentacle – which can be delivered from the end of a standard bronchoscope to reach the periphery of the lungs. In addition, the tentacles possesses a laser fibre designed to enable targeted photo-thermal therapy to cancer cells.

In their study, which was published in Nature Engineering Communications, the team initially developed a three dimensional model of the bronchial tree, down to the sub-segmental bronchi, using data generated from a CT scan of the full lung. Once the tentacle was in position, laser light was delivered through the embedded fibre to induce thermal ablation of the tumour.

Following this initial and successful virtual experiment, the researchers next used the magnetic tentacle robot on the lungs of a cadaver. They were able to successfully navigate in three branches of the left bronchi, compared to only two using a standard catheter, which corresponded to a mean improvement in navigation depth of 37%.

Transforming lung cancer treatment

Commenting on the results, Professor Pietro Valdastri, the project‘s research supervisor, said: ‘This is a really exciting development. This new approach has the advantage of being specific to the anatomy, softer than the anatomy and fully shape-controllable via magnetics. These three main features have the potential to revolutionise navigation inside the body.‘

Lung cancer has the highest worldwide cancer mortality rate. In early-stage non-small cell lung cancer, which accounts for around 84% of lung cancer cases, surgical intervention is the standard of care. In addition to being able to navigate within the lungs during a biopsy, the magnetic tentacle robot could pave the way for far less invasive treatment, allowing clinicians to target only cancer cells while allowing healthy tissue and organs to continue normal function.

Dr Giovanni Pittiglio, who carried out the research as part of his PhD, added: ‘Our goal was, and is, to bring curative aid with minimal pain for the patient. Remote magnetic actuation enabled us to do this using ultra-soft tentacles which can reach deeper, while shaping to the anatomy and reducing trauma.‘

England’s first-ever lung cancer screening programme to see national rollout

26th June 2023

All smokers and ex-smokers aged 55-74 will have their risk of cancer assessed in the England’s first-ever national lung cancer screening programme.

The programme will be based on the Targeted Lung Health Check (TLHC) programme, which has been piloted in parts of England.

Under the plans, which will cost £270m annually once fully implemented, GP records will be used to identify patients for screening.

The first phase of the lung cancer screening scheme will reach 40% of the eligible population by March 2025, with the aim of 100% coverage by March 2030, the Government’s announcement said.

Patients will have their risk of cancer assessed based on their smoking history and other factors and those considered high risk will be invited for specialist scans every two years.

It is estimated the rollout will mean 325,000 people will be eligible for a first scan each year with 992,000 scans expected per year in total.

Easy access to lung cancer screening

The UK National Screening Committee recommended in November that all four nations in the UK should implement a national lung cancer screening programme.

It said the TLHC programme would be a ‘practical starting point’ for implementation in England while a UK-wide programme needed ‘more modelling’.

During the pilots, approximately 70% of the screening took place in mobile units to ‘ensure easy access’ and ‘focused on more deprived areas where people are four times more likely to smoke’.

Almost 900,000 people were invited for checks, 375,000 risk assessments made and 200,000 scans were carried out.

Of these, more than 2,000 people were detected as having lung cancer, with 76% identified at an earlier stage compared to 29% identified outside of the pilot programme in 2019.

Urging patients receiving an invitation for lung cancer screening to go to their GP and take it up, NHS chief executive Amanda Pritchard said: ‘The NHS lung trucks programme is already delivering life-changing results, with people living in the most deprived areas now more likely to be diagnosed at an earlier stage, giving them a better chance of successful treatment.’

Health secretary Steve Barclay said: ‘Through our [lung cancer] screening programme we are now seeing more diagnoses at stage 1 and stage 2 in the most deprived communities, which is both a positive step and a practical example of how we are reducing health inequalities.

‘Rolling this out further will prolong lives by catching cancer earlier and reducing the levels of treatment required not just benefiting the patient but others waiting for treatment.

‘I am determined to combat cancer on all fronts through better prevention, detection, treatment and research.‘

‘Sufficient diagnostic equipment and staff‘

Cancer Research UK’s chief executive, Michelle Mitchell, said: ‘This is really positive news for a cancer type that takes more lives than any other. Targeted lung screening across England could diagnose people most at risk at an earlier stage, when treatment is more likely to be successful.   

‘For the screening programme to succeed, the UK Government must ensure that sufficient diagnostic equipment and staff are in place – a comprehensive and fully-funded NHS workforce plan for England will be vital to this. 

‘Given smoking is the leading cause of lung cancer, it’s good to see that smoking cessation will be part of the programme. This needs to be embedded across all sites and stop smoking services must be properly funded to ensure people can quit smoking for good.

‘Other UK nations now need to follow suit to ensure everyone eligible can benefit from these potentially lifesaving lung checks.‘

A version of this story was originally published by our sister publication Pulse.

Under the microscope: Essex Cardiothoracic Centre

11th May 2023

The Essex Cardiothoracic Centre celebrates its 16-year anniversary this summer, and with a recent funding injection leading to the development of a new cardiac catheter lab, the centre is gearing up to support more patients requiring thoracic procedures in the county.

The Essex Cardiothoracic Centre (CTC), located at Basildon Hospital and part of Mid and South Essex NHS Foundation Trust, serves a population of 1.8 million people across the county.

Each year, approximately 900 cardiac surgeries, 500 thoracic operations and close to 2,400 cardiology procedures are performed.

The CTC recently received £2.3m in national funding, which has been spent on a new 60 square metre cardiac catheter lab, expected to open in May 2023. The development will free up theatre space for thoracic surgery and increase lung cancer surgery numbers by a third.

Hospital Healthcare Europe caught up with Michael Catling, deputy director of operations for the Essex Cardiothoracic Centre and Mid and South Essex Cardiology, to find out more.

Why was the Essex CTC originally established?

Pre-2007, patients who needed heart or lung treatment had to travel to London as there was poor provision for these services in the county. The CTC was set up following a national requirement to increase capacity for cardiac surgery and specialist interventional cardiology procedures. The Department of Health selected Basildon as the site for a new Essex centre.

How will the latest investment improve thoracic services?

Our core capacity for thoracic surgery will increase by around 150 cases annually as heart procedures that were previously carried out in the hybrid theatre will be moved to the new cath lab, freeing up space.

We perform around 500 thoracic surgeries per annum of which around 180 are lung cancer cases. Demand has risen over the past five years, and until now, we have been reliant upon ad hoc additional lists, often taking capacity from cardiac surgery, which is not sustainable.

The ability to have an extra thoracic list every week in core capacity on the schedule without having to take any other service away releases the pressure and gives us the capacity to meet increasing demand in the coming years.

We provide a wide range of thoracic services for conditions of the lung, airway, pleura, mediastinum, chest wall and diaphragm. These incorporate cancer and benign disease with both open and minimally invasive approaches.

Why has there been an increase in referrals for lung cancer surgery?

The main driver is improvements in diagnostic services for lung cancer, including targeted screening, which increases the detection of early-stage cancers. Local community and hospital services are shortening diagnostic pathways and increasing access to diagnostics.

One of our communities within Essex was in the first wave of the national Targeted Lung Health Check (TLHC) programme that launched in November 2020. In April 2022, this rolled out to a second location and current plans are to extend this to all populations.

As of March, at least nine people in Southend had previously undiscovered lung cancer found and treated thanks to the TLHC. The same programme is also benefiting residents living in Thurrock. The latest data shows that 4,834 checks have been completed in Southend.

In addition, there has been a total of 1,827 CT scans and 127 referrals into hospitals after those scans to follow up care linked to cardiovascular disease, gallbladder, respiratory, breast, gastro, urology, liver and renal findings.

What facilities does the Essex CTC have?

A 16-bed cardiothoracic ITU, 32-bed cardiothoracic surgery ward, 28-bed cardiology ward, cardiothoracic theatre suite with four theatres including a hybrid IR theatre, cath lab suite including EP (electrophysiology) and structural labs, cardiac imaging including CT, MRI, special echo, outpatient suite, cardiac rehab department, pulmonary physiology department and overnight facilities for on-call teams and for relatives.

We offer a wide range of specialist tertiary services. Our higher volume procedures within cardiology are PCI (percutaneous coronary intervention), cardiac pacing, TAVI (transcatheter aortic valve implantation) and EP. Within the surgical service these are CABG (coronary artery bypass graft), AVR (aortic valve replacement), MVR (mitral valve repair), and complex aortic.

Additionally, over the past three years there has been a move from open lung surgery to minimally invasive lung surgery and our programme includes VATS (video-assisted thoracoscopic surgery).

How many employees does the CTC employ?

Around 600. This includes consultant cardiologists, surgeons, anaesthetists, thoracic histopathologists, specialist nursing teams, cardiac physiologists, clinical perfusion scientists, surgical care and operating department practitioners.

We also have UK training posts and international clinical fellows and have developed a strong national and international reputation for research within the centre. This is supported by our excellent relationship with the Anglia Ruskin University Medical School faculty with which we have a research fellow programme.

We have several colleagues with roles in external organisations and learned societies such as the British Cardiovascular Intervention Society. They contribute regularly to national and international events including presentations at Society for Cardiothoracic Surgery 2023, and by providing live-streamed cath lab cases for the 2023 physiology course at the Cardiovascular Centre in Aalst, Belgium.

How do you develop and retain your staff?

We’re very focused on doing what we do well, developing genuine tertiary services and particularly looking after our talented and passionate staff through training opportunities.

As a centre we are committed to offering excellent specialist training both to our own specialists and to related teams across Essex. The surgical team has delivered a programme of eight clinical simulation training events and wet labs over the past 12 months.

This has included two specifically related to the thoracic surgery service. In November 2022, we ran a lung resection day covering the teaching of both anaesthetic and surgical perspective with attendees from several other major tertiary centres in the UK.

In January 2023, we conducted a chest drain insertion day run jointly with the respiratory team, including hands-on simulation. Other courses in the past year have covered CABG, aortic and mitral valve surgery. This helps with staff development and retention.

What plans does the CTC have for the future?

As a specialist centre serving a large population and a number of local hospitals, our clinical plans incorporate continued development of specialist interventions and increased collaboration with local hospitals and primary care teams. This will include introduction of mitral TEER (transcatheter edge-to-edge repair), minimally invasive cardiac surgery, complex aortic surgery and thoracic port surgery techniques. We will be extending multi-disciplinary team working in chronic long-term conditions such as heart failure and atrial fibrillation through virtual ward models supported by latest technologies.

Our most important asset is our workforce, and we will continue to invest in training and education for our teams as well as developing new extended scope roles for advanced care practitioners.

The role of AI in transforming lung cancer care 

Dr Sumeet Hindocha has a passion for artificial intelligence, with his work focusing on radiomics and deep learning in lung cancer. He speaks to Hospital Healthcare Europe about his latest research and the uses and considerations of AI-enabled diagnostics in medicine.

Dr Sumeet Hindocha is a clinical oncology specialist registrar at The Royal Marsden NHS Foundation Trust and a researcher in artificial intelligence (AI). He is currently leading the trust’s OCTAPUS-AI study to investigate how this technology can help identify which patients with non-small cell lung cancer are at higher risk of recurrence.

Why are you interested in lung cancer and AI?

Lung cancer is the leading cause of cancer deaths worldwide. Non-small cell lung cancer (NSCLC) is behind almost 85% of cases and is often curable when detected early enough. Radiotherapy is a key treatment modality for it, but, unfortunately, recurrence can occur in over a third (36%) of patients treated with radiotherapy.

We know that the earlier we detect recurrence the better the outcomes generally are for patients. It means we can get them on to the next line of treatment or offer the best support as soon as possible. This could reduce the impact the disease has on their lives and help patients live longer.

The aim of our study is to see whether AI could help identify the risk of cancer returning in these patients using CT scans. The study addresses the National Institute of Healthcare and Clinical Excellence’s call for further research into using prognostic factors to develop risk-stratification models to inform optimal surveillance strategies after treatment for lung cancer.

Where does your enthusiasm for AI stem from?

Artificial intelligence has had a big impact in improving various aspects of our lives and work, from automating routine tasks to even things like the programmes recommended to us on Netflix or smart home devices like Siri or Alexa. What’s really exciting about its application in healthcare is its significant potential to improve patient outcomes and experience. We have a huge amount of data from imaging and electronic patient records that can be readily applied to AI. It gives us the ability to detect patterns of disease that would otherwise be difficult to uncover, to develop new drugs and even streamline how we deliver healthcare.

Who are you working with on the OCTAPUS-AI study?

Researchers from the Institute of Cancer Research, Imperial College London and the Early Diagnosis and Detection Centre, which aims to accelerate early diagnosis of cancer and is supported by funding from the Royal Marsden Cancer Charity and the National Institute for Health and Care Research. 

What did the first phase of the study involve?

We compared different models of machine learning (ML) – a type of type of AI that enables computer software to learn complex data patterns and automatically predict outcomes – to determine which could most accurately identify NSCLC patients at risk of recurrence following curative radiotherapy.

Anonymised, routinely available clinical data from 657 NSCLC patients treated at five UK hospitals was used to compare different ML algorithms based on various prognostic factors such as age, gender and the tumour’s characteristics on scans to predict recurrence and survival at two years from their treatment. We then developed and tested models to categorise patients into low and high risk of recurrence, recurrence-free survival and overall survival.

A patient’s tumour size and stage, the type and intensity of radiotherapy, and their smoking status, BMI and age were the most important clinical factors in the final AI model’s algorithm for predicting patient outcomes.

The results suggested that this technology could be used to help personalise, and therefore improve, the surveillance of patients following treatment based on their risk. This could lead to recurrence being detected earlier in high-risk patients, ensuring that they receive urgent access to the next line of treatment that could potentially improve their outcomes. 

Results from the second phase of the study were recently published. Can you tell us more about this work?

In this phase, as well as clinical data, we used imaging data describing the tumours’ characteristics – a technique known as radiomics – taken from radiotherapy treatment planning CT scans on over 900 NSCLC patients in the UK and Netherlands.

Radiomic data can also be linked with biological markers. We believe it could be a useful tool in both personalising medicine and improving post-treatment surveillance. This data was used to develop and test ML models to see how accurately they could predict recurrence. 

The TNM staging system, which describes the amount and spread of cancer in a patient’s body, is the current gold standard in predicting prognosis. However, our model was found to better correctly identify which NSCLC patients were at a higher risk of recurrence within two years of completing radiotherapy than a model built on the TNM staging system.

How could your findings benefit patients?

We are at an early stage, and there’s a lot more work to do before we have a tool ready for use in the clinic. However, our results suggest that our AI model could be better at predicting tumour regrowth than traditional methods. This means that, using our technology, clinicians may eventually be able to identify which patients are at a higher risk of recurrence and offer them more targeted follow up. If recurrence did occur, this would be detected earlier so patients could be offered the next line of treatment as soon as possible. Meanwhile, low-risk patients could potentially be spared unnecessary follow-up scans and hospital visits.

This is also an exciting project because we don’t have to put patients through extra procedures for the model to work, as the data is routinely collected during the course of their normal treatment. Furthermore, in theory, there’s no reason why we can’t adapt the same tool to predict recurrence for other cancers.

What are the next steps?

So far, we’ve looked at CT scans and clinical data. We know from other areas of research [see next question] that some models have been developed using other patient data, for instance previous biopsy results or blood markers.

The next stage would look to improve the performance of the algorithm with more advanced AI techniques, such as deep learning or multimodal approaches, that incorporate different forms of data. Once the model is optimised, the next stage would likely be a prospective study to see if it can accurately predict risk of recurrence in patients currently starting radiotherapy treatment.

Have you published any other papers on AI recently, and what were the conclusions?

Our group has published a review paper that provides an overview of how AI is being used across the spectrum of cancer care, from screening and diagnosis through to treatment and follow up. We explore its implementation in primary care, radiology, pathology and oncology.

AI application in healthcare data has the potential to revolutionise early cancer diagnosis and may provide support for capacity concerns through automation. It can also allow us to effectively analyse complex data from many modalities, including clinical text, genomic, metabolomic and radiomic data.

In the review, we discuss myriad convolutional neural network – or CNN – models that can detect early-stage cancers on scan or biopsy images with high accuracy. Some had a proven impact on workflow triage. Many commercial solutions for automated cancer detection are becoming available, and we are likely to see increasing adoption in the coming years.

What other advantages could the adoption of AI bring to the sector, and what are some of the cons?

One of the biggest challenges facing healthcare right now is increasing demand, more complex cases and a shortage of workers. AI could augment our workflow, not replacing people, but doing some of the easier jobs so staff can focus on the more challenging tasks.

In the setting of patient decision-support, caution is needed to ensure that models are robustly validated before use.

In our review, we also highlight several challenges around the implementation of AI, including data anonymisation and storage, which can be time-consuming and costly for healthcare institutions.  

We also discuss model bias, including the under-reporting of important demographic information, such as race and ethnicity, and the implications this can have on generalisability.

In terms of how study quality and model uptake can be improved going forwards, quality assurance frameworks, such as SPIRIT-AI, and methods to standardise radiomic feature values across institutions, as proposed by the image biomarker standardisation initiative, may help. Moreover, disease-specific, gold-standard test sets could help clinicians benchmark multiple competing models more readily. 

Despite the above challenges, the implications of AI for early cancer diagnosis are highly promising, and this field is likely to grow rapidly in the coming years.

Medical marijuana reduces opiate use among cancer patients

20th December 2022

Medical marijuana has been found to be associated with a reduced use of opiates among patients with breast, colorectal and lung cancer

Widespread state medical marijuana legalisation in the US is associated with a lower rate of opioid dispensing and pain-related hospital events among some adults receiving treatment for newly diagnosed cancer according to an analysis by US researchers.

Pain is an extremely common cancer symptom with a 2022 meta-analysis of 12 studies (10 with breast cancer and 2 lung cancer) patients, finding a pooled pain prevalence rate of 40%. Although paracetamol and non-steroidal anti-inflammatory drugs are universally accepted as part of the treatment of cancer pain at any stage of the WHO analgesic ladder, strong opioids are the mainstay of analgesic therapy in treating moderate to severe cancer-related pain. Nevertheless, with tightened regulations leading to a decrease in opioid prescribing across the United States, evidence points to a decline in opioid use among end-of-life care in those with cancer although there has been a rise in pain-related emergency department visits, suggesting that end of life cancer pain management may be worsening. Although medical marijuana has been studied and found to be efficacious for relief of pain in patients with advanced cancer pain not fully relieved by strong opioids, a 2016 review suggested that while marijuana may have the potential for refractory cancer pain, much of the data are based on animal data, small trials, or are outdated.

With the potential to help patients with cancer pain, in the current study, US researchers set out to assess the associations between medical marijuana legalisation and opioid-related and pain-related outcomes for adult patients receiving cancer treatment. The team used data from national commercial claims between 2012 to 2017. The researchers assessed several measures including the proportion of patients having 1 or more days of opioids and 1 or more pain-related emergency department visits or hospital events, during the 6 months after a new cancer diagnosis.

Medical marijuana and opiate use

A total of 38,189 patients with newly diagnosed breast cancer, 12,816 with colorectal cancer (55.4% male) and 7,190 (51.1% female) with lung cancer were included in the analysis.

Medical marijuana legalisation was associated with a reduction in the rate of 1 or more opioid days from 90.1% to 84.4% (difference = 5.6, 95% CI 2.2 – 9.0, p = 0.01) among breast cancer patients. For colorectal cancer patients, there was also a reduction, this time from 89.4% to 84.4% (difference = 4.9, 95% CI 0.5 – 9.4, p = 0.03). Finally, opioid use reduced from 31.5% to 22.1% (difference = 9.4, 95% CI 0.8 – 17.9, p = 0.03) among patients with lung cancer with recent opioids.

Medical marijuana legalisation was also associated with a reduction in the rate of 1 or more pain-related hospital events from 19.3% to 13.0% (difference = 6.3, 95% CI 0.70 – 12.0, p = 0.03) among patients with lung cancer with recent opioids. However, the difference for the other two forms of cancer was not significant.

The authors concluded that medical marijuana legalisation was associated with a lower rate of opioid dispensing and pain-related hospital events among some adults receiving treatment for newly diagnosed cancer.

Citation
Bao Y et al. Medical Marijuana Legalization and Opioid- and Pain-Related Outcomes Among Patients Newly Diagnosed With Cancer Receiving Anticancer Treatment. JAMA Oncol 2022

Particulate matter in air pollution may cause lung cancer in never smokers

23rd September 2022

Exposure to particulate matter from air pollution appears associated with an increased risk of lung cancer in those who have never smoked

The exposure to particulate matter derived from air pollution represents a mechanism through which lung cancer can develop among individuals who have never smoked according to the findings of research presented at the European Society for Medical Oncology (ESMO) Congress 2022 by scientists of the Francis Crick Institute and University College London.

Globally in 2020 there were an estimated 2.21 million cases of lung cancer and 1.80 million deaths. There are two primary forms of lung cancer, small cell lung cancer and non-small cell lung cancer (NSCLC) with this latter form accounting for approximately 84% of all cases.

It has been recognised for several years that particulate matter in outdoor air pollution with a size of at least 2.5 micrometers, leads to an 18% higher risk of lung cancer among those who had never smoked. However, the mechanisms driving this increased risk among those who do not smoke has remained unclear.

In the study presented at the ESMO congress, researchers focused on lung cancers due to a mutation in the epidermal growth factor receptor (EGFR), which is a transmembrane receptor tyrosine kinase protein, expressed in some normal epithelial, mesenchymal, and neurogenic tissue.

Moreover, research suggests that EGFR protein expression is a risk factor in patients with NSCLC. Using normal lung tissue samples from humans and mice, the team investigated the consequences of increasing 2.5um particulate matter (PM2.5) concentrations with cancer risk.

Particulate matter exposure and cancer risk

Samples were analysed from 463,679 individuals and the team found that increasing PM2.5 levels were associated with a greater risk for EGFR mutated NSCLC samples from England, South Korea and Taiwan.

This was also associated with an increased risk of mesothelioma (hazard ratio, HR = 1.19), lung (HR = 1.16), anal (HR = 1.23), small intestine (HR=1.30), glioblastoma (HR=1.19), lip, oral cavity and pharynx (HR = 1.15) and laryngeal carcinomas (HR = 1.26) in UK Biobank samples, for each 1 ug/m3 PM2.5 increment. 

A further interesting finding was the presence of EGFR driver mutations in 18% of normal lung samples and a further mutation (KRAS) in 33% of samples. The team also showed that PM promoted a macrophage response and a progenitor-like state in lung epithelium harbouring mutant EGFR.

Consistent with particulate matter promoting NSCLC in at-risk epithelium harbouring driver mutations, PM increased tumour burden in three EGFR or KRAS driven lung cancer models in a dose-dependent manner.

Discussing their findings, Charles Swanton who presented the findings at ESMO, said: ‘We found that driver mutations in EGFR and KRAS genes, commonly found in lung cancers, are actually present in normal lung tissue and are a likely consequence of ageing. In our research, these mutations alone only weakly potentiated cancer in laboratory models.

‘However, when lung cells with these mutations were exposed to air pollutants, we saw more cancers and these occurred more quickly than when lung cells with these mutations were not exposed to pollutants, suggesting that air pollution promotes the initiation of lung cancer in cells harbouring driver gene mutations. The next step is to discover why some lung cells with mutations become cancerous when exposed to pollutants while others don’t.’

Citation
Mechanism of action and an actionable inflammatory axis for air pollution induced non-small cell lung cancer: Towards molecular cancer prevention

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