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.
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.’
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.