Oesophageal cancer – a disease that affects the food pipe – is a big problem. Long-term survival rates are poor. In the UK, it’s the sixth most common cause of cancer death – and almost as many people die from the disease each year as are diagnosed.
This would change if we could diagnose the disease earlier – oesophageal cancer can be cured if it’s spotted early, and survival is much higher.
That’s why a trial of something called the ‘Cytosponge’ is absorbing a lot of interest.
Led by Professor Rebecca Fitzgerald from the University of Cambridge, the trial – called BEST-2 – is looking at the accuracy of this ‘sponge on a string’, which aims to help doctors diagnose oesophageal cancer at an early stage.
We wrote about BEST-2 when it launched in 2011. But recently, the trial team published encouraging new findings, so we thought it would be time for a quick update on how it’s progressing.
Oesophageal cancer – a big problem
But first, a quick recap. The challenge with oesophageal cancer is that many people don’t realise there is a problem until they start to have trouble swallowing – something this post highlights.
But there’s often an intermediate phase to developing full blown cancer, called Barrett’s oesophagus. This is much more common, and doesn’t always develop into cancer – but it presents an opportunity for doctors to intervene at this stage, and spot problems before it’s too late.
Barrett’s oesophagus is caused by acid reflux – not the kind that will be cured by reaching for the Rennies, but long-term acid reflux that causes the cells at the bottom of the gullet to change.
These cells are usually happy, flat pink cells. But with constant irritation from stomach acid they can morph into tall, red, cells, similar to those found in the harsh conditions of the stomach. It’s a bit like trying to live by a volcano in a tent; to survive you’d need to turn it into a lava-proof, reinforced house.
But this shape-shifting is costly, and the cells run the risk of forming abnormally – known as dysplasia (from the ancient Greek for ‘bad formation’). A cell with dysplasia is not cancerous, but is more likely than other cells to develop into cancer. And it’s these suspicious looking cells that doctors need to spot in order to detect early signs that could become oesophageal cancer.
This is done via an endoscopy – a tube with a camera inserted down your throat into your oesophagus to look for problems.
This can be uncomfortable (and costs the NHS several hundred pounds a pop).
Of course, not everyone with Barrett’s will go on to develop cancer. So, once they’ve been diagnosed, people with Barrett’s are regularly monitored with annual endoscopies .
So – both to detect and monitor Barrett’s – it would be better if there were a cheaper, simpler way to investigate people with long-term heartburn – after all, given how common the condition is, it’s simply not possible to send everyone for an endoscopy.
And researchers desperately need a better way to identify people whose heartburn might be Barrett’s oesophagus, and then from those diagnosed, find the people at risk of developing cancer.
Enter the Cytosponge. We’ve talked a lot about this nifty, sponge-on-a-string device in the past, and you can watch how it works by watching the video below.
So what’s new?
The BEST2 trial has now recruited over 1000 patients from Centres across the country, half of whom had Barrett’s oesophagus, the other half didn’t.
To test the performance of the Cytosponge, every participant on the trial first had to swallow the small, sponge-containing capsule. Next, each patient went on to have the slightly more cumbersome standard endoscopy to allow the sponge-based analysis to be compared with the current test for Barrett’s.
And the researchers analysing the samples from the sponges had no idea whether the sample had come from a patient with Barrett’s or not.
They used the sponge samples to search for the presence of a protein called Trefoil factor 3 (TFF3) – known to be produced by cells that are becoming ‘gut-like’ – and a hallmark of the onset of Barrett’s (a bit like looking for evidence of the bricks and mortar of the lava-proof house, to return to our earlier analogy).
The results of this analysis, presented at this year’s NCRI Cancer Research Conference, showed that, not only is the Cytosponge preferred by patients over other methods, but crucially, that it is able to accurately diagnose Barrett’s oesophagus just as well as an endoscopy.
So what next?
The team are now aiming to identify which patients with Barrett’s oesophagus are more likely to develop cancer, by looking for tell-tale markers in the cells captured by the sponge, such as known cancer-related red flags like mutations in the p53 gene, which seem to occur as Barrett’s develops into oesophageal cancer.
As with many challenges faced by cancer researchers, progress is slow and incremental. These are just the first of what we hope to be a string of interesting results from this trial.
There are almost certainly going to be challenges ahead. But smarter thinking, like the Cytosponge, will help us to diagnose these cancers sooner.
Emily Hoggar is a science communications manager at Cancer Research UK