New test could prevent oesophageal cancer
Oesophageal cancers have become more common over the last 50 years and most are diagnosed at advanced stage, when prognosis is dismal. Overall ~85% of patients die within 5 years.
Early diagnosis would make a huge difference and the BEST-2 trial confirms a new screening method using the Cytosponge® could be key to saving lives.
Barrett’s oesophagus is a condition in which the normal lining of the oesophagus (the squamous epithelium) is replaced by cells that resemble the intestine (columnar epithelium).
A: the Cytosponge® apparatus, with a £1 coin for scale. B: Barrett’s cells labelled with anti-TFF3 antibodies
Barrett’s oesophagus is generally without symptoms but is more likely to occur in people suffering from acid refluxand it is sometimes diagnosed while investigating heartburn. The majority of Barrett’s oesophagus still goes undiagnosed.
This would not be a problem except individuals with Barrett’s oesophagus are at increased risk of oesophageal adenocarcinoma (the most common kind of oesophageal cancer, which forms from glands that produce mucus) and many people think that virtually all oesophageal adenocarcinoma is preceded by Barrett’s oesophagus.
By identifying individuals with Barrett’s oesophagus and offering them surveillance (scheduled screening tests) it should be possible to diagnose the cancer early, when it is still curable. Better still, by identifying and treating patients with pre-cancerous changes (dysplasia) we could actually prevent oesophageal adenocarcinoma.
The BEST-2 clinical trial
This is the idea behind the BEST-2 study run by the Cancer Prevention Trials Unit in collaboration with Professor Rebecca Fitzgerald and colleagues from Cambridge. Professor Fitzgerald’s team have developed a device calledCytosponge®, which, together with a biomarker (TFF3), can be used to diagnose Barrett’s oesophagus without the need to offer endoscopy to hundreds of patients.
Professor Peter Sasieni said:
“This study has demonstrated that the Cytosponge® can be easily and safely administered to patients in an outpatient clinic by a trained nurse. It has good sensitivity and specificity and could be used to more easily identify patients with Barrett’s oesophagus.
“By identifying such patients early it is hoped that it should be possible to prevent oesophageal adenocarcinoma or at the very least diagnose it whilst still curable.”
The Cytosponge® is a small sponge with a thread attached, compressed inside a gelatine capsule. Under the supervision of a nurse, the patient swallows the Cytosponge®, which is the same size as an antiobiotic capsule, while holding on to the thread.
Once in the stomach the gelatin casing dissolves and the sponge expands. After a few minutes the nurse pulls the thread and removes the sponge. As the sponge passes through the oesophagus it collects cells and these can then be examined under a microscope.
The BEST-2 study was designed to see how good the Cytosponge® and TFF3 is at identifying Barrett’s oesophagus.
How the study worked
The study spanned 11 centres in the UK, with patients who were booked for endoscopy. 647 patients with Barrett’s oesophagus and 463 with acid reflux (but without Barrett’s oesophagus) were recruited. The Cytosponge® was well tolerated although about 6% of patients (more often those with Barrett’s oesophagus) were unable to swallow the capsule.
Overall 80% of Cytosponge® specimens from patients with Barrett’s oesophagus stained positive for TFF3, compared with 7.6% of those without Barrett’s oesophagus, so the test was excellent at differentiating between Barrett’s oesophagus and normal tissue.
The sensitivity* was over 80% in those patients with more extensive Barrett’s oesophagus. This is important as the risk of cancer is greater when Barrett’s oesophagus is more extensive. The sensitivity and specificity** were largely independent of age, sex, and body mass index (BMI).
This trial shows that this new screening technique could help us detect oesophageal cancer, and pre-cancerous changes, earlier – and save lives.
Sensitivity: The proportion of patients with disease who will be correctly identified by a test
**Specificity: The proportion of patients without disease who will be correctly identified by a test
Evaluation of a Minimally Invasive Cell Sampling Device Coupled with Assessment of Trefoil Factor 3 Expression for Diagnosing Barrett's Esophagus: A Multi-Center Case–Control Study
CS Ross-Innes, I Debiram-Beecham, M O'Donovan, E Walker, S Varghese, P Lao-Sirieix, L Lovat, M Griffin, K Ragunath, R Haidry, SS Sami, P Kaye, M Novelli, B Disep, R Ostler, B Aigret ,BV North, P Bhandari ,A Haycock, D Morris, S Attwood, A Dhar, C Rees, MDD Rutter, PD Sasieni, RC Fitzgerald. (2015) 29;12(1):e1001780 PMID:25634542
With thanks to Marianne Baker & Peter Sasieni