Research

We hope that this section of our website will give you a summary of the research that is being carried out, and how this may affect outcomes in due course.

 

Early Diagnosis

Cytosponge:

 

Professor Rebecca Fitzgerald at Cambridge and her team are working on Cytosponge, a ‘pill on a string’ that would enable nurses in GP surgeries to collect samples that would be analysed to diagnose Barrett’s Oesophagus, a precursor to oesophageal adenocarcinoma (sensitivity 79.9%, specificity 92.4% in BEST2 trial).   In 2020 the BEST3 trial concluded.   Barrett's Oesophagus is identified by reference to the TFF3 protein.   Cytosponge might be introduced to clinical practice, subject to passing NICE Guidance process (a process possibly taking 2-3 years).    This is now the subject of the Delta project to develop the device for clinical practice.   Hopefully the artificial intelligence based analysis of the samples will also identify dysplasia, signs of squamous cell carcinoma and perhaps other conditions in due course.

https://www.cytosponge.org/

https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-looking-at-the-cytosponge-test-in-gp-surgeries-for-people-with-heartburn-symptoms-best3

 

Breath test:

 

Being developed by Professor George Hanna at Imperial College, a breath test would identify cells relative to oesophageal adenocarcinoma using volatile organic compounds.   It is known that some dogs can smell cancer, and this project could potentially identify other cancers.

https://www.imperial.nhs.uk/about-us/blog/new-breath-test-tackles-oesophageal-cancer     

More recently, the breath test also being looked at by Professor Rebecca Fitzgerald

https://www.medicalnewstoday.com/articles/324099.php

A Dutch study by Yonne Peters, Peter D Siersema and colleagues have used an Aenose device as a Barrett's Oesophagus prediction model (sensitivity 91%, specificity 74%) using volatile organic compounds.

https://gut.bmj.com/content/early/2020/01/07/gutjnl-2019-320273

 

Saliva test:

 

Professor Laurence Lovat at University College Hospital, London, is conducting the SPIT study, examining saliva tests.

https://gutscharity.org.uk/research/current-active-research/professor-laurence-lovat/

When combined with a questionnaire related to cancer risks, the saliva test can apparently predict cancer to a very significant level.

 

Blood test:

 

On 27 November 2020 it was announced that the NHS would be undertaking a trial of the Galleri blood test developed by Grail that may potentially identify early stage signs of more than 50 types of cancer based on molecular changes.   It is not clear how effective this test might be in identifying oesophageal adenocarcinoma or oesophageal squamous cell carcinoma, but the trial is reported to aim to include 140,000 people aged 50-79 who will have blood tests for three years who have no symptoms, and a further 25,000 with possible cancer-related symptoms.

Sensitive and specific multi-cancer detection and localization using methylation signatures in cell-free DNA - Annals of Oncology

 

UK Barrett's Oesophagus Registry

The registry contains data on around 14,500 patients registered by gastroenterologists at 48 centres, and is the largest registry in the world for this condition.

 

http://barrettscancer.org/the-uk-national-barretts-oesophagus-registry

 

The objective of the Registry is to identify groups of Barrett’s (BO) patients who are most likely to progress towards oesophageal adenocarcinoma (OAC).  They have considered several different groups but identified men with Barrett’s who were blood group rhesus negative as being three times more likely than other groups to progress to cancer.  There was a logical connection because of the distribution of nitric oxide, but more studies are needed to replicate the research.   Other bodies may not have recorded blood groups.  They are a very small group but a perfect example of a BO group at greater risk of OAC.

 

BO is being diagnosed at a younger age, possibly due to greater awareness by GPs.

 

A study using the government’s index of multi-deprivation from postcodes using an index from 1 to 6 where 6 was the most deprived.  The second least deprived segment was most likely to get BO.  In a separate study using occupation to get social class it was the Skilled Manual workers social class IIIM who were most at risk, possibly due to heavy and repetitive lifting and bending.

 

Mortality among people with Barrett’s was found to be greater than that of the general population, but only because of the effect of OAC oesophageal cancer.  20x as much mortality was being caused amongst the Barrett’s population from OAC.  However, this had not been confirmed by all papers.

 

The Registry is unique; the most similar in the UK was one set up in Northern Ireland by the late Liam Murray, but it had not included blood groups.

 

In the US there has been a tendency to diagnose patients as having BO only when they had Intestinal Metaplasia (IM).    UKBOR's research showed there was no statistical difference on progression to OAC between those with Barrett’s and IM and those just with Barrett’s at diagnosis.

 

Segmentation was well covered by the database, with 3cm being the criterion qualifying it as short segment.  The shorter segments could give significant risk, but generally the longer the segment the higher the risk.

 

The biggest problem for the Registry is patient consent making it difficult to get data.  Whereas patient consent for cancer research is on an 'opt in' basis, for pecursor conditions it is more difficult and expensive to achieve informed consent with limited clinic time. 

 

Oelixir & OCCAMS

The Oelixir project comprises a number of cancer treatment centres collaborating to improve the biological understanding of oesphageal adenocarcinoma.   After a series of negative Phase 2/3 trials, there is now more concentration on gaining genomic insights and using precision biology to explain why some oncological therapies worked and others did not for some patients.   23 OCCAMS centres are collaborating together.   The projects within Oelixir are PREDICT, PROPER, RISE, CITADEL, ELEVATE and RISE.

"The OCCAMS (Oesophageal Cancer Clinical and Molecular Stratification) study is a network of clinical centres recruiting OAC patients for tissue collection. OAC patient data and tissue samples are used to attempt to identify clinical, demographic and molecular factors affecting disease progression"

https://www.mrc-cu.cam.ac.uk/research/rebecca-fitzgerald/clinical-studies/occams

RHBDF2 mutations in Tylosis OSCC

In February 2020 it was reported that the RHBDF2 gene mutation found in a small number of people who suffer from tylosis, an inherited skin condition with an association with squamous cell oesophageal adenocarcinoma (OSCC), may have implications for other sufferers of OSCC.   This work is carried out by Professor David P Kelsell of Queen Mary College London and colleagues.

https://www.fiercebiotech.com/biotech/high-risk-oesophageal-cancer-gene-discovered

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3276661/