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Breath volatile organic compound analysis for the diagnosis of oesophago-gastric cancer; multi-centre blinded validation clinical trial
Interview with Dr. Sheraz Markar
Dr. Sheraz Markar – Department of Surgery and Cancer, Imperial College London, UK
- How is oesophageal cancer usually diagnosed?
- Can you tell us what we learned in today’s presentation at ECCO17 regarding the use of volatile organic compounds in breath for diagnosing oesophageal cancer today?
- How will this change how we investigate patients with suspected oesophageal cancer?
- What are the next steps which are necessary in order to develop this test as a clinically available investigation?
Sheraz Markar, Clinical Lecturer working at Department of Surgery and Cancer at Imperial College, London shared some insights on analysis of the breath volatile organic compounds for the diagnosis of oesophago-gastric cancer. Oesophageal cancer is typically diagnosed with a diagnostic endoscopy which is an expensive and invasive investigation. The primary care physician has to identify the right patient for an endoscopy. Hence it was imperative to evaluate whether or not oesophageal cancer can be non-invasively diagnosed or at least evaluate the patients at risk for oesophageal cancer who can then benefit from further endoscopy later. A study was conducted on 210 patients of which 83 had cancer and the investigators were able to diagnose cancer with a good accuracy of over 90%. They then further reduced the number of volatile organic compound based signatures in the breath analysis from thirteen and evaluated it in a multi-centre trial whose results were presented during the conference. A study with 325 patients in three centres in London was able to diagnose cancer with an accuracy of 85% based upon breath analysis using the five volatile compounds. However an important challenge is implementation of this test in the primary care setting at the point of referral for endoscopy. Patients with aggressive symptoms such as the inability to swallow and dysphagia, those patients should still be referred for an endoscopy. At present breath analysis is being evaluated in primary care in terms of the challenges associated with that. One of the interesting things with regards to this type of technology is its potential applicability to other types of cancer, so the same technique can be utilized to diagnose pancreatic cancer or colorectal cancer making it even more useful in primary care.
So my name is Sheraz Markar. I’m an NIHR Clinical Lecturer working at Imperial College in London within the Department of Surgery and Cancer.
How is oesophageal cancer usually diagnosed?
So oesophageal cancer is typically diagnosed with a diagnostic endoscopy which is a quite expensive and invasive investigation. The cost of endoscopy is about £415 to £600 per patient and currently in the UK most centres would typically diagnose cancer in around 2-5% of endoscopies they perform within their centre.
Can you tell us what we learned in today’s presentation at ECCO17 regarding the use of volatile organic compounds in breath for diagnosing oesophageal cancer today?
So the major problem with diagnosis at the moment is that as I said, it’s based upon endoscopy but the primary care physician has to recognise that the patient has certain symptoms and therefore refer the patient for an endoscopy.
At the moment, those symptoms typically are what we would describe as alarm-type symptoms or symptoms that are present often when the cancer is very large and therefore curative treatment is quite challenging at that stage and that’s really illustrated by only 35% of patients in the UK being treated curatively with this type of cancer.
So that’s really the ethos of our work and what we are really trying to do is try to look at whether or not we can non-invasively diagnose this type of cancer or at least assign patients at risk of this type of cancer who they then may benefit from further endoscopy at a later time.
So the work that I presented was based upon work that was previously undertaken at Imperial College. We studied 210 patients within our centre at St Mary’s Hospital, 83 of whom had cancer and we were able to diagnose cancer with a good accuracy of over 90%.
We then reduced our number of volatile organic compounds within the breath from 13 to a five compound based signature and we took that forward to a multi-centre trial and that’s really what I presented here today which were the results of a study across 325 patients across three centres in London and we were able to diagnose cancer with an accuracy of 85% based upon breath analysis using the five volatile compounds.
How will this change how we investigate patients with suspected oesophageal cancer?
So I think it’s important to be clear about where the test sits and we have done lots of work with primary care physicians as to where exactly the test will sit and I think it really belongs in the primary care setting at the point of referral for endoscopy. And really what we are trying to do is we are trying to provide general practitioners and primary care physicians with an objective test for this type of cancer that then they can refer for an endoscopy.
The thing to say is that I don’t think it will replace clinical suspicion, so if you have a patient with aggressive type symptoms such as the inability to swallow and dysphagia, those patients should still be referred for an endoscopy.
However, patients with softer type symptoms such as gastroesophageal reflux or just vague abdominal pain, these really make up a large cohort of patients seen in the primary care clinic who may benefit from having a breath test and therefore more appropriately allocating endoscopy to those patients.
What are the next steps which are necessary in order to develop this test as a clinically available investigation?
A lot of people publish what we call Phase I biomarker studies because they are exciting and they are, you know, novel and very interesting. This is really validation for that which has not previously been undertaken in the breath analysis world for a cancer type.
So the next steps in terms of moving this forward is try to look at the barriers to implementing this test in the primary care setting so we are currently undertaking a study to look at that, so they are doing breath testing in primary care and look at the challenges associated with that and also I think in actual fact one of the most interesting things with this type of technology is that it’s potentially applicable to other types of cancer, so using the same platform you could profile pancreatic cancer or colorectal cancer to a certain degree and therefore that would actually increase the clinical utility of the test and therefore make it more likely to be taken up in primary care.
So the next two steps in terms of investigations that we have planned, one is a primary care study and the second is a secondary care study whereby we take all patients coming for a diagnostic endoscopy and we know that the diagnostic yield is around 2-5% and then the question is whether or not we can pick out I guess the needle in the haystack and that’s really what we’re planning next.
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