Breath testing for a deadly cancer

Diagnostic tools that save lives

Breath tests aren’t just the tools of police and parents trying to detect alcohol or drugs. What if we could use a simple test to diagnose a deadly cancer? This is the brainchild of gastrointestinal surgeon Professor David Watson and breath analysis researcher Dr Roger Yazbek.

Dr Roger Yazbek (L) and Professor David Watson (R)

Professor David Watson and Dr Roger Yazbek want to save lives by catching oesophageal cancer before it becomes deadly. We already have machines that can capture breath. We also know that oesophageal cancer can be detected on the breath; other researchers have been able to identify a difference between a person with late stage oesophageal cancer and one without based only on their breath. But by the time people have late stage oesophageal cancer, it’s usually obvious and the treatment options shrink. For David and Roger, it’s not helpful unless they can detect the disease when it really makes a difference.

If you diagnose oesophageal cancer early, patients have an 80-99% chance of recovery. Surgeons can remove small bits of the lining of the oesophagus, burn off that lining, or attempt to reverse the damage. But oesophageal cancer is difficult to catch in time. If it’s not diagnosed until late—when the person is struggling to swallow properly—the cure rate drops to 15%. Many people with late stage oesophageal cancer are unfit for treatment (David says about 2/3 of people he sees are not able to undergo surgery). For those who are, treatment options become much more severe and invasive: a surgery where the oesophagus is removed and the stomach is moved up into the chest. In Australia this procedure’s death rate averages 3%. Patients typically spend about two weeks in hospital for the surgery that will forever change their life. At Flinders Medical Centre around 20 of these surgeries are performed each year.

It’s a pretty miserable operation to go through. I once worked with a Professor of Surgery who used to say, “Research is not about coming up with a better operation, but to eliminate the need for an operation in the first place.” In our case, that’s certainly true.

Professor David Watson

David’s focus is actually wider than breath testing. He’s also looking at biomarkers in blood using one of the world’s biggest bio-banks for oesophageal tissue specimens, which runs over four Australian states and which Flinders University has been collaborating in for the past 14 years. For David, it’s a race to see which solution—blood or breath?—is the best. Or perhaps clinicians could use a combination of the two.

For their breath test, the challenge is not only identifying the markers of early stage oesophageal cancer. It’s also in reducing the size of the equipment used to test breath samples (currently the size of a washing machine), while maintaining its high sensitivity and ability to detect small trace quantities. Roger uses a selected ion flow tube mass spectrometer (SIFT MS) to identify individual gases within a complex mixture. It’s the only machine of its type being used in Australia for clinical research—so it’s quite unique in that way. It will need to be much smaller if it will ever be used in clinical or remote environments.

This issue of practicality is why Australia doesn’t currently screen for oesophageal cancer using the current technique, an endoscopy; it’s just not cost effective even in people who present with the condition known as Barrett’s oesophagus, which can develop into cancer. One of David’s passions is health economics. Are we being efficient? Are we wasting money? When it comes to this type of cancer, David says that our resources are being poorly managed. Perhaps, if we knew which people were likely to develop oesophageal cancer, we could start screening and catch the disease earlier. With a less resource intensive test, the standard practices could change for the better. A test like the ones they’re trying to develop (blood or breath) could shift the current cost structure and reduce the endoscopy workload, as well as save lives. At each stage, he and Roger ask themselves: does it work, will it be used by clinicians and patients, can it be commercially produced, and is it affordable?

We can take a breath sample and identify what type of volatile organic compounds might be present. We then ask whether it’s due to the presence of cancer and try to establish a relationship between those two things: the chemicals, or the combination of chemicals, and early stage cancer.

Professor Roger Yazbek

That angle of improving health economics makes David and Roger’s jobs that little bit more interesting, enjoyable and satisfying. They are always asking ‘why.’ For David, it’s often looking around operating theatres and seeing things like single use items that could be replaced with a reusable item for a lower cost. It motivates him to push for change. For Roger, it was working as a technician at the Women’s and Children’s Hospital and putting probes down the throats of kicking, screaming and crying young children—probes that then need to stay up their noses and down their throats for a whole day. He knew there had to be better ways of doing these tests so they weren’t invasive.

There are other laboratories around the world working on this type of diagnostics technology, including in Austria and Germany. What sets David and Roger apart is their collaboration—and not just with each other. David explains, ‘We’re based in a hospital, Flinders Medical Centre, and have ready access to patients and experts in clinical practice, to be able to advise how these tests might be useful.’ Their connection to the real-world of oesophageal cancer is a major advantage that they hope will lead to lives saved.

You can come up with great ideas that are never going to take off because they’re too expensive or not going to be adopted by clinicians—or patients, because patients aren’t brought into the equation and won’t actually go along with what you’ve created.

Professor David Watson

Fast Facts

Dr Roger Yazbek is supported by the Catherine Marie Enright Kelly fellowship.
Over past 20 years Professor David Watson has received more than $24.5M in research funding, including 17 major grants from National Health and Medical Research Council (NHMRC).
Professor David Watson has been a recipient of significant research awards for his work in oesophageal disease, including the John Mitchell Crouch Fellowship from the Royal Australasian College of Surgeons, a James IV Travelling Fellowship, a fellowship ad hominem of the Royal College of Surgeons of Edinburgh, election to the Fellowship of the Australian Academy of Health and Medical Sciences, and appointment to a Matthew Flinders Distinguished Professorship at Flinders University.
David and Roger have been working together ever since Roger commenced at Flinders in 2014

Professor David Watson is Professor and Head of Surgery at Flinders University and an oesophago-gastric surgeon. His interests include gastro-oesophageal reflux and oesophageal and gastric cancer. He leads clinical and laboratory research addressing benign and malignant esophageal disease, integrating laboratory, clinical and population research streams. He has published around 400 papers and book chapters, led the development of Australian national guidelines for the management of esophageal and gastric cancer, and contributed to national guidelines for the management of Barrett’s esophagus. He led the establishment of the Australia and New Zealand Gastric and Oesophageal Surgery Association as its foundation president, and he currently serves as Vice-President of the International Society for Diseases of the Esophagus.

Dr Roger Yazbek completed his PhD from Flinders University in 2009 and in 2011, he received a highly competitive NHMRC Early Career Research fellowship to continue his research into dipeptidyl peptidases and gastrointestinal disease. After several years, he returned to Flinders as the Catherine Marie Enright Kelly Research Fellow and established the South Australian Breath Analysis Research laboratory, where he oversees an innovative research program to develop new breath analysis tools for the non-invasive detection of cancer, infectious disease and gastrointestinal dysfunction. He also works with the International Atomic Energy Agency to develop and validate new stable isotope tests for gastrointestinal damage in children. Dr Yazbek is internationally recognised for his research and his contributions to science were recognised by a 2013 Tall Poppy Award. He has co-authored 25 publications, attacting about 1000 citations, and served on the board of the Australian Society for Medical Research since 2010—including holding the position of president in 2018.