Wednesday 15 April 2015

Breath test shows promise in diagnosing stomach cancer

Breath test shows promise in diagnosing stomach cancer "A simple breath test could help predict whether people with gut problems are at high risk of developing stomach cancer," BBC News reports. The test is designed to detect a distinctive pattern of chemicals associated with stomach cancer.

The study involved 484 people with a known diagnosis – 99 who had established stomach cancer and others who had different stages of pre-cancer.

Pre-cancer is when abnormal changes have affected certain cells and these changes could trigger cancer at a later date. Not all cases of pre-cancer will progress to "full-blown" cancer.

Overall, the study found that the breath analyser had fairly high accuracy for distinguishing between established cancer and pre-cancer. However, it was less reliable at distinguishing between the different severities of pre-cancer.

The researchers suggest that this could possibly provide a new method of screening for stomach cancer, allowing a method of surveillance for people with pre-cancer. However, it is far too early to say whether this idea could come to fruition.

The breath test could potentially be of value when combined with other methods in the diagnosis of stomach cancer or pre-cancer. However, further study will need to confirm that the test is reliable and that it gives any additional benefit over standard methods.


Stomach cancer is fairly uncommon in the UK (with an estimated 7,300 new cases each year) and is not currently screened for. Even if the test were demonstrated to be accurate, many issues would need to be considered before introducing this as a screening test for the general population, including the cost-effectiveness and other risks and benefits.

Where did the story come from?

The study was carried out by researchers from the Israel Institute of Technology and the University of Latvia. It was funded by the European Research Council and the Latvian Council of Science. The study was published in the peer-reviewed medical journal Gut.

The UK media’s reporting of the study was accurate and informative.

What kind of research was this?

This was a cross-sectional study, which aimed to look at the use of different types of breath analyser for distinguishing between stomach (gastric) cancer and early pre-cancerous lesions.

As the researchers say, there are well-recognised pre-cancerous changes in stomach cancer, only a minority of which will actually progress to cancer. However, there is currently no non-invasive tool to reliably detect these lesions and stratify their risk for cancerous development. Current diagnostic methods, such as an endoscopy (where a camera attached to a tube is placed into the stomach) can be expensive, time-consuming and not particularly pleasant for the patient (although having an endoscopy is usually a pain-free experience).

An emerging approach is the detection of volatile organic compounds (VOCs) in exhaled breath. These are chemicals that develop due to the biological changes associated with both pre-cancer and stomach cancer.

The potential benefits are that it is non-invasive, pain-free and does not have any side effects.

The researchers propose an approach of possibly distinguishing between and classifying different pre-cancerous lesions by analysing breath samples.

What did the research involve?

The research involved 484 people recruited from the University Hospital in Latvia, all of whom had known diagnostic status. This included 99 who were diagnosed with stomach cancer and 325 who had pre-cancerous conditions. These were graded in risk/severity from 0 to IV on the OLGIM staging system (Operative Link on Gastric Intestinal Metaplasia assessment). This is a validated system that assesses both the extent of abnormal change and potential "aggression" of the pre-cancer.

A further seven had more abnormal cell changes at high risk of developing into cancer (dysplasia). They also included 53 people with stomach ulcers (non-cancerous).

Exhaled breath samples were collected from the participants after fasting for 12 hours and refraining from smoking. Two breath samples were collected from each person, which were analysed using two different methods. The first method was gas chromatography linked to mass spectrometry (GCMS), which quantifies the types of VOCs in each patient group. The second was a nanoarray sensor method, which aimed to look at the patterns of VOCs in the exhaled breath, rather than quantify specific VOCs. A nanoarray consists of an array of extremely tiny sensors that can detect individual proteins.

The researchers looked at how reliable the methods were at distinguishing people with gastric cancer from the pre-cancerous and non-cancerous conditions. Analyses were adjusted for various potential confounding factors, including patient age, gender, smoking, alcohol and use of medications to reduce stomach acid production.

What were the basic results?

Using the first chemical analysis method (GCMS), the researchers found that of 130 VOCs analysed, the concentrations of eight of them were significantly different between the patient groups. However, no single VOC could reliably distinguish between the groups.

Using the second nanoarray method, the researchers found that the pattern analyser had a high level of accuracy for distinguishing between gastric cancer and the OLGIM stages of pre-cancerous lesion.

For distinguishing between people with gastric cancer compared to any pre-cancerous stage, the test had very high specificity (98% – i.e. almost all people without cancer accurately tested as not having cancer).

It had lower sensitivity, at 73% (i.e. the proportion of people with cancer who accurately tested as having cancer).

Looking by specific OLGIM stage, the test was slightly more reliable for distinguishing between people with gastric cancer and early OLGIM stages 0-II (sensitivity 97%, specificity 84%), than it was at distinguishing between people with gastric cancer and later OLGIM stages III-IV (sensitivity 93%, specificity 80%).

The test was much less reliable, however, at distinguishing between the different stages of pre-cancerous lesion. For distinguishing between stomach ulcer and stomach cancer, the specificity and sensitivity were 87%.

How did the researchers interpret the results?

The researchers say that: "Nanoarray analysis could provide the missing non-invasive screening tool for gastric cancer and related pre-cancerous lesions, as well as for surveillance of the latter."

Conclusion

This is a useful proof of concept study that has demonstrated how the measurement of VOCs in exhaled breath may be of use in distinguishing different stages of pre-cancerous change from established stomach cancer. The researchers show that the new nanoarray system that looks at the pattern of VOCs in exhaled breath has high accuracy for distinguishing cancer from pre-cancer. However, it was less reliable at distinguishing between different stages of pre-cancer.

The researchers suggest possible benefits of the nanoarray system in that it is non-invasive, quick, easy to use and inexpensive. They suggest that it could potentially provide a new method of screening for stomach cancer and pre-cancer, allowing a method of surveillance of people with pre-cancer who may be at different levels of risk for developing cancer in the future. However, this is too early to say whether this will come to fruition.

So far, this study has only examined the breath analyser in a sample of people with known diagnostic status. It would next need to be tested in samples of people with stomach symptoms and no established diagnosis, to see how accurate it was at indicating the diagnosis. It would also need to show whether it offers any benefits compared to current diagnostic methods.

Stomach cancer is not currently screened for in the UK. Even if further study confirms that this test is reliable, the balance of benefits against risks need to be carefully considered before thinking about introducing any new potential screening test for cancer.

Overall, the research is of value, but further study is needed before it is known whether this could one day be introduced as a screening test for stomach cancer or pre-cancerous changes.

It is more likely that the test would be used to assess patients with symptoms associated with stomach cancer, who would then go on to have further testing for stomach cancer.


Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Join theHealthy Evidence forum.

Links To The Headlines

Breath test 'could give clues to stomach cancer risk'. BBC News, April 14 2015

Now a breath test to stop stomach cancer: Screening spots chemical signals that are linked to development of tumours. Mail Online, April 14 2015

Breath test can reveal stomach cancer scientists believe. ITV News, April 14 2015

Breath test to predict risk of stomach cancer developed by scientists. The Daily Telegraph, April 13 2015

New breath test could be used to detect stomach cancer. The Independent, April 14 2015

Breath sample predicts stomach cancer. The Times, April 14 2015

Simple breath test could soon screen for stomach cancer following breakthrough. Daily Express, April 14 2015

Links To Science

Amal H, Leja M, Funka K, et al. Detection of precancerous gastric lesions and gastric cancer through exhaled breath. Gut. Published online April 13 2015

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