Breath Test for Early Diagnosis of Upper GI Cancer

Liam Davenport

January 31, 2017

AMSTERDAM — An investigational breath test is showing promise for the detection of esophageal and gastric cancers, potentially avoiding expensive endoscopies for patients who do not need them, say UK researchers.

A study that included more than 300 patients indicated that analysis of five volatile organic compounds (VOCs) in exhaled breath can differentiate between cancer patients and control patients with an overall accuracy of 85%.

The findings were presented here at the inaugural meeting of the European CanCer Organisation (ECCO) Congress 2017.

Sheraz Markar, MD, PhD, a National Institute of Health research clinical trials fellow from Imperial College London, the United Kingdom, said in a statement: "At present, the only way to diagnose esophageal cancer or stomach cancer is with endoscopy. This method is expensive, invasive, and has some risk of complications.

"A breath test could be used as a noninvasive, first-line test to reduce the number of unnecessary endoscopies. In the longer term, this could also mean earlier diagnosis and treatment and better survival," he said.

Dr Markar acknowledged that more work was needed to verify the findings in a larger sample of patients before the test could be used in the clinic.

Approached for comment, William H. Allum, MD, from the Royal Marsden National Health Service (NHS) Foundation Trust in London, agreed. He told Medscape Medical News after the presentation: "It needs more data."

As the researchers themselves acknowledge, this is a pilot study, he said. "They've got a modest number of cases, and it needs to be validated and to explore the imponderables that have come out of what they've shown."

Increasing Incidence of Esophagogastric Cancer

Dr Markar began his presentation by noting that in the United Kingdom, the incidence of esophagogastric cancer is rising and that the prognosis is typically poor, with a 5-year survival of 15%, largely owing to late presentation.

Interest in the potential for breath analysis of VOCs to diagnose a variety of conditions has been growing. In a previous study, the researchers used selected ion flow tube mass spectrometry to identify a group of 13 VOCs in exhaled breath for the diagnosis of esophagogastric cancer.

They then reanalyzed the data using vector-based analysis to reduce the model to five VOCs (butyric acid, pentanoic acid, hexanoic acid, butanal, and decanal), all of which were significantly associated with the presence of esophagogastric cancer on multivariate analysis.

This smaller model had a sensitivity and specificity of 84% and 88%, respectively, for the detection of esophagogastric cancer, with an area under the curve of 0.90 ± 0.02.

To determine the diagnostic accuracy of the breath model, the researchers conducted a multicenter blinded validation study in 163 stage I-III esophagogastric cancer patients and 172 control patients older than 18 years who had upper gastrointestinal symptoms. The patients underwent endoscopy or surgery one of three hospitals.

The median age of the control patients was 55 years; for the cancer patients, the median age was 68 years (P < .001). There were significantly more men in the group with cancer than among the control patients, at 82.2% vs 47.4% (P < .001), and cancer patients were more likely to be white, at 69.9% vs 51.5% (P = .001).

Dr Markar noted that 69.3% of patients had T3 or T4 disease; 65.1% had node-positive disease. All patients were on a curative treatment pathway.

Four of the five VOCs in the model were significantly associated with demographic factors linked to esophagogastric cancer; the exception was pentanoic acid. Multivariate analysis, which took into account patient age, medical comorbidities, and medications, indicated that all five VOCs were significantly associated with the disease.

Further analysis revealed that the five-VOC model had a sensitivity for the diagnosis of esophagogastric cancer of 80% and a specificity of 81%. The area under the curve was 0.85 ± 0.02.

The researchers will now conduct a larger version of the study in patients not yet diagnosed with cancer. The study will include a subset of individuals who will have their breath tested with two systems to validate the test's accuracy. They are also working on breath tests for other types of cancer.

Dr Markar suggested that in the future, a patient who presents to their primary care physician with nonspecific upper gastrointestinal symptoms could undergo the exhaled breath test as a first step.

"If the test is positive, the patient can then be referred for endoscopy. If the test is negative, the patient can be commenced on a medication or reassessed by his GP. So, really, it's a triage test, potentially, for endoscopy," he commented.

Dr Markar noted that the potential benefits of the test are that it could offer an earlier diagnosis at a curable stage, as well as earlier treatment, which would improve survival. "We also really believe that they'll be improved patient satisfaction due to the noninvasive nature of the test," he said.

"There are benefits to our National Health Service," he suggested. "Hopefully, we'll be improving the referral pattern for primary care. Also, we think there will be cost savings through avoiding unnecessary endoscopy, as our diagnostic yield of cancer from upper GI endoscopy in the UK is remarkably low at the moment."

Dr Markar's work was funded by the National Institute of Health Research (NIHR). This research was supported by the NIHR Diagnostic Evidence Cooperative London at Imperial College Healthcare NHS Trust. The other authors have disclosed no relevant financial relationships.

European CanCer Organisation (ECCO) Congress 2017. Abstract 6LBA, presented January 30, 2017.


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