A study looking at breath samples to detect cancer early (PAN Cancer Early Detection Study)
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This study looked at whether it was possible to analyse breath samples to diagnose cancer early.
The study was supported by Cancer Research UK. It was open for people to join between 2018 and 2022. The team published some results in 2020 and 2023.
More about this trial
Cancer is easier to treat when it is diagnosed early. This is because it might be smaller and won’t have spread to other parts of the body. But finding some types of cancer early isn’t easy as they don’t always cause symptoms.
Previous research showed that cells inside the body make substances that end up in the blood and are breathed out from the lungs (exhaled). These substances are called volatile organic compounds (VOCs). The studies showed that the substances might be different if someone had cancer.
This was a pilot study. Researchers compared breath samples from people who had:
- liver cirrhosis and a type of liver cancer called hepatocellular carcinoma (HCC).
- cirrhosis only
- no liver problems
Liver cirrhosis is long term damage (scarring) of the liver, causing it to work less well.
Doctors measure how well the liver is working by using a classification system called the Child-Pugh system, grouping people from class A to C:
- class A means the liver is working normally
- class B means mild to moderate damage
- class C means severe damage
The researchers looked at an exhaled VOC called limonene. They wanted to see if having HCC and cirrhosis changes the levels of limonene in the breath.
Breath test
The team used the ReCIVA breath sampler to collect breath samples.
People who took part wore a special mask over their nose and mouth and breathed normally for a maximum of 12.5 minutes.
The mask was attached to a small device that collected the sample. The study team stored the breath of people who took part in several small tubes. These were sent to the laboratory to be analysed.
The main aim of the study was to find out if analysing breath samples can detect patterns of substances that might help diagnose cancer early.
Summary of results
This study showed that any increase in limonene in breath samples is mostly caused by liver cirrhosis and not much by liver cancer.
Results
The researchers put people who joined this trial into 3 groups. There were:
- 40 healthy people who had no signs of liver disease in the
control group 
- 32 people in the cirrhosis group
- 12 people in the cirrhosis and liver cancer (HCC) group
The researchers were able to analyse the results for most people who took part.
They looked at the levels of exhaled limonene in the different groups. They found it was:
- lower in the control group
- higher in the cirrhosis group
- highest in the cirrhosis and HCC group
The researchers also found that people with a Child-Pugh class B score had higher levels of exhaled limonene. This is compared to those with a class A score. They didn’t have enough information to say about class C.
The researchers looked at certain substances in the blood of people taking part. Doctors usually use these to see how well the liver is working. They looked at:
bilirubin albumin - international normalised ratio (INR) – a measurement of how long it takes for blood to clot
- alanine aminotransferase (ALT) – an
enzyme in the liver that is a biomarker for liver damage
They found that for people who had higher levels of exhaled limonene levels:
- bilirubin was higher
- albumin was lower
- INR was higher
- ALT was not changed
The researchers looked at other factors that may change the levels of exhaled limonene. They found that:
- eating citrus products daily increased the levels
- certain medicines that might affect how well the body processes limonene did not affect the levels
In 2023, the researchers also looked at other exhaled volatile organic compounds (VOCs). The results showed a difference between people with liver disease and the . There were:
- 42 healthy people in the control group
- 46 people with cirrhosis, of whom 14 had liver cancer, in the liver disease group
The researchers identified 7 exhaled compounds that they might be able to use as tests to help diagnose and monitor liver cirrhosis in future.
The trial team concluded that the levels of exhaled limonene were higher in people with cirrhosis, but that HCC did not affect it very much.
Sometimes trials show a different test isn’t useful to diagnose a particular type of cancer. But these trials still add to our knowledge and understanding of cancer and how to diagnose it.
More detailed information
There is more information about this research in the references below.
Please note, the information we link to here is not in plain English. It has been written for healthcare professionals and researchers.
Breath Biopsy Assessment of Liver Disease Using an Exogenous Volatile Organic Compound—Toward Improved Detection of Liver Impairment
G Ferrandino and others
Clinical and Translational Gastroenterology, 2020. Volume 11, issue 9, pages e00239.
Breath Biopsy to Identify Exhaled Volatile Organic Compounds Biomarkers for Liver Cirrhosis Detection
G Ferrandino and others
Journal of Clinical and Translational Hepatology, 2023. Volume 11, issue 3, pages 638-648.
Where this information comes from
We have based this summary on the information in the articles above. These have been reviewed by independent specialists () and published in medical journals. We have not analysed the data ourselves. As far as we are aware, the links we list above are active and the articles are free and available to view.
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How to join a clinical trial
Please note: In order to join a trial you will need to discuss it with your doctor, unless otherwise specified.
Chief Investigator
Professor Rebecca Fitzgerald
Supported by
Owlstone Medical Ltd
Cambridge University Hospitals NHS Foundation Trust
Cancer Research UK
Other information
These studies were part of a bigger project called the Owl stone Medical’s PAN-study.
There is more information on the PAN study website.
If you have questions about the trial please contact our cancer information nurses
Freephone 0808 800 4040
