A blood test may reveal whether lung cancer is truly gone after treatment – such as chemotherapy or surgery – or whether it is starting to recur. This enables follow-up treatment to begin sooner and significantly improves survival.
Many people with lung cancer relapse, even after treatment that could have eliminated it. To optimise survival – even in recurrence – doctors need to determine, as early as possible, whether the cancer is completely gone or whether microscopic remnants still linger in the body.
Positron emission tomography (PET) and computed tomography (CT) have been the standard tools for follow-up but are not ideal for frequent monitoring.
New research offers a better alternative. Doctors can now detect the recurrence of lung cancer by testing blood for traces of tumour DNA. Sampling blood is relatively easy, enabling doctors to monitor patients closely over time and respond rapidly if the cancer recurs.
“About 50% of people with lung cancer experience recurrence, and we have long been searching for an easy, accessible way to identify this large group,” says Boe Sandahl Sørensen, Professor from The Department of Clinical Biochemistry, Aarhus University Hospital and Department of Clinical Medicine, Aarhus University. “Our study shows that cancer recurrence can be monitored by analysing tumour DNA in the blood,” he adds.
Tumour DNA: a genetic fingerprint in the blood
The concept of using tumour DNA to detect cancer is not new and is not limited to lung cancer. Cancer cells are constantly dividing and dying. When they die, fragments of their DNA are released into the bloodstream. However, because tumour DNA is mostly identical to normal DNA, researchers must find the unique mutations that distinguish cancer cells from healthy ones.
The principle is simple: if cancer cells remain in the body, tumour DNA is present in the blood. Once all cancer cells are gone, tumour DNA disappears from the blood within days to weeks.
“The challenge,” explains co-author Barbara Malene Fischer, Research Director at Rigshospitalet, Copenhagen, Denmark, “is to identify what is unique about the tumour DNA and detect those few fragments circulating in the blood.”
A genetic detective story
Researchers already know a lot about the common mutations that differentiate cancer cells from healthy cells in lung cancer. These include ALK fusions and mutations in EGFR and p53.
In this study, the researchers used a panel of about 500 genome regions – each known to differ between healthy and cancerous tissue – to detect tumour DNA in blood samples from 45 pateint who had completed treatment for lung cancer.
They also underwent CT and PET to directly compare the blood-based method with established techniques for detecting recurrence. In addition, the researchers had access to long-term follow-up records, enabling them to confirm whether the cancer recurred. Boe Sandahl Sørensen refers to this as the study’s “answer key”.
The team also investigated how long tumour DNA lingers in the bloodstream after various treatments.
How long does tumour DNA linger after treatment?
The study showed that tumour DNA in blood can be used to identify people with residual cancer cells after treatment.
Interestingly, the treatment method determines how long tumour DNA can be detected in blood. For people undergoing surgery, the tumour DNA often disappeared from the blood within days or weeks. In contrast, three to six months elapsed before it disappeared after radiotherapy.
“This matters because it affects how we interpret the results,” Boe Sandahl Sørensen says. “Detecting tumour DNA in the blood two months after radiotherapy does not necessarily mean that the cancer has not been cured – it may simply take longer for the DNA to disappear.”
What is next: could blood tests replace scanning?
Both Boe Sandahl Sørensen and Barbara Malene Fischer are encouraged by the results, which open the door to new ways of monitoring lung cancer. Tumour DNA testing could be used diagnostically to confirm the presence of lung cancer.
Perhaps most promising, it could detect recurrence earlier. Instead of waiting for symptoms or routine scans, doctors could monitor tumour DNA levels and act at the first sign of recurrence.
“The dream is to monitor using just a blood test. This is much easier than bringing them in for PET or CT,” says Barbara Malene Fischer. “If tumour DNA is detected, we can then follow up with imaging to locate and assess the tumour. But this method could help us catch recurrence earlier than we can today.”
However, getting blood-based monitoring to become routine will take time. The team is already conducting a larger follow-up study involving 750 people, comparing blood tests directly with PET.
“If we can replicate the results, we will seek to implement this approach clinically,” says Boe Sandahl Sørensen. “This could help us to ensure that scanning is only used when necessary.”
He adds that the method could potentially be extended to other types of cancer.
