Liquid biopsy can spot cancer recurrence a year before conventional scans

A revolutionary blood test has been shown to diagnose the recurrence of cancer up to a year in advance of conventional scans in a major lung cancer trial (The Guardian, 2017).

The test, known as a liquid biopsy, could buy crucial time for doctors by indicating that cancer is growing in the body when tumours are not yet detectable on CT scans and long before the patient becomes aware of physical symptoms.

It works by detecting free-floating mutated DNA, released into the bloodstream by dying cancer cells. In the trial of a hundred lung cancer patients, scientists saw precipitous rises in tumour DNA in the blood of patients who would go on to relapse months, or even a year, later.

The findings add to building anticipation that the technology, which is already in widespread use in non-invasive prenatal tests for Down’s syndrome, will have a major impact in cancer medicine.

Nitzan Rosenfeld of the Cancer Research UK Cambridge Institute, who was not involved in the latest trial, predicts that “most if not all” cancer patients will be given the DNA-based tests in future. “Even if only a fraction of cancers that are currently detected at a lethal stage will in future be detected at an early curable stage this will represent a great benefit in lives saved” he said.

In the latest trial, reported in Nature, a hundred patients with non-small cell lung cancer were followed from diagnosis through surgery and chemotherapy, having blood tests every six to eight weeks.

By analysing the patchwork of genetic faults in cells across each tumour, scientists created personalised genomic templates for each patient. This was then compared to the DNA floating in their blood, to assess whether a fraction of it matched that seen in their tumour.

Professor Charlie Swanton, a cancer geneticist at the Francis Crick Institute who led the work, described how circulating tumour DNA tracked the patient’s disease status with remarkable precision. Of patients who would remain in remission, he said that “Within 48 hours of surgery, the DNA drops down to undetectable.”

By contrast, rising tumour DNA levels were seen in patients whose disease would later recur, indicating that cancer remained in the lungs or had migrated to other organs, where it was lying dormant. When the tests of twenty four patients were analysed in detail, the scientists could say with 92% accuracy who would relapse. “I think this is going to be very useful clinically” said Charlie Swanton. “This allows us to identify high risk patients. We have predictive value of 92% that your cancer is going to recur within 350 days.”

The tests even revealed an apparent outlier, a patient whose cancer had not yet resurfaced, but whose blood test showed high levels of circulating tumour DNA. “We said either there’s something wrong with our assay or this patient’s got recurring disease” said Charlie Swanton. Almost a year later, cancer showed up on a CT scan.

The liquid biopsies also showed whether chemotherapy was working or if the disease had evolved resistance, as happens in the majority of stage 2 and 3 cancers. In future, this could allow doctors to switch to a more effective drug and spare patients gruelling but futile treatment.

“We’re giving all this toxic chemotherapy on the basis that only 1 in 20 patients will ever benefit” said Charlie Swanton. “We could say this patient is not benefiting from chemotherapy so we should stop it. Or this patient’s disease is coming back but we can’t see it on a CT scan so we should give more treatment. This has got real, clear practical relevance now in lung cancer.”

Eileen Rapley, 74, a retired art teacher from London, entered the trial after being diagnosed with lung cancer a year ago. Since treatment, doctors discovered that she had also developed a brain tumour, for which she has also been treated. Although the liquid biopsy did not guide her own care, she hopes the new test might lead to the kinds of improvements that screening techniques like mammograms have brought about for breast cancer. “That sort of research has helped so many,” she said. “Friends of mine with breast cancer, I can’t think of any for years and years who have died, because there were early tests and early diagnosis.”

The test used in the study relied on building a bespoke genetic template for each patient based on detailed analysis of tumour samples, with an estimated cost of over £1,300 per patient. However, Charlie Swanton predicts the same kind of profile could be built using computational methods from just an initial blood test, making the technology viable outside a purely research setting. He said “We’re not a million miles away from that; it will probably happen in the next 2-3 years.”

Lung cancer causes more than one in five of all cancer deaths in the UK and, although incidence of the disease is falling, survival has only improved fractionally in the past forty years.

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