An ultrasensitive blood test which detects even low levels of circulating tumour DNA (ctDNA) could help to improve disease stratification in early-stage lung adenocarcinoma (LUAD), a UK study suggests.
It was known that ctDNA detection could predict clinical risk in early-stage tumours, the UK research team wrote in the journal Nature Medicine. However, it was challenging to detect preoperative ctDNA in early-stage LUADs due to low levels of ctDNA in plasma – frequently below 100 ppm.
In the Cancer Research UK-funded study, scientists from University College London (UCL), the Francis Crick Institute, University College London Hospitals NHS Foundation Trust (UCLH), and the biotechnology firm Personalis, collaborated to test the company’s NeXT Personal platform.
Described as an ultrasensitive, tumour-informed liquid-biopsy platform, the researchers said NeXT Personal had been analytically validated for ultrasensitive ctDNA detection at 1-3 ppm of ctDNA with 99.9% specificity.
ctDNA impact on relapse and survival
They used the platform to analyse preoperative ctDNA in 171 adults with early-stage lung cancer from Cancer Research UK’s TRACERx study.
It detected ctDNA preoperatively in 81% of the patients with LUAD, including 57% of those with pathological tumour-node-metastasis (pTNM) stage 1 disease.
Analysis showed people with a low level of ctDNA before surgery were less likely to relapse and also had improved overall survival rates compared with people with a high level of ctDNA.
The researchers were also able to show that patients with <80 ppm preoperative ctDNA levels had reduced overall survival compared with ctDNA-negative patients with LUAD.
‘Although prospective studies are needed to confirm the clinical utility of the assay, these data show that our approach has the potential to improve disease stratification in early-stage LUADs,’ the study authors concluded.
The data from TRACERx was analysed retrospectively, the researchers acknowledged, with future data from prospective cohorts needed to evaluate the clinical utility of the assay.
‘Although NeXT Personal is already in use as a clinical diagnostic test, it, like other tumour-informed ctDNA detection assays, is of higher complexity and requires a longer turnaround period to develop the panel and obtain a clinically actionable result, compared with non-tumour-informed approached,’ they wrote.
Supporting more informed decisions
Study first author Dr James Black, a postdoctoral clinical fellow at the Francis Crick Institute and the Cancer Research UK Lung Cancer Centre of Excellence at UCL, said the study had shown the presence or absence of tumour DNA in the blood was strongly predictive of prognosis.
‘ctDNA testing, especially using ultrasensitive platforms, could help clinicians make more informed decisions about treatment and give patients a more accurate idea of how their disease might progress,’ he said, adding that ‘more research to validate these tests will help to get them on the agenda for regular clinical use.’
Study senior author Professor Charles Swanton, who holds positions at the UCL Cancer Institute, the Francis Crick Institute and UCLH and is chief investigator of the TRACERx study, noted that lung cancer is one of the most common types of cancer in the UK and has a high relapse rate.
‘It’s vital to understand who would benefit from more aggressive treatment, especially for patients with stage 1 disease who are often diagnosed during CT screening for those at a higher risk,’ he said.
‘Using sensitive ctDNA tests is one way to do this, which we hope will maximise clinical benefit and minimise unnecessary treatment for individual patients.’
Speaking at Hospital Healthcare Europe’s recent Clinical Excellence in Respiratory Care event, Dr Zaheer Mangera,the lung cancer lead at North Middlesex University Hospital NHS Trust in London, said ctDNA tests were among the innovations to watch in lung cancer care, with the Trust involved in a ctDNA pilot in recent months.
