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Personalised blood test can be used to identify risk of lung cancer returning, say University of Cambridge scientists



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A personalised blood test is capable of identifying patients at higher risk of their lung cancer returning, researchers at the University of Cambridge have shown.

The test - a type of liquid biopsy - is able to pick up tiny fragments of DNA released into the blood as tumours grow.

Professor Robert Rintoul, professor of thoracic oncology at the University of Cambridge, honorary respiratory physician at Royal Papworth Hospital, with patient Aart Alders
Professor Robert Rintoul, professor of thoracic oncology at the University of Cambridge, honorary respiratory physician at Royal Papworth Hospital, with patient Aart Alders

A study by scientists at the Cancer Research UK Cambridge Institute shows how this circulating tumour DNA (ctDNA) is able to reveal the state of the tumour, its location and potentially its weaknesses, which could help clinicians to select the most appropriate treatments for an individual patient.

Dr Nitzan Rosenfeld, group leader at the CRUK Cambridge Institute, chief scientific officer of Inivata and co-lead author of a study published in the Annals of Oncology, said: “If cancer cells remain in the body after treatment a tumour can regrow. If that happens, it is a big setback for patients and the doctors treating them.

“Liquid biopsy can be used to detect tiny amounts of residual cancer after treatment, flagging those patients who have signs that their tumour may not have been eradicated completely with treatment.

“We’re hoping that this technology could help doctors decide when additional rounds of treatment are needed, and could save lives.”

Dr Nitzan Rosenfeld, group leader at the CRUK Cambridge Institute and chief scientific officer of Inivata
Dr Nitzan Rosenfeld, group leader at the CRUK Cambridge Institute and chief scientific officer of Inivata

Surgery, radiotherapy or sometimes chemoradiotherapy are able to cure many patients treated for early-stage non-small cell lung cancer.

Patients then receive follow-up tests including CT scans to find out if the treatment has removed the tumour.

However, these scans do not pick up minimal residual disease (MRD) - tiny numbers of cancer cells - which could regrow into further tumours.

Being able to spot these following treatment could improve the survival chances of patients at higher risk, and reduce side effects for those in lower risk groups.

In the Lung Cancer Circulating Tumour DNA (LUCID-DNA) study, funded by Cancer Research UK, the aim was to discover of circulating DNA could be detected in early stage lung cancers using the liquid biopsy test known as RaDaR, which analyses up to 48 mutations unique to each patient’s tumour.

RaDaR was developed by Granta Park-based biotech company Inivata, which was co-founded by Dr Rosenfeld, and is based on technologies developed initially by his lab at the CRUK Cambridge Institute.

The study enrolled 88 patients treated at Royal Papworth Hospital and Addenbrooke’s Hospital for early stage non-small cell lung cancer (NSCLC), which accounts for more than 85 per cent of all lung cancer cases.

DNA from the patients’ tumour samples was extracted and sequenced to find the combinations of mutations unique to each of their lung cancers.

This genetic ‘fingerprint’ was used by Inivata to create a blood test personalised to the patient’s tumour.

Tumour DNA in blood samples collected before treatment and for up to nine months after treatment was then identified by the liquid biopsy.

The researchers found patients who had tumour DNA present between two weeks and four months after treatment were much more likely to have a recurrence of their lung cancer or to die from it.

Professor Robert Rintoul, professor of thoracic oncology at the University of Cambridge and honorary respiratory physician at Royal Papworth Hospital
Professor Robert Rintoul, professor of thoracic oncology at the University of Cambridge and honorary respiratory physician at Royal Papworth Hospital

Professor Robert Rintoul, professor of thoracic oncology at the University of Cambridge, honorary respiratory physician at Royal Papworth Hospital and co-lead author of the study, said: “We need to study these liquid biopsies further to find the best ways to deploy them, but these results clearly show that they can potentially be an effective tool to help decide which patients need further treatment.

“Being able to offer patients personalised monitoring and treatment will ultimately save more lives and help us to beat cancer sooner.”

The data showed that ctDNA was detected by before clinical detection of the recurrence of a primary tumour by a median of 212.5 days, demonstrating the potential for earlier intervention using the test.

And in 30 per cent of those patients with detectable ctDNA, the researchers found the variant allele frequency was less than 0.01 per cent - or 100 parts per million of ctDNA - highlighting the importance of using a highly sensitive assays to detecting residual disease and recurrence in lung cancer patients.

Dr David Eberhard, chief medical officer of Inivata, said: “The LUCID study provides further evidence in a clinical setting of the potential of RaDaR to detect residual disease across a range of tumor types. We look forward to conducting additional studies to provide further validation of our personalised, tumour-informed assay as we move closer to its commercialisation.”

About 48,500 people are diagnosed with lung cancer each year in the UK, and around 35,100 die from the disease annually in the UK.

Michelle Mitchell, chief executive of Cancer Research UK, said: “Lung cancer is one of the biggest killers in the UK. The earlier it is caught, the more likely it is to be treated successfully.

“Detecting signs of cancer before or after treatment without the need for invasive surgery has huge potential for both patients and doctors.

“I look forward to seeing more research that will develop liquid biopsy further, which will ultimately make it much easier for doctors to offer treatment that best matches the patient’s needs, increasing their chance of survival.”

‘I’ve been very fortunate’

Aart Alders, who participated in the liquid biopsy study
Aart Alders, who participated in the liquid biopsy study

Aart Alders was among those who participated in the Lung Cancer Circulating Tumour DNA (LUCID-DNA) observational clinical study at Royal Papworth Hospital, following his lung cancer surgery.

“I was first diagnosed with an early-stage lung cancer about five years ago and underwent a surgical operation to remove it,” he said.

“Although some people need further treatment with chemotherapy, I have been very fortunate and my original lung cancer has not returned.

“I was very pleased to be able to help with the LUCID-DNA research study. By trying to develop a blood test to help doctors predict whether a lung cancer might come back or not, we will increase the chance of curing more people.”

Read more

NeoGenomics to acquire liquid biopsy specialist Inivata in two-stage $415m acquisition

Inivata launches RaDaR test to identify residual disease and relapse in cancer patients



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