Researchers in Manchester have, for the first time, created a blood test to help doctors decide when to change treatments to get the best outcome for patients with melanoma, the most serious form of skin cancer.
The pioneering clinical trial shows that a simple blood test can rapidly track how patients with advanced melanoma are responding to treatment, potentially allowing doctors to make the right treatment decisions for each individual patient at the right time, and crucially much earlier than is currently possible. The test looks for tiny fragments of tumour DNA circulating in the bloodstream (called circulating tumour DNA, or ctDNA).
The results of the CAcTUS clinical trial, published in the medical journal, Nature Communications, demonstrate that circulating tumour DNA (ctDNA) testing can be delivered quickly enough in routine NHS practice to help guide treatment decisions for patients with advanced melanoma who are carrying the BRAF mutation.
The study led by researchers at the Cancer Research UK National Biomarker Centre and The Manchester Cancer Research Centre and funded by The Christie Charity and Cancer Research UK, explored whether ctDNA could be used to monitor how patients are responding to treatment in real time and help inform when it’s best to switch to a new treatment.
At the moment, eligible patients are usually treated with either targeted therapy or immunotherapy. However, doctors currently face the challenge of deciding the best sequence and timing of treatments, particularly for patients with the aggressive form of the disease.
The CAcTUS trial investigated whether patients could begin with a short course of targeted therapy to quickly shrink tumours before switching to immunotherapy once ctDNA levels showed a major response. The study showed that ctDNA levels fell rapidly in patients responding to treatment and often provided an indication of success, or resistance, weeks before conventional scans, saving vital time.
Professor Paul Lorigan, chief investigator for the CAcTUS clinical trial and Professor of medical oncology at The University of Manchester, said: “This study shows that we can use a simple blood test to monitor melanoma in real time and potentially adapt treatment much earlier than has previously been possible. For patients with advanced melanoma, particularly those with rapidly progressing disease, having this information quickly is incredibly important. I hope in the future analysing the tiny pieces of DNA coming from the cancer found in the patient’s bloodstream could be commonly used to tell when a patient is responding to treatment, and when the best time to change to a new therapy.”
Dr Rebecca Lee (pictured), consultant oncologist and clinician scientist at The Christie and The University of Manchester, who helped develop the trial said: “This blood test has proved to be accurate, reliable, and sensitive. What is particularly exciting is that ctDNA changes can tell us whether treatment is working before we could see it on scans. This opens the possibility of making faster, more personalised treatment decisions for patients in the future.
“We now know we can use this blood test in patients as a tool to guide treatment, which will be important in developing personalised treatments in the future. This study also highlights the growing role of blood tests in cancer care, where blood samples can provide ongoing insights into tumour behaviour without invasive tissue biopsies.”
Professor Caroline Dive, Director of the CRUK National Biomarker Centre in Manchester where the blood test was developed and validated said: “We’re so delighted that results from the blood testing we performed in our laboratories have been shown to be effective in helping our clinical colleagues make informed decisions for patients with melanoma.”
The CAcTUS trial involved using two types of treatment in sequence to attack the melanoma in two different ways. One is targeted therapy, which interferes with how cancer cells grow and survive. The other is immunotherapy, which helps the immune system ‘see’ the melanoma and attack it.
The trial recruited 21 patients between 2019 and 2022 and focused on patients with a poorer prognosis who had advanced melanoma that could not be removed with surgery. Patients participated in the research at the National Institute for Health and Care Research (NIHR) Manchester Clinical Research Facility (CRF) at The Christie.
