Scientists have discovered that a test designed to identify circulating tumor DNA can effectively predict outcomes for lung cancer patients.
A study funded by Cancer Research UK, conducted by researchers from the Francis Crick Institute, UCL, UCLH, and Personalis, reveals the potential of a test for circulating tumor DNA as a predictor of lung cancer outcomes.
Circulating tumor DNA (ctDNA) consists of tiny segments of DNA that are released into the bloodstream by tumors. While ctDNA is known to play a crucial role in understanding disease prognosis, measuring it accurately can be a challenge.
The latest research, published in Nature Medicine, involved a collaboration between scientists at Crick and UCL and the company Personalis. They utilized a platform named NeXT Personal, which is capable of detecting very low levels of ctDNA—down to 1 part per million. This technique builds upon previous work by the Crick team that identified blood signals indicating the presence of cancer cells after treatment, potentially highlighting a risk of relapse.
Applying this platform to blood plasma samples from 171 individuals with early-stage lung cancer in the TRACERx cohort, the researchers found that patients with low levels of ctDNA prior to surgery experienced fewer relapses and better overall survival rates compared to those with higher ctDNA levels1.
The test’s high sensitivity enabled the detection of smaller quantities of ctDNA, ensuring that individuals with minimal ctDNA levels were not misclassified as ctDNA negative2.
Typically, early-stage lung cancer is treated through surgical tumor removal, followed by chemotherapy or immunotherapy based on the tumor’s stage, aiming for the best chance of a cure.
The next phase will involve evaluating this test on samples from patients with very early-stage lung cancer who have undergone surgery, to determine whether the presence of ctDNA in postoperative blood samples can indicate future relapse risks. This could empower physicians to recommend further treatments after surgery, enhancing the chances of curing their patients.
James Black, a Postdoctoral Clinical Fellow at the Francis Crick Institute and part of the CRUK Lung Cancer Centre of Excellence at UCL, stated: “Our findings indicate that the detection of tumor DNA in blood is a strong predictor of patient prognosis. Utilizing ctDNA testing, especially with ultrasensitive technologies, could assist healthcare providers in making better treatment decisions and offer patients clearer expectations regarding disease progression. Further validation research will be essential to integrate these tests into standard clinical practices.”
Charles Swanton, Deputy Clinical Director at the Crick and a medical oncologist at UCLH, highlighted the importance of this research: “With lung cancer being one of the most prevalent types of cancer in the UK and known for its high relapse rates, it is critical to identify patients who might benefit from more aggressive treatment, particularly those diagnosed at Stage 1 during CT screenings targeted at high-risk groups. Sensitive ctDNA testing is a valuable approach in this regard, with hopes of optimizing clinical benefits and reducing unnecessary treatments for patients.”
Richard Chen, Chief Medical Officer and Executive Vice President of R&D at Personalis, explained: “We developed NeXT Personal to detect lingering or recurring cancer at very early stages, and this study emphasizes the critical role such ultra-sensitive detection plays in early-stage lung cancer. Tests like NeXT Personal hold promise for earlier detection and treatment for patients. Moreover, a negative result can potentially offer patients reassurance and lessen the need for unnecessary future treatments.”
Marianne Baker, Research Information Manager at Cancer Research UK, noted: “TRACERx is our main lung cancer research initiative, focused on monitoring the disease’s evolution over time. Understanding how lung cancer progresses aids us in developing better treatment strategies.
“Tests like NeXT Personal pave the way for personalized medicine, allowing clinicians to provide the appropriate treatment to the right patients by accurately categorizing them based on their disease prognosis. This can enhance quality of life and survival rates, ensuring that those at higher risk receive comprehensive care while sparing others from burdensome treatments they may not require.”
“While additional research is necessary, this study marks a significant advancement toward personalized treatment approaches for lung cancer. The next phase of TRACERx, dubbed TRACERx EVO, is currently seeking participants to delve deeper into the biological mechanisms of lung cancer.”
The research received support from the National Institute for Health and Care Research UCLH Biomedical Research Centre.
Note:
- Pre-surgery ctDNA negative status was associated with significantly improved overall survival rates — 100% survived within 5 years, compared to 48.8% for those with elevated (above-average) ctDNA levels.
- Detection of ctDNA at levels below 80 parts per million was still indicative of poorer outcomes, suggesting that less sensitive tests might miss clinically meaningful signals.
