An ultrasensitive circulating tumor DNA (ctDNA) test has demonstrated the ability to predict lung cancer outcomes in early-stage patients, according to research published in Nature Medicine. The study, a collaboration between scientists at the Francis Crick Institute, UCL, UCLH, Personalis, and Cancer Research UK, highlights the potential of the NeXT Personal platform to detect minimal residual disease and inform treatment strategies.
The NeXT Personal test, capable of detecting ctDNA at a sensitivity of 1 part per million, was applied to blood plasma samples from 171 individuals with early-stage lung cancer enrolled in the TRACERx study. Researchers found that patients with low levels of ctDNA before surgery experienced lower relapse rates and improved overall survival compared to those with higher ctDNA levels.
Enhanced Sensitivity for Improved Prognosis
The enhanced sensitivity of the NeXT Personal platform allowed for the detection of smaller quantities of ctDNA, preventing false negatives in patients with minimal disease. This is particularly relevant for early-stage lung adenocarcinoma (LUAD), a subtype known for low ctDNA shedding. The study reported a 100% detection rate in non-adenocarcinomas and 81% in LUAD.
"We've shown that the presence or absence of tumour DNA in the blood was strongly predictive of prognosis," said James Black, Postdoctoral Clinical Fellow at the Francis Crick Institute and the CRUK Lung Cancer Centre of Excellence at UCL. "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."
Impact on Treatment Decisions
Early-stage lung cancer is typically treated with surgery, followed by chemotherapy or immunotherapy based on tumor stage. The ability to identify patients at high risk of relapse using ctDNA testing could enable clinicians to offer additional, targeted therapies post-surgery, potentially increasing cure rates. Conversely, patients with undetectable ctDNA might be spared unnecessary treatments.
In the study, early-stage LUAD patients who tested negative for ctDNA with NeXT Personal prior to surgery exhibited a 100% 5-year overall survival rate, while patients testing positive had a high overall risk of relapse during that same period. Furthermore, patients who tested positive for very low traces of cancer (below 80 PPM of ctDNA) still had a high risk of recurrence, suggesting the importance of ultra-sensitive MRD testing with NeXT Personal.
Future Directions
The NeXT Personal test will be further evaluated in patients who have undergone surgery for early-stage lung cancer to determine if postoperative ctDNA detection can predict future relapse risk. This could pave the way for personalized treatment approaches based on individual risk profiles.
"Using sensitive ctDNA tests is one way to do this, which we hope will maximise clinical benefit and minimise unnecessary treatment for individual patients," noted Charles Swanton, Deputy Clinical Director and Head of the Cancer Evolution and Genome Instability Laboratory at the Crick.
Richard Chen, Chief Medical Officer and Executive Vice President of R&D at Personalis, added, "A more sensitive test like NeXT Personal offers the potential of earlier detection and earlier treatment for patients. Similarly, as we see in this study, a negative test can potentially reassure patients, and offer the hope of avoiding unnecessary therapy in the future."
