Cell-free DNA (cfDNA) assessment in blood tests provides a noninvasive option for lung cancer detection, according to research published in Nature Communications.
Low-dose computed tomography (LDCT) of the chest is a current screening method for lung cancer, but it is underused because of risks of radiation exposure and false-positives. Peripheral blood contains cfDNA fragments, which can be used to detect cancer-related features.
The study authors developed a genome-wide approach to analyze cfDNA “fragmentomes” to increase sensitivity of detection of early-stage cancers. They applied this methodology, called DELFI (DNA evaluation of fragments for early interception), in a prospective, real-world cohort.
The study used blood samples of 365 individuals collected during a prospective observational trial in Copenhagen, Denmark. A total of 90% of cohort individuals had pulmonary or smoking-related symptoms and were at high risk of developing lung cancer. The remaining 10% were asymptomatic, but had suspicious findings on chest imaging.
A total of 129 of the 365 individuals were diagnosed with lung cancer a few days after blood collection.
The study authors analyzed plasma from each individual in the cohort and found consistent fragmentation profiles among individuals without cancer. People with cancer had widespread genome-wide variation.
The authors used a machine learning model to examine cfDNA profiles. Each patient had a DELFI score based on fragmentation and chromosomal changes that were altered in patients with cancer and predictive of risk.
Patients without cancer had low DELFI scores, whereas patients with cancer had higher scores that increased with later stages of cancer. The DELFI approach was also able to detect cancer across stages and distinguish between histologic subtypes.
The authors validated the predictive performance of the DELFI score with an independent cohort. The validation cohort included 385 people without cancer and 46 with predominantly early-stage cancer.
The original cohort had a follow-up of 7 to 8 years, which allowed for analysis of DELFI scores and survival. Higher DELFI scores were associated with decreased overall survival.
“These results substantiate the relationship between fragmentation patterns and tumor burden or aggressiveness, and may provide clinical insights into long-term lung cancer outcomes,” the authors wrote.
The DELFI approach could be a noninvasive prescreening tool to discover people with lung cancer, increasing the options for screening high-risk individuals and the general population.
Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Mathios D, Johansen JS, Cristiano S, et al. Detection and characterization of lung cancer using cell-free DNA fragmentomes. Nat Commun. 2021;12(1):5060. doi:10.1038/s41467-021-24994-w