Genome sequencing that analyzes cell-free DNA in blood samples may be a useful approach for detecting lung cancer: In preliminary results from the ongoing Circulating Cell-Free Genome Atlas study, three different sequencing approaches detected lung cancer in 38% to 51% of patients with early-stage disease and in 87% to 89% of patients with late-stage disease, with 98% specificity.

It may be possible to detect early-stage lung cancer from blood samples using genome sequencing, according to preliminary results from the ongoing Circulating Cell-Free Genome Atlas (CCGA) study presented on June 2 at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, IL (J Clin Oncol 36, 2018 [suppl; abstr LBA8501]). Three different assays showed high sensitivity and specificity in detecting the disease by analyzing cell-free DNA, generating data that could be used to develop a blood-based detection test.

“This is not cancer genotyping, where you're looking in the blood for a gene mutation and targeting that mutation,” explained Geoffrey Oxnard, MD, of Dana-Farber Cancer Institute in Boston, MA, who presented the findings. “This is cancer detection, and it requires a different approach—we have to look broadly across the entire genome.” Oxnard adds that although low-dose CT lung cancer screening improves survival, it has not been widely adopted, and thus a blood-based test that relies on genome sequencing “could address an unmet medical need.”

Oxnard and his team reported results from 127 patients with lung cancer and 580 healthy controls enrolled in the prospective, longitudinal CCGA study. They analyzed blood samples with three tests: targeted sequencing of 507 genes for single-nucleotide variants and small insertions and/or deletions, whole-genome sequencing (WGS) to detect copy-number variation, and whole-genome bisulfite sequencing (WGBS) to detect abnormal methylation patterns.

“Each of these allows you to query for all major somatic and epigenetic features within the cell-free DNA,” while also sequencing white blood cells, which contain mutations that can look like cancer, Oxnard explained. “You screen out this interference from white blood cells and other biologic noise, and you're left with the final features: mutations, copy-number variations, and methylation signatures.”

Targeted sequencing detected 51% of early-stage (stage I–IIIa) and 89% of late-stage (stage IIIb–IV) cancers, whereas WGS detected 38% of early-stage and 87% of late-stage cancers, and WGBS detected 41% of early-stage and 89% of late-stage cancers. The specificity of all three tests was 98%.

“This first interim analysis of the CCGA study demonstrates that comprehensive sequencing of the plasma cell-free DNA can generate high-quality data across the entire genome, and it permits noninvasive cancer detection,” Oxnard said. “Together, these results support the promise of using cell-free DNA-based assays to develop an early cancer detection test with high specificity.”

David Graham, MD, of the Levine Cancer Institute in Charlotte, NC, who is not involved in the CCGA study, called the results “an important first step toward an easier way to detect lung cancer at earlier—and hopefully more curable—stages,” because CT screening rates are incredibly low. In fact, in the United States only 1.9% of more than 7 million current and former heavy smokers were screened for lung cancer in 2016, according to findings also presented at ASCO (J Clin Oncol 36, 2018 [suppl; abstr 6504]).

“If the promise of this report holds, we could easily see a day when a person could be screened for lung cancer and possibly other cancers simply by going into their regular doctor's office for a blood draw,” he said. –Catherine Caruso

For more news on cancer research, visit Cancer Discovery online at