Liquid Biopsies Take Step Closer To DiagnosesA Grail funded study shows that a liquid biopsy approach might be able to detect early-stage lung cancer.

This is one of the first studies exploring the feasibility of sequencing blood-borne DNA as an approach for early cancer detection, and was presented at the ASCO (American Society of Clinical Oncology) Annual Meeting this month.

“We’re excited that the initial results from the CCGA (Circulating Cell-Free Genome Atlas) study show it is possible to detect early-stage lung cancer from blood samples using genome sequencing,” said lead study author Geoffrey R. Oxnard, MD, of Dana-Farber Cancer Institute. “There is an unmet need globally for early-detection tests for lung cancer that can be easily implemented by health-care systems. These are promising early results and the next steps are to further optimize the assays and validate the results in a larger group of people.”

Liquid biopsies are already being used in some instances to help choose appropriate targeted therapies for patients already diagnosed with cancer. It’s a method that holds a lot of promise to improve early detection of cancer. Before such tests can be widely used, there is still much more validation works that needs to happen. But the early signs are positive. 

The CCGA study has enrolled more than 12,000 of the planned 15,000 participants (70% with cancer, 30% without cancer) across 141 sites in the United States and Canada.

The new report is from the first sub-study from the CCGA, in which three prototype sequencing assays were performed on blood samples from approximately 1,700 participants. Twenty different cancer types of all stages were included in the sub-study.

In this initial analysis, researchers explored the ability of the three assays to detect cancer in 127 people with stage I-IV lung cancer. The assays were designed to detect cancer-defining signals (mutations and other genomic changes) that could be used in an early cancer detection test:

  • Targeted sequencing to detect non-inherited (somatic) mutations, such as single nucleotide variants and small insertions and/or deletions;
  • Whole-genome sequencing (WGS) to detect somatic gene copy number changes;
  • Whole-genome bisulfite sequencing (WGBS) of cell-free DNA to detect epigenetic changes.
  • At 98% specificity, the WGBS assay detected 41% of early-stage (stage I-IIIA) lung cancers and 89% of late-stage (stage IIIB-IV) lung cancers. The WGS assay was similarly effective, detecting 38% of early-stage cancers and 87% of late-stage cancers,
  • Whereas the targeted assay detected 51% of early-stage cancers and 89% of late-stage cancers.

The initial results showed that all three assays could detect lung cancer with a low rate of false positives (in which a test indicates a person has cancer when there is no cancer). Of the 580 samples from people without cancer at the time of enrolment in the sub-study, five (less than 1%) had a cancer-like signal across all three assays. Of those five participants, two were subsequently diagnosed with cancer (one with stage III ovarian cancer and one with stage II endometrial cancer) – highlighting the potential for such tests to identify early-stage cancers.

Among participants with lung cancer, the study found that more than 54% of the somatic (non-inherited) mutations detected in blood samples were derived from white blood cells and not from tumours. These mutations are likely the result of natural aging processes (so-called clonal hematopoiesis of indeterminate potential, or CHIP) and will need to be taken into account when developing blood tests for early detection of blood cancers, noted Oxnard.

The researchers are verifying these results in an independent group of approximately 1,000 participants from CCGA as part of the same sub-study. Following this, they will continue to optimize the assays, then validate them in an even larger data set from CCGA. With increased sample sizes, machine learning approaches are expected to improve assay performance, Oxnard noted.