Blood Test Detects Early-Stage Cancers

A blood test being developed by Grail may not only detect early-stage cancers, but also determine where those cancers originated. In an ongoing study, the test detected more than half of cancers and correctly identified the tissue of origin in almost all cases, findings essential for the development of a broadly deployed early-detection tool. Data were presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting in June.

At last year's ASCO meeting, Grail outlined three potential cell-free DNA assays tested in the Circulating Cell-Free Genome Atlas Study: whole-genome DNA sequencing, targeted DNA sequencing, and DNA methylation analysis via whole-genome bisulfite sequencing. “What we were trying to do was take a very comprehensive and rigorous approach to determine the right technology that we could take forward to develop a multicancer early-detection test,” explains Anne-Renee Hartman, MD, vice president of clinical development at Grail. The results led researchers to develop a methylation-based approach.

They have now refined their approach from whole-genome bisulfite sequencing to targeted sequencing that focuses on key methylation regions, as identified by Grail's methylation-sequencing database. Researchers performed an initial training run of the test on blood samples from 1,422 people with 20 types of cancer, ranging from stage I to IV, and 879 participants without cancer.

In this training run, the test had a sensitivity of 55.1% across cancer types and stages at a specificity of 99%, including 76.1% for 12 cancers deemed clinically significant due to a lack of screening tools, 43.8% for all cancers diagnosed at an early stage (stages I to III), and 68.8% for clinically significant early-stage cancers, with a false-positive rate of less than 1%. The test established a tissue of origin in 94% of cases, and, of those, 90.2% were accurate.

“We believe our technology meets the fundamental requirements for a multicancer early-detection test,” says Hartman, which include high sensitivity for clinically significant cancers, the ability to determine the tissue of origin, and a low false-positive rate. “This is a really important step on our path to offering this multicancer early-detection test very broadly to the population,” she adds, noting that, in particular, knowing where a cancer originates will allow a clinician to run the appropriate diagnostic test to localize the disease. Next, Grail will study the test in the clinic.

“They are detecting a significant minority of early-stage cancers of different histologies from the blood—that's quite an accomplishment,” says Ash Alizadeh, MD, PhD, of Stanford University School of Medicine in California, who is not involved in the trial. He is especially intrigued by the test's potential to determine where a cancer originates. However, he notes that the test is less likely to uncover a large fraction of stage I and II cancers, which he considers the goal of early cancer detection. Ultimately, he thinks the test may be most useful in populations with a higher cancer risk than the general population.

Grail is not the only company working on early cancer detection: Thrive Earlier Detection is developing CancerSEEK, a blood test that combines DNA sequencing and protein biomarker analysis to identify tumor-specific mutations. In a study of 1,005 patients with eight types of cancer, stages I to III, the test had a sensitivity of 70% and correctly determined the tissue of origin in 68% of cases, with a false-positive rate of less than 1%.

“The takeaway is that multiple, separate analytes have power in allowing early detection of cancer,” Alizadeh says. “That gives me hope that we will have sharp tools for making a dent in the emerging, rising rate of early-stage cancers in an aging population.” –Catherine Caruso