A blood-based screening test using cell-free DNA to identify methylation signals of hard-to-detect gastrointestinal (GI) cancers could potentially help detect disease at earlier stages. This research will be presented by Brian M. Wolpin, MD, MPH, and colleagues at the 2020 Gastrointestinal Cancers Symposium (Abstract 283).
Brian M. Wolpin, MD, MPH
“The potential of this test is to diagnose cancer earlier, when it’s more treatable. The ability to do that across cancer types could be quite valuable. Many of the cancer types that this test detects don’t currently have screening tests that allow earlier cancer detection before the cancers cause symptoms,” said Dr. Wolpin, Director of the Gastrointestinal Cancer Center and Director of the Hale Family Center for Pancreatic Cancer Research at Dana-Farber Cancer Institute.
In the Circulating Cell-Free Genome Atlas (CCGA) study, researchers included patients with more than 20 tumor types at all disease stages, as well as noncancer controls. In the second substudy of CCGA, plasma DNA underwent targeted methylation analysis to develop an algorithm that could identify whether the patient had cancer and the tissue of origin of the cancer, including cancers of the esophagus/stomach (n = 67), pancreas/gallbladder/extrahepatic bile duct (n = 95), liver/intrahepatic bile duct (n = 29), and colon/rectum (n = 121). Data included training and validation sets.
The test to be presented by Dr. Wolpin’s team used cell-free DNA—degraded DNA fragments circulating through the bloodstream, which can come from a number of sources, including tumor cells that have died and released DNA fragments. This test is based on DNA methylation. The researchers used a technique called bisulfite sequencing, which allowed them to identify a pattern of methylation in the cell-free DNA.
Effectiveness of the Test
The technology had an overall sensitivity of 82% (95% confidence interval = 77%–86%) for cancer detection for the training set and 81% for the validation set, with a specificity of more than 99%. Overall accuracy for defining the GI tissue of origin among the samples for which tissue of origin was assigned was 91% and was 89% for the training and validation sets.
“The data show that evaluating methylation of cell-free DNA within a blood sample may detect a variety of gastrointestinal cancers with good sensitivity and with a low rate of false-positives,” said Dr. Wolpin.
The test’s developers are also conducting two large population-based studies to further validate the screening potential of the test: the STRIVE study has enrolled nearly 100,000 women undergoing screening mammograms, and the SUMMIT study is enrolling 50,000 men and women without a known cancer diagnosis.
Disclosure: The study was funded by GRAIL, Inc. For full disclosures of the study authors, visit coi.asco.org.
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