Results from a study funded by GRAIL, a healthcare company focused on the early detection of cancer, to be presented at 2020 Gastrointestinal Cancers Symposium, taking place January 23-25, 2020 in San Francisco, California, confirms that a blood-based screening test – referred to a liquid biopsy – using circulating cell-free DNA (cfDNA) to identify methylation signals of hard-to-detect gastrointestinal (GI) cancers could potentially help detect cancer at earlier stages. 
Circulating cell-free DNA (cfDNA) refers to extracellular DNA present in body fluid that may be derived from both normal and diseased cells.
Using these blood-based ‘liquid biopsies’ has not only great application value for disease early diagnosis, but also for real-time progression monitoring, curative effect observation and evaluation, prognosis assessment, and metastasis risk analysis. The truly beneficial added benefit is that this test, in contrast to tissue biopsy, is noninvasive and flexible for repeat tumor sampling.
“The potential of this (liquid biopsy) 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 lead investigator Brian M. Wolpin, MD, MPH, who is Director of the Gastrointestinal Cancer Center and Director of the Hale Family Center for Pancreatic Cancer Research at Dana-Farber Cancer Institute in Boston.
Difficult to identify
In general, gastrointestinal cancers are difficult to identify early. The gastrointestinal organs are deep inside the body, so small tumors can’t easily be seen or felt during routine physical exams.
Today, no screening tests are available for cancers like gallbladder, bile duct, and pancreatic cancer. Screening exams do exist for other types of gastrointestinal cancers, such as colorectal and stomach cancer, but many of these tests are invasive.
When gastrointestinal cancers are diagnosed, they are often at advanced stages that are more difficult to treat. An accurate test based on a simple blood sample could lead to earlier diagnosis for gastrointestinal cancers.
The study results, to be presented at the ASCO Gastrointestinal Cancers Symposium, uses 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 — a chemical process that can change how a gene’s function is carried out by the body without changing the order of the DNA bases. Methylation plays a role in many processes in the body, including the development of cancer. The researchers use a technique called bisulfite sequencing, which allows them to identify a pattern of methylation, or signature, in the cell-free DNA. For this presented abstract, the researchers will provide data from patients with gastrointestinal cancer and individuals without known cancer (non-cancer controls).
In the Circulating Cell-free Genome Atlas (CCGA) study, the researchers included patients with more than 20 tumor types at all disease stages. and non-cancer controls. The study will enrolled 10,500 cancer patients and 4,500 ‘controls,’ or participants without a clinical diagnosis of cancer.
In the second sub-study of CCGA, plasma DNA underwent targeted methylation analysis to develop an algorithm that could identify the whether the patient had cancer and the tissue of origin of the cancer — the presence or absence of cancer and its location in the body, 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 technology had an overall sensitivity of 82% 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 gastrointestinal tissue of origin among the samples for which tissue of origin was assigned was 91% and 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. If further validated with additional testing, this approach has the potential to allow us to diagnose gastrointestinal cancers earlier, when they’re more treatable,” Wolpin said.
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.
Commenting on the study results to be presented at 2020 Gastrointestinal Cancers Symposium, Muhammad Shaalan Beg, MD, an ASCO expert, noted: “Blood tests that can identify cancer in asymptomatic individuals, particularly gastrointestinal cancers that can be difficult to detect in early stages, could change cancer diagnostics by making it easier to accurately screen for and identify these cancers earlier.”
“The preliminary results seen in this study, will, however, need to be validated by screening large populations of asymptomatic individuals,” he concluded.
 283 Rapid Abstract Session, Thu, 11:15 AM-12:00 PM and Poster Session (Board #A2), Thu, 12:00 PM-1:30 PM and 4:45 PM-5:45 PM Performance of a blood-based test for the detection of multiple cancer types.2020 Gastrointestinal Cancers Symposium [Proceedings]
 Chan KC, Jiang P, Chan CW, et al. Noninvasive detection of cancer-associated genome-wide hypomethylation and copy number aberrations by plasma DNA bisulfite sequencing. Proc Natl Acad Sci U S A. 2013;110(47):18761–18768. doi:10.1073/pnas.1313995110