A blood-based screening test using cell-free DNA to identify methylation signals of hard-to-detect gastrointestinal (GI) cancers that could potentially help detect cancer at earlier stages will be presented 2020 Gastrointestinal Cancers Symposium, taking place January 23-25 in San Francisco, California.

“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 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.

In general, GI cancers are difficult to identify early.

The GI organs are deep inside the body, so small tumours can’t easily be seen or felt during routine physical exams.

No screening tests are available for cancers like gallbladder, bile duct, and pancreatic cancer.

Screening exams do exist for other types of GI cancers, such as colorectal and stomach cancer, but many of these tests are invasive.

When GI 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 GI cancers.

About the study

The test 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 tumour 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 GI cancer and individuals without known cancer (non-cancer controls).

Key findings

In the Circulating Cell-free Genome Atlas (CCGA) study, the researchers included patients with more than 20 tumour types at all disease stages and non-cancer controls.

In the second substudy 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 oesophagus/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 GI 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,” said Wolpin.

Next steps

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. 

Source: 2020 Gastrointestinal Cancers Symposium