Retrievable capsule detects methylated DNA markers tied to Barrett's esophagus

Last Updated: 2020-07-27

By Will Boggs MD

NEW YORK (Reuters Health) - A capsule sponge-on-string (SOS) device detects methylated DNA markers associated with Barrett's esophagus (BE), researchers report.

"This minimally invasive method for BE screening is safe, well tolerated, can be done successfully by a nurse, and is accurate for the detection of BE," Dr. Prasad G. Iyer of Mayo Clinic, in Rochester, Minnesota, told Reuters Health by email. "We were also able to develop a 5-marker panel of methylated DNA markers for testing in subsequent studies."

Endoscopy is commonly used to screen for BE, a controversial practice, but the uptake of endoscopy in patients with gastroesophageal reflux disease (GERD) remains low. Methylated DNA markers (MDMs) have shown promise in BE detection.

In a previous report, Dr. Iyer and colleagues identified and validated MDM candidates for BE detection and pilot tested the most promising MDMs for the nonendoscopic diagnosis of BE using DNA extracted from cytology samples taken from a 25-mm SOS device.

In the current study, they assessed the accuracy of promising MDMs for nonendoscopic BE detection using the SOS device and a recently validated commercial grade assay in 268 participants, including 112 with BE, 89 controls and 67 with indeterminate findings on endoscopy.

SOS administration and withdrawal were well tolerated, and most participants (94%) stated that they would choose the SOS test again for BE detection and preferred the SOS test over endoscopy, the researchers report in the American Journal of Gastroenterology.

A five-marker panel of MDMs provided 93% sensitivity at 90% specificity and 90% sensitivity at 95% specificity, with an overall accuracy of 97% for predicting BE.

The sensitivity of this panel was similar for BE without dysplasia (89%) and for BE with any grade of dysplasia (95%), and its accuracy did not differ by age, sex, body mass index or smoking status.

Among patients with indeterminate status, positivity rates using this panel ranged from 0% for those with gastric intestinal metaplasia or eosinophilic gastritis to 26.1% for those with esophagitis to 56.5% for those with <1 cm noncircumferential BE to 100% for those with gastroesophageal junction cancer only without visible BE.

"We know that only 10% of current patients who are eligible for BE screening are currently undergoing endoscopy," Dr. Iyer said. "This is likely the reason that more than two-thirds of all BE in the community is not diagnosed since endoscopy is an invasive and expensive test. Our hope is that this test can be done in primary care offices, increasing access to screening in a cost-effective manner. Patients with a positive SOS test can then be sent for endoscopy for diagnosis and surveillance purposes."

"Additional steps are required to bring this to the clinic, but these results are encouraging," he said. "Additional studies are ongoing. We need to identify patients in whom this test is best applied and has the highest yield."

Dr. Stephen J. Meltzer of Johns Hopkins University School of Medicine, in Baltimore, Maryland, who recently evaluated a similar approach to diagnosis BE, told Reuters Health by email that the new research "confirms previous smaller studies by this group and others suggesting that methylated DNA markers perform well when used in conjunction with a swallowable, tethered sponge-in-a-capsule device. Marker-panel performance was quite good, suggesting the need for further prospective trials in the intended screening population (e.g., patients above age 50 with a longstanding history of gastroesophageal reflux disease)."

"This approach would be best applied in primary-care settings, where at-risk patients (those with GERD and other risk factors) would be screened," he said. "If prospective study results are supportive, patients testing positive would then proceed to have upper gastrointestinal endoscopy."

Dr. Meltzer added, "In the era of COVID-19, even a technique as safe as minimally invasive screening of a device retrieved through the mouth may prove challenging. It is hoped that COVID-related obstacles to this (and other types of) human-subjects research will be overcome."

The study did not have commercial funding, but Exact Science provided Materials, reagents and blinded TELQAS assays. Dr. Iyer reports financial ties to the company, as do a number of his coauthors, some of whom are company employees.

SOURCE: https://bit.ly/38knWak American Journal of Gastroenterology, online June 15, 2020.