SAN FRANCISCO—Physicians know that patients with Barrett's esophagus have a significantly higher risk of esophageal cancer compared with that in the general public. The problem is distinguishing between individuals likely to develop the cancer and those less likely. Now, researchers are developing a set of optical biomarkers that might make finding those high-risk patients easier, according to work presented here at the Gastrointestinal Cancer Symposium.
The current surveillance technique relies on random four-quadrant biopsies taken at 1 to 2 cm intervals along the esophagus. Pathologists then examine the samples for features of high-grade dysplasia and invasive cancer. However, the success depends in part on luck—luck that the biopsy is taken from the dysplastic area.
The optical biomarkers, though, can identify problems in cells as far as 4 cm away from the dysplasia due to a field effect in which normal-appearing cells have genetic or morphological changes due to the presence of neighboring dysplasia or cancer. In other words, the technique would enable pathologists to identify an individual at high risk who needs further follow-up or closer surveillance, even if the biopsy falls outside the troublesome area.
“The biggest challenge is to identify patients with areas of high-grade dysplasia or who will eventually progress into this condition just based on what looks like normal mucosa with an endoscope,” said Randall Brand, MD, Professor of Medicine at the University of Pittsburgh, who presented the work (Abstract 14). “We believe our quantitative phase microscopy biomarkers provide a promising approach for detecting dysplastic or neoplastic Barrett's epithelium from non-dysplastic intestinal metaplasia.”
The team used a special kind of microscopy called spatial-domain low-coherence quantitative phase microscopy (SL-QPM) to evaluate the tissue. Whereas standard pathology techniques rely on light coming through the tissue sample, this technique uses a spectrometer to measure the pattern of light reflected off the tissue. The researchers identified three biomarkers that signal the presence of high-grade dysplasia or cancer in the surrounding tissue: the density of the cell nucleus, the random structure of the cell nucleus, and the texture uniformity of the cell nucleus.
To evaluate the biomarkers, they examined those three traits in biopsy samples from 60 individuals with Barrett's esophagus, 33 without dysplasia, 21 with high-grade dysplasia, and 6 with invasive cancer. All of the biopsy samples evaluated with the optical technique contained only intestinal metaplasia; in patients with dysplasia or cancer, the biopsy samples had been taken 1 to 4 cm from the diseased area. Despite the lack of dysplasia in the samples, the SL-QPM biomarkers were able to distinguish the dangerous samples from the less dangerous ones with 87% accuracy (76% specificity and 89% sensitivity).
“We are so limited in how we accurately identify those individuals who have garden-variety Barrett's and can be surveyed every six months or even every year, and those who have high-grade dysplasia or, even more concerning, small foci of invasive cancer, who need surgical treatment,” said Morton Kahlenberg, MD, Medical Director of Surgical Oncology Associates of South Texas in San Antonio and a member of the ASCO Communications Committee.
“Aside from rudimentary endoscopic surveillance and random four-quadrant biopsies, we don't have very much else. So what I found very appealing about this work was utilizing the optical spectroscopy to have another pattern that helps to recognize those individuals who truly harbor high-risk disease.
“If you put on your Carnac-the-Magnificent hat and look into the future, the technique is not ready for primetime, but I think it does provide another approach to what is a tough diagnosis to make.”
Brand said that he and his colleagues are now working to improve the sensitivity and specificity of the approach by identifying additional biomarkers and refining the ones they have, and that if they can prove the value of the technique in a broader group of patients, he thinks it will alter the pattern of care for Barrett's esophagus -patients.
The GI Cancers Symposium is cosponsored by the American Society of Clinical Oncology, the American Gastroenterological Association Institute, the American Society for Radiation Oncology, and the Society of Surgical Oncology.