DNA Sequencing Panel Aids Cancer Detection in Biliary Strictures
NEW YORK (Reuters Health) – In patients with suspicious biliary strictures, a new next-generation sequencing (NGS) assay called Bilemut improved malignancy detection and reduced treatment delays compared to an initial pathological diagnosis, researchers say.
“Despite recent advances in imaging and intraductal biopsy analyses, the etiological diagnosis of biliary strictures remains a clinical challenge,” Dr. Matias Avila of the University of Navarra in Spain told Reuters Health by email.
The sensitivity of endoscopic retrograde pancreatography (ERCP) for diagnosing biliary cancer, even when combined with brush cytology, fluorescent in situ hybridization, and CA19-9 analysis, “is still suboptimal, ranging from 14% to 60%,” he noted. “Thus, a significant proportion of patients require repeat diagnostic interventions, which increment healthcare expenses and delay the diagnosis of malignancy.”
“We reasoned that mutational analysis of cell-free DNA (cfDNA) present in bile collected at the first diagnostic ERCP could constitute a sensitive way for the early detection of pancreatobiliary cancer,” he explained. “We named this test the Bilemut assay.”
As reported in Gut, Dr. Avila and colleagues analyzed data on 68 patients (median age, 72.5; 40% women) with suspicious biliary strictures. They compared the initial pathological diagnosis with that of the mutational analysis of bile cfDNA collected at the time of first ERCP using Bilemut.
Initial pathological diagnosis classified 26 strictures as benign; nine, indeterminate; and 33, malignant. On follow-up, 14 of the 26 “benign” and eight of the nine “indeterminate” strictures turned out to be malignant. Therefore, the sensitivity and specificity of the diagnoses were 60% and 100%, respectively.
By contrast, Bilemut’s sensitivity and specificity for malignancy were 96.4% and 69.2%, respectively. Further, one of the four Bilemut “false positives” developed pancreatic cancer after extended follow-up.
In addition, the sensitivity for malignancy of Bilemut was 100% in patients with an initial diagnosis of benign or indeterminate strictures.
An analysis of 30 paired bile and tissue samples also demonstrated Bilemut’s superior performance. Specifically, Bilemut detected 66 mutations while the Oncomine Comprehensive Assay (OCA) panel v. 3 (Thermo Fisher) tissue analysis identified only 43 alterations.
Thirty-two mutations were detected in both tissue and bile samples with the OCA assay, while the Bilemut assay detected 34 additional mutations not found in the corresponding tissues.
Dr. Avila said, “Bilemut can really change the scenario in a diagnostic area that is still far from satisfactory. Moreover, it may also help in selecting patients to be treated with the new targeted drugs.”
“To hasten the translation of this analysis to the clinical practice we chose a commercial NGS panel for liquid biopsy open to clinical laboratory implementation (the Oncomine Pan-Cancer Cell-Free assay),” he said. “This assay is available and can be performed in hospital laboratories equipped with conventional NGS technologies (for) routine application.”
Dr. Christopher Wolfgang, a hepatobiliary and pancreatic surgeon at NYU Langone Health’s Perlmutter Cancer Center in New York City, commented on the study in an email to Reuters Health. “One of the most difficult diagnoses to make is the etiology of a biliary stricture This initial study is highly promising and an important contribution to the literature, yet the results are still too preliminary for the application to clinical practice.”
“There are several limitations acknowledged by the authors, such as the risk of false positive tests and an unclear negative predictive value,” he said. “However, these limitations are surmountable.”
“The next step toward the clinical use of this test is to validate the study in a large, multi-institutional prospective cohort,” he said. “In addition, potential improvements to the test can be explored, such as creating a multi-anylate test combining serum markers such as CA19-9 into statistical models for improved discriminatory power.”
SOURCE: https://bit.ly/3AhLvgv Gut, online July 20, 2021.
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