PITTSBURGH, Oct. 2, 2017 – A genetic test developed at UPMC proved highly sensitive at determining which pancreatic cysts are most likely to be associated with one of the most aggressive types of pancreatic cancer, UPMC and University of Pittsburgh School of Medicine scientists reported in Gut, the journal of the British Society of Gastroenterology.
The successful results are a critical step toward a precision medicine approach to detecting and treating pancreatic cancer, which has one of the lowest survival rates of all cancers.
Pancreatic cysts — small pockets of fluid in the pancreas — are increasingly detected on medical scans by happenstance. For the most part, the cysts are benign. But because some can progress to pancreatic cancer, doctors must determine whether it is surgically necessary to remove the cysts.
"On the one hand, you never want to subject a patient to unneeded surgery. But survival rates for pancreatic cancer are much better if it is caught before symptoms arise, so you also don't want to ignore an early warning sign," said lead author Aatur D. Singhi, M.D., Ph.D., a surgical pathologist in the UPMC Division of Anatomic Pathology. "This rapid, sensitive test will be useful in guiding physicians on which patients would most benefit from surgery."
Singhi and his team at UPMC developed PancreaSeq®, which requires a small amount of fluid removed from the cyst to test for 10 different tumor genes associated with pancreatic cancer. It was the first such prospective study, testing pancreatic cysts before surgery, rather than analyzing cysts after surgery as had been done by previous efforts.
The study, funded in part by the Pancreatic Cancer Action Network and The National Pancreas Foundation, also was the first to evaluate a test that employed a more sensitive genetic sequencing method called next-generation sequencing and the first to be performed in a certified and accredited clinical laboratory as opposed to a research setting.
"This was important to us," said Singhi. "If PancreaSeq is going to be used to make clinical decisions, then it needed to be evaluated in a clinical setting in real time, with all the pressures that go with a clinical diagnosis."
In this analysis phase, the test was not intended to be used as the sole factor in determining whether to remove the cyst or not, so doctors relied on current guidelines when deciding on a course of treatment. A total of 595 patients were tested, and the team followed up with analysis of surgically removed cysts, available for 102 of the patients, to evaluate the accuracy of the test.
The study showed that with 100 percent accuracy, PancreaSeq correctly classified every patient in the evaluation group who had intraductal papillary mucinous neoplasm (IPMN) — a common precursor to pancreatic cancer — based on the presence of mutations in two genes, KRAS and GNAS. Furthermore, by analyzing mutations in three additional genes, the test also identified the cysts that would eventually progress to being cancerous lesions, also with 100 percent accuracy. The test was less accurate for the less prevalent pancreatic cyst type called mucinous cystic neoplasm (MCN) — catching only 30 percent of the cases. Importantly, PancreaSeq did not identify any false positives in either cyst type, making it a highly specific test.
The researchers noted that the results could be biased by choice of which patients had their cysts surgically removed, but plan to monitor those who did not have their cysts removed to continue evaluation of the test's reliability. An improved version of PancreaSeq that incorporates additional tumor genes associated with pancreatic cancer currently is undergoing rigorous clinical testing, according to Singhi. In the future, the team notes, clinical guidelines will need to be revisited to explore incorporating tests like PancreaSeq.
The PancreaSeq test currently is available to patients and ordered through UPMC.
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Marina N. Nikiforova, M.D., is the senior author on this study. Additional authors are Kevin McGrath, M.D., Randall E. Brand, M.D., Asif Khalid, M.D., Herbert J. Zeh, M.D., Jennifer S. Chennat, M.D., Kenneth E. Fasanella, M.D., Georgios I. Papachristou, M.D., Ph.D., Adam Slivka, M.D., Ph.D., David L. Bartlett, M.D., Anil K. Dasyam, M.D., Melissa Hogg, M.D., Kenneth K. Lee, M.D., James Wallis Marsh, M.D., Sara E. Monaco, M.D., N. Paul Ohori, M.D., James F. Pingpank, M.D., Allan Tsung, M.D., Amer H. Zureikat, M.D., and Abigail I. Wald, Ph.D., all of Pitt or UPMC, or both.
About the University of Pittsburgh School of Medicine
As one of the nation's leading academic centers for biomedical research, the University of Pittsburgh School of Medicine integrates advanced technology with basic science across a broad range of disciplines in a continuous quest to harness the power of new knowledge and improve the human condition. Driven mainly by the School of Medicine and its affiliates, Pitt has ranked among the top 10 recipients of funding from the National Institutes of Health since 1998. In rankings recently released by the National Science Foundation, Pitt ranked fifth among all American universities in total federal science and engineering research and development support.
Likewise, the School of Medicine is equally committed to advancing the quality and strength of its medical and graduate education programs, for which it is recognized as an innovative leader, and to training highly skilled, compassionate clinicians and creative scientists well-equipped to engage in world-class research. The School of Medicine is the academic partner of UPMC, which has collaborated with the University to raise the standard of medical excellence in Pittsburgh and to position health care as a driving force behind the region's economy. For more information about the School of Medicine, see http://www.medschool.pitt.edu.
About UPMC
A $16 billion world-renowned health care provider and insurer, Pittsburgh-based UPMC is inventing new models of patient-centered, cost-effective, accountable care. UPMC provides more than $900 million a year in benefits to its communities, including more care to the region's most vulnerable citizens than any other health care institution. The largest nongovernmental employer in Pennsylvania, UPMC integrates 80,000 employees, more than 30 hospitals, 600 doctors' offices and outpatient sites, and a 3.2 million-member Insurance Services Division, the largest medical insurer in western Pennsylvania. As UPMC works in close collaboration with the University of Pittsburgh Schools of the Health Sciences, U.S. News & World Report consistently ranks UPMC on its annual Honor Roll of America's Best Hospitals. UPMC Enterprises functions as the innovation and commercialization arm of UPMC, and UPMC International provides hands-on health care and management services with partners on four continents. For more information, go to UPMC.com.
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