Image: A new genetic test was highly sensitive at determining which pancreatic cysts are most likely to be associated with one of the most aggressive types of pancreatic cancer (Photo courtesy of Shutterstock).
A newly developed genetic test was highly sensitive at determining which pancreatic cysts are most likely to be associated with one of the most aggressive types of pancreatic cancer. The successful results are a critical step toward a precision medicine approach to detecting and treating pancreatic cancer.
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.
“You never want to subject a patient to unneeded surgery,” said lead author Aatur D. Singhi, MD, PhD, a surgical pathologist at University of Pittsburgh Medical Center Health System (UPMC; Pittsburgh, PA, USA), “This rapid, sensitive test will be useful in guiding physicians on which patients would most benefit from surgery.” Marina N. Nikiforova, MD, of UPMC is the study’s senior author.
The team 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 a first-in-the-field prospective study testing pancreatic cysts before surgery rather than analyzing cysts after surgery as had been done by previous efforts.
The study also was the first to evaluate a test that employed the more sensitive next-generation sequencing (NGS) and first to be performed in a certified and accredited clinical laboratory as opposed to a research setting. “This was important to us,” said Dr. 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% 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 2 genes, KRAS and GNAS. Furthermore, by analyzing mutations in 3 additional genes, the test also identified the cysts that would eventually progress to being cancerous lesions, also with 100% accuracy. The test was less accurate for the less prevalent pancreatic cyst type mucinous cystic neoplasm (MCN) – catching only 30% of the cases.
Importantly, PancreaSeq did not any false positives in either cyst type, making it also a highly specific test.
The results could be biased by choice of which patients had their cysts surgically removed, so the researchers 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. In the future, 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.
The study, by Singhi AD et al, was published September 28, 2017, in the journal Gut.
University of Pittsburgh Medical Center Health System