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Molecular, clinical features may help categorize pancreatic cysts
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Researchers developed a composite panel of molecular markers and clinical features that may help to classify pancreatic cysts and differentiate between those that are harmless and those that are precancerous, requiring surgery.
The research team, led by Johns Hopkins University, previously identified a panel of genetic markers to characterize pancreatic cyst type, and also previously used an algorithm of clinical markers to identify pancreatic cyst type and grade. The aim of this study was twofold: A) to evaluate the utility of genetic testing of cyst fluid in classifying cyst types and identifying those that require surgery; and B) to evaluate whether combining the molecular and clinical markers would improve diagnostic accuracy.
“The combination of genetic tests and clinical evaluation of patients’ cysts may change the way we guide patients on whether surgery to remove cysts is necessary,” Anne Marie Lennon, MD, PhD, associate professor of medicine at the Johns Hopkins University School of Medicine and director of the Multidisciplinary Pancreatic Cyst Program, said in a press release. “Most people who are evaluated for pancreatic cysts are older adults in their 60s and 70s and have comorbidities that can make surgery more risky. We want to avoid unnecessary surgery whenever we can.”
Lennon and colleagues retrospectively studied 130 patients who underwent resection of pancreatic cystic neoplasms at multiple centers between September 2004 and September 2013. Twelve patients had serous cystadenomas, 10 had solid pseudopapillary neoplasms, 12 had mucinous cystic neoplasms and 96 had intraductal papillary mucinous neoplasms.
Cyst fluid was analyzed to identify mutations in BRAF, CDKN2A, CTNNB1, GNAS, KRAS, NRAS, PIK3CA, RNF43, SMAD4, TP53, and VHL; to identify loss of heterozygosity at CDKN2A, RNF43, SMAD4, TP53 and VHL tumor suppressor loci; and to identify aneuploidy.
Then, the previously developed algorithm of clinical markers was applied to the current cohort independently and in combination with the molecular markers.
“Our study shows that our expanded panel of genetic markers, combined with clinical acumen, can accurately differentiate between types of pancreatic cysts and identify cysts that are safe to watch over time and cysts that need to be removed,” Ralph Hruban, MD, Baxley Professor in Pathology and director of the pathology department for the Johns Hopkins University School of Medicine and director of the Sol Goldman Pancreatic Cancer Research Center, said in the press release.
The sensitivity and specificity of the combined panel of molecular and clinical markers ranged from 90% to 100% and 92% to 98%, respectively. The composite molecular markers also correctly identified 67 of the 74 patients who were retrospectively determined to not meet criteria for surgery, which would have decreased the number of unnecessary resections by 91%.
“Correctly identifying whether pancreatic cysts pose a high risk for malignancy is key to preventing an often deadly cancer, or avoiding a needless surgery for cysts not likely to be a problem,” Bert Vogelstein, MD, Clayton Professor of Oncology and director of the Ludwig Center at the Johns Hopkins Kimmel Cancer Center, said in the press release.
The researchers plan to further validate their findings on larger numbers of patients, in newly diagnosed patients and in more varieties of pancreatic cysts, according to the press release. They also plan to evaluate its cost effectiveness. – by Adam Leitenberger
Disclosures: Vogelstein and others report they are founders of Personal Genome Diagnostics Inc. and PapGene Inc., and scientific advisory board members of Syxmex-Inostics. These companies and others have licensed technologies from the Johns Hopkins University, of which Hruban, Vogelstein and others are inventors and receive royalties. Please see the full study for a list of all other researchers’ relevant financial disclosures.
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