Fine needle aspirates allow genetic analysis of pancreatic cancer

Last Updated: 2015-06-23

By Will Boggs MD

NEW YORK (Reuters Health) - Fine needle aspirates (FNAs) of pancreatic cancers provide sufficient material to allow detection of somatic mutations with next-generation sequencing, researchers have found.

Until now it was assumed that FNA yielded insufficient cells to allow accurate determination of a tumor's genetic status, they write in Annals of Surgery, online May 27. But the advent of next-generation sequencing may overcome this limitation.

"This is one of the first steps in personalized care for pancreatic cancer patients -- in particular, for resectable patients," said Dr. Christopher L. Wolfgang from The Johns Hopkins University School of Medicine in Baltimore, Maryland.

"Personalized therapy for pancreatic cancer has the best chance of improving survival once the cancer develops," he told Reuters Health by email.

Dr. Wolfgang's team investigated whether next-generation sequencing could identify somatically altered genes in FNA specimens obtained from three treatment-naïve patients with pancreatic ductal adenocarcinoma (PDAC) and one patient with ampullary carcinoma of the pancreas.

They sequenced tumor tissue from each cancer as well as each patient's normal duodenal mucosa to facilitate the distinction between germline variants and somatic mutations.

All four carcinomas demonstrated somatic alterations in the FNAs. Missense mutations accounted for 13 of the 15 variants, and the remaining two variants were nonsense mutations.

All driver-gene single-base substitutions present in the carcinomas were also detected in the FNAs. Moreover, the concordance between the FNAs and tissue was 100% for three patients and 80% for one patient.

The somatic mutations found in the FNA of the fourth patient suggested that the patient had either a nonductal form of pancreatic neoplasia or a metastasis to the pancreas from a different primary site.

The researchers also prospectively obtained pretreatment FNAs and peripheral blood samples from 19 patients with unresectable, nonmetastatic pancreatic masses. These samples yielded 77 somatic alterations in 17 of the samples, all of which included at least one mutation in a known driver gene.

In two of these patients, sequencing of FNA samples significantly informed clinical management, the researchers say.

"These findings will dramatically facilitate the development of personalized medicine in the surgical care of PDAC," they conclude. "In particular, this work has immediate application in the design of trials that evaluate the sequence of surgical resection, use of radiation, and systemic therapy."

Dr. Wolfgang said that sequencing costs "about $1,000/ patient and it is not available in most diagnostic labs but it is widely used in research labs. FNA is routine. Insurance will not reimburse cost of this now because it is not standard care. It will first be done in the context of a trial."

He added that a prospective validation study is underway, but it will likely be a couple of years before the procedure finds its way to clinical practice.

Dr. Ramaswamy Narayanan, who studies system's biology and personalized medicine at Florida Atlantic University in Boca Raton, told Reuters Health by email that sequencing of FNAs could become the standard of care for patients with pancreatic and other cancers "within the next 5-8 years. More likely within 5 years."

One of the challenges is to get the insurance industry to embrace the technology, he said. "We need a strong patient advocacy to convince healthcare systems, Medicare and Medicaid providers, and the insurance industry," Dr. Narayanan said.

Dr. Aldo Scarpa from the University of Verona's Center for Applied Research on Cancer, in Italy, said molecular diagnostics with multigene testing "helps in refining a correct diagnosis which is -- and must be -- based on histopathology, but gives great information on prognosis and highlighting anomalies that address the choice of the most potentially efficacious therapy."

"The cost of these tests is negligible when considering the information (they) furnish and when we consider the costs of hospitalization and chemotherapy with its site effect that imply additional costs," he told Reuters Health by email.

"The promise is that if we can step forward personalization, we expect a cut of costs through reduction of useless chemotherapies," Dr. Scarpa concluded. "We are at the starting point and what we can do today is inform doctors and patients."

SOURCE: http://bit.ly/1CqdmXs

Ann Surg 2015.