Liquid Biopsy Accurately Detects Early-Stage Pancreatic Ductal Adenocarcinoma

A liquid biopsy test with the ability to screen for a panel of biomarkers rather than just one can reportedly detect pancreatic ductal adenocarcinoma (PDAC), the most common form of pancreatic cancer, in the early stages of disease, Penn Medicine announced in a press release.

“Right now, the majority of patients who are diagnosed already have metastatic disease, so there is a critical need for a test that can not only detect the disease earlier but also accurately tell us who might be at a point where we can direct them to a potentially curative treatment,” the study’s co-senior author Erica L. Carpenter, MBA, PhD, director of the Liquid Biopsy Laboratory and a research assistant professor of medicine at Penn Medicine, said in a statement.

Findings for the liquid biopsy test were published in Clinical Cancer Research showing that combinations of blood-based biomarkers can potentially improve early detection and identify patients who are candidates for surgery.

Plasma from 204 individuals was analyzed in the study, and of those subjects, 71 samples were from healthy participants, 44 were from patients with pancreatic disease but without PDAC, and 89 were from patients with PDAC. Based on these samples, and through computer learning, the investigators selected a total of 14 biomarkers used to distinguish patients with PDAC from healthy controls and those with noncancerous pancreatic disease.

For the control group, investigators determined that a set of 5 different biomarkers: EV-CK18 mRNA, EV-CD63 mRNA, EV-miR.409, ccfDNA concentration, and CA19-9, was the best performing panel. It showed an area under the curve (AUC) of 0.93.

These 5 biomarkers were used to differentiate patients with cancer from noncancer controls in an independent blinded test group of 136 subjects. An AUC of 0.95 was achieved along with an accuracy of 92%, a sensitivity of 88%, and a specificity of 95%, following the application of the classification model to the blinded test group. These data showed superiority to CA19-9, the best individual biomarker (accuracy, 89%).

CK18 was the best performing extra-cellular vesicle (EV) mRNA marker with an accuracy of 66% (95% CI, 58%-73%). And miR.409, a marker that is often associated with pancreatic oncogenesis, was the best performing EV miRNA marker with an accuracy of 59% (95% CI, 55%-63%).

In an independent blinded cohort of 37 patients with PDAC, the study investigators trained their model in comparison with standard imaging alone to differentiate between metastatic and nonmetastatic PDAC. Twenty-five of these patients had resectable, nonmetastatic disease. The addition of the applied test to imaging of patents demonstrated 84% accuracy in detecting distant metastasis compared with the 65% accuracy seen with imaging alone (P <.05).

These data provide proof of concept for the use of a liquid biopsy–based multi-analyte panel to detect early-stage PDAC and aid in surgery selection, the study authors noted.

The liquid biopsy test used in the study could serve to fill an unmet medical need considering that most patients with PDAC are diagnosed in the advanced stages of the disease. In addition, the prior development of blood-based liquid biopsy biomarkers had low sensitivity for detecting PDAC in the early stages of the disease.

The next step with this research is to validate the accuracy in a larger cohort of patients, the study authors suggested.

“If validated, this test could not only provide a key tool for at-risk patients, but also a monitoring tool for patients with certain known risk factors like BRCA mutations,” Carpenter added.
References

1. Blood test may help doctors catch pancreatic cancer early [new release]. Philadelphia, Pennsylvania: Penn Medicine; April 16, 2020. https://bit.ly/2XIIndB. Accessed April 16, 2020.
2. Xang Z, LaRiviere MJ, Ko J, et al. A multi-analyte panel consisting of extracellular vesicle miRNAs and mRNAs, cfDNA, and CA19-9 shows utility for diagnosis and staging of pancreatic adenocarcinoma [Published online April 16, 2020]. Clin Can Res. doi: 10.1158/1078-0432.CCR-19-3313.