Pancreatic ductal adenocarcinoma (PDAC), the most common form of pancreatic cancer, is the third leading cause of cancer deaths. The overall five-year survival rate is just nine percent, and most patients live less than one year following their diagnosis. One of the biggest challenges is catching the disease before it has progressed or spread. If the disease is caught early, patients may be candidates for surgery to remove the cancer, which can be curative. For locally advanced patients—meaning patients whose cancer has not spread beyond the pancreas but who are not candidates for surgery based on the size or location of the tumor—treatment involves three months of systemic therapy like chemo or radiation, then reassessing to see if surgery is an option. For patients whose disease has spread, there are currently no curative treatment options.
“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,” said the study’s co-senior author Erica L. Carpenter, MBA, PhD, director of the Liquid Biopsy Laboratory and a research assistant professor of Medicine. The study’s other co-senior author is David Issadore, PhD, an associate professor of Bioengineering and Electrical and Systems Engineering.
Researchers in this study developed a blood test to screen for a panel of biomarkers instead of just one biomarker on its own. These markers include carbohydrate antigen 19-9 (CA19-9) and KRAS mutational burden, which are known to be associated with PDAC. In a blinded test group of 47 patients (20 with PDAC, 27 who were cancer free), the test was 92 percent accurate in its ability to detect disease, which outperforms the best-known biomarker, CA19-9 (89 percent), alone.
The researchers then used samples from the 25 patients who imaging showed did not have metastatic disease. The Penn test was 84 percent accurate in determining disease staging, which is significantly higher than imaging alone (64 percent).
While the test still needs to be validated in a larger cohort, researchers say they are excited by the promise of what it could potentially mean for a patient population in need of this kind of advancement.
“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,” said Carpenter.
The researchers also note this work would not have been possible without cooperation and coordination across multiple disciplines at Penn, including Hematology-Oncology, Radiation Oncology, Pathology and Laboratory Medicine, Mechanical Engineering and Applied Mechanics, Bioengineering, Surgery, and more. The study also received critical financial support from the Pancreatic Cancer Action Network, the University of Pennsylvania Pancreatic Cancer Research Center, and the Abramson Cancer Center Pancreatic Translational Center of Excellence.
The study’s first author is Zijian Yang, a PhD student at the University of Pennsylvania. Additional Penn authors include Michael J. LaRiviere, Jina Ko, Jacob E. Till, Theresa E. Christensen, Stephanie S. Yee, Taylor A. Black, Kyle Tien , Andrew Lin, Hanfei Shen, Neha Bhagwat, Daniel Herman, Andrew Adallah, Mark H. O’Hara, Charles M. Vollmer,Bryson W. Katona, and Ben Z. Stanger.
Additional support for this study came from the Pennsylvania Department of Health, the National Institutes of Health (R21MH118170), the American Cancer Society (RSG-15-227-01-CSM), and Congressionally Directed Medical Research Programs (W81XWH-19-2-0002).