ctDNA Plus Protein Biomarker Test Allows Early Detection of Pancreatic Cancer

A single blood draw that combines the detection of DNA and protein markers could be more sensitive to the earlier detection of pancreatic cancer, according to a new study published in Proceedings of the National Academy of Sciences.

With less than a 9% 5-year survival rate, pancreatic cancer is currently the third leading cause of cancer death in the United States, the primary reason being diagnosis when the patient is already at an advanced disease stage. Tumor size is also a significant determinant of survival: the smaller the tumor, the better the prognosis, even in the presence of metastasis to distant sites.

According to Jin He, MD, assistant professor of surgery at the Johns Hopkins University School of medicine, early-stage pancreatic cancers are generally asymptomatic and are incidental findings from an imaging scan.

For the present study, the authors worked on a hypothesis that earlier detection of pancreatic cancer can successfully contribute to reducing cancer-related mortality. Toward that goal, they determined analyzing circulating tumor DNA (ctDNA) and protein biomarkers together could increase the sensitivity of detecting resectable pancreatic cancer.

The study included 221 patients with surgically resectable pancreatic cancer and 182 age-matched healthy volunteers. Twenty percent of patients had no typical disease symptoms; the primary tumor ranged in size from 0.6 cm to 13 cm. The following distribution of disease stage was documented in the patients:

• Stage IA: 5%
• Stage IB: 8%
• Stage IIA: 10%
• Stage IIB: 77%

Patient blood samples were analyzed for KRAS mutations in the ctDNA, along with analysis of mutations in specific protein biomarkers: CA19-9, CEA, HGF, OPN, and prolactin. The study found that compared with the ctDNA test or the CA19-9 test alone, the combination assay was more successful at detecting the cancer, irrespective of tumor size.

The scientists could identify 30% patients (66/221) with early-stage pancreatic cancer using the KRAS gene test alone. Adding CA19-9 to the detection strategy improved the rate of detection to 49% (109/221). However, including the remaining protein biomarkers pushed the detection rate to 64% (141/221).

“A single marker on its own won’t identify early cancers in most people,” said 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, in a press release. “This study shows that it may be possible to use multiple markers to nail down the detection of early pancreatic cancer with a blood test, and treat those patients earlier and better.”

The authors concluded that mining genetic and protein alterations together can significantly improve the sensitivity of a blood test for early-stage pancreatic cancer. They acknowledged that excluding advanced stage (stage III and IV) patients from their study reduced the sensitivity that could be achieved, but noted that resectable cases are better suited for evaluating a screening strategy.

Reference

Cohen JD, Javed AA, Thoburn C, et al. Combined circulating tumor DNA and protein biomarker-based liquid biopsy for the earlier detection of pancreatic cancers [published online, September 5, 2017]. PNAS. doi: 10.1073/pnas.1704961114.