Utilizing Liquid Biopsy to Diagnose Pancreatic Cancer

Researchers from the Mayo Clinic and other institutions conducted a study to determine the feasibility and efficacy of circulating tumor DNA (ctDNA) profiling for the diagnosis of pancreatic ductal adenocarcinoma (PDAC).

CtDNA profiling is a non-invasive liquid biopsy method that measures DNA fragments from cancer cells that have been released into the bloodstream. PDAC is typically diagnosed using results from an endoscopic ultrasound or endoscopic retrograde cholangiopancreatography.

“PDAC has a poor prognosis often due to late presentation of disease. Biopsy tissue sampling is invasive, and samples are often inadequate, requiring repeated invasive procedures and delays in treatment,” wrote the study authors. “Non‐invasive methods to identify PDAC early in its course may improve prognosis in PDAC.”

For this study, the researchers performed ctDNA testing on 357 samples from 282 patients with advanced or metastatic pancreatic ductal adenocarcinoma (PDAC), utilizing a 73-gene panel. Results were compared with data on clinical outcomes from 165 patients in the cohort.

Three-quarters of patients had alterations to at least one of the genes examined. After exclusions of variants of unknown significance, nearly half (48%) of patients had alterations in therapeutically relevant genes, including KRAS (G12C), EGFR, ATM, MYC, BRCA, PIK3CA, and BRAF mutations. The alterations with the highest frequency among patients with advanced disease were KRAS, SMAD, CCND2, and TP53.

“Our study is the largest cohort to date that demonstrates the feasibility of ctDNA testing in PDAC,” the researchers concluded. “We provide a benchmark landscape upon which the field can continue to grow. Future applications may include use of ctDNA to guide treatment and serial monitoring of ctDNA during disease course to identify novel therapeutic targets for improved prognosis.”

Findings from this study were published in The Oncologist.