Image: A histopathology of pancreatic adenocarcinoma, where the adenocarcinoma has wrapped around a nerve (center) (Photo courtesy of Johns Hopkins Medicine).
Pancreatic cancer remains a devastating disease, with the diagnosis typically being made late. Circulating Tumor DNA (ctDNA) has shown promise as a screening test for various tumor types.
The detection of ctDNA post curative intent surgery has been associated with a high risk of recurrence in multiple solid tumors. The potential of ctDNA to improve pancreatic cancer outcomes has been explored.
A multinational team of scientists working with those at The Walter and Eliza Hall Institute of Medical Research (Parkville, Australia) collected plasma samples prior to surgery in two studies and post-operative samples were collected in Australia from cases undergoing curative intent surgery. Clinicians were blinded to ctDNA results and adjuvant therapy was at clinician discretion. Tissue samples from both series were analyzed at Johns Hopkins University (Baltimore, MD, USA). Next generation sequencing was used to search for somatic KRAS mutations in the primary tumors and in cell-free DNA in the plasma.
The investigators analyzed plasma from a 119 patients who had a ctDNA sample at diagnosis and 66 (55.5 %) had detectable ctDNA, including 3/7 (42.9%) with stage I disease, 54/99 (54.5%) with stage II disease, 4/8 (50%) with stage III disease and 5/5 (100%) with metastases. Specific codon 12 KRAS (G12D, G12V or G12R) mutations were identified in the tumor tissue of 12/16 (75%) patients who had a ctDNA sample collected post-surgery. At a median follow-up of 15.2 months, 7/12 (58.3%) patients had recurred, including 3/8 (37.5%) with no detectable ctDNA and 4/4 (100%) with detectable ctDNA post-surgery. Detectable ctDNA post-surgery was significantly associated with poor overall survival with a median of eight months for patients with detectable ctDNA.
The authors concluded that ctDNA shows promise as a pancreatic cancer screening test, being detectable in a high proportion of patients with early stage disease. The detection of ctDNA post operatively predicts a very high risk of recurrence. The clinical utility of ctDNA to guide adjuvant therapy decision-making, and its potential as a real-time marker of treatment effect are being explored.
Anna Jewell, Director of Operations at Pancreatic Cancer UK (London, UK) said, “Currently, there isn’t a reliable blood test to detect pancreatic cancer at an early stage and finding such a test would be a game changer for tackling the disease. We urgently need to find new ways to diagnose pancreatic cancer earlier as 80% of people with the disease are diagnosed at an advanced stage, when surgery, the only treatment that can save lives, is not possible.” The study was presented at the American Society of Clinical Oncology (ASCO) Annual Meeting held June 2-6, 2017, in Chicago, IL, USA.
The Walter and Eliza Hall Institute of Medical Research
Johns Hopkins University
Pancreatic Cancer UK