Translational research in pancreatic adenocarcinoma has been limited by the difficulty of obtaining sufficient quality and quantity tumor tissue from patients. A study by Pietrasz et al assessing the feasibility and prognostic value of circulating tumor DNA (ctDNA) in pancreatic adenocarcinoma has found that ctDNA is an independent prognostic marker in patients with advanced pancreatic cancer and is associated with poorer outcomes. Identifying ctDNA in blood samples using next-generation sequencing offers great potential as a noninvasive strategy for patient care and follow-up, according to the study results.
Jean-Baptiste Bachet, MD, PhD, of the Gastroenterology and Digestive Oncology Department at Sorbonne University in Paris, France, is the corresponding author of this study published in Clinical Cancer Research.
From 2011 to 2015, the researchers collected blood samples from 135 patients with pancreatic adenocarcinoma, including patients with resectable, locally advanced, and metastatic disease. Blood samples were collected just before the first cycle of adjuvant treatment, after surgical resection in patients who had curative resection, or during the first cycle of chemotherapy in patients with locally advanced or metastatic disease.
Of the 135 patients, 31 had resectable tumors, 36 had locally advanced disease, and 68 had metastatic disease. The researchers extracted DNA from the plasma samples and performed next-generation sequencing to detect low-allele frequency mutations. They also screened for the three most frequent KRAS mutations in pancreatic adenocarcinoma—p.G12V, p.G12D, and p.G12R—by picoliter droplet-based digital polymerase chain reaction using the RainDrop system.
Major Study Findings
The researchers found that in the patients with advanced pancreatic adenocarcinoma (n = 104), 48% (n = 50) had ctDNA detectable with a median mutation allelic frequency of 6.1%. The presence of ctDNA was strongly correlated with poor overall survival (6.5 vs 19.0 months; P < .001) in univariate and multivariate analyses (hazard ratio [HR] = 1.96; P = .007). To evaluate the impact of ctDNA level, patients were grouped according to mutation allelic frequency tertiles: overall survival was 18.9, 7.8, and 4.9 months (P < .001), respectively.
Among patients who had curative-intent resection (n = 31), 6 had ctDNA detectable after surgery, with a mutation allelic frequency of 4.4%. The presence of ctDNA was associated with a shorter disease-free survival (4.6 vs 17.6 months; P = .03) and shorter overall survival (19.3 vs 32.2 months; P = .027).
“This study demonstrates that ctDNA can be detected in peripheral blood in pancreatic adenocarcinoma and that it appears as an independent prognostic marker of [overall survival] in locally advanced or metastatic diseases. Furthermore, it arises as an indicator of shorter [disease-free survival] and [overall survival] in resected patients when detected after surgery. The described procedure may have great potential as a new simple and noninvasive strategy for patients’ care and follow-up,” concluded the study authors.