Abstract
Pancreatic cancer is an aggressive, solid tumor, with a grave prognosis. Despite surgical treatment in patients with pancreatic cancer, the rate of recurrence is high. In addition, although tumor biomarkers are frequently used to confirm advanced pancreatic cancer, this is not accurate and the biomarkers currently used cannot indicate prognosis. This study sought to evaluate circulating tumor DNA as a tumor biomarker to prognosticate pancreatic cancer. Patients with advanced pancreatic cancer and liver metastasis (N = 104) were included, and blood samples were collected from all patients. The mutant allele frequency was measured using amplicon-based deep sequencing on a cell-free DNA panel covering 14 genes with > 240 hot spots. In patients with advanced pancreatic cancer, 50% (N = 52) had detectable ctDNA levels, with TP53 (45%, N = 47) and KRAS (42.3%, N = 44) mutations the most common. Patients with detectable circulating tumor DNA levels also had significantly worse overall survival and progression free survival than ctDNA negative patients (8.4 vs 16 months, P<0.0001 for overall survival; 3.2 vs 7.9 months, P<0.0001 for progression-free survival). In a multivariate analysis, ctDNA status was independently associated with overall survival and progression-free survival (HR = 3.1, 95%CI = 1.9–5.0, P<0.0001; HR 2.6, 95%CI = 1.7–4.0, P<0.0001, respectively). Moreover, circulating tumor DNA significantly correlated with a higher number of liver metastases, the presence of lung and/or peritoneal metastases, tumor burden, and higher carbohydrate antigen 19–9 levels. This study supports the use of circulating tumor DNA as an independent prognostic marker for advanced pancreatic cancer.
Highlights
Pancreatic cancer is one of the deadliest diseases, with a very poor prognosis
Surgery was performed before blood sampling for 21 patients and after blood sampling in two patients because of the disappearance of liver metastases following chemotherapy
More recent studies have shown that circulating tumor DNA (ctDNA)— which can be obtained through liquid biopsies and is detectable by next-generation sequencing or ddPCR with high sensitivity—is released from the primary tumor and/or its metastases [26,27,28,29] and could be used to detect cancer and/or its recurrence at very early stages
Summary
Pancreatic cancer is one of the deadliest diseases, with a very poor prognosis. Patients with metastatic pancreatic cancer have a 5-year overall survival (OS) rate of only 2% [1], and fewer than 5% of patients with advanced pancreatic cancer who receive chemotherapy are expected to survive 5 years [2,3,4,5]. The prognosis remains poor despite improvements in treatment, the introduction of new chemotherapies and surgical techniques, especially as cancer is usually detected in advanced stages. Patients with advanced pancreatic cancer must be monitored often to evaluate tumor burden and response to treatment. Serum protein biomarkers, such as carcinoembryonic antigen (CEA) and carbohydrate antigen 19–9 (CA19-9), are frequently measured, but these biomarkers do not accurately predict prognosis [6]. A stringent yet minimally invasive biomarker that measures patient status with high sensitivity and specificity is urgently needed
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