Abstract
Recent improvements in next-generation sequencing (NGS) technology have enabled detection of biomarkers in cell-free DNA in blood and may ultimately replace invasive tissue biopsies. However, a better understanding of the performance of blood-based NGS assays is needed prior to routine clinical use. As part of an IRB-approved molecular profiling registry trial of pancreatic ductal adenocarcinoma (PDA) patients, we facilitated blood-based NGS testing of 34 patients from multiple community-based and high-volume academic oncology practices. 23 of these patients also underwent traditional tumor tissue-based NGS testing. cfDNA was not detected in 9/34 (26%) patients. Overall concordance between blood and tumor tissue NGS assays was low, with only 25% sensitivity of blood-based NGS for tumor tissue NGS. Mutations in KRAS, the major PDA oncogene, were only detected in 10/34 (29%) blood samples, compared to 20/23 (87%) tumor tissue biopsies. The presence of mutations in circulating DNA was associated with reduced overall survival (54% in mutation-positive versus 90% in mutation-negative). Our results suggest that in the setting of previously treated, advanced PDA, liquid biopsies are not yet an adequate substitute for tissue biopsies. Further refinement in defining the optimal patient population and timing of blood sampling may improve the value of a blood-based test.
Highlights
Pancreatic ductal adenocarcinoma (PDA) is an aggressive cancer that is projected to become the second leading cause of cancer-related death by 2025 [1]
To evaluate the feasibility of incorporating circulating DNA-based next-generation sequencing (NGS) assays into a precision medicine strategy for pancreatic cancer, blood-based NGS assays were performed on 34 patients
Despite the promise of noninvasive liquid biopsies, our data suggest that circulating DNA-based NGS assays do not yet appear ready to replace tumor tissue biopsies in detecting actionable mutations for use in pancreatic cancer precision oncology strategies
Summary
Pancreatic ductal adenocarcinoma (PDA) is an aggressive cancer that is projected to become the second leading cause of cancer-related death by 2025 [1]. This is, in part, due to poor early detection strategies: most cases are detected at an advanced stage [2] despite the long amount of time required for metastatic disease www.impactjournals.com/oncotarget to develop [3]. With the advent of new commercially available CLIA/CAP accredited lab testing for next-generation sequencing (NGS) panels, detection of actionable mutations from tissue biopsies no longer requires that the patient be seen at a specialized high-volume tertiary care academic medical center. Detection of circulating tumor DNA (ctDNA) in cell-free DNA (cfDNA), circulating tumor cells (ctcDNA), and tumor exosome-containing genomic material has created the possibility of a noninvasive method for diagnosing and monitoring cancer [6]
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