Metastatic Pancreatic Cancer
Liquid Versus Tissue Biopsies in Advanced Pancreatic Cancer
Clinical Study Title:
A Pilot Study Evaluating Concordance Between Blood-Based and Patient-Matched Tumor Molecular Testing Within Pancreatic Cancer Patients Participating in the Know Your Tumor (KYT) Initiative
Clinical Study 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 institutional review board-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. Of these patients, 23 also underwent traditional tumor tissue-based NGS testing. Circulating free DNA 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 vs 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.
Pishvaian MJ, Bender RJ, Matrisian LM, et al. A pilot study evaluating concordance between blood-based and patient-matched tumor molecular testing within pancreatic cancer patients participating in the Know Your Tumor (KYT) initiative. Oncotarget. November 8, 2016. doi: 10.18632/oncotarget.13225. [Epub ahead of print].
Co-Director, Pancreas Oncology
Pancreatic cancer is not really a lifestyle malignancy, and it doesn’t happen because of lifestyle choices. It is somehow a function of our modern age, and unfortunately, it’s going to become a second-most-common cause of cancer death in the near future. Our understanding of the disease has grown immensely, and our approach is changing rapidly. I, along with Pishvaian and colleagues, conducted a molecular profiling registry trial of pancreatic cancer patients to evaluate concordance between blood-based and patient-matched tumor molecular testing in an effort to better understand the performance of blood-based NGS assays. The study demonstrated that the overall concordance was low between blood and tumor tissue NGS (25% sensitivity of blood-based NGS for tumor tissue NGS). We concluded that, in the setting of previously treated, advanced PDA, liquid biopsies are not an adequate substitute for tissue biopsies. Additional studies are needed.
“Unfortunately, at this time, in the setting of previously treated, advanced PDA, liquid biopsies do not appear to be an adequate substitute for tissue biopsies.”