Monitoring Tumor Burden in Response to FOLFIRINOX Chemotherapy Via Profiling Circulating Cell-Free DNA in Pancreatic Cancer

Molecular Cancer Therapeutics - Tập 18 Số 1 - Trang 196-203 - 2019
Tao Wei1,2, Qi Zhang1,2, Xiang Li1,2, Wei Su1,2, Guogang Li1,2, Tao Ma1,2, Shunliang Gao1,2, Jianying Lou1,2, Risheng Que1,2, Lei Zheng3, Xueli Bai1,2, Qi Zhang1,2
11Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, China.
22Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, China.
33Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.

Tóm tắt

Abstract We aimed to explore the application of circulating cell-free DNA (cfDNA) profiling in monitoring tumor burden in patients with pancreatic ductal adenocarcinoma (PDAC). Thirty-eight patients with advanced PDAC receiving first-line FOLFIRINOX chemotherapy were prospectively enrolled. Next-generation sequencing for a panel of 560 genes covering a wide range of cancer-related loci was performed to profile cfDNA. In total, 25 patients (65.8%) had at least one common driver gene alterations (KRAS, TP53, SMAD4, CDKN2A) detected within cfDNA. In contrast, no above tumor-related recurrent mutations were found in plasma from 13 healthy individuals. Concordant alterations in plasma cfDNA and tumor tissue DNA was confirmed in two of three patients with available tissues. Further analysis showed that mutant allele fraction (MAF) for altered loci in cfDNA correlated with tumor stage, metastatic burden, and overall survival. Serial blood samples were collected from 17 patients after chemotherapy. We found that allele fraction for specific altered loci declined in chemotherapy-responding subjects. For cases who were resistant to this therapeutic regimen, increased ctDNA MAF was observed at the time of disease progression. Meanwhile, the dynamics of total cfDNA concentration correlated with tumor burden following chemotherapy. Collectively, we provide evidence that pretreatment ctDNA level correlates with tumor burden in PDAC, and serial cfDNA analysis is a robust tool for monitoring cancer response to chemotherapy.

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Molecular Cancer Therapeutics

Tập 18 Số 1

196-203

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