Mol Cancer Ther. 2018 Jul 11. pii: molcanther.1306.2017. doi: 10.1158/1535-7163.MCT-17-1306. [Epub ahead of print]
Targeted Sequencing of Circulating Tumor DNA to Monitor Genetic Variants and Therapeutic Response in Metastatic Colorectal Cancer.
Hsu HC1, Lapke N2, Wang CW3, Lin PY2, You JF4, Yeh CY4, Tsai WS4, Hung HY4, Chang SF4, Chen HC5, Chen SJ5, Hsu A5, Yang TS6.
Abstract
Substantial improvements have been made in the management of metastatic colorectal cancer (mCRC) in the last two decades, but disease monitoring remains underdeveloped. Circulating tumor DNA (ctDNA) is a promising prognostic and predictive biomarker, however, ctDNA as a marker for mCRC patients is not well-established, and there is still no consensus about how to utilize it most cost-effectively. In this study, we aim to investigate plasma ctDNA levels as a biomarker for therapeutic response of mCRC patients. We performed next generation sequencing (NGS) by using a 12-gene panel to identify genetic variants in 136 tumor tissue and ctDNA samples from 32 mCRC patients. Genetic variants were detected in approximately 70% of samples, and there was a high concordance (85%) between tumor tissue and plasma ctDNA. We observed ctDNA changes in 18 follow-up patients, including the emergence of new variants. Changes in ctDNA levels significantly correlated with tumor shrinkage (P=0.041), and patients with a ctDNA decrease >80% after treatment had a longer progression-free survival compared to patients with a ctDNA decrease <80% (HR=0.22; P=0.015). The objective response rate among patients with a ctDNA decrease >80% was better compared to those with a ctDNA decrease <80% (OR=0.026; P=0.007). In conclusion, this study demonstrates that monitoring of genetic ctDNA variants can serve as a valuable biomarker for therapeutic efficacy in mCRC patients, and that using a moderate-sized 12-gene NGS panel may be suitable for such clinical monitoring.
- PMID:
- 29997152
- DOI:
- 10.1158/1535-7163.MCT-17-1306
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