In:
Molecular Cancer Therapeutics, American Association for Cancer Research (AACR), Vol. 17, No. 10 ( 2018-10-01), p. 2238-2247
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 & gt;80% after treatment had a longer progression-free survival compared with patients with a ctDNA decrease of & lt;80% (HR, 0.22; P = 0.015). The objective response rate among patients with a ctDNA decrease of & gt;80% was better than those with a ctDNA decrease & lt;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. Mol Cancer Ther; 17(10); 2238–47. ©2018 AACR.
Type of Medium:
Online Resource
ISSN:
1535-7163
,
1538-8514
DOI:
10.1158/1535-7163.MCT-17-1306
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2018
detail.hit.zdb_id:
2062135-8
SSG:
12
