Division of Hematology-Oncology, Chang Gung Memorial Hospital at Linkou, Tao-Yuan, Taiwan.
College of Medicine, Chang Gung University, Tao-Yuan, Taiwan.
Mol Cancer Ther. 2018 Oct;17(10):2238-2247. doi: 10.1158/1535-7163.MCT-17-1306. Epub 2018 Jul 11.
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 ( = 0.041), and patients with a ctDNA decrease >80% after treatment had a longer progression-free survival compared with patients with a ctDNA decrease of <80% (HR, 0.22; = 0.015). The objective response rate among patients with a ctDNA decrease of >80% was better than those with a ctDNA decrease <80% (OR, 0.026; = 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. .
在过去的二十年中，转移性结直肠癌（mCRC）的治疗取得了重大进展，但疾病监测仍不够发达。循环肿瘤 DNA（ctDNA）是一种很有前途的预后和预测生物标志物；然而，ctDNA 作为 mCRC 患者的标志物尚未得到很好的确立，并且如何最有效地利用它仍然没有共识。在这项研究中，我们旨在研究血浆 ctDNA 水平作为 mCRC 患者治疗反应的生物标志物。我们对 32 名 mCRC 患者的 136 个肿瘤组织和 ctDNA 样本进行了下一代测序（NGS），使用 12 基因panel 鉴定遗传变异。大约 70%的样本中检测到了遗传变异，肿瘤组织和血浆 ctDNA 之间存在高度一致性（85%）。我们观察了 18 名随访患者的 ctDNA 变化，包括新变异的出现。ctDNA 水平的变化与肿瘤缩小显著相关（= 0.041），治疗后 ctDNA 下降>80%的患者与 ctDNA 下降<80%的患者相比，无进展生存期更长（HR，0.22；= 0.015）。ctDNA 下降>80%的患者客观缓解率优于 ctDNA 下降<80%的患者（OR，0.026；= 0.007）。总之，这项研究表明，监测遗传 ctDNA 变异可以作为 mCRC 患者治疗效果的有价值的生物标志物，并且使用中等大小的 12 基因 NGS panel 可能适合这种临床监测。
