Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
Cancer Precision Medicine Center, Research Institute, Japanese Foundation for Cancer Research, Tokyo, Japan.
Sci Rep. 2019 Nov 22;9(1):17358. doi: 10.1038/s41598-019-53711-3.
The impact of ctDNA changes after chemotherapy on the clinical outcomes of patients with metastatic colorectal cancer (mCRC) remains unclear. The present study evaluated the clinical implications of the early change in ctDNA levels as a predictor of objective response and clinical outcome in mCRC patients who received chemotherapy. We investigated the effects of after/before ratio of ctDNA levels 2 and 8 weeks after initiation of second-line chemotherapy, on objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). ctDNA was detected using amplicon-based deep sequencing with a molecular barcode encompassing >240 hotspot mutations in 14 colon cancer-related genes. In multivariate analysis, as compared to baseline, patients with lower ctDNA level (≤50%) 8 weeks after initiation of chemotherapy showed significantly longer PFS and OS than the patients with higher (>50%) ctDNA level. In patients achieving a partial response or stable disease, the after/before ratio of ctDNA level 8 weeks after initiation of chemotherapy was significantly lower than those in patients with progressive disease. The present study suggests that an early change in the ctDNA level might serve as a biomarker to predict the chemotherapeutic efficacy and clinical outcomes in patients with mCRC.
ctDNA 变化对转移性结直肠癌（mCRC）患者化疗后临床结局的影响尚不清楚。本研究评估了 ctDNA 水平早期变化作为预测 mCRC 患者接受化疗后客观缓解和临床结局的指标的临床意义。我们研究了二线化疗开始后第 2 周和第 8 周 ctDNA 水平的前后比值对客观缓解率（ORR）、无进展生存期（PFS）和总生存期（OS）的影响。使用基于扩增子的深度测序检测 ctDNA，该方法采用分子条码覆盖 14 个结肠癌相关基因中的>240 个热点突变。多变量分析显示，与基线相比，化疗开始后第 8 周 ctDNA 水平较低（≤50%）的患者 PFS 和 OS 明显长于 ctDNA 水平较高（>50%）的患者。在获得部分缓解或疾病稳定的患者中，化疗开始后第 8 周的 ctDNA 水平的前后比值明显低于疾病进展的患者。本研究表明，ctDNA 水平的早期变化可能成为预测 mCRC 患者化疗疗效和临床结局的生物标志物。
