转移性结直肠癌cfDNA的早期动态变化与一线化疗疗效的相关性分析

Association of early dynamic changes of cfDNA in metastatic colorectal cancer with the efficacy of first-line chemotherapy

目的探讨转移性结直肠癌患者一线化疗期间循环游离DNA(cfDNA)的早期动态变化与一线化疗疗效及预后的相关性。方法纳入南京医科大学附属肿瘤医院2018年7月至2020年4月接受一线化疗的118例转移性结直肠癌患者,对其血浆中的cfDNA进行定量检测。分析患者的cfDNA基线水平与临床特征、cfDNA动态变化与无进展生存期(PFS)及治疗反应之间的相关性。结果患者的病理类型、有无肝转移、原发灶位置的不同分组间cfDNA水平差异有统计学意义(P<0.05)。而4周期化疗后cfDNA比值(化疗后cfDNA水平/cfDNA基线水平)≤1.215的患者PFS更长,客观缓解率(ORR)更高。通过多变量Cox回归分析,我们还发现一线化疗4周期后cfDNA比值是晚期结直肠癌患者一线化疗的独立预后因素。结论转移性结直肠癌cfDNA的基线水平与肿瘤侵袭性、肿瘤负荷相关,一线化疗期间cfDNA的早期动态变化可有效预测一线化疗疗效及预后。

Objective To investigate the association between the early dynamic changes of circulating cell-free DNA(cfDNA)and the efficacy and prognosis of first-line chemotherapy in patients with metastatic colorectal cancer(mCRC).Methods mCRC patients who received first-line chemotherapy from July 2018 to April 2020 were included and cfDNA in plasma was quantified.The association of dynamic changes in cfDNA with progression free survival(PFS)and therapy response were analyzed.Furthermore,we studied the correlations between baseline levels of cfDNA and clinical characteristics.Results There were statistically significant differences in cfDNA levels between different subgroups of patients in terms of pathological type,liver metastases,and location of the primary tumors(P<0.05).And patients with cfDNA(Ratio post-chemotherapy cfDNA levels/cfDNA baseline levels)≤1.215 after 4 cycles of chemotherapy had longer PFS and higher overall response rate(ORR).By multivariate COX regression analysisthe,we also found that cfDNA Ration after 4 cycles of first-line chemotherapy was an independent prognostic factor for first-line chemotherapy in mCRC patients.Conclusions The cfDNA baseline levels were correlated with tumor aggressiveness and tumor burden the early dynamic changes of cfDNA could effectively predict the efficacy and prognosis of first-line chemotherapy in mCRC patients.