Circulating Tumor DNA Dynamics and Clinical Outcomes in Patients with Advanced Colorectal Cancer Treated with Cetuximab-Based Induction and Maintenance Treatment.

experimental_design

ctDNA samples were collected at four time points from baseline until disease progression during the first chemotherapy-free interval and analyzed using next-generation sequencing and methylation marker approaches.

在基线时以及在第一次化疗间期直至疾病进展期间的四个时间点收集ctDNA样本，并使用下一代测序和甲基化标记方法进行分析。

Progression-free survival(PFS) and overall survival(OS) from randomization were analyzed according to ctDNA kinetics and EGFR-MAPK pathway alterations.

根据循环肿瘤DNA (ctDNA) 动力学和 EGFR-MAPK 通路改变，分析了从随机分组开始的无进展生存期（PFS）和总生存期（OS）。

Results

Among 139 randomized patients, 104 (74.8%) had paired samples available.

在 139 名随机分组的患者中，有 104 名（74.8%）患者有配对样本可用。

Patients with negative baseline ctDNA remaining negative after 4-month induction chemotherapy had significantly longer PFS from randomization (9.6 months) as compared with patients with a ctDNA decrease of ≥80% (3.4 months) or a ctDNA decrease of <80% (2.1 months; P = 0.013).

在基线时ctDNA阴性的患者，在接受4个月诱导化疗后仍保持ctDNA阴性，与ctDNA减少≥80%的患者（3.4个月）或ctDNA减少<80%的患者（2.1个月）相比，从随机分组开始的无进展生存期显著更长（9.6个月；P = 0.013）。

Patients with EGFR-MAPK pathway alterations identified either in tissue or baseline ctDNA had worse PFS and OS from randomization.

在组织或基线ctDNA中发现EGFR-MAPK通路改变的患者，其从随机分组开始的无进展生存期和总生存期均较差。

Acquired alterations found in 17 of 63 (26.9%) patients at disease progression during the first chemotherapy-free interval were associated with worse OS from reintroduction of the full induction chemotherapy (14.9 vs. 19.4 months; P = 0.025).

在63名患者中，有17名（26.9%）在首次化疗间歇期疾病进展时发现获得性改变，这些改变与从重新引入完整诱导化疗开始的总生存期较差相关（14.9个月对比19.4个月；P = 0.025）。

Conclusions

Our findings show the prognostic impact of both ctDNA kinetics and EGFR-MAPK pathway alteration dynamics following induction chemotherapy with FOLFIRI-cetuximab in patients with mCRC.

我们的发现显示了在使用FOLFIRI-西妥昔单抗诱导化疗后，循环肿瘤DNA（ctDNA）动力学和EGFR-MAPK通路改变动态对转移性结直肠癌（mCRC）患者的预后影响。

Prospective studies evaluating ctDNA-guided treatment strategies are needed to validate the clinical utility of ctDNA monitoring to improve patient selection for first-line treatment de-escalation and anti-EGFR-based maintenance regimens, including treatment adaptation over time.

需要进行前瞻性研究来评估基于循环肿瘤DNA（ctDNA）指导的治疗策略，以验证ctDNA监测的临床效用，从而改善患者对于一线治疗降阶和基于抗表皮生长因子受体（EGFR）的维持治疗方案的选择，包括随时间进行治疗调整。