PO.CL01.10 · 临床研究
循环肿瘤DNA检测食管癌食管切除术后的微小残留病灶并预测结局
Circulating tumor DNA detects minimal residual disease and predicts outcomes in esophageal cancer after esophagectomy
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
背景：循环肿瘤DNA（ctDNA）监测在检测微小残留病灶（MRD）和预测各种癌症预后方面显示出前景。本研究评估了ctDNA在检测食管癌（EC）患者食管切除术后MRD和预测结局方面的作用。方法：我们开展了一项两步观察性研究，包括一个回顾性队列（队列1）和一个前瞻性队列（队列2），共40例接受直接手术或新辅助化疗（NAC）后行食管切除术的EC患者。在六个时间点采集血浆样本：治疗前、NAC后以及术后1、3、6和12个月。使用250基因panel评估ctDNA，并分析其与临床结局的关联。结果：肿瘤指导的ctDNA水平与肿瘤分期显著相关（P=0.01）。ctDNA水平的变化预测了肿瘤进展，曲线下面积为0.77。与ctDNA阴性患者相比，术后ctDNA阳性与队列1中降低的无复发生存期（RFS）（n=6，Log-rank P=0.034）和队列2中降低的无进展生存期（PFS）（n=34，Log-rank P=0.025）相关。综合分析显示，在所有患者（n=40）中，术后ctDNA阳性与更短的PFS相关（风险比[HR]=12.6，95%置信区间[CI]：1.6-99.0；P=0.002），在接受R0切除的患者（n=37）中与更短的RFS相关（HR=11.1，95% CI：1.4-89.0；P=0.006）。ctDNA阳性比影像学证据中位提前90天预测复发。结论：本研究显示了ctDNA状态与EC患者术后预后之间的强相关性。ctDNA评估能够有效检测MRD并指导术后管理策略。
查看英文原文 English abstract
Background Circulating tumor DNA (ctDNA) monitoring shows promise for detecting minimal residual disease (MRD) and predicting prognosis in various cancers. This study evaluated ctDNA for detecting MRD and predicting outcomes in patients with esophageal cancer (EC) after esophagectomy. Methods We conducted a two-step observational study with a retrospective cohort (cohort 1) and a prospective cohort (cohort 2) of 40 EC patients who underwent upfront surgery or neoadjuvant chemotherapy (NAC) followed by esophagectomy. Plasma samples were collected at six time points: pre-therapy, post-NAC, and 1, 3, 6, and 12 months post-surgery. ctDNA was assessed using a 250-gene panel and its association with clinical outcomes was analyzed. Results Tumor-informed ctDNA levels were significantly correlated with tumor stage ( P =0.01). Changes in ctDNA levels predicted tumor progression, with an area under the curve of 0.77. Postsurgical ctDNA positivity correlated with reduced recurrence-free survival (RFS) in cohort 1 (n=6, Log-rank P =0.034) and progression-free survival (PFS) in cohort 2 (n=34, Log-rank P =0.025) compared to ctDNA-negative patients. Combined analysis showed that postsurgical ctDNA positivity was associated with shorter PFS (hazard ratio [HR]=12.6, 95% confidence interval [CI]: 1.6-99.0; P =0.002) across all patients (n=40) and shorter RFS (HR=11.1, 95% CI: 1.4-89.0; P =0.006) in those who underwent R0 resection (n=37). ctDNA positivity predicted recurrence at a median of 90 days before radiographic evidence. Conclusions This study showed a strong correlation between ctDNA status and postsurgical prognosis in EC patients. ctDNA assessments can effectively detect MRD and guide postoperative management strategies.
利益披露 Disclosure
Q. Hu, None..
E. Oki, None..
Y. Kimura, None..
H. Otsu, None..
Y. Yonemura, None..
K. Mimori, None.