循环肿瘤 DNA 在食管癌中的临床价值更新：系统评价和荟萃分析。

An update of clinical value of circulating tumor DNA in esophageal cancer: a systematic review and meta-analysis.

机构信息

Department of Infectious diseases, the Fourth Hospital of Hebei Medical University, Shijiazhuang, China.

Department of Emergency, the Fourth Hospital of Hebei Medical University, Shijiazhuang, China.

出版信息

BMC Cancer. 2024 Jan 24;24(1):129. doi: 10.1186/s12885-024-11879-6.

DOI:10.1186/s12885-024-11879-6

PMID:38267901

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10809487/

Abstract

BACKGROUND

Esophageal cancer (EC) is a deadly disease with limited therapeutic options. Although circulating tumor DNA (ctDNA) could be a promising tool in this regard, the availiable evidence is limited. We performed a systematic review and meta-analysis to summarize the clinical applicability of the next-generation sequencing (NGS) and droplet digital polymerase chain reaction (ddPCR) technology on the ctDNA detection of the EC and listed the current challenges.

METHODS

We systematically searched MEDLINE (via PubMed), Embase (via OVID), ISI Web of Science database and Cochrane Library from January, 2000 to April, 2023. Progression-free survival (PFS) and overall survival (OS) were set as primary outcome endpoints. Pathologic response was evaluated by tumor regression grade (TRG), according to the eighth edition of the American Joint Committee on Cancer (AJCC). Major pathologic regression (MPR) was defined as TRG 1 and 2. The MPR was set as secondary endpoint. Hazard rate (HR) and associated 95% CI were used as the effect indicators the association between ctDNA and prognosis of EC. MPR rates were also calculated. Fixed-effect model (Inverse Variance) or random-effect model (Mantel-Haenszel method) was performed depending on the statistically heterogeneity.

RESULTS

Twenty-two studies, containing 1144 patients with EC, were included in this meta-analysis. The results showed that OS (HR = 3.87; 95% CI, 2.86-5.23) and PFS (HR = 4.28; 95% CI, 3.34-5.48) were shorter in ctDNA-positive patients. In the neoadjuvant therapy, the sensitivity analysis showed the clarified HR of ctDNA-positive was 1.13(95% CI, 1.01-1.28). We also found that TP53, NOTCH1, CCND1 and CNKN2A are the most frequent mutation genes.

CONCLUSIONS

Positive ctDNA is associated with poor prognosis, which demonstrated clinical value of ctDNA. Longitudinal ctDNA monitoring showed potential prognostic value in the neoadjuvant therapy. In an era of precision medicine, ctDNA could be a promising tool to individualize treatment planning and to improve outcomes in EC.

PROSPERO REGISTRATION NUMBER

CRD42023412465.

摘要

背景

食管癌（EC）是一种致命疾病，治疗选择有限。尽管循环肿瘤 DNA（ctDNA）可能是这方面有前途的工具，但现有证据有限。我们进行了系统评价和荟萃分析，以总结下一代测序（NGS）和液滴数字聚合酶链反应（ddPCR）技术在 EC 中 ctDNA 检测的临床适用性，并列出了当前的挑战。

方法

我们系统地检索了 2000 年 1 月至 2023 年 4 月期间 MEDLINE（通过 PubMed）、Embase（通过 OVID）、ISI Web of Science 数据库和 Cochrane 图书馆。无进展生存期（PFS）和总生存期（OS）被设定为主要的终点。根据第八版美国癌症联合委员会（AJCC），通过肿瘤消退分级（TRG）评估病理缓解。主要病理缓解（MPR）定义为 TRG1 和 2。MPR 被设定为次要终点。风险比（HR）和相关的 95%置信区间（CI）被用作 ctDNA 与 EC 预后之间关联的效应指标。还计算了 MPR 率。根据统计学异质性，采用固定效应模型（Inverse Variance）或随机效应模型（Mantel-Haenszel 方法）。

结果

这项荟萃分析纳入了 22 项研究，共包含 1144 名 EC 患者。结果表明，ctDNA 阳性患者的 OS（HR=3.87；95%CI，2.86-5.23）和 PFS（HR=4.28；95%CI，3.34-5.48）更短。在新辅助治疗中，敏感性分析显示 ctDNA 阳性的明确 HR 为 1.13（95%CI，1.01-1.28）。我们还发现，TP53、NOTCH1、CCND1 和 CNKN2A 是最常见的突变基因。