循环肿瘤DNA评估预测局部晚期食管鳞状细胞癌患者术后复发风险：一项前瞻性观察研究

Circulating Tumor DNA Assessment to Predict Risk of Recurrence after Surgery in Patients with Locally Advanced Esophageal Squamous Cell Carcinoma: A Prospective Observational Study.

作者信息

Takei Shogo, Kotani Daisuke, Laliotis George, Sato Kazuma, Fujiwara Naoto, Kawazoe Akihito, Hashimoto Tadayoshi, Mishima Saori, Nakayama Izuma, Nakamura Yoshiaki, Bando Hideaki, Kuboki Yasutoshi, Sakashita Shingo, Spickard Erik, George Giby V, Dutta Punashi, Sharma Shruti, Malhotra Meenakshi, Sethi Himanshu, Jurdi Adham, Liu Minetta C, Yoshino Takayuki, Shitara Kohei, Kojima Takashi, Fujita Takeo

机构信息

Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan.

Natera, Inc., Austin, TX.

出版信息

Ann Surg. 2025 Mar 21. doi: 10.1097/SLA.0000000000006699.

DOI:10.1097/SLA.0000000000006699

PMID:40115982

Abstract

OBJECTIVE

To investigate the association between perioperative ctDNA status and prognosis in patients with esophageal squamous cell carcinoma (ESCC).

BACKGROUND

Circulating tumor DNA (ctDNA) has emerged as a promising biomarker for assessing molecular residual disease (MRD) in various malignancies. However, there are limited studies evaluating the utility of ctDNA for predicting recurrence risk in patients with ESCC.

METHODS

We prospectively enrolled patients with locally advanced ESCC who were scheduled to receive neoadjuvant chemotherapy (NAC) followed by surgery. This report retrospectively analyzed ctDNA with a personalized, tumor-informed 16-plex mPCR-NGS assay at multiple time points: pre-NAC, post-NAC but before surgery, postoperatively, and longitudinally during follow-up.

RESULTS

A total of 28 patients who underwent curative surgery, and had successful whole-exome sequencing analysis of tumor tissue samples were included in this report. At the pre-NAC time point, ctDNA was detected in 50% of patients with stage I and 100% of those with stages II, III, and IV. Post-NAC but before surgery, ctDNA was detected in 33.3% of patients. The recurrence rate was 77.8% in ctDNA-positive patients compared to 27.8% in ctDNA-negative patients, with significantly worse recurrence-free survival (RFS) for ctDNA-positive patients vs. ctDNA-negative patients (HR: 4.56, P =0.01). In patients analyzed during the MRD window (2-16 weeks post-surgery), the recurrence rate was 100% in ctDNA-positive patients compared to 30.4% in ctDNA-negative patients, with significantly worse RFS (HR: 30.99, P <0.0001). Similarly, during surveillance (>16 weeks post-surgery), detectable ctDNA was significantly associated with poor RFS (HR: 27.34, P =0.003).

CONCLUSION

This study suggests that ctDNA-based MRD assessment may be valuable for evaluating patients with ESCC, particularly in post-NAC and postsurgical settings.

摘要

目的

探讨食管鳞状细胞癌（ESCC）患者围手术期循环肿瘤DNA（ctDNA）状态与预后之间的关联。

背景

循环肿瘤DNA（ctDNA）已成为评估各种恶性肿瘤分子残留病（MRD）的一种很有前景的生物标志物。然而，评估ctDNA在预测ESCC患者复发风险方面效用的研究有限。

方法

我们前瞻性纳入计划接受新辅助化疗（NAC）后行手术的局部晚期ESCC患者。本报告回顾性分析了在多个时间点使用个性化的、基于肿瘤信息的16重多重PCR-下一代测序（mPCR-NGS）检测法检测的ctDNA，这些时间点包括：NAC前、NAC后但手术前、术后以及随访期间的纵向检测。

结果

本报告纳入了28例行根治性手术且肿瘤组织样本全外显子测序分析成功的患者。在NAC前时间点，I期患者中50%检测到ctDNA，II、III和IV期患者中100%检测到ctDNA。NAC后但手术前，33.3%的患者检测到ctDNA。ctDNA阳性患者的复发率为77.8%，而ctDNA阴性患者为27.8%，ctDNA阳性患者的无复发生存期（RFS）明显差于ctDNA阴性患者（风险比：4.56，P =0.01）。在MRD窗口期（术后2 - 16周）分析的患者中，ctDNA阳性患者的复发率为100%，而ctDNA阴性患者为30.4%，RFS明显更差（风险比：30.99，P <0.0001）。同样，在监测期（术后>16周），可检测到的ctDNA与不良RFS显著相关（风险比：27.34，P =0.003）。