{"title":"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","authors":"Shogo Takei, Daisuke Kotani, George Laliotis, Kazuma Sato, Naoto Fujiwara, Akihito Kawazoe, Tadayoshi Hashimoto, Saori Mishima, Izuma Nakayama, Yoshiaki Nakamura, Hideaki Bando, Yasutoshi Kuboki, Shingo Sakashita, Erik Spickard, Giby V George, Punashi Dutta, Shruti Sharma, Meenakshi Malhotra, Himanshu Sethi, Adham Jurdi, Minetta C Liu, Takayuki Yoshino, Kohei Shitara, Takashi Kojima, Takeo Fujita","doi":"10.1097/SLA.0000000000006699","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>To investigate the association between perioperative ctDNA status and prognosis in patients with esophageal squamous cell carcinoma (ESCC).</p><p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusion: </strong>This study suggests that ctDNA-based MRD assessment may be valuable for evaluating patients with ESCC, particularly in post-NAC and postsurgical settings.</p>","PeriodicalId":8017,"journal":{"name":"Annals of surgery","volume":" ","pages":""},"PeriodicalIF":7.5000,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Circulating Tumor DNA Assessment to Predict Risk of Recurrence after Surgery in Patients with Locally Advanced Esophageal Squamous Cell Carcinoma: A Prospective Observational Study.\",\"authors\":\"Shogo Takei, Daisuke Kotani, George Laliotis, Kazuma Sato, Naoto Fujiwara, Akihito Kawazoe, Tadayoshi Hashimoto, Saori Mishima, Izuma Nakayama, Yoshiaki Nakamura, Hideaki Bando, Yasutoshi Kuboki, Shingo Sakashita, Erik Spickard, Giby V George, Punashi Dutta, Shruti Sharma, Meenakshi Malhotra, Himanshu Sethi, Adham Jurdi, Minetta C Liu, Takayuki Yoshino, Kohei Shitara, Takashi Kojima, Takeo Fujita\",\"doi\":\"10.1097/SLA.0000000000006699\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>To investigate the association between perioperative ctDNA status and prognosis in patients with esophageal squamous cell carcinoma (ESCC).</p><p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusion: </strong>This study suggests that ctDNA-based MRD assessment may be valuable for evaluating patients with ESCC, particularly in post-NAC and postsurgical settings.</p>\",\"PeriodicalId\":8017,\"journal\":{\"name\":\"Annals of surgery\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":7.5000,\"publicationDate\":\"2025-03-21\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Annals of surgery\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1097/SLA.0000000000006699\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"SURGERY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annals of surgery","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/SLA.0000000000006699","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"SURGERY","Score":null,"Total":0}
引用次数: 0
摘要
目的：探讨食管鳞癌（ESCC）患者围手术期ctDNA水平与预后的关系。背景：循环肿瘤DNA （ctDNA）已成为评估各种恶性肿瘤分子残留疾病（MRD）的一种有前景的生物标志物。然而，评估ctDNA在预测ESCC患者复发风险方面的应用的研究有限。方法：我们前瞻性地招募了局部晚期ESCC患者，他们计划接受新辅助化疗（NAC），然后进行手术。本报告回顾性分析了多个时间点的ctDNA，包括nac前、nac后、术前、术后和随访期间的个性化、肿瘤信息的16倍mPCR-NGS测定。结果：本报告共纳入28例接受根治性手术并成功进行肿瘤组织样本全外显子组测序分析的患者。在nac前时间点，50%的I期患者检测到ctDNA， 100%的II、III和IV期患者检测到ctDNA。nac后手术前，33.3%的患者检测到ctDNA。ctdna阳性患者的复发率为77.8%，而ctdna阴性患者的复发率为27.8%，ctdna阳性患者的无复发生存期（RFS）明显低于ctdna阴性患者（HR: 4.56, P =0.01）。在MRD窗口（术后2-16周）分析的患者中，ctDNA阳性患者的复发率为100%，而ctDNA阴性患者的复发率为30.4%，RFS明显较差（HR: 30.99， P术后16周），可检测的ctDNA与较差的RFS显著相关（HR: 27.34, P =0.003）。结论：这项研究表明，基于ctdna的MRD评估可能对ESCC患者的评估有价值，特别是在nac后和手术后的情况下。
Circulating Tumor DNA Assessment to Predict Risk of Recurrence after Surgery in Patients with Locally Advanced Esophageal Squamous Cell Carcinoma: A Prospective Observational Study.
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.
期刊介绍：
The Annals of Surgery is a renowned surgery journal, recognized globally for its extensive scholarly references. It serves as a valuable resource for the international medical community by disseminating knowledge regarding important developments in surgical science and practice. Surgeons regularly turn to the Annals of Surgery to stay updated on innovative practices and techniques. The journal also offers special editorial features such as "Advances in Surgical Technique," offering timely coverage of ongoing clinical issues. Additionally, the journal publishes monthly review articles that address the latest concerns in surgical practice.
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