Circulating tumor DNA predicts recurrence and survival in patients with resectable gastric and gastroesophageal junction cancer.

IF 6 1区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Gastric Cancer Pub Date : 2024-10-05 DOI:10.1007/s10120-024-01556-9

Cecilie Riis Iden, Salah Mohammad Mustafa, Nadia Øgaard, Tenna Henriksen, Sarah Østrup Jensen, Lise Barlebo Ahlborn, Kristian Egebjerg, Lene Baeksgaard, Rajendra Singh Garbyal, Mette Kjølhede Nedergaard, Michael Patrick Achiam, Claus Lindbjerg Andersen, Morten Mau-Sørensen

{"title":"Circulating tumor DNA predicts recurrence and survival in patients with resectable gastric and gastroesophageal junction cancer.","authors":"Cecilie Riis Iden, Salah Mohammad Mustafa, Nadia Øgaard, Tenna Henriksen, Sarah Østrup Jensen, Lise Barlebo Ahlborn, Kristian Egebjerg, Lene Baeksgaard, Rajendra Singh Garbyal, Mette Kjølhede Nedergaard, Michael Patrick Achiam, Claus Lindbjerg Andersen, Morten Mau-Sørensen","doi":"10.1007/s10120-024-01556-9","DOIUrl":null,"url":null,"abstract":"Background: Gastric and gastroesophageal junction (GEJ) cancer represents a significant global health challenge, with high recurrence rates and poor survival outcomes. This study investigates circulating tumor DNA (ctDNA) as a biomarker for assessing recurrence risk in patients with resectable gastric and GEJ adenocarcinomas (AC).Methods: Patients with resectable gastric and GEJ AC, undergoing perioperative chemotherapy and surgery, were prospectively enrolled. Serial plasma samples were collected at baseline, after one cycle of chemotherapy, after preoperative chemotherapy, and after surgery. ctDNA was assessed by a ddPCR test (TriMeth), which targets the gastrointestinal cancer-specific methylation patterns of the genes C9orf50, KCNQ5, and CLIP4.Results: ctDNA analysis was performed on 229 plasma samples from 86 patients. At baseline, ctDNA was detected in 56% of patients, which decreased to 37% following one cycle of chemotherapy, 25% after preoperative chemotherapy and 15% after surgical resection. The presence of ctDNA after one cycle of chemotherapy was associated with reduced recurrence-free survival (RFS) (HR = 2.54, 95% confidence interval (CI) 1.33-4.85, p = 0.005) and overall survival (OS) (HR = 2.23, 95% CI 1.07-4.62, p = 0.032). Similarly, ctDNA after surgery was associated with significantly shorter RFS (HR = 6.22, 95% CI 2.39-16.2, p < 0.001) and OS (HR = 6.37, 95% CI 2.10-19.3, p = 0.001). Multivariable regression analysis confirmed ctDNA after surgery as an independent prognostic factor (p < 0.001).Conclusion: ctDNA analysis has the potential to identify patients at elevated risk of recurrence, thus providing personalized treatment strategies for patients with resectable gastric and GEJ cancer. Further validation in larger cohorts and ctDNA-guided interventions are needed for future clinical use.","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":" ","pages":""},"PeriodicalIF":6.0000,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Gastric Cancer","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s10120-024-01556-9","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background: Gastric and gastroesophageal junction (GEJ) cancer represents a significant global health challenge, with high recurrence rates and poor survival outcomes. This study investigates circulating tumor DNA (ctDNA) as a biomarker for assessing recurrence risk in patients with resectable gastric and GEJ adenocarcinomas (AC).

Methods: Patients with resectable gastric and GEJ AC, undergoing perioperative chemotherapy and surgery, were prospectively enrolled. Serial plasma samples were collected at baseline, after one cycle of chemotherapy, after preoperative chemotherapy, and after surgery. ctDNA was assessed by a ddPCR test (TriMeth), which targets the gastrointestinal cancer-specific methylation patterns of the genes C9orf50, KCNQ5, and CLIP4.

Results: ctDNA analysis was performed on 229 plasma samples from 86 patients. At baseline, ctDNA was detected in 56% of patients, which decreased to 37% following one cycle of chemotherapy, 25% after preoperative chemotherapy and 15% after surgical resection. The presence of ctDNA after one cycle of chemotherapy was associated with reduced recurrence-free survival (RFS) (HR = 2.54, 95% confidence interval (CI) 1.33-4.85, p = 0.005) and overall survival (OS) (HR = 2.23, 95% CI 1.07-4.62, p = 0.032). Similarly, ctDNA after surgery was associated with significantly shorter RFS (HR = 6.22, 95% CI 2.39-16.2, p < 0.001) and OS (HR = 6.37, 95% CI 2.10-19.3, p = 0.001). Multivariable regression analysis confirmed ctDNA after surgery as an independent prognostic factor (p < 0.001).

Conclusion: ctDNA analysis has the potential to identify patients at elevated risk of recurrence, thus providing personalized treatment strategies for patients with resectable gastric and GEJ cancer. Further validation in larger cohorts and ctDNA-guided interventions are needed for future clinical use.

查看原文本刊更多论文

循环肿瘤DNA可预测可切除胃癌和胃食管交界处癌患者的复发率和生存率。

背景：胃癌和胃食管交界处癌（GEJ）复发率高、生存率低，是全球健康面临的重大挑战。本研究将循环肿瘤 DNA（ctDNA）作为一种生物标记物，用于评估可切除胃癌和胃食管连接部腺癌（AC）患者的复发风险：方法：对接受围手术期化疗和手术的可切除胃癌和胃食管腺癌患者进行前瞻性研究。ctDNA通过ddPCR检测（TriMeth）进行评估，该检测针对C9orf50、KCNQ5和CLIP4基因的胃肠癌特异性甲基化模式。结果：对86名患者的229份血浆样本进行了ctDNA分析。基线时，56%的患者检测到ctDNA，化疗一个周期后降至37%，术前化疗后降至25%，手术切除后降至15%。一个化疗周期后出现ctDNA与无复发生存期（RFS）（HR = 2.54，95% 置信区间（CI）1.33-4.85，p = 0.005）和总生存期（OS）（HR = 2.23，95% 置信区间（CI）1.07-4.62，p = 0.032）降低有关。同样，手术后ctDNA与明显较短的RFS相关（HR = 6.22，95% CI 2.39-16.2，p 结论：ctDNA分析有可能识别复发风险较高的患者，从而为可切除胃癌和GEJ癌患者提供个性化治疗策略。未来的临床应用还需要在更大的队列中进一步验证，并在ctDNA指导下进行干预。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Gastric Cancer 医学-胃肠肝病学

CiteScore

14.70

自引率

2.70%

发文量

审稿时长

6-12 weeks

期刊介绍： Gastric Cancer is an esteemed global forum that focuses on various aspects of gastric cancer research, treatment, and biology worldwide. The journal promotes a diverse range of content, including original articles, case reports, short communications, and technical notes. It also welcomes Letters to the Editor discussing published articles or sharing viewpoints on gastric cancer topics. Review articles are predominantly sought after by the Editor, ensuring comprehensive coverage of the field. With a dedicated and knowledgeable editorial team, the journal is committed to providing exceptional support and ensuring high levels of author satisfaction. In fact, over 90% of published authors have expressed their intent to publish again in our esteemed journal.