cfDNA 和 ctDNA 在改善子宫内膜癌患者风险分层和疾病随访中的作用:走向临床应用。

IF 11.4 1区 医学 Q1 ONCOLOGY Journal of Experimental & Clinical Cancer Research Pub Date : 2024-09-20 DOI:10.1186/s13046-024-03158-w
Carlos Casas-Arozamena, Ana Vilar, Juan Cueva, Efigenia Arias, Victoria Sampayo, Eva Diaz, Sara S Oltra, Cristian Pablo Moiola, Silvia Cabrera, Alexandra Cortegoso, Teresa Curiel, Alicia Abalo, Mónica Pamies Serrano, Santiago Domingo, Pablo Padilla-Iserte, Marta Arnaez de la Cruz, Alicia Hernández, Virginia García-Pineda, Juan Ruiz-Bañobre, Rafael López, Xavier Matias-Guiu, Eva Colás, Antonio Gil-Moreno, Miguel Abal, Gema Moreno-Bueno, Laura Muinelo-Romay
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引用次数: 0

摘要

背景:子宫内膜癌(EC)发病率上升,导致死亡率增加。为应对这一趋势,改善手术后复发风险分层、预测疾病复发和耐药性至关重要。液体活检分析为应对这些临床挑战提供了一种前景广阔的工具,但将其应用于子宫内膜癌的最佳策略仍有待确定。本研究旨在确定 cfDNA/ctDNA 监测在改善局部复发患者临床管理方面的价值:方法:收集了 198 例子宫内膜癌患者手术时和手术后的血浆样本和子宫腔穿刺液(UA)。采用靶向测序技术确定了子宫穿刺抽液的遗传特征。根据UA的突变情况,分析了cfDNA总量,以确定是否存在ctDNA:结果:高水平的 cfDNA 和基线时可检测到的 ctDNA 与 DFS 的不良预后相关(p 值 结论:高水平的 cfDNA 和基线时可检测到的 ctDNA 与 DFS 的不良预后相关(p 值):这是关于 EC 中 cfDNA/ctDNA 特征的最全面研究,证明了其在改善局部疾病患者的风险分层和预测疾病复发方面的价值。CtDNA 动力学评估补充了目前监测疾病演变和治疗反应的策略。因此,在临床常规中实施 cfDNA/ctDNA 监测为改善心血管疾病的管理提供了一个独特的机会:该研究表明,基线高水平的 cfDNA 和可检测到的 ctDNA 是预后不良的有力指标。除了传统的组织病理学因素外,这还能进行更准确的风险分层,使临床医生能够识别可能受益于更积极治疗和更密切监测的高危患者。此外,对 cfDNA/ctDNA 的纵向分析可以在临床症状或影像学证据出现前几个月发现疾病复发。这种早期预警系统在临床实践中具有显著优势,为早期干预提供了机会之窗,并有可能改善患者的预后。
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Role of cfDNA and ctDNA to improve the risk stratification and the disease follow-up in patients with endometrial cancer: towards the clinical application.

Background: There has been a rise in endometrial cancer (EC) incidence leading to increased mortality. To counter this trend, improving the stratification of post-surgery recurrence risk and anticipating disease relapse and treatment resistance is essential. Liquid biopsy analyses offer a promising tool for these clinical challenges, though the best strategy for applying them in EC must be defined. This study was designed to determine the value of cfDNA/ctDNA monitoring in improving the clinical management of patients with localized and recurrent disease.

Methods: Plasma samples and uterine aspirates (UA) from 198 EC patients were collected at surgery and over time. The genetic landscape of UAs was characterized using targeted sequencing. Total cfDNA was analyzed for ctDNA presence based on the UA mutational profile.

Results: High cfDNA levels and detectable ctDNA at baseline correlated with poor prognosis for DFS (p-value < 0.0001; HR = 9.25) and DSS (p-value < 0.0001; HR = 11.20). This remained clinically significant when stratifying tumors by histopathological risk factors. Of note, cfDNA/ctDNA analyses discriminated patients with early post-surgery relapse and the ctDNA kinetics served to identify patients undergoing relapse before any clinical evidence emerged.

Conclusions: This is the most comprehensive study on cfDNA/ctDNA characterization in EC, demonstrating its value in improving risk stratification and anticipating disease relapse in patients with localized disease. CtDNA kinetics assessment complements current strategies to monitor the disease evolution and the treatment response. Therefore, implementing cfDNA/ctDNA monitoring in clinical routines offers a unique opportunity to improve EC management.

Translational relevance: The study demonstrates that high levels of cfDNA and detectable ctDNA at baseline are strong indicators of poor prognosis. This enables more accurate risk stratification beyond traditional histopathological factors, allowing clinicians to identify high-risk patients who may benefit from more aggressive treatment and closer monitoring. Moreover, longitudinal analysis of cfDNA/ctDNA can detect disease recurrence months before clinical symptoms or imaging evidence appear. This early warning system offers a significant advantage in clinical practice, providing a window of opportunity for early intervention and potentially improving patient outcomes.

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来源期刊
CiteScore
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自引率
1.80%
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333
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期刊介绍: The Journal of Experimental & Clinical Cancer Research is an esteemed peer-reviewed publication that focuses on cancer research, encompassing everything from fundamental discoveries to practical applications. We welcome submissions that showcase groundbreaking advancements in the field of cancer research, especially those that bridge the gap between laboratory findings and clinical implementation. Our goal is to foster a deeper understanding of cancer, improve prevention and detection strategies, facilitate accurate diagnosis, and enhance treatment options. We are particularly interested in manuscripts that shed light on the mechanisms behind the development and progression of cancer, including metastasis. Additionally, we encourage submissions that explore molecular alterations or biomarkers that can help predict the efficacy of different treatments or identify drug resistance. Translational research related to targeted therapies, personalized medicine, tumor immunotherapy, and innovative approaches applicable to clinical investigations are also of great interest to us. We provide a platform for the dissemination of large-scale molecular characterizations of human tumors and encourage researchers to share their insights, discoveries, and methodologies with the wider scientific community. By publishing high-quality research articles, reviews, and commentaries, the Journal of Experimental & Clinical Cancer Research strives to contribute to the continuous improvement of cancer care and make a meaningful impact on patients' lives.
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