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使用循环肿瘤DNA检测肿瘤信息性微小残留病在卵巢癌一线治疗中的预后价值。

The prognostic value of tumor-informed minimal residual disease detection using circulating tumor DNA in first-line treatment of ovarian cancer.

作者信息

Shu Tong, Liang Yiming, Zhang Siwen, Sun Tianqi, Gao Yunong, Guo Chang, Li Zhe, Gao Min, Zhang Nan, Song Nan, Zhang Naiyi, Gao Weijiao, Wang Wei, Wang Hongguo, Cai Yan, Zhang Feng, Ji Xuwo, Dong Yu, Zheng Hong

机构信息

Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gynecologic Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China.

Precision Scientific (Beijing) Co., Ltd., Building D, Jinyujiahua Plaza, Haidian District, Beijing 100123, China.

出版信息

Gynecol Oncol. 2025 Jan;192:94-101. doi: 10.1016/j.ygyno.2024.11.002. Epub 2024 Nov 22.

Abstract

OBJECTIVE

This study aims to assess the application and effectiveness of tumor-informed Minimal Residual Disease (MRD) detection using circulating tumor DNA (ctDNA) for predicting disease recurrence and survival outcomes in ovarian cancer patients.

METHODS

Between 2020 and 2022, 31 newly diagnosed stage II-IV ovarian cancer patients were enrolled in this retrospective study. All patients completed standard treatment, including cytoreductive surgery and platinum-based chemotherapy, achieving a complete remission (CR) without receiving first-line PARP inhibitor maintenance therapy. Archived tumor tissue, as well as plasma samples collected pre- and post-treatment, were tested using Whole Exome Sequencing (WES) to identify personalized somatic variants for MRD detection.

RESULTS

All pre-treatment (baseline) blood samples showed a 100 % MRD positive rate, demonstrating the high sensitivity of ctDNA-based MRD detection. This rate decreased to 25.8 % in post-treatment (landmark) samples, indicating a significant reduction of ctDNA levels following effective treatment. The median follow-up time until Sep 2023 was 21.4 months, during which 15 patients experienced recurrence. Landmark MRD-positive patients exhibited a markedly shorter median progression-free survival (PFS) compared to MRD-negative patients (5.8 months vs 24.7 months, HR = 6.678, p = 0.01). Furthermore, a strong correlation was observed between post-treatment MRD status and recurrence, with a higher relapse rate in the MRD-positive group.

CONCLUSION

The study establishes MRD detection via ctDNA analysis as a valuable tool for early and accurate prediction of ovarian cancer recurrence, potentially leading to improved clinical outcomes. As a result, integrating MRD detection into routine clinical practice is advocated to enable more effective and personalized treatment strategies for ovarian cancer patients.

摘要

目的

本研究旨在评估使用循环肿瘤DNA(ctDNA)进行肿瘤信息指导的微小残留病(MRD)检测在预测卵巢癌患者疾病复发和生存结局方面的应用及有效性。

方法

2020年至2022年期间,31例新诊断的II-IV期卵巢癌患者纳入了这项回顾性研究。所有患者均完成了标准治疗,包括肿瘤细胞减灭术和铂类化疗,在未接受一线PARP抑制剂维持治疗的情况下实现了完全缓解(CR)。使用全外显子测序(WES)对存档的肿瘤组织以及治疗前后采集的血浆样本进行检测,以识别用于MRD检测的个性化体细胞变异。

结果

所有治疗前(基线)血样的MRD阳性率均为100%,表明基于ctDNA的MRD检测具有高灵敏度。该比率在治疗后(标志性)样本中降至25.8%,表明有效治疗后ctDNA水平显著降低。截至2023年9月的中位随访时间为21.4个月,在此期间有15例患者复发。与MRD阴性患者相比,标志性MRD阳性患者的中位无进展生存期(PFS)明显更短(5.8个月对24.7个月,HR = 6.678,p = 0.01)。此外,观察到治疗后MRD状态与复发之间存在强相关性,MRD阳性组的复发率更高。

结论

该研究确立了通过ctDNA分析进行MRD检测是早期准确预测卵巢癌复发的有价值工具,可能会改善临床结局。因此,提倡将MRD检测纳入常规临床实践中,以便为卵巢癌患者制定更有效和个性化的治疗策略。

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