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循环肿瘤DNA检测可改善上皮性卵巢癌的复发预测。

Circulating tumor DNA detection improves relapse prediction in epithelial ovarian cancer.

作者信息

Zhang Ying, Guan Yanfang, Xiao Xiao, Xu Sicong, Zhu Shan, Cao Dongyan, Yu Mei, Peng Peng, Wang Jing, Wang Yongjun, Yin Rutie, Guo Jianting, Gao Wei, Li Pansong, Bai Jing, Gong Yuhua, Xia Xuefeng, Yi Xin, Yang Ling, Xiang Yang

机构信息

Department of Obstetrics and Gynecology, National Clinical Research Centre for Obstetric and Gynecologic Diseases, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Geneplus-Beijing Institute, Peking University Medical Industrial, 9th Floor, No.6 Building, Park, Zhongguancun Life Science Park, Beijing, China.

出版信息

BMC Cancer. 2024 Dec 22;24(1):1565. doi: 10.1186/s12885-024-13222-5.

DOI:10.1186/s12885-024-13222-5
PMID:39710659
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11663307/
Abstract

BACKGROUND

Epithelial ovarian cancer (EOC) is a lethal form of gynecological malignancy. Some EOC patients experience relapse after standard primary debulking surgery (PDS) and adjuvant chemotherapy (ACT). Identifying molecular residual disease (MRD) by circulating tumor DNA (ctDNA) detection can timely signal the potential for relapse. However, research on the usage of ctDNA for MRD detection in EOC is limited.

METHODS

Fifty-one EOC patients who received standard PDS and ACT were included. Targeted sequencing based on a panel of 1021 cancer-related genes, along with further validation using Enrich-rare-mutation sequencing, was performed on tumor tissues acquired during PDS and on plasma samples collected before and after PDS/ACT to identify variants reflecting tumor signals.

RESULTS

Post-surgery MRD was associated with relapse (Log-rank p = 0.0006) and was identified as an independent prognostic factor (HR, 3.4; 95% CI, 1.02-11.42; p = 0.047). The negative and positive predictive values were 0.83 and 0.62 respectively. Additionally, post-surgery MRD outperformed CA125 in predicting relapse, and integrating both parameters could provide more accurate risk stratification. Post-ACT MRD detection identified the patients with ctDNA clearance who were still at risk of relapse. Furthermore, baseline ctDNA detection could help determine patients who are not suitable for further tests after surgery.

CONCLUSIONS

Post-surgery MRD is superior to CA125 in predicting relapse in EOC. Patients exhibiting transient ctDNA clearance, as evaluated by post-ACT MRD, may require longitudinal monitoring. Baseline ctDNA detection could help determine whether post-surgery ctDNA monitoring should be performed.

摘要

背景

上皮性卵巢癌(EOC)是一种致命的妇科恶性肿瘤。一些EOC患者在接受标准的初次肿瘤细胞减灭术(PDS)和辅助化疗(ACT)后会复发。通过循环肿瘤DNA(ctDNA)检测来识别分子残留病(MRD)能够及时提示复发的可能性。然而,关于ctDNA在EOC的MRD检测中的应用研究有限。

方法

纳入51例接受标准PDS和ACT的EOC患者。对PDS期间获取的肿瘤组织以及PDS/ACT前后采集的血浆样本进行基于1021个癌症相关基因的靶向测序,并使用富集罕见突变测序进行进一步验证,以识别反映肿瘤信号的变异。

结果

术后MRD与复发相关(对数秩检验p = 0.0006),并被确定为独立的预后因素(风险比,3.4;95%置信区间,1.02 - 11.42;p = 0.047)。阴性和阳性预测值分别为0.83和0.62。此外,术后MRD在预测复发方面优于CA125,整合这两个参数可提供更准确的风险分层。ACT后MRD检测识别出仍有复发风险但ctDNA已清除的患者。此外,基线ctDNA检测有助于确定术后不适合进一步检测的患者。

结论

术后MRD在预测EOC复发方面优于CA125。通过ACT后MRD评估显示ctDNA短暂清除的患者可能需要长期监测。基线ctDNA检测有助于确定是否应进行术后ctDNA监测。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31e6/11663307/29eeee61fa34/12885_2024_13222_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31e6/11663307/9c55132c5ad2/12885_2024_13222_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31e6/11663307/fd72b53fd00c/12885_2024_13222_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31e6/11663307/912d5df764d1/12885_2024_13222_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31e6/11663307/0e79365f8008/12885_2024_13222_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31e6/11663307/29eeee61fa34/12885_2024_13222_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31e6/11663307/9c55132c5ad2/12885_2024_13222_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31e6/11663307/fd72b53fd00c/12885_2024_13222_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31e6/11663307/912d5df764d1/12885_2024_13222_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31e6/11663307/0e79365f8008/12885_2024_13222_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31e6/11663307/29eeee61fa34/12885_2024_13222_Fig5_HTML.jpg

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