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晚期上皮性卵巢癌患者诊断时循环肿瘤DNA的预后价值及其新辅助化疗一个周期后的早期下降。CHIVA II期GINECO试验的辅助分析。

Prognostic value of circulating tumor DNA at diagnosis and its early decrease after one cycle of neoadjuvant chemotherapy for patients with advanced epithelial ovarian cancer. An ancillary analysis of the CHIVA phase II GINECO trial.

作者信息

Azaïs Henri, Brochard Camille, Taly Valérie, Benoit Louise, Ferron Gwenaël, Ray-Coquard Isabelle, You Benoit, Abadie-Lacourtoisie Sophie, Lebreton Coriolan, Venat Laurence, Louvet Christophe, Favier Laure, Blonz Cyriac, Dohollou Nadine, Malaurie Emmanuelle, Dubot Coraline, Kurtz Jean-Emmanuel, Pujade-Lauraine Eric, Rouleau Etienne, Leary Alexandra, Bats Anne-Sophie, Blons Hélène, Laurent-Puig Pierre

机构信息

AP-HP (Assistance Publique des Hôpitaux de Paris), Department of Gynaecological Oncological and Breast Surgery, Hôpital Européen Georges-Pompidou, Paris, France; Université de Paris Cité, Paris CARPEM Cancer Institute, Paris, France; INSERM UMR-S 1147, University of Paris Cité, Centre de Recherche des Cordeliers, Paris, France.

Université de Paris Cité, Paris CARPEM Cancer Institute, Paris, France; INSERM UMR-S 1147, University of Paris Cité, Centre de Recherche des Cordeliers, Paris, France; AP-HP (Assistance Publique des Hôpitaux de Paris), Department of Pathology, Hôpital Européen Georges-Pompidou, Paris, France.

出版信息

Gynecol Oncol. 2025 Jan;192:145-154. doi: 10.1016/j.ygyno.2024.12.004. Epub 2024 Dec 12.

DOI:10.1016/j.ygyno.2024.12.004
PMID:39671779
Abstract

OBJECTIVE

To evaluate the prognostic impact of circulating tumor DNA (ctDNA) detection at diagnosis (T0) and its early decrease after one cycle (T1) of neoadjuvant chemotherapy (NACT) in patients with advanced epithelial ovarian cancer (EOC) included in the CHIVA trial (NCT01583322).

METHODS

Blood samples were collected at T0 and before each administration of NACT. Circulating tumor DNA detection was performed by next-generation sequencing. Multivariate analysis was performed. A p-value of 0.05 was considered significant. Progression-free survival (PFS) and overall survival (OS) were compared between groups defined by ctDNA kinetic profile. Cox survival model was used to search variables associated with PFS and OS. Kaplan-Mayer curve was used to graphically express the differences in PFS and OS. A log-rank test compared the two curves.

RESULTS

188 patients were included. Blood samples were available for 168 patients at T0 and for 160 patients at T0 and T1 to assess ctDNA ratio kinetics. At T0, 107 patients (63.7 %) had detectable ctDNA. At T1, 137 (85.6 %) patients had negative ctDNA or a decrease of more than 80 %. There was a significant benefit in either PFS (p = 0.0017) or OS (p = 0.0036) in favor of early decrease of ctDNA ratio. A favorable decrease was associated with a greater likelihood of being able to perform CRS (OR: 3.94 (CI95 % 1.45-10.70), p = 0.0074).

CONCLUSIONS

Early decrease of ctDNA ratio can provide prognostic information early in the management of patients, allowing a more accurate information to patients and an early preparation for CRS (prehabilitation).

摘要

目的

评估在CHIVA试验(NCT01583322)纳入的晚期上皮性卵巢癌(EOC)患者中,诊断时(T0)循环肿瘤DNA(ctDNA)检测及其在新辅助化疗(NACT)一个周期后(T1)早期下降的预后影响。

方法

在T0以及每次NACT给药前采集血样。通过下一代测序进行循环肿瘤DNA检测。进行多变量分析。p值为0.05被视为具有显著性。比较由ctDNA动力学特征定义的组间无进展生存期(PFS)和总生存期(OS)。使用Cox生存模型搜索与PFS和OS相关的变量。使用Kaplan - Meier曲线以图形方式表达PFS和OS的差异。采用对数秩检验比较两条曲线。

结果

纳入188例患者。168例患者在T0时可获得血样,160例患者在T0和T1时可获得血样以评估ctDNA比率动力学。在T0时,107例患者(63.7%)可检测到ctDNA。在T1时,137例(85.6%)患者ctDNA呈阴性或下降超过80%。ctDNA比率早期下降在PFS(p = 0.0017)或OS(p = 0.0036)方面均有显著益处。有利的下降与能够进行细胞减灭术(CRS)的可能性更大相关(OR:3.94(CI95% 1.45 - 10.70),p = 0.0074)。

结论

ctDNA比率的早期下降可为患者管理早期提供预后信息,可以为患者提供更准确的信息并为细胞减灭术(术前准备)进行早期准备。

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