Tumor-intrinsic chemosensitivity assessed by KELIM and prognosis by BRCA status in patients with advanced ovarian carcinomas.

IF 4.1 2区医学 Q1 OBSTETRICS & GYNECOLOGY International Journal of Gynecological Cancer Pub Date : 2024-10-31 DOI:10.1136/ijgc-2024-005815

Ondine Becker, Alice Durand, Marion Chevrier, Laetitia Collet, Laurence Gladieff, Florence Joly, Baptiste Sauterey, Christophe Pomel, Hélène Costaz, Patricia Pautier, Cécile Guillemet, Thibault de la Motte Rouge, Renaud Sabatier, Jean-Marc Classe, Thierry Petit, Eric Leblanc, Frédéric Marchal, Pierre-Emmanuel Colombo, Emmanuel Barranger, Aude-Marie Savoye, Lise Bosquet, Isabelle Ray-Coquard, Matthieu Carton, Oliver Colomban, Benoit You, Manuel Rodrigues

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Abstract

Objective: Treatment of high-grade serous ovarian carcinomas relies on surgery and chemotherapy, potentially followed by bevacizumab and/or poly (ADP-ribose) polymerase inhibitors (PARPi). The modeled CA-125 ELIMination rate constant K (KELIM) is a pragmatic indicator of tumor primary chemosensitivity. Although it is well established that BRCA mutations are associated with platinum sensitivity, the relationship between BRCA status and KELIM score has yet to be elucidated. This study aimed to evaluate the interactions between BRCA and KELIM, and their respective prognostic values.

Methods: We retrospectively collected data from 743 patients with high-grade serous ovarian carcinomas included in a French nationwide registry (NCT03275298) treated with neoadjuvant platinum-based chemotherapy followed by surgery. We analyzed the interactions between BRCA and KELIM, and their impacts on progression-free survival and overall survival.

Results: BRCA-mutated (BRCAm) patients had higher standardized KELIM than BRCA-wild type (BRCAwt) tumors (median 1.16 vs 1.06, respectively; p=0.001). The prognostic value of the KELIM score was independent of BRCA in multivariate analyses. KELIM score and BRCA could be combined to define three prognostic groups: (1) an unfavorable prognostic group with both BRCAwt and unfavorable KELIM (median progression-free survival 12.0 months); (2) an intermediate prognostic group with either BRCAm and unfavorable KELIM, or BRCAwt and favorable KELIM (median progression-free survival of 16.0 and 18.8 months, respectively; HR 0.64 compared with the unfavorable group, p<0.001); and (3) a favorable prognostic group with both BRCAm and favorable KELIM (median progression-free survival 28.8 months; HR 0.37 compared with the unfavorable group, p<0.001).

Conclusions: The KELIM score provides complementary prognostic information with respect to BRCA, and discriminates different prognoses within BRCAm or BRCAwt patients. Patients with both BRCAwt/unfavorable KELIM have a poor prognosis, underscoring the urgent need for novel therapeutic strategies.

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通过 KELIM 评估晚期卵巢癌患者的肿瘤内在化疗敏感性，并通过 BRCA 状态评估预后。

目的：高分化浆液性卵巢癌的治疗主要依靠手术和化疗，随后可能使用贝伐单抗和/或多（ADP-核糖）聚合酶抑制剂（PARPi）。建模的 CA-125 ELIMination 率常数 K (KELIM) 是肿瘤原发化疗敏感性的实用指标。虽然 BRCA 基因突变与铂类药物敏感性相关的观点已经得到证实，但 BRCA 状态与 KELIM 评分之间的关系仍有待阐明。本研究旨在评估 BRCA 和 KELIM 之间的相互作用及其各自的预后价值：我们回顾性地收集了743名高级别浆液性卵巢癌患者的数据，这些患者被纳入法国全国范围的登记处（NCT03275298），接受了以铂为基础的新辅助化疗，随后进行了手术。我们分析了 BRCA 和 KELIM 之间的相互作用及其对无进展生存期和总生存期的影响：结果：BRCA突变型（BRCAm）患者的标准化KELIM高于BRCA野生型（BRCAwt）肿瘤（中位数分别为1.16 vs 1.06；P=0.001）。在多变量分析中，KELIM评分的预后价值与BRCA无关。KELIM 评分和 BRCA 可合并定义三个预后组：(1) BRCAwt 和不利 KELIM 的不利预后组（中位无进展生存期为 12.0 个月）；(2) BRCAm 和不利 KELIM 或 BRCAwt 和有利 KELIM 的中间预后组（中位无进展生存期分别为 16.0 个月和 18.8 个月）；(3) BRCAm 和不利 KELIM 或 BRCAwt 和有利 KELIM 的中间预后组（中位无进展生存期分别为 16.0 个月和 18.8 个月）。0个月和18.8个月；与不利组相比，HR为0.64，pBRCAm和有利KELIM（中位无进展生存期为28.8个月；与不利组相比，HR为0.37，p结论：KELIM 评分提供了与 BRCA 相关的补充预后信息，并能区分 BRCAm 或 BRCAwt 患者的不同预后。同时患有 BRCAwt/不利 KELIM 的患者预后较差，这说明迫切需要新的治疗策略。

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来源期刊

International Journal of Gynecological Cancer 医学-妇产科学

CiteScore

6.60

自引率

10.40%

发文量

280

审稿时长

3-6 weeks

期刊介绍： The International Journal of Gynecological Cancer, the official journal of the International Gynecologic Cancer Society and the European Society of Gynaecological Oncology, is the primary educational and informational publication for topics relevant to detection, prevention, diagnosis, and treatment of gynecologic malignancies. IJGC emphasizes a multidisciplinary approach, and includes original research, reviews, and video articles. The audience consists of gynecologists, medical oncologists, radiation oncologists, radiologists, pathologists, and research scientists with a special interest in gynecological oncology.