Becker Ondine, Durand Alice, Chevrier Marion, Collet Laetitia, Gladieff Laurence, Joly Florence, Sauterey Baptiste, Pomel Christophe, Costaz Hélène, Pautier Patricia, Guillemet Cécile, Rouge Thibault de la Motte, Sabatier Renaud, Classe Jean-Marc, Petit Thierry, Leblanc Eric, Marchal Frédéric, Colombo Pierre-Emmanuel, Barranger Emmanuel, Savoye Aude-Marie, Bosquet Lise, Ray-Coquard Isabelle, Carton Matthieu, Colomban Oliver, You Benoit, Rodrigues Manuel
Medical Oncology, Institut Curie, Paris, France.
Medical Oncology, Hospices Civils de Lyon, Lyon, France.
Int J Gynecol Cancer. 2025 May;35(5):101866. doi: 10.1136/ijgc-2024-005815. Epub 2025 Apr 19.
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.
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.
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 12.0months); (2) an intermediate prognostic group with either BRCAm and unfavorable KELIM, or BRCAwt and favorable KELIM (median progression-free survival of 16.0 and 18.8months, 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).
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.
高级别浆液性卵巢癌的治疗依赖于手术和化疗，可能随后使用贝伐单抗和/或聚（ADP - 核糖）聚合酶抑制剂（PARPi）。模拟的CA - 125消除率常数K（KELIM）是肿瘤原发性化疗敏感性的实用指标。虽然已充分证实BRCA突变与铂敏感性相关，但BRCA状态与KELIM评分之间的关系尚未阐明。本研究旨在评估BRCA与KELIM之间的相互作用及其各自的预后价值。
我们回顾性收集了法国全国性登记处（NCT03275298）中743例接受新辅助铂类化疗后手术的高级别浆液性卵巢癌患者的数据。我们分析了BRCA与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。
BRCA突变（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和1.06；p = 0.001）。在多变量分析中，KELIM评分的预后价值独立于BRCA。KELIM评分和BRCA可结合起来定义三个预后组：（1）预后不良组，包括BRCAwt和不良KELIM（无进展生存期中位数为12.0个月）；（2）中间预后组，包括BRCAm和不良KELIM，或BRCAwt和良好KELIM（无进展生存期中位数分别为16.0和18.8个月；与不良组相比，风险比为0.64，p < 0.001）；（3）预后良好组，包括BRCAm和良好KELIM（无进展生存期中位数为28.8个月；与不良组相比，风险比为0.37，p < 0.001）。
KELIM评分提供了关于BRCA的补充预后信息，并在BRCAm或BRCAwt患者中区分不同的预后。BRCAwt/不良KELIM的患者预后较差，凸显了对新型治疗策略的迫切需求。
