EA UCBL/HCL 3738, Centre pour l'lnnovation en Cancérologie de Lyon (CICLY), Faculty of Medicine Lyon-Sud, Claude Bernard University Lyon 1, Lyon, France; Medical Oncology, Institut de Cancérologie et d'Hématologie Universitaire de Saint-Étienne (ICHUSE), Centre Hospitalier Universitaire de Saint-Etienne, France.
EA UCBL/HCL 3738, Centre pour l'lnnovation en Cancérologie de Lyon (CICLY), Faculty of Medicine Lyon-Sud, Claude Bernard University Lyon 1, Lyon, France; Medical Oncology, Institut de Cancérologie des Hospices Civils de Lyon (IC-HCL), CITOHL, Centre Hospitalier Lyon-Sud, GINECO, GINEGEPS, Lyon, France.
Eur J Cancer. 2023 Sep;191:112966. doi: 10.1016/j.ejca.2023.112966. Epub 2023 Jul 4.
In patients with advanced ovarian cancer, the modelled CA-125 ELIMination rate constant K (KELIM) is an early indicator of the tumour intrinsic chemosensitivity. We assessed the prognostic and surrogate values of KELIM with respect to those of surgery outcome (based on post-operative residual lesions) in the Gynaecologic Cancer Intergroup (GCIG) individual patient data meta-analysis MAOV (Meta-Analysis in OVarian cancer) built before the emergence of poly(ADP-ribose) polymerase (PARP) inhibitors.
The dataset was split into learning and validation cohorts (ratio 1:2). The individual modelled KELIM values were estimated, standardised by the median value, then scored as unfavourable (<1.0) or favourable (≥1.0). Overall survival (OS) and progression-free survival (PFS) analyses were performed with a two-step meta-analytic approach and surrogacy through a two-level meta-analytic model.
KELIM was assessed in 5884 patients from eight first-line trials (learning, 1962; validation, 3922). A favourable KELIM score was significantly associated with longer OS (validation set, median, 78.8 versus 28.4 months, hazard-ratios [HR] 0.46, 95% confidence interval [CI], 0.41-0.50, C-index 0.68), and longer PFS (validation set, median 30.5 versus 9.8 months, HR 0.49, 95% CI, 0.45-0.54, C-index 0.68), as were International Federation of Gynaecology and Obstetrics (FIGO) stage and debulking surgery outcome. Three prognostic groups were identified based on the surgery outcome and KELIM score, with large differences in OS (105.1, ∼45.0, and 22.1 months) and PFS (58.1, ∼15.0, and 8.0 months). Surrogacy for OS and for PFS was not established.
KELIM is an independent prognostic biomarker for survival, complementary to surgery outcome, representing a new determinant of first-line treatment success.
在晚期卵巢癌患者中，模型化的 CA-125 消除率常数 K（KELIM）是肿瘤内在化疗敏感性的早期指标。我们评估了 KELIM 的预后和替代价值，相对于妇科癌症国际组（GCIG）个体患者数据荟萃分析 MAOV（卵巢癌荟萃分析）中基于术后残留病变的手术结果（在聚（ADP-核糖）聚合酶（PARP）抑制剂出现之前建立）。
数据集分为学习和验证队列（比例 1:2）。估计个体模型化的 KELIM 值，通过中位数标准化，然后评分不佳（<1.0）或良好（≥1.0）。使用两步荟萃分析方法进行总体生存（OS）和无进展生存（PFS）分析，并通过两级荟萃分析模型进行替代。
在来自八项一线试验的 5884 名患者中评估了 KELIM（学习，1962；验证，3922）。有利的 KELIM 评分与较长的 OS 显著相关（验证集，中位数 78.8 与 28.4 个月，风险比[HR]0.46，95%置信区间[CI]0.41-0.50，C 指数 0.68）和较长的 PFS（验证集，中位数 30.5 与 9.8 个月，HR 0.49，95%CI 0.45-0.54，C 指数 0.68），以及国际妇产科联合会（FIGO）分期和减瘤手术结果。根据手术结果和 KELIM 评分确定了三个预后组，在 OS（105.1、∼45.0 和 22.1 个月）和 PFS（58.1、∼15.0 和 8.0 个月）方面存在较大差异。OS 和 PFS 的替代未建立。
KELIM 是生存的独立预后生物标志物，与手术结果互补，代表一线治疗成功的新决定因素。
