PDF(1009 KB)
PDF(1009 KB)
PDF(1009 KB)
糖类抗原125消除常数K对复发性卵巢癌患者预后评估的临床价值研究
CA125 elimination rate constant K（KELIM）in the prognostic assessment of patients with recurrent ovarian cancer
目的 探讨糖类抗原125消除常数K（KELIM）对接受规范治疗复发性卵巢癌（ROC）患者的化疗敏感性预测价值和其在预后评估中的临床意义。 方法 回顾性分析2015年1月至2022年12月重庆医科大学附属第一医院收治的311例晚期上皮性卵巢癌患者临床资料，其中复发组121例。通过受试者工作特征曲线确定KELIM预测化疗敏感性的最佳临界值，并分为优势组与劣势组，比较两组无铂间期、无进展生存期和总生存期的差异。采用Cox回归模型分析影响预后的独立因素。 结果 在复发组中，KELIM预测化疗敏感性的曲线下面积为0.696（P<0.001），最佳临界值为0.82。优势组患者的中位无铂间期显著长于劣势组（9.4个月vs. 5.0个月，P<0.001）。优势组的中位无进展生存期（13.4个月vs. 10.7个月，P=0.006）和总生存期（77.3个月vs. 50.6个月，P<0.001）均优于劣势组。多因素分析显示，KELIM≥0.82是影响患者总生存期的独立预测因素。 结论 在复发性卵巢癌患者中，KELIM是预测化疗敏感性及评估预后的有效指标，有助于早期识别铂耐药患者。
Objective To investigate the predictive value of the CA125 elimination rate constant K（KELIM）for chemotherapy sensitivity and its clinical significance in prognostic assessment among patients with recurrent ovarian cancer（ROC）receiving standard treatment. Methods A retrospective analysis was conducted on the clinical data of 311 patients with advanced epithelial ovarian carcinoma admitted to the First Affiliated Hospital of Chongqing Medical University between January 2015 and December 2022，including 121 patients in the recurrence cohort. The optimal cut-off value of KELIM for predicting chemotherapy sensitivity was determined using the receiver operating characteristic（ROC）curve. Patients were divided into favorable and unfavorable KELIM groups. The platinum-free interval（PFI），progression-free survival（PFS），and overall survival（OS）were compared between the two groups. Independent prognostic factors were identified using the Cox regression model. Results In the recurrence cohort，the area under the ROC curve（AUC）of KELIM for predicting chemotherapy sensitivity was 0.696（P<0.001），with an optimal cut-off value of 0.82. The median PFI was significantly longer in the favorable KELIM group than in the unfavorable group（9.4 months vs. 5.0 months，P<0.001）. Both median PFS（13.4 months vs. 10.7 months，P=0.006）and median OS（77.3 months vs. 50.6 months，P<0.001）were higher in the favorable KELIM group than in the unfavorable KELIM group. Multivariate analysis confirmed that a KELIM≥0.82 was an independent predictive factor for OS. Conclusion In the population with recurrent ovarian cancer，KELIM serves as an effective indicator for predicting chemotherapy sensitivity and assessing prognosis，potentially aiding in the early identification of platinum-resistant patients.
复发性卵巢癌 / 糖类抗原125消除常数K / 化疗敏感性 / 预后
recurrent ovarian cancer / KELIM / chemotherapy sensitivity / prognosis
| [1] |
关惋婷, 张肖翠, 张荣雪, 等. 环状RNA在卵巢上皮性癌耐药机制中的研究进展[J]. 中国实用妇科与产科杂志, 2024, 40(6):669-672.DOI:10.19538/j.fk2024060120.
|
| [2] |
卢淮武, 徐冬冬, 赵喜博, 等. 《2024 NCCN卵巢癌包括输卵管癌及原发性腹膜癌临床实践指南(第1版)》解读[J]. 中国实用妇科与产科杂志, 2024, 40(2):187-197. DOI:10.19538/j.fk2024020113.
|
| [3] |
张若, 杨茜, 张国楠. KELIM评分在晚期卵巢癌治疗中的应用价值[J]. 中国实用妇科与产科杂志, 2024, 40(8):855-858. DOI:10.19538/j.fk2024080117.
|
| [4] |
|
| [5] |
The development of guidelines recommendations is one of the core activities of the European Society for Medical Oncology (ESMO) and European Society of Gynaecologial Oncology (ESGO), as part of the mission of both societies to improve the quality of care for patients with cancer across Europe. ESMO and ESGO jointly developed clinically relevant and evidence-based recommendations in several selected areas in order to improve the quality of care for women with ovarian cancer. The ESMO-ESGO consensus conference on ovarian cancer was held on 12-14 April 2018 in Milan, Italy, and comprised a multidisciplinary panel of 40 leading experts in the management of ovarian cancer. Before the conference, the expert panel worked on five clinically relevant questions regarding ovarian cancer relating to each of the following four areas: pathology and molecular biology, early-stage and borderline tumours, advanced stage disease and recurrent disease. Relevant scientific literature, as identified using a systematic search, was reviewed in advance. During the consensus conference, the panel developed recommendations for each specific question and a consensus was reached. The recommendations presented here are thus based on the best available evidence and expert agreement. This article presents the recommendations of this ESMO-ESGO consensus conference, together with a summary of evidence supporting each recommendation.© 2019 THE AUTHORS. Published by Elsevier Ltd on behalf of the European Society for Medical Oncology. This is an open access article under the CC-BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
|
| [6] |
|
| [7] |
The Gynecological Cancer Intergroup (GCIG) has previously reached consensus regarding the criteria that should be used in clinical trial protocols to define progression-free survival after first-line therapy as well as the criteria to define response to treatment in recurrent disease using the serum marker CA 125 and has specified the situations where these criteria should be used. However, the publications did not include detailed definitions, nor were they written to accommodate the new version of Response Evaluation Criteria In Solid Tumors (RECIST) criteria (version 1.1) now available. Thus, we recommend that the definitions described later in detail are incorporated into clinical trial protocols to maintain consistency. The criteria for defining progression are now acceptable in clinical trials of recurrent disease as they have since been validated (Pujade-Lauraine, personal communication, 2010). The GCIG requests that data from all clinical trials using these definitions are made available to GCIG trial centers so that continual validation and improvement can be accomplished. These definitions were developed from analyzing patients receiving cytotoxic chemotherapy and have not yet been validated in patients receiving molecular targeting agents.
|
| [8] |
We used data from 886 patients from the CAELYX in Platinum Sensitive Ovarian Patients (CALYPSO) trial, recruited between April 2005 and September 2007, to examine the role of early decline in cancer antigen 125 (CA125) and early tumor response as prognostic factors and surrogates for superiority of treatment with carboplatin-pegylated liposomal doxorubicin (CPLD) compared with carboplatin-paclitaxel (CP) in a landmark analysis. Progression-free survival (PFS) was estimated by Kaplan-Meier analyses. We used univariate and multivariable Cox proportional hazards analyses to assess early decline and early response as surrogates for CPLD treatment benefit compared with CP. All statistical tests were two-sided. Early decline (defined as rate of CA125 decrease of at least 50% per month) was associated with improved PFS (adjusted hazard ratio [HR] for progression = 0.81, 95% confidence interval [CI] = 0.67 to 0.97, P =.02) but early response (complete or partial responses) was not. CPLD was associated with improved PFS compared with CP (HR = 0.82, 95% CI = 0.69 to 0.96, P =.01). However, fewer CPLD patients had an early decline (161 [37.4%] vs 233 [51.2%], P <.001) or an early response (146 [33.9%] vs 176 [38.7%], P =.14) compared with CP patients. The PFS for CPLD patients did not change statistically significantly after adjustment for early decline (adjusted HR = 0.80, 95% CI = 0.68 to 0.94, P =.007). These findings are opposite to what would be expected if these markers were good surrogates for treatment benefit.
|
| [9] |
Unexpected results were recently reported about the poor surrogacy of Gynecologic Cancer Intergroup (GCIG) defined CA-125 response in recurrent ovarian cancer (ROC) patients. Mathematical modeling may help describe CA-125 decline dynamically and discriminate prognostic kinetic parameters.Data from CALYPSO phase III trial comparing 2 carboplatin-based regimens in ROC patients were analyzed. Based on population kinetic approach, serum [CA-125] concentration-time profiles during first 50 treatment days were fit to a semi-mechanistic model with following parameters: "d[CA-125]/dt=(KPROD∗exp (BETA∗t))∗Effect-KELIM∗[CA-125]" with time, t; tumor growth rate, BETA; CA-125 tumor production rate, KPROD; CA-125 elimination rate, KELIM and K-dependent treatment indirect Effect. The predictive values of kinetic parameters were tested regarding progression-free survival (PFS) against other reported prognostic factors.Individual CA-125 kinetic profiles from 895 patients were modeled. Three kinetic parameters categorized by medians had predictive values using univariate analyses: K; KPROD and KELIM (all P<0.001). Using Cox multivariate analysis, 5 independent predictors of PFS remained significant: GCIG CA-125 response (favoring carboplatin-paclitaxel arm), treatment arm, platinum free-interval, measurable lesions and KELIM (HR=0.53; 95% CI 0.45-0.61; P<0.001).Mathematical modeling of CA-125 kinetics in ROC patients enables understanding of the time-change components during chemotherapy. The contradictory surrogacy of GCIG-defined CA-125 response was confirmed. The modeled CA-125 elimination rate KELIM, potentially assessable in routine, may have promising predictive value regarding PFS. Further validation of this predictive marker is warranted.Copyright © 2013 Elsevier Inc. All rights reserved.
|
| [10] |
Ovarian cancer is the gynecological cancer with the worst prognosis and the highest mortality rate because 75% of patients are diagnosed with advanced stage III–IV disease. About 50% of patients are now treated with neoadjuvant chemotherapy followed by interval debulking surgery (IDS). In that context, there is a need for accurate predictors of tumor primary chemosensitivity, as it may impact the feasibility of subsequent IDS. Across seven studies with more than 12,000 patients, including six large randomized clinical trials and a national cancer registry, along with a mega-analysis database with 5842 patients, the modeled CA-125 ELIMination rate constant K (KELIM), the calculation of which is based on the longitudinal kinetics during the first three cycles of platinum-based chemotherapy, was shown to be a reproducible indicator of tumor intrinsic chemosensitivity. Indeed, KELIM is strongly associated with the likelihood of complete IDS, subsequent platinum-free interval, progression-free survival, and overall survival, along with the efficacy of maintenance treatment with bevacizumab or veliparib. As a consequence, KELIM might be used to guide more subtly the medical and surgical treatments in a first-line setting. Moreover, it could be used to identify the patients with poorly chemosensitive disease, who will be the best candidates for innovative treatments meant to reverse the chemoresistance, such as cell cycle inhibitors or immunotherapy.
|
| [11] |
The objective of this study is to externally validate the KELIM (rate of elimination of CA-125 elimation) score in patients with high grade serous ovarian cancer(HGSC)undergoing NACT and determine its relation to outcome of cytoreduction, platinum sensitivity, progression free(PFS) and overall survival(OS).This is a retrospective cohort study of patients with Stage III-IV HGSC diagnosed between January 1, 2010 and December 31, 2019 and treated with NACT. KELIM score was calculated using at least 3 CA-125 values within the first 100 days of chemotherapy. Demographic parameters were collected and Kaplan Meier survival analyses were performed for PFS and OS. This study was approved by local ethics board.217 patients met inclusion criteria. Median follow-up was 28.93 months(range 2.86-135.06). There was no significant difference in stage, functional status, cytoreductive outcome or BRCA status(germline or somatic) between patients with a KELIM ≥ 1 and <1. Patients with a KELIM<1 had a lower median PFS (13.58 vs 19.69, p < 0.001), median platinum free interval(PFI) (7.66 vs 13.64, p < 0.001) and 5-year OS (57% vs 72%, p = 0.0140) compared to patients with KELIM≥1. After adjusting for stage, treatment delays, bevacizumab or poly adenosine diphosphate-ribose polymerase(parp)-inhibitor use, and BRCA status, patients with KELIM<1 had a high risk of disease progression(HR = 1.57 (95% CI 1.08-2.28) and death(HR = 1.99 (95% CI 1.01-3.95) compared to KELIM≥1. BRCA status was independently associated to an increase on KELIM score (OR = 1.917, 95% CI 1.046-3.512, p = 0.035).Patients with advanced HGSC undergoing NACT with a KELIM <1 were more likely to have platinum-resistant disease, worse PFS and worse OS when compared to patients with KELIM≥1. The KELIM score can be a helpful tool to predict chemo-response and aid in treatment decision making.Copyright © 2022 Elsevier Inc. All rights reserved.
|
| [12] |
刘浚源, 刘原, 张祎, 等. 糖类抗原125动力学变化在卵巢癌初次肿瘤细胞减灭术患者预后评估中的应用研究[J]. 中国实用妇科与产科杂志, 2023, 39(5): 547-551. DOI:10.19538/j.fk2023050114.
|
| [13] |
倪丽, 王莹莹, 朱晨辰, 等. 卵巢癌高风险患者行预防性手术105例临床资料分析[J]. 中国实用妇科与产科杂志, 2025, 41(7):738-741.DOI:10.19538/j.fk2025070115.
|
| [14] |
|
| [15] |
|
| [16] |
| [17] |
| [18] |
|
| [19] |
|
| [20] |
|
| [21] |
|
| [22] |
Most patients with advanced ovarian cancer (AOC) ultimately relapse after platinum-based chemotherapy. Combining bevacizumab, olaparib, and durvalumab likely drives synergistic activity. This open-label phase 2 study (NCT04015739) aimed to assess activity and safety of this triple combination in female patients with relapsed high-grade AOC following prior platinum-based therapy. Patients were treated with olaparib (300 mg orally, twice daily), the bevacizumab biosimilar FKB238 (15 mg/kg intravenously, once-every-3-weeks), and durvalumab (1.12 g intravenously, once-every-3-weeks) in nine French centers. The primary endpoint was the non-progression rate at 3 months for platinum-resistant relapse or 6 months for platinum-sensitive relapse per RECIST 1.1 and irRECIST. Secondary endpoints were CA-125 decline with CA-125 ELIMination rate constant K (KELIM-B) per CA-125 longitudinal kinetics over 100 days, progression free survival and overall survival, tumor response, and safety. Non-progression rates were 69.8% (90%CI 55.9%-80.0%) at 3 months for platinum-resistant relapse patients (N = 41), meeting the prespecified endpoint, and 43.8% (90%CI 29.0%-57.4%) at 6 months for platinum-sensitive relapse (N = 33), not meeting the prespecified endpoint. Median progression-free survival was 4.1 months (95%CI 3.5–5.9) and 4.9 months (95%CI 2.9–7.0) respectively. Favorable KELIM-B was associated with better survival. No toxic deaths or major safety signals were observed. Here we show that further investigation of this triple combination may be considered in AOC patients with platinum-resistant relapse.
|
| [23] |
|
| [24] |
Selecting the maintenance strategy for advanced tubo-ovarian high-grade serous carcinoma (HGSC) is challenging. This study evaluates the correlation among chemotherapy response score (CRS), homologous recombination deficiency (HRD) status, and KELIM score; identifies predictors of Poly (ADP-ribose) polymerase (PARP) inhibitor (PARPi) efficacy and stratifies recurrence risk in PARPi-treated population.Median Progression-free Survival (mPFS) and hazard ratios (HRs) were retrospectively calculated in HGSC patients after neoadjuvant chemotherapy (3/4 cycles), interval cytoreductive surgery, and adjuvant treatment. Variables included HRD status, disease stage, KELIM, radiological response, residual tumor, and CRS at surgery. A risk-stratification model predicting PARPi efficacy was developed.Among overall population (N = 373), 66.9 % of CRS3 patients reached favorable KELIM, 17.3 % had complete radiological response, and 97.8 % achieved complete surgery, with higher frequencies than CRS1/2 (p < 0.001). Univariate analysis of PFS on PARPi (N = 210) showed favorable covariates: CRS3 (HR 2.37, 95 % CI 1.39-4.04 and HR 1.59, 95 % CI 1.03-2.47 vs CRS1 and CRS2), BRCA mutation (HR 3.41 95 % CI 2.15-5.39 and HR 2.00 95 % CI 1.13-3.56 vs BRCAwt-HRDneg and -HRDpos) and continuum KELIM (HR 0.66, 95 % CI 0.45-0.96). At multivariate, CRS3 and BRCA mutation were confirmed significant. Combining HRD status, CRS, and KELIM four prognostic groups with different PARPi efficacy were identified (mPFS 38 vs 26 vs 18 vs 6 months for Low, Intermediate, High-Intermediate, and High-risk groups).CRS is a prognostic factor in PARPi-treated population as a PARPi efficacy surrogate. Integrating HRD status, CRS, and KELIM allows patients risk stratification and tailored maintenance. These results should be considered hypothesis-generating.Copyright © 2025. Published by Elsevier Inc.
|
| [25] |
BRCA mutation and homologous recombination deficiency (HRD) are the criteria for the administration of PARP inhibitor (PARPi) maintenance therapy. It is known that PARPi efficacy is related to platinum sensitivity and that the latter can be demonstrated from the CA-125 elimination rate constant (KELIM). This study aims to investigate if KELIM can be another tool in the identification of patients that could be benefit from PARPi therapy. Retrospective analysis of patients with high-grade serous advanced ovarian cancer that underwent cytoreduction and was further tested for HRD status. The HRD status was tested either by myChoice HRD CDx assay or by RediScore assay. KELIM score was measured in both neoadjuvant and adjuvant settings with the online tool biomarker-kinetics.org. A total of 39 patients had available data for estimating both HRD status and KELIM score. When assuming KELIM as a binary index test with the value 1 as the cut-off point, the sensitivity was 0.86, 95% CI (0.64–0.97) and the specificity was 0.83, 95% CI (0.59–0.96). On the other hand, when assuming KELIM as a continuous index test, the area under the curve (AUC) was 81% and the optimal threshold, using the Youden index, was identified as 1.03 with a sensitivity of 85.7% and a specificity of 83.3%. KELIM score seems to be a new, cheaper, and faster tool to identify patients that can benefit from PARPi maintenance therapy.
|
| [26] |
|
| [27] |
|
| [28] |
|
| [29] |
中国医师协会微无创医学专业委员会妇科肿瘤学组, 中国抗癌协会中西整合卵巢癌专业委员会. 铂敏感复发性卵巢癌诊治中国专家共识(2023年版)[J]. 中国实用妇科与产科杂志, 2023, 39(9):935-942.DOI:10.19538/j.fk2023090117.
|
| [30] |
In patients with ovarian cancer receiving neoadjuvant chemotherapy, the first-line treatment success will depend on both the tumor-primary chemosensitivity and the completeness of interval debulking surgery (IDS). The modeled CA-125 ELIMination rate constant K (KELIM), calculated with the CA-125 longitudinal kinetics during the first 100 chemotherapy days, is a validated early marker of tumor chemosensitivity. The objective was to investigate the role of the chemosensitivity relative to the success of first-line medical–surgical treatment.
|
| [31] |
张钰豪, 李婧, 林仲秋, 等. 白蛋白结合型紫杉醇在上皮性卵巢癌一线辅助化疗中疗效及安全性分析[J]. 中国实用妇科与产科杂志, 2025, 41(9):941-945.DOI:10.19538/j.fk2025090116.
|
利益冲突 所有作者均声明不存在利益冲突
/
| 〈 |
|
〉 |
