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一种用于评估接受乐伐替尼联合帕博利珠单抗治疗的晚期子宫内膜癌的潜在炎症生物标志物。

A potential inflammatory biomarker for advanced endometrial cancer treated with lenvatinib plus pembrolizumab.

作者信息

Yanazume Shintaro, Kobayashi Yusuke, Kirita Yukari, Kitazono Ikumi, Nagata Chikako, Kozai Ayumi, Tanimoto Akihide, Kobayashi Hiroaki

机构信息

Department of Obstetrics and Gynecology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.

Department of Pathology, Kagoshima University hospital, Kagoshima, Japan.

出版信息

J Obstet Gynaecol Res. 2025 Jan;51(1):e16182. doi: 10.1111/jog.16182.

Abstract

INTRODUCTION

To identify prognostic biomarkers that could predict how well patients will respond to lenvatinib/pembrolizumab (LEN/PEM). The utility of certain inflammatory biomarkers in endometrial liquid-based cytology (LBC) or peripheral blood samples, such as neutrophil counts, lymphocyte counts, and neutrophil-to-lymphocyte ratio (NLR) were explored.

METHODS

The study included 25 patients with advanced or recurrent endometrial cancer who had received LEN/PEM between August 2018 and March 2024. Predictors for overall response (OR), disease control, and progression-free survival, based on neutrophil/lymphocyte counts, NLR scores of the endometrial LBC prior to initial treatment, and peripheral blood prior to initial treatment and prior to LEM/PEM treatment were compared using a receiver operating characteristic curve. Significant predictors were evaluated using the log-rank test, and multivariate analysis.

RESULTS

Although neutrophil counts and NLR score in endometrial LBC prior to initial treatment were better effective predictors for OR, the most accurate predictor of a progression-free status was NLR score in peripheral blood prior to LEM/PEM (0.722, 95% CI: 0.45-0.99, sensitivity: 57.1%, specificity: 94.4%). In peripheral blood prior to LEN/PEM, the lower NLR (NLR <5.39) group had a significantly longer PFS than the higher NLR (5.39 ≤ NLR) group (p = 0.023, median survival: 13.5 vs. 3.0 months), and tended to be independently correlated with PFS (hazard ratio = 2.571; 95% CI = 0.857-7.719; p = 0.092).

CONCLUSION

Inflammatory biomarkers in endometrial LBC failed to predict the efficacy of LEN/PEM, while peripheral blood NLR score sampled prior to LEN/PEM potentially could be a significant predictor.

摘要

引言

确定能够预测患者对乐伐替尼/帕博利珠单抗(LEN/PEM)反应程度的预后生物标志物。探讨了某些炎症生物标志物在子宫内膜液基细胞学(LBC)或外周血样本中的效用,如中性粒细胞计数、淋巴细胞计数和中性粒细胞与淋巴细胞比值(NLR)。

方法

该研究纳入了25例在2018年8月至2024年3月期间接受LEN/PEM治疗的晚期或复发性子宫内膜癌患者。基于初始治疗前子宫内膜LBC的中性粒细胞/淋巴细胞计数、NLR评分,以及初始治疗前和LEN/PEM治疗前的外周血,使用受试者工作特征曲线比较总缓解(OR)、疾病控制和无进展生存期的预测指标。使用对数秩检验和多变量分析评估显著预测指标。

结果

尽管初始治疗前子宫内膜LBC中的中性粒细胞计数和NLR评分是OR的更好有效预测指标,但无进展状态的最准确预测指标是LEN/PEM治疗前外周血中的NLR评分(0.722,95%CI:0.45 - 0.99,敏感性:57.1%,特异性:94.4%)。在LEN/PEM治疗前的外周血中,较低NLR(NLR <5.39)组的无进展生存期显著长于较高NLR(5.39≤NLR)组(p = 0.023,中位生存期:13.5个月对3.0个月),并且倾向于与无进展生存期独立相关(风险比 = 2.571;95%CI = 0.857 - 7.719;p = 0.092)。

结论

子宫内膜LBC中的炎症生物标志物未能预测LEN/PEM的疗效,而LEN/PEM治疗前采集的外周血NLR评分可能是一个重要的预测指标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25d7/11664300/562834f0bf91/JOG-51-0-g003.jpg

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