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中性粒细胞与淋巴细胞比值和乳酸脱氢酶在免疫检查点抑制剂治疗黑色素瘤患者中的预后价值:系统评价和荟萃分析。

Prognostic value of neutrophil-lymphocyte ratio and lactate dehydrogenase in melanoma patients treated with immune checkpoint inhibitors: A systematic review and meta-analysis.

机构信息

Cancer Center, Beijing Ditan Hospital, Capital Medical University, Beijing, China.

Department of Microbiology, Biochemistry and Molecular Genetics, Newark, NJ.

出版信息

Medicine (Baltimore). 2022 Aug 12;101(32):e29536. doi: 10.1097/MD.0000000000029536.

Abstract

BACKGROUND

Immune checkpoint inhibitors (ICIs) showed promising therapeutic efficacy on melanoma. Neutrophil-to-lymphocyte ratio (NLR) and serum lactate dehydrogenase (LDH) showed predictive values on prognosis of various tumors, but not on melanoma yet. This meta-analysis was conducted to investigate the prognostic role of NLR and LDH levels in melanoma treated with ICIs.

METHODS

A search was conducted for all reports published till March 2020 in PubMed, Web of Science, Cochrane Library, EMBASE, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform (ICTRP). Studies were included if they investigated the association between pretreatment NLR/LDH and prognosis in melanoma patients treated with ICIs. Subgroup analysis, publication bias, and meta-regression were conducted to investigate heterogeneity.

RESULTS

A total of 6817 melanoma patients were included. Overall, high pretreatment NLR and LDH were associated with poor overall survival (OS) (P < .001) and PFS (P < .001). Subgroup analyses revealed that elevated NLR and LDH levels were associated with poor OS and PFS in patients treated with anti-CTLA-4 or anti-PD-1/PD-L1 alone. NLR level was superior in predicting OS if compared with LDH level in patients treated with anti-PD-1/PD-L1 + anti-CTLA-4. In subgroup analysis stratified by cutoff value, high NLR level was associated with poor OS and PFS regardless of cutoff value, but LDH works when cutoff value = upper normal limit (UNL). The predictive value of NLR and LDH levels on OS and PFS was partially compromised in the Asian populations, compared with the Western countries.

CONCLUSION

Blood NLR and LDH levels showed great potential to be used as early prognostic biomarkers in melanoma patients treated with ICIs.

摘要

背景

免疫检查点抑制剂(ICIs)在黑色素瘤的治疗中显示出了有前景的疗效。中性粒细胞与淋巴细胞比值(NLR)和血清乳酸脱氢酶(LDH)在各种肿瘤的预后中具有预测价值,但在黑色素瘤中尚未得到证实。本荟萃分析旨在研究 NLR 和 LDH 水平在接受 ICI 治疗的黑色素瘤患者中的预后作用。

方法

在 PubMed、Web of Science、Cochrane 图书馆、EMBASE、ClinicalTrials.gov 和世界卫生组织国际临床试验注册平台(ICTRP)中搜索截至 2020 年 3 月发表的所有报告。如果研究调查了 NLR/LDH 与接受 ICI 治疗的黑色素瘤患者预后之间的关系,则纳入研究。进行亚组分析、发表偏倚和荟萃回归以调查异质性。

结果

共纳入 6817 例黑色素瘤患者。总体而言,高 NLR 和 LDH 与总生存期(OS)(P<0.001)和无进展生存期(PFS)(P<0.001)较差相关。亚组分析显示,升高的 NLR 和 LDH 水平与接受抗 CTLA-4 或抗 PD-1/PD-L1 单独治疗的患者的 OS 和 PFS 较差相关。与 LDH 水平相比,NLR 水平在接受抗 PD-1/PD-L1+抗 CTLA-4 治疗的患者中预测 OS 更具优势。在按截断值分层的亚组分析中,高 NLR 水平与 OS 和 PFS 较差相关,无论截断值如何,但 LDH 在截断值=上正常范围(UNL)时有效。与西方国家相比,NLR 和 LDH 水平对 OS 和 PFS 的预测价值在亚洲人群中部分受损。

结论

血液 NLR 和 LDH 水平有望成为接受 ICI 治疗的黑色素瘤患者的早期预后生物标志物。

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