Prognostic role of dynamic changes in inflammatory indicators in patients with non-small cell lung cancer treated with immune checkpoint inhibitors-a retrospective cohort study.

IF 4 2区 医学 Q2 ONCOLOGY Translational lung cancer research Pub Date : 2024-08-31 Epub Date: 2024-08-28 DOI:10.21037/tlcr-24-637
Liang Guo, Juanjuan Li, Jing Wang, Xinru Chen, Chenlei Cai, Fei Zhou, Anwen Xiong
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Abstract

Background: Immune checkpoint inhibitors (ICIs) have become one of the standard treatments for non-small cell lung cancer (NSCLC) patients without driver mutations. However, a considerable proportion of patients suffer from severe immune side effects and fail to respond to ICIs. As effective biomarkers, programmed cell death ligand 1 (PD-L1) expression, microsatellite instability (MSI), the tumor mutation burden (TMB) and tumor-infiltrating lymphocytes (TILs) require invasive procedures that place heavy physical and psychological burdens on patients. This study aims to identify simple and effective markers to optimize patient selection through therapeutic decisions and outcome prediction.

Methods: This retrospective study comprised 95 patients with metastatic NSCLC who were treated with ICIs either as the standard of care or in a clinical trial. The following data were extracted from the medical records. The baseline and dynamic neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were calculated in the present study. Responses were assessed by computed tomography (CT) imaging and classified according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 every 6-12 weeks during treatment.

Results: In total, 95 patients were included in the present study. The median age of patients was 61 years, 83.2% (79/95) patients were male, 62.1% (59/95) were former or current smokers, 66.3% (63/95) had adenocarcinoma, 93.7% (89/95) had stage IV disease, and 87.4% were without molecular alterations. A higher overall response rate (ORR) and prolonged median progression-free survival (PFS) was observed in patients with a lower cycle 3 (C3) NLR [7.7 vs. 5.5 months, hazard ratio (HR): 1.70, 95% confidence interval (CI): 0.90-3.22; P=0.12] and derived NLR (dNLR) (8.2 vs. 5.6 months, HR: 1.67, 95% CI: 0.94-2.97; P=0.08). After two cycles of ICI treatment, patients who had an increased NLR, dNLR, and PLR had a lower ORR and an inferior median PFS than those with a decreased NLR (5.5 vs. 8.5 months, HR: 1.87, 95% CI: 1.09-3.21; P=0.02), dNLR (5.6 vs. 8.4 months, HR: 1.49, 95% CI: 0.87-2.57; P=0.15), and PLR (11.8 vs. 5.5 months, HR: 2.28, 95% CI: 1.32-3.94; P=0.003). Moreover, patients with both an increased NLR and PLR had a worse ORR and median PFS than those with either an increased NLR or PLR, or both an increased NLR and PLR (11.8 vs. 5.5 vs. 5.6 months, P=0.003). In addition, the dynamic changes in the PLR could serve as an independent predictive factor of PFS in NSCLC patients treated with ICIs.

Conclusions: Elevated dynamic changes in the NLR and PLR were associated with lower response rates and shorter PFS in the patients with NSCLC treated with ICIs. Our results also highlight the role of dynamic changes in the PLR in identifying patients with NSCLC who could benefit from ICIs.

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接受免疫检查点抑制剂治疗的非小细胞肺癌患者炎症指标动态变化的预后作用--一项回顾性队列研究。
背景:免疫检查点抑制剂(ICIs)已成为治疗无驱动基因突变的非小细胞肺癌(NSCLC)患者的标准疗法之一。然而,相当一部分患者患有严重的免疫副作用,对 ICIs 治疗无效。作为有效的生物标志物,程序性细胞死亡配体1(PD-L1)表达、微卫星不稳定性(MSI)、肿瘤突变负荷(TMB)和肿瘤浸润淋巴细胞(TILs)需要进行侵入性操作,给患者带来了沉重的生理和心理负担。本研究旨在找出简单有效的标记物,通过治疗决策和结果预测来优化患者选择:这项回顾性研究包括 95 例转移性 NSCLC 患者,他们均接受了 ICIs 作为标准疗法或在临床试验中接受了 ICIs 治疗。从病历中提取了以下数据。本研究计算了基线和动态中性粒细胞与淋巴细胞比值(NLR)和血小板与淋巴细胞比值(PLR)。在治疗期间,每6-12周通过计算机断层扫描(CT)成像评估反应,并根据实体瘤反应评估标准(RECIST)1.1版进行分类:本研究共纳入95名患者。患者的中位年龄为61岁,83.2%(79/95)的患者为男性,62.1%(59/95)的患者曾经或正在吸烟,66.3%(63/95)的患者为腺癌,93.7%(89/95)的患者为 IV 期疾病,87.4%的患者无分子改变。第三周期(C3)NLR(7.7 个月对 5.5 个月,危险比(HR):1.70,95% 置信区间(CI):0.90-3.22;P=0.12)和衍生 NLR(dNLR)(8.2 个月对 5.6 个月,HR:1.67,95% CI:0.94-2.97;P=0.08)较低的患者总反应率(ORR)较高,中位无进展生存期(PFS)延长。经过两个周期的 ICI 治疗后,NLR、dNLR 和 PLR 增高的患者的 ORR 和中位 PFS 均低于 NLR 降低的患者(5.5 个月 vs. 8.5个月,HR:1.87,95% CI:1.09-3.21;P=0.02)、dNLR(5.6 vs. 8.4个月,HR:1.49,95% CI:0.87-2.57;P=0.15)和PLR(11.8 vs. 5.5个月,HR:2.28,95% CI:1.32-3.94;P=0.003)降低的患者ORR更低,中位PFS更差。此外,NLR和PLR均增高的患者比NLR或PLR均增高或NLR和PLR均增高的患者的ORR和中位PFS更差(11.8个月 vs. 5.5个月 vs. 5.6个月,P=0.003)。此外,PLR的动态变化可作为接受ICIs治疗的NSCLC患者PFS的独立预测因素:结论:在接受 ICIs 治疗的 NSCLC 患者中,NLR 和 PLR 的动态变化升高与较低的应答率和较短的 PFS 相关。我们的研究结果还强调了PLR的动态变化在识别可从ICIs中获益的NSCLC患者中的作用。
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来源期刊
CiteScore
7.20
自引率
2.50%
发文量
137
期刊介绍: Translational Lung Cancer Research(TLCR, Transl Lung Cancer Res, Print ISSN 2218-6751; Online ISSN 2226-4477) is an international, peer-reviewed, open-access journal, which was founded in March 2012. TLCR is indexed by PubMed/PubMed Central and the Chemical Abstracts Service (CAS) Databases. It is published quarterly the first year, and published bimonthly since February 2013. It provides practical up-to-date information on prevention, early detection, diagnosis, and treatment of lung cancer. Specific areas of its interest include, but not limited to, multimodality therapy, markers, imaging, tumor biology, pathology, chemoprevention, and technical advances related to lung cancer.
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