表皮生长因子突变型非小细胞肺癌生存的系统炎症标志物：单机构分析、系统评价和荟萃分析。
Systemic Inflammatory Markers of Survival in Epidermal Growth Factor-Mutated Non-Small-Cell Lung Cancer: Single-Institution Analysis, Systematic Review, and Meta-analysis.
机构信息
Medical Oncology and Hematology, Princess Margaret Cancer Centre, and Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
Medical Oncology and Hematology, Princess Margaret Cancer Centre, and Department of Medicine, University of Toronto, Toronto, Ontario, Canada; Epidemiology, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
出版信息
Clin Lung Cancer. 2021 Sep;22(5):390-407. doi: 10.1016/j.cllc.2021.01.002. Epub 2021 Jan 10.
BACKGROUND
Systemic inflammatory response (SIR) may influence prognosis in epidermal growth factor receptor (EGFR)-mutated (m) non-small-cell lung cancer (NSCLC). Pretreatment SIR markers (neutrophil-to-lymphocyte ratio [NLR], platelet-to-lymphocyte ratio, lymphocyte-to-monocyte ratio [LMR], lactate dehydrogenase [LDH], and lung immune prognostic index [LIPI]) were assessed as prognostic factors in NSCLC survival.
PATIENTS AND METHODS
Retrospective survival analysis (overall survival [OS] and progression-free survival [PFS]) of EGFR-mutated NSCLC patients at Princess Margaret Cancer Centre were performed separately for early (I-IIIa) and late (IIIb-IV) stage disease for individual SIR variables, dichotomized by optimal cutoff points by Kaplan-Meier survival analysis and multivariable Cox proportional hazard modeling. A systematic review and meta-analysis of known SIR studies in patients with late-stage EGFR-mutated were also performed.
RESULTS
From 2012 to 2019, in 530 patients, significant adjusted hazard ratios (aHR) for OS comparing high versus low NLR were 2.12 for early stage and 1.79 for late stage disease. Additionally, late stage cohorts had significant associations, as follows: high versus low derived NLR, aHR = 1.53; LMR, aHR = 0.62; LDH, aHR = 2.04; and LIPI, aHR = 2.04. Similar patterns were found for PFS in early stage NLR (aHR = 1.96) and late stage NLR (aHR = 1.46), while for PFS, only late stage derived NLR (aHR = 1.34), LDH (aHR = 1.75), and LIPI (aHR = 1.66) were significant. A meta-analysis confirmed that NLR, LMR, LDH, and LIPI were all significantly associated with OS and PFS in the late stage.
CONCLUSION
This primary study and meta-analysis demonstrated that LMR and LDH were significantly associated with late stage EGFR-mutated NSCLC outcomes, and the LIPI scoring system was prognostic. NLR remained an independent prognostic factor across all stages and could represent an early marker of immuno-oncology interactions.
背景
全身炎症反应（SIR）可能会影响表皮生长因子受体（EGFR）突变（m）非小细胞肺癌（NSCLC）的预后。在 NSCLC 生存中，预处理 SIR 标志物（中性粒细胞与淋巴细胞比值 [NLR]、血小板与淋巴细胞比值、淋巴细胞与单核细胞比值 [LMR]、乳酸脱氢酶 [LDH]和肺免疫预后指数 [LIPI]）被评估为预后因素。
患者和方法
对玛格丽特公主癌症中心 EGFR 突变 NSCLC 患者的回顾性生存分析（总生存期 [OS]和无进展生存期 [PFS]）分别针对早期（I-IIIa）和晚期（IIIb-IV）疾病进行，对每个 SIR 变量进行单独分析，并通过 Kaplan-Meier 生存分析和多变量 Cox 比例风险建模对最佳截断点进行二分。还对晚期 EGFR 突变患者的已知 SIR 研究进行了系统评价和荟萃分析。
结果
在 2012 年至 2019 年间，在 530 名患者中，早期和晚期疾病 NLR 高 versus 低的调整后危险比（aHR）分别为 2.12 和 1.79。此外，晚期队列存在显著相关性，如下所示：高 versus 低 NLR 衍生比值，aHR=1.53；LMR，aHR=0.62；LDH，aHR=2.04；LIPI，aHR=2.04。早期阶段 NLR（aHR=1.96）和晚期阶段 NLR（aHR=1.46）的 PFS 也存在相似模式，而晚期阶段 NLR（aHR=1.34）、LDH（aHR=1.75）和 LIPI（aHR=1.66）的 PFS 仅具有显著相关性。荟萃分析证实，NLR、LMR、LDH 和 LIPI 均与晚期 NSCLC 的 OS 和 PFS 显著相关。
结论
本研究和荟萃分析表明，LMR 和 LDH 与晚期 EGFR 突变 NSCLC 结果显著相关，LIPI 评分系统具有预后价值。NLR 是所有阶段的独立预后因素，可能代表免疫肿瘤学相互作用的早期标志物。
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