NLR和PLR对接受一线含铂化疗的小细胞肺癌患者预后影响的Meta分析

doi:10.13481/j.1671-587X.20210526

摘要/Abstract

摘要： 目的

探讨中性粒细胞/淋巴细胞比值（NLR）和血小板/淋巴细胞比值（PLR）与接受一线含铂化疗的小细胞肺癌（SCLC）患者预后的关联性，阐明NLR和PLR在SCLC患者预后中的意义。

方法

检索PubMed、EMbase、Web of Science、Cochrane Library和中国知网（CNKI）数据库，检索时限从建库到2021年3月，收集接受一线含铂化疗的SCLC［包括局限期SCLC（LS-SCLC）和广泛期SCLC（ES-SCLC）］患者的临床研究。使用STATA 14.0软件对符合纳入与排除标准的研究进行Meta分析，观察NLR和PLR在不同疾病分期和不同病理类型SCLC患者的预后作用。

结果

共检索1 012篇文献，最终纳入11篇文献共3 634例SCLC患者。高NLR组患者的总生存期（OS）［风险比（HR）=1.45，95%置信区间（95%CI）：1.26~1.67，P<0.01］和无进展生存期（PFS）（HR=1.53，95%CI：1.29~1.82，P<0.01）明显低于低NLR组；高PLR组患者的OS与低PLR组患者比较差异无统计学意义（HR=1.17，95%CI：0.87~1.56，P=0.293）。亚组分析，在不同疾病分期、不同病理类型、不同种族、分析模式和NLR 临界（cutoff）值≥4的亚组，高NLR组患者的OS明显低于低NLR组（P<0.05）；在LS-SCLC人群和PLR cutoff值<160人群，高PLR组患者的OS明显低于低PLR组（P<0.01）。

结论

在接受一线含铂化疗的SCLC患者中，高NLR与SCLC患者的预后不良有关，高PLR与LS-SCLC患者的预后不良有关。

关键词: 中性粒细胞/淋巴细胞比值, 血小板/淋巴细胞比值, 癌，小细胞肺, Meta分析

Abstract: Objective

To investigate the associations of the neutrophil/lymphocyte ratio（NLR） and platelet/lymphocyte ratio（PLR） with the prognosis in the small-cell lung cancer（SCLC） patients received platinum-based first-line chemotherapy， and to clarify the significance of NLR and PLR in the prognosis of the SCLC patients.

Methods

Literature retrieval were conducted in PubMed， EMbase， Web of Science， Cochrane Library and China National Knowledge Internet（CNKI）databases. The retrieval period was from the establishment to March 2021. The clinical studies of patients with SCLC including limited stage SCLC （LS-SCLC） and extensive stage SCLC（ES-SCLC） received platinum-based first-line chemotherapy. Meta-analysis was performed on the literatures that met the inclusion and exclusion criteria by STATA 14.0 software， and the prognostic effects of NLR and PLR in the SCLC patients with different disease stages and pathological types were observed.

Results

A total of 1 012 literatures were retrieved. Finally， eleven studies encompassing 3 634 SCLC patients were included. The combined outcomes demonstrated that the overall survival（OS）［hazard ratio（HR）=1.45， 95%confidence interval（95%CI）： 1.26－1.67，P<0.01］ and progression-free survival（PFS）（HR=1.53，95%CI：1.29－1.82，P<0.01） of the patients in high NLR group were lower than those in low NLR group， while there was no difference in the OS between high NLR group and low NLR group（HR=1.17， 95%CI：0.87－1.56，P=0.293）. In subgroup analysis， the OS in higher NLR group in different stages，different pathological types， different regions， analysis modes，and NLR cutoff value≥4 in subgroups were lower than those in lower NLR group（P<0.05）；the OS in LS-SCLC and PLR cutoff value<160 patients in higher NLR group were lower than those in lower PLR group.

Conclusion

In the SCLC patients received platinum-based first-line chemotherapy， higher NLR is associated with poor prognosis in the SCLC patients， and higher PLR is associated with poor prognosis in the LS-SCLC patients.

Key words: neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, cancer，small-cell lung, Meta-analysis

中图分类号:

R734.2

万广财,孙洪帅,朱华,于秀艳. NLR和PLR对接受一线含铂化疗的小细胞肺癌患者预后影响的Meta分析[J]. 吉林大学学报(医学版), 2021, 47(5): 1264-1272.

Guangcai WAN,Hongshuai SUN,Hua ZHU,Xiuyan YU. Effect of NLR and PLR on prognosis of small-cell lung cancer patients received platinum-based first-line chemotherapy: A Meta-analysis[J]. Journal of Jilin University(Medicine Edition), 2021, 47(5): 1264-1272.

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参考文献 33

1	PAZ-ARES L， DVORKIN M， CHEN Y， et al. Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer （CASPIAN）：a randomised， controlled， open-label， phase 3 trial［J］.Lancet，2019， 394（10212）：1929-1939.
2	KASMANN L， ABDO R， EZE C， et al. External validation of a survival score for limited-stage small cell lung cancer patients treated with chemoradiotherapy［J］. Lung， 2020， 198（1）： 201-206.
3	WU Q， XIONG Y T， ZHANG S J， et al. A meta-analysis of the efficacy and toxicity of twice-daily vs. once-daily concurrent chemoradiotherapy for limited-stage small cell Lung Cancer Based on randomized controlled trials［J］. Front Oncol， 2019， 9： 1460.
4	HORN L， MANSFIELD A S， SZCZESNA A， et al. First-line atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer［J］. N Engl J Med， 2018， 379（23）： 2220-2229.
5	SHEN X B， WANG Y， SHAN B J， et al. Prognostic significance of platelet-to-lymphocyte ratio （PLR） and mean platelet volume （MPV） during etoposide-based first-line treatment in small cell lung cancer patients［J］. 2019， 11： 8965-8975.
6	SACDALAN D B， LUCERO J A， SACDALAN D L. Prognostic utility of baseline neutrophil-to-lymphocyte ratio in patients receiving immune checkpoint inhibitors： a review and meta-analysis［J］. Onco Targets Ther， 2018， 11： 955-965.
7	BAGLEY S J， KOTHARI S， AGGARWAL C， et al. Pretreatment neutrophil-to-lymphocyte ratio as a marker of outcomes in nivolumab-treated patients with advanced non-small-cell lung cancer ［J］.Lung Cancer，2017，106： 1-7.
8	BOWEN R C， LITTLE N A B， HARMER J R， et al. Neutrophil-to-lymphocyte ratio as prognostic indicator in gastrointestinal cancers： a systematic review and meta-analysis［J］. Oncotarget， 2017， 8（19）： 32171-32189.
9	KANG M H， GO S I， SONG H N， et al. The prognostic impact of the neutrophil-to-lymphocyte ratio in patients with small-cell lung cancer［J］. Br J Cancer， 2014， 111（3）： 452-460.
10	SAKIN A， SAHIN S， YASAR N， et al. The relation between hemogram parameters and survival in extensive-stage small cell lung cancer［J］. Oncol Res Treat， 2019， 42（10）： 506-515.
11	PAN Z C， ZHANG L， LIU C， et al. Cisplatin or carboplatin？ Neutrophil to lymphocyte ratio may serve as a useful factor in small cell lung cancer therapy selection［J］. Oncol Lett， 2019， 18（2）： 1513-1520.
12	XIE D， MARKS R， ZHANG M， et al. Nomograms predict overall survival for patients with small-cell lung cancer incorporating pretreatment peripheral blood markers［J］. J Thorac Oncol， 2015， 10（8）： 1213-1220.
13	MOHER D， LIBERATI A， TETZLAFF J， et al. Preferred reporting items for systematic reviews and meta-analyses： the PRISMA statement［J］. J Clin Epidemiol， 2009， 62（10）： 1006-1012.
14	CAO S B， JIN S， SHEN J， et al. Selected patients can benefit more from the management of etoposide and platinum-based chemotherapy and thoracic irradiation-a retrospective analysis of 707 small cell lung cancer patients［J］. Oncotarget， 2017， 8（5）： 8657-8669.
15	KASMANN L， BOLM L， SCHILD S E， et al. Neutrophil-to-lymphocyte ratio predicts outcome in limited disease small-cell lung cancer ［J］. Lung， 2017， 195（2）： 217-224.
16	PENG H， LUO X. Prognostic significance of elevated pretreatment systemic inflammatory markers for patients with prostate cancer： a meta-analysis［J］. Cancer Cell Int， 2019， 19： 70.
17	GUO W， LU X， LIU Q， et al. Prognostic value of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio for breast cancer patients： an updated meta-analysis of 17079 individuals［J］. Cancer Med， 2019， 8（9）： 4135-4148.
18	YANG S S， ZHAO K， DING X， et al. Prognostic significance of hematological markers for patients with nasopharyngeal carcinoma： a meta-analysis［J］.J Cancer， 2019， 10（11）： 2568-2577.
19	WEN Q， MENG X， XIE P， et al. Evaluation of factors associated with platinum-sensitivity status and survival in limited-stage small cell lung cancer patients treated with chemoradiotherapy［J］. Oncotarget，2017，8（46）： 81405-81418.
20	SUZUKI R， LIN S H， WEI X， et al. Prognostic significance of pretreatment total lymphocyte count and neutrophil-to-lymphocyte ratio in extensive-stage small-cell lung cancer［J］. Radiother Oncol， 2018， 126（3）： 499-505.
21	SUZUKI R， WEI X， ALLEN P K， et al. Prognostic significance of total lymphocyte count， Neutrophil-to-lymphocyte ratio， and Platelet-to-lymphocyte ratio in Limited-stage Small-cell lung cancer［J］. Clin Lung Cancer， 2019， 20（2）： 117-123.
22	SHAO N， CAI Q. High pretreatment neutrophil-lymphocyte ratio predicts recurrence and poor prognosis for combined small cell lung cancer［J］. Clin Transl Oncol， 2015， 17（10）： 772-778.
23	WANG X， JIANG R， LI K. Prognostic significance of pretreatment laboratory parameters in combined small-cell lung cancer［J］.Cell Biochem Biophys，2014，69（3）： 633-640.
24	HARAM A， BOLAND M R， KELLY M E， et al. The prognostic value of neutrophil-to-lymphocyte ratio in colorectal cancer： a systematic review［J］. J Surg Oncol， 2017， 115（4）： 470-479.
25	LUCCA I， JICHLINSKI P， SHARIAT S F， et al. The neutrophil-to-lymphocyte ratio as a prognostic factor for patients with urothelial carcinoma of the bladder following radical cystectomy： validation and meta-analysis［J］. Eur Urol Focus， 2016， 2（1）： 79-85.
26	YANG T， ZHU J， ZHAO L， et al. Lymphocyte to monocyte ratio and neutrophil to lymphocyte ratio are superior inflammation-based predictors of recurrence in patients with hepatocellular carcinoma after hepatic resection［J］. J Surg Oncol， 2017， 115（6）： 718-728.
27	DIEM S， SCHMID S， KRAPF M， et al. Neutrophil-to-Lymphocyte ratio （NLR） and Platelet-to-Lymphocyte ratio （PLR） as prognostic markers in patients with non-small cell lung cancer （NSCLC） treated with nivolumab［J］. Lung Cancer， 2017， 111： 176-181.
28	FERRUCCI P F， ASCIERTO P A， PIGOZZO J，et al. Baseline neutrophils and derived neutrophil-to-lymphocyte ratio： prognostic relevance in metastatic melanoma patients receiving ipilimumab［J］. Ann Oncol， 2016， 27（4）： 732-738.
29	ZHANG Q， QU Y L， LIU H Y， et al. Initial platelet-to-lymphocyte count as prognostic factor in limited-stage small cell lung cancer［J］. Biomark Med， 2019， 13（4）： 249-258.
30	ROTONDO R， BERTOLOTTO M， BARISIONE G， et al. Exocytosis of azurophil and arginase 1-containing granules by activated polymorphonuclear neutrophils is required to inhibit T lymphocyte proliferation［J］. J Leukoc Biol， 2011， 89（5）： 721-727.
31	NIESWANDT B， HAFNER M， ECHTENACHER B， et al. Lysis of tumor cells by natural killer cells in mice is impeded by platelets［J］.Cancer Res，1999，59（6）：1295-1300.
32	YANG H B， XING M， MA L N， et al. Prognostic significance of neutrophil-lymphocyteratio/platelet-lymphocyteratioin lung cancers： a meta-analysis［J］. Oncotarget， 2016， 7（47）：76769-76778.
33	万广财，孙洪帅，朱华，等. 中性粒细胞/淋巴细胞比值与接受EGFR-TKIs治疗的非小细胞肺癌患者预后关系的Meta分析［J］.吉林大学学报（医学版），2020，46（6）：1267-1273.

First author	Publication year	Region	Nation	Sample size	Age(year)
SAKIN,et al ^[10]	2019	Asia	Turkey	113	Median 61(35－81)
PAN,et al ^[11]	2019	Asia	China	73	Mean 61.64(39－83)
SUZUKI,et al ^[20]	2018	North America	America	252	Median 63(56－69)
SUZUKI,et al ^[21]	2018	North America	America	122	Median 65 (60－72)
WEN,et al ^[19]	2017	Asia	China	452	Median 56(27－82)
KASMANN,et al ^[15]	2017	Europe	Germany	65	NG
CAO,et al ^[14]	2016	Asia	China	707	Mean 56.24(23－75)
SHAO,et al ^[22]	2015	Asia	China	112	Median 62(45－82)
XIE,et al ^[12]	2015	North America	America	938	Median 68(27－91)
KANG,et al ^[9]	2014	Asia	Korea	187	Median 68(43－84)
WANG,et al ^[23]	2014	Asia	China	613	Mean 59.31
First author	Follow-up /months	Analysis mode	NLR cutoff	PLR cutoff	Outcome endpoint	NOS score
SAKIN,et al ^[10]	Median 6(1－33)	MV+UV	3.00	150.0	OS	7
PAN,et al ^[11]	NG	UV	3.80	NG	OS^KM, PFS^KM	6
SUZUKI,et al ^[20]	NG	MV+UV	4.00	194.7	OS	8
SUZUKI,et al ^[21]	NG	MV+UV	2.90	140.1	OS	8
WEN,et al ^[19]	Median 35.1	MV	4.00	NG	OS，PFS	9
KASMANN,et al ^[15]	NG	MV	4.00	180.0	OS	7
CAO,et al ^[14]	NG	MV	3.18	176.5	OS	9
SHAO,et al ^[22]	Median 68.5	MV	4.15	150.0	OS，PFS	8
XIE,et al ^[12]	Median 10.8	MV	5.00	210.0	OS	7
KANG,et al ^[9]	Median 40.28(2.60－89.20)	MV	4.00	160.0	OS，PFS	8
WANG,et al ^[23]	NG	MV	3.00	150.0	OS	7

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