Prognostic and clinicopathologic significance of neutrophil-to-lymphocyte ratio in esophageal squamous cell carcinoma: evidence from a meta-analysis

Figures & data

Figure 1 The flow diagram of the included studies.

Abbreviation: NLR, neutrophil-to-lymphocyte ratio.

Table 1 Main characteristics of all the studies included in the meta-analysis

Study	Year	Study design	Country	Study period	No (male/female)	Mean age ± SD (years)	Survival type	CV	Treatment	Stage	HR
Feng et al^Citation23	2014	R	People’s Republic of China	2005–2008	483 (411/72)	59.1±8.0 (34–80)	OS	3.5	Surgery	NR*	M/U
Hirahara et al^Citation18	2015	R	Japan	2006–2014	141 (127/14)	NR (≥70, n=46; <70, n=95)	OS	2.5	Surgery	I–III	U
Han et al^Citation24	2015	R	People’s Republic of China	2007–2008	218 (177/41)	60.5 (32–84)	OS, DFS	2.6	Mix	I–III	M/U
Shao et al^Citation6	2015	R	People’s Republic of China	2002–2012	633 (484/149)	60 (37–83)	OS	1.7	Surgery	I–III	M/U
He et al^Citation17	2016	NR	People’s Republic of China	2000–2010	317 (268/49)	60 (37–77)	OS, DFS	3.3	Mix	I–IV	M
Ji et al^Citation22	2016	R	People’s Republic of China	2009–2012	41 (38/3)	56.6±7.2	OS, PFS	5	Mix	I–III	M/U
Kosumi et al^Citation21	2016	R	Japan	2005–2011	283 (248/35)	NR (≥65, n=165; <65, n=118)	OS	1.94	Mix	I–IV	M/U
Toyokawa et al^Citation7	2016	R	Japan	2000–2014	185 (152/33)	64 (59–70)	OS	3.612	Mix	I–IV	M
Zhang et al^Citation20	2016	R	People’s Republic of China	2006–2011	212 (166/46)	60 (37–81)	OS, PFS	3	Chemoradiotherapy	NR**	M

Notes: R: retrospective study; M: HR from multivariate analysis; U: HR from univariate analysis; Mix: mixed treatment with at least two anticancer methods including chemotherapy, surgery, radiotherapy, or chemoradiotherapy.

* No patients had metastasis.

** A few patients had metastasis.

Abbreviations: CV, cutoff value; HR, hazard ratio; OS, overall survival; NR, not reported; DFS, disease-free survival; PFS, progression-free survival; SD, standard deviation.

Figure 2 Meta-analysis of the association between NLR and OS in ESCC. Results are presented as individual and pooled HR, and 95% CI.

Abbreviations: NLR, neutrophil-to-lymphocyte ratio; OS, overall survival; ESCC, esophageal squamous cell carcinoma; HR, hazard ratio; CI, confidence interval; ES, effect size.

Table 2 Summary of the meta-analysis results

Factor	No of studies	No of patients	Effects model	HR (95% CI)	P-value	Heterogeneity
						I^2 (%)	Ph
OS
Overall	9	2,513	Fixed	1.314 (1.164–1.484)	<0.001	0	0.593
Country
People’s Republic of China	6	609	Fixed	1.291 (1.132–1.472)	<0.001	0	0.533
Japan	3	1,904	Fixed	1.463 (1.063–2.015)	0.02	0	0.394
Treatment
Surgery	3	1,257	Fixed	1.283 (1.077–1.528)	0.005	0	0.902
Mixed	5	1,044	Fixed	1.404 (1.152–1.71)	0.001	26.4	0.245
Cutoff value
≤2.5	3	1,057	Fixed	1.345 (1.098–1.647)	0.004	12.2	0.32
>2.5	6	1,456	Fixed	1.297 (1.114–1.51)	0.001	0	0.531
Sample size
<300	6	1,080	Fixed	1.316 (1.083–1.598)	0.006	20.4	0.28
>300	3	1,433	Fixed	1.313 (1.124–1.534)	0.001	0	0.905
Survival analysis
Univariate	6	1,799	Fixed	1.335 (1.149–1.55)	<0.001	16	0.311
Multivariate	8	2,372	Fixed	1.321 (1.167–1.495)	<0.001	0	0.502
DFS
Overall	2	525	Fixed	1.268 (1.01–1.592)	0.041	0	0.845
PFS
Overall	2	253	Fixed	1.221 (0.9–1.655)	0.2	0	0.484

Note: P_h: P-value of Q test for heterogeneity.

Abbreviations: HR, hazard ratio; CI, confidence interval; OS, overall survival; DFS, disease-free survival; PFS, progression-free survival; No, number.

Table 3 Meta-analysis of the association between NLR and clinicopathologic features of ESCC

Variable	No of studies	No of patients	OR (95% CI)	P-value	Heterogeneity		Publication bias Begg’s P
					I^2 (%)	Ph
TNM stage (III–IV vs I–II)	3	576	1.578 (1.11–2.243)	0.011	0	0.623	1
Tumor differentiation (poor vs moderate/high)	4	1,059	1.51 (1.106–2.061)	0.01	35.1	0.202	0.734
Depth of invasion (T3–T4 vs T1–T2)	4	954	2.742 (1.997–3.765)	<0.001	14.9	0.318	0.734
Tumor size (>3 cm vs <3 cm)	3	1,018	2.825 (1.675–4.764)	<0.001	62.9	0.067	1
Lymph node metastasis (yes vs no)	5	1,271	1.424 (0.862–2.355)	0.168	68.9	0.012	0.806
Vascular invasion (yes vs no)	2	524	1.383 (0.859–2.228)	0.182	0	0.336	1

Note: P_h: P-value of Q test for heterogeneity.

Abbreviations: NLR, neutrophil-to-lymphocyte ratio; ESCC, esophageal squamous cell carcinoma; OR, odds ratio; CI, confidence interval; TNM, tumor node metastasis; No, number.

Figure 3 (A) Begg’s funnel plot for the assessment of potential publication bias. (B) Sensitivity analysis of the relationship between NLR and OS.

Abbreviations: NLR, neutrophil-to-lymphocyte ratio; OS, overall survival; SE, standard error; lnhr, natural logarithm of hazard ratio; CI, confidence interval.

FengJFHuangYChenQXPreoperative platelet lymphocyte ratio (PLR) is superior to neutrophil lymphocyte ratio (NLR) as a predictive factor in patients with esophageal squamous cell carcinomaWorld J Surg Oncol2014125824641770

 PubMed Web of Science ®Google Scholar

HiraharaNMatsubaraTHayashiHTakaiKFujiiYTajimaYImpact of inflammation-based prognostic score on survival after curative thoracoscopic esophagectomy for esophageal cancerEur J Surg Oncol201541101308131526235238

 PubMed Web of Science ®Google Scholar

HanLHJiaYBSongQXWangJBWangNNChengYFPrognostic significance of preoperative lymphocyte-monocyte ratio in patients with resectable esophageal squamous cell carcinomaAsian Pac J Cancer Prev20151662245225025824745

 PubMedGoogle Scholar

ShaoYNingZChenJPrognostic nomogram integrated systemic inflammation score for patients with esophageal squamous cell carcinoma undergoing radical esophagectomySci Rep201551881126689680

 PubMed Web of Science ®Google Scholar

HeYFLuoHQWangWPreoperative NLR and PLR in the middle or lower ESCC patients with radical operationEur J Cancer Care (Engl) Epub20163710.1111/ecc.12445

 PubMedGoogle Scholar

JiWHJiangYLJiYLLiBMaoWMPrechemotherapy neutrophil: lymphocyte ratio is superior to the platelet: lymphocyte ratio as a prognostic indicator for locally advanced esophageal squamous cell cancer treated with neoadjuvant chemotherapyDis Esophagus201629540341125625421

 PubMedGoogle Scholar

KosumiKBabaYIshimotoTNeutrophil/lymphocyte ratio predicts the prognosis in esophageal squamous cell carcinoma patientsSurg Today201646440541326036223

 PubMed Web of Science ®Google Scholar

ToyokawaTKuboNTamuraTThe pretreatment Controlling Nutritional Status (CONUT) score is an independent prognostic factor in patients with resectable thoracic esophageal squamous cell carcinoma: results from a retrospective studyBMC Cancer20161672227599460

 PubMed Web of Science ®Google Scholar

ZhangPXiMZhaoLComparison of two inflammation-based prognostic scores in patients with thoracic esophageal cancer undergoing chemoradiotherapyInt J Clin Exp Med20169217641771

 Web of Science ®Google Scholar