Prognosis of neutrophil-to-lymphocyte ratio in clinical early-stage tongue (cT1/T2N0) cancer

Figures & data

Table 1 Clinicopathological characteristics and outcomes of 262 patients who were diagnosed with clinical early-stage tongue cancer (cT1/T2N0)

Factor	Number (%)
Gender
Male	228 (87.0)
Female	34 (13.0)
Drinks alcohol
No	182 (69.5)
Yes	80 (30.5)
Betel nut chewing
No	69 (26.3)
Yes	193 (73.7)
Smoker
No	64 (24.4)
Yes	198 (75.6)
T classification
T1	149 (56.9)
T2	113 (43.1)
N classification
N0	205 (78.2)
N+	57 (21.8)
Tumor thickness
<5 mm	101 (38.5)
≥5 mm	161 (61.5)
PNI
No	214 (81.7)
Yes	48 (18.3)
LVI
No	232 (88.5)
Yes	30 (11.5)
ENE
No	245 (93.5)
Yes	17 (6.5)
LND
<0.031	218 (83.2)
≥0.031	44 (16.8)
NLR
<2.95	214 (81.7)
≥2.95	48 (18.3)

Abbreviations: ENE, extranodal extension; LND, lymph node density; LVI, lymphovascular invasion; NLR, neutrophil-to-lymphocyte ratio; PNI, perineural invasion.

Figure 1 Receiver operating characteristic curve of (A) NLR and (B) LND for predicting the survival of early-stage tongue cancer patients with AUC equal to 68.1% and 86.9%, respectively.

Abbreviations: AUC, area under the curve; LND, lymph node density; NLR, neutrophil-to-lymphocyte ratio.

Figure 2 Kaplan–Meier analysis of patients with early-stage tongue cancer, by NLR with cutting in 2.95.

Note: (A) Overall survival, (B) disease-specific survival, and (C) disease-free survival.
Abbreviations: OS, overall survival; DSS, disease-specific survival; DFS, disease-free survival; NLR, neutrophil-to-lymphocyte ratio.

Table 2 Association analysis between NLR and other clinical/pathological factors

Factor	NLR		P-value
	<2.95	≥2.95
Gender			0.913
Male	186	42
Female	28	6
Drinks alcohol			0.905
No	149	33
Yes	65	15
Betel nut chewing			0.041
No	62	7
Yes	152	41
Smoker			0.521
No	54	10
Yes	160	38
T classification			0.007
T1	130	19
T2	84	29
N classification			0.011
N0	174	31
N+	40	17
Tumor thickness			0.005
<5 mm	91	10
≥5 mm	123	38
PNI			<0.001
No	184	30
Yes	30	18
LVI			0.801
No	190	42
Yes	24	6
ENE			0.941
No	200	45
Yes	14	3
LND			0.092
<0.031	182	36
≥0.031	32	12

Abbreviations: ENE, extranodal extension; LND, lymph node density; LVI, lymphovascular invasion; NLR, neutrophil-to-lymphocyte ratio; PNI, perineural invasion.

Figure 3 Kaplan–Meier analysis of patients with early-stage tongue cancer, by LND with cutting in 0.031.

Note: (A) Overall survival, (B) disease-specific survival, and (C) disease-free survival.
Abbreviations: OS, overall survival; DSS, disease-specific survival; DFS, disease-free survival; LND, lymph node density.

Table 3 Univariate survival analysis of prognostic factors

Factor	5-year	OS	5-year	DSS	5-year	DFS
NLR		P<0.001		P=0.002		P=0.004
<2.95	86.0%		90.4%		85.3%
≥2.95	57.6%		73.3%		67.7%
LND		P<0.001		P<0.001		P<0.001
<0.031	86.2%		92.8%		87.8%
≥0.031	54.2%		60.7%		54.1%
T classification		P<0.001		P<0.001		P<0.001
T1	88.2%		94.5%		90.5%
T2	70.9%		77.7%		71.0%
N classification		P<0.001		P<0.001		P<0.001
N0	85.3%		92.3%		87.1%
N+	64.6%		69.8%		64.6%
Tumor thickness		P<0.001		P<0.001		P<0.001
<5 mm	94.8%		100.0%		97.0%
≥5 mm	72.0%		79.3%		72.8%
PNI		P=0.001		P<0.001		P<0.001
No	84.0%		91.8%		87.2%
Yes	65.9%		67.4%		59.5%
LVI		P=0.074		P=0.043		P=0.065
No	88.4%		88.9%		83.8%
Yes	67.1%		74.7%		68.8%
ENE		P<0.001		P<0.001		P<0.001
No	82.7%		89.8%		85.0%
Yes	52.9%		52.9%		41.2%
Drinks alcohol		P=0.078		P=0.383		P=0.15
No	82.9%		88.6%		84.3%
Yes	76.0%		84.7%		77.2%
Betel nut chewing		P=0.003		P=0.055		P=0.009
No	92.8%		94.1%		92.7%
Yes	76.5%		84.9%		78.3%
Smoker		P=0.016		P=0.035		P=0.10
No	92.2%		95.1%		89.0%
Yes	77.1%		84.8%		79.9%

Abbreviations: DFS, disease-free survival; DSS, disease-specific survival; ENE, extranodal extension; LND, lymph node density; LVI, lymphovascular invasion; NLR, neutrophil-to-lymphocyte ratio; OS, overall survival; PNI, perineural invasion.

Table 4 Multivariate analysis of prognostic factors for 5-year overall survival

Factor	Hazard ratio	95% CI	P-value
NLR			0.003
<2.95	1
≥2.95	2.292	(1.326–3.962)
LND			0.001
<0.031	1
≥0.031	2.573	(1.476–4.487)
Tumor thickness			0.004
<5 mm	1
≥5 mm	3.383	(1.482–7.722)

Abbreviations: LND, lymph node density; NLR, neutrophil-to-lymphocyte ratio.

Table 5 Multivariate analysis of prognostic factors for 5-year disease-specific survival

Factor	Hazard ratio	95% CI	P-value
NLR			0.048
<2.95	1
≥2.95	2.106	(1.007–4.405)
LND			<0.001
<0.031	1
≥0.031	5.157	(2.551–10.427)
T classification			0.006
T1	1
T2	3.196	(1.39–7.352)
LVI			0.036
No	1
Yes	2.499	(1.06–5.892)

Abbreviations: LND, lymph node density; LVI, lymphovascular invasion; NLR, neutrophil-to-lymphocyte ratio.

Table 6 Multivariate analysis of prognostic factors for 5-year disease-free survival

Factor	Hazard ratio	95% CI	P-value
NLR			0.043
<3.0	1
≥3.0	1.914	(1.02–3.595)
LND			0.070
<0.031	1
≥0.031	1.987	(0.946–4.171)
Tumor thickness			0.002
<5 mm	1
≥5 mm	6.909	(2.083–22.917)
ENE			0.057
No	1
Yes	2.371	(0.976–5.759)

Abbreviations: ENE, extranodal extension; LND, lymph node density; NLR, neutrophil-to-lymphocyte ratio.

Table 7 Different studies about the lymph node density in head and neck cancer

Reference	Site	Case number	Cutoff for LND	5-year OS	5-year DSS	5-year DFS
Gil et al^Citation28	Oral cancer	386	0.06	58% vs 28%	65% vs 34%	–
Shrime et al^Citation29	Oral cancer	143	0.13	44.7% vs 16.1%	–	–
Kim et al^Citation30	Oral cancer	78	0.06	75% vs 38%	80% vs 47%	–
Amar et al^Citation31	Oral cancer	182	0.06	–	–	44% vs 28%
Liao et al^Citation32	Oral cancer	148	0.048	66% vs 21%	78% vs 28%	75% vs 24%
Patel et al^Citation33	Oral cancer	4,254	0.07	49% vs 35%	60% vs 41%	–
Rudra et al^Citation34	HNSCC	38	0.2	79% vs 50%	–	89% vs 68%
Ong et al^Citation35	Tongue cancer	99	0.06	58% vs 47%	58% vs 48%	–
Our current study	Early tongue cancer	262	0.031	86% vs 54%	93% vs 61%	88% vs 54%

Abbreviations: DFS, disease-free survival; DSS, disease-specific survival; HNSCC, head and neck squamous cell carcinoma; LND, lymph node density; OS, overall survival.

Table 8 Different studies about neutrophil-to-lymphocyte ratio in head and neck cancer

Reference	Site	Case number	Cutoff for NLR	Outcome measurement
He et al^Citation13	Nasopharyngeal carcinoma	1,410	1.54	OS and PFS
Fang et al^Citation14	Oral cancer	226	2.44	OS and DFS
Perisanidis et al^Citation15	Locally advanced oral cancer	97	1.9	DSS
Rassouli et al^Citation17	HNSCC	273	4.27	DSS
Salim et al^Citation18	Recurrent/metastatic HNSCC	79	2.93	DSS
Haddad et al^Citation16	Locally advanced HNSCC	46	5	OS, MFS, LRRFS
Our current study	Early tongue cancer	262	2.95	OS, DSS, DFS

Abbreviations: DFS, disease-free survival; DSS, disease-specific survival; HNSCC, head and neck squamous cell carcinoma; LRRFS, local/regional relapse-free survival; MFS, metastatic-free survival; NLR, neutrophil-to-lymphocyte ratio; OS, overall survival; PFS, progression free survival.

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