Peripheral venous blood neutrophil-to-lymphocyte ratio predicts survival in patients with advanced gastric cancer treated with neoadjuvant chemotherapy

Figures & data

Table 1 Demographic and clinicopathological characteristics of 91 patients with gastric cancer

Parameters	N	Low NLR <2.17	High NLR ≥2.17	χ^2	P-value
Age, years				3.963	0.046
<57	45	27 (60.0%)	18 (40.0%)
≥57	46	18 (39.1%)	28 (60.9%)
Gender				5.275	0.022
Male	70	30 (42.9%)	40 (57.1%)
Female	21	15 (71.4%)	6 (28.6%)
BMI				0.011	0.916
<22.32	45	22 (48.9%)	23 (51.1%)
≥22.32	46	23 (50.0%)	23 (50.0%)
ABO blood type				7.627	0.055*
A	23	15 (65.2%)	8 (34.8%)
B	32	12 (37.5%)	20 (62.5%)
O	27	11 (40.7%)	16 (59.3%)
AB	9	7 (77.8%)	2 (22.2%)
Chemotherapy regimen				2.032	0.154
SOX	35	14 (40.0%)	21 (60.0%)
XELOX	56	31 (55.4%)	25 (44.6%)
Radical resection				1.673	0.433
R0	51	26 (51.0%)	25 (49.0%)
R1	21	8 (38.1%)	13 (61.9%)
R2	19	11 (57.9%)	8 (42.1%)
Type of surgery				1.707	0.462*
Distal gastrectomy	52	24 (46.2%)	28 (53.8%)
Proximal gastrectomy	6	2 (33.3%)	4 (66.7%)
Total gastrectomy	33	19 (57.6%)	14 (42.4%)
Differentiation				5.656	0.066*
Poorly differentiated	54	30 (55.6%)	24 (44.4%)
Moderately differentiated	32	15 (46.9%)	17 (53.1%)
Well differentiated	5	0 (0%)	5 (100.0%)
Primary tumor site				0.133	0.936
Upper 1/3	11	5 (45.5%)	6 (54.5%)
Middle 1/3	31	15 (48.4%)	16 (51.6%)
Lower 1/3	49	25 (51.0%)	24 (49.0%)
Pathology				8.297	0.066*
Adenocarcinoma	64	30 (46.9%)	34 (53.1%)
Mucinous carcinoma	10	2 (20.0%)	8 (80.0%)
Signet ring cell carcinoma	12	9 (75.0%)	3 (25.0%)
Others	5	4 (80.0%)	1 (20.0%)
Clinical TNM classification
T stage					1.000*
T3	6	3 (50.0%)	3 (50.0%)
T4	85	42 (49.4%)	43 (50.6%)
N stage				0.925	0.630
N0	24	10 (41.7%)	14 (58.3%)
N1	51	26 (51.0%)	25 (49.0%)
N2	16	9 (56.2%)	7 (43.8%)
TNM stage					1.000*
II	2	1 (50.0%)	1 (50.0%)
III	89	44 (49.4%)	45 (50.6%)
Pathological TNM classification
T stage				8.977	0.077*
T0	5	5 (100.0%)	0 (0%)
T1	7	4 (57.1%)	3 (42.9%)
T2	14	9 (64.3%)	5 (35.7%)
T3	43	16 (37.2%)	27 (62.8%)
T4	22	11 (50.0%)	11 (50.0%)
N stage				1.844	0.605
N0	24	14 (58.3%)	10 (41.7%)
N1	23	9 (39.1%)	14 (60.9%)
N2	15	7 (46.7%)	8 (53.3%)
N3	29	15 (51.7%)	14 (48.3%)
TNM stage				6.482	0.110*
Tis	5	5 (100.0%)	0 (0%)
I	9	5 (55.6%)	4 (44.4%)
II	29	12 (41.4%)	17 (58.6%)
III	45	21 (46.7%)	24 (53.3%)
IV	3	2 (66.7%)	1 (33.3%)
HER-2				1.980	0.159
0−+	54	30 (55.6%)	24 (44.4%)
++−+++	37	15 (40.5%)	22 (59.5%)
Neutrophil count				26.381	<0.001
<3.70	44	34 (77.3%)	10 (22.7%)
≥3.70	47	11 (23.4%)	36 (76.6%)
Lymphocyte count				6.920	0.009
<1.68	43	15 (34.9%)	28 (65.1%)
≥1.68	48	30 (62.5%)	18 (37.5%)
Response				5.740	0.095*
CR	5	5 (100.0%)	0 (0%)
PR	65	30 (46.2%)	35 (53.8%)
SD	7	4 (57.1%)	3 (42.9%)
PD	14	6 (42.9%)	8 (57.1%)

Note:

* Performed using Fisher’s exact test.

Abbreviations: BMI, body mass index; CR, complete response; HER, human epidermal growth factor receptor; NLR, neutrophil-to-lymphocyte ratio; PD, progressive disease; PR, partial response; SD, stable disease; SOX, S-1 plus oxaliplatin; Tis, tumor in situ; TNM, tumor–node–metastasis; XELOX, oxaliplatin and capecitabine.

Figure 1 Disease-free survival of 91 patients with gastric cancer.

Abbreviation: Cum, cumulative.

Figure 2 Overall survival of 91 patients with gastric cancer.

Abbreviation: Cum, cumulative.

Table 2 Univariate and multivariate Cox regression analyses of disease-free survival in 91 patients with gastric cancer

Parameters	Univariate analysis	P-value	Multivariate analysis	P-value
	Hazard ratio (95% CI)		Hazard ratio (95% CI)
Age (<57 vs ≥57 years)	1.026 (0.566–2.932)	0.199	–	–
Gender (male vs female)	0.812 (0.346–1.905)	0.632	–	–
BMI (<22.32 vs ≥22.32)	0.609 (0.315–1.181)	0.142	–	–
ABO blood type (A vs B vs O vs AB)	1.328 (0.868–2.030)	0.191	–	–
Chemotherapy regimen (SOX vs XELOX)	1.199 (0.571–2.515)	0.632	–	–
Radical resection (R0 vs R1 vs R2)	2.274 (1.455–3.555)	<0.001	3.084 (2.001–4.753)	<0.001
Type of surgery (distal vs proximal vs total gastrectomy)	0.802 (0.493–1.305)	0.375	–	–
Differentiation (poorly vs moderately vs well differentiated)	0.595 (0.323–1.093)	0.094	–	–
Primary tumor site (upper vs middle vs low 1/3)	0.544 (0.262–1.132)	0.103	–	–
Pathology (adenocarcinoma vs mucinous vs signet ring cell carcinoma vs others)	1.352 (0.946–1.933)	0.097	–	–
Clinical T stage (T3 vs T4)	4.017 (0.437–36.888)	0.219	–	–
Clinical N stage (N0 vs N1 vs N2)	1.275 (0.747–2.176)	0.373	–	–
Clinical TNM stage (II vs III)	0.166 (0.007–3.876)	0.264	–	–
Pathological T stage (T0 vs T1 vs T2 vs T3 vs T4)	0.876 (0.517–1.485)	0.623	–	–
Pathological N stage (N0 vs N1 vs N2 vs N3)	6.600 (2.066–21.085)	0.001	4.289 (1.682–10.937)	0.002
Pathological TNM stage (Tis vs I vs II vs III vs IV)	3.140 (1.313–7.507)	0.010	2.782 (1.829–4.233)	<0.001
HER2 (0−+ vs ++−+++)	1.867 (0.930–3.748)	0.079	–	–
Neutrophil count (<3.70 vs ≥3.70)	1.355 (0.548–3.351)	0.510	–	–
Lymphocyte count (<1.68 vs ≥1.68)	1.212 (0.536–2.741)	0.644	–	–
NLR (<2.17 vs ≥2.17)	1.282 (0.569–2.889)	0.550	–	–
Response (CR vs PR vs SD vs PD)	1.042 (0.628–1.729)	0.873	–	–

Abbreviations: BMI, body mass index; CI, confidence interval; CR, complete response; HER, human epidermal growth factor receptor; NLR, neutrophil-to-lymphocyte ratio; PD, progressive disease; PR, partial response; SD, stable disease; SOX, S-1 plus oxaliplatin; Tis, tumor in situ; TNM, tumor–node–metastasis; XELOX, oxaliplatin and capecitabine.

Table 3 Univariate and multivariate Cox regression analyses of overall survival in 91 patients with gastric cancer

Parameters	Univariate analysis	P-value	Multivariate analysis	P-value
	Hazard ratio (95% CI)		Hazard ratio (95% CI)
Age (<57 vs ≥57 years)	1.019 (0.978–1.063)	0.371	–	–
Gender (male vs female)	0.914 (0.377–2.213)	0.842	–	–
BMI (<22.32 vs ≥22.32)	0.596 (0.302–1.180)	0.137	–	–
ABO blood type (A vs B vs O vs AB)	0.987 (0.655–1.489)	0.951	–	–
Chemotherapy regimen (SOX vs XELOX)	1.732 (0.809–3.706)	0.157	–	–
Radical resection (R0 vs R1 vs R2)	2.999 (1.895–4.746)	<0.001	2.494 (1.730–3.595)	<0.001
Type of surgery (distal vs proximal vs total gastrectomy)	0.713 (0.440–1.155)	0.170	–	–
Differentiation (poorly vs moderately vs well differentiated)	0.781 (0.421–1.449)	0.434	–	–
Primary tumor site (upper vs middle vs low 1/3)	0.640 (0.314–1.303)	0.218	–	–
Pathology (adenocarcinoma vs mucinous vs signet ring cell carcinoma vs others)	1.181 (0.807–1.728)	0.393	–	–
Clinical T stage (T3 vs T4)	3.456 (0.334–35.745)	0.298	–	–
Clinical N stage (N0 vs N1 vs N2)	1.256 (0.723–2.181)	0.418	–	–
Clinical TNM stage (II vs III)	0.097 (0.004–2.478)	0.158	–	–
Pathological T stage (T0 vs T1 vs T2 vs T3 vs T4)	0.946 (0.552–1.623)	0.841	–	–
Pathological N stage (N0 vs N1 vs N2 vs N3)	7.532 (2.227–25.477)	0.001	4.263 (1.680–10.815)	0.002
Pathological TNM stage (Tis vs I vs II vs III vs IV)	2.704 (1.057–6.921)	0.038	3.401 (1.949–4.746)	<0.001
HER2 (0−+ vs ++−+++)	1.483 (0.776–2.834)	0.234	–	–
Neutrophil count (<3.70 vs ≥3.70)	0.968 (0.413–2.271)	0.941	–	–
Lymphocyte count (<1.68 vs ≥1.68)	1.220 (0.554–2.685)	0.621	–	–
NLR (<2.17 vs ≥2.17)	1.228 (0.539–2.802)	0.625	–	–
Response (CR vs PR vs SD vs PD)	1.135 (0.671–1.919)	0.638	–	–

Abbreviations: BMI, body mass index; CI, confidence interval; CR, complete response; HER, human epidermal growth factor receptor; NLR, neutrophil-to-lymphocyte ratio; PD, progressive disease; PR, partial response; SD, stable disease; SOX, S-1 plus oxaliplatin; Tis, tumor in situ; TNM, tumor–node–metastasis; XELOX, oxaliplatin and capecitabine.

Figure 3 Disease-free survival in relation to NLR.

Abbreviations: Cum, cumulative; NLR, neutrophil-to-lymphocyte ratio.

Figure 4 Overall survival in relation to NLR.

Abbreviations: Cum, cumulative; NLR, neutrophil-to-lymphocyte ratio.

Figure 5 Disease-free survival in relation to neutrophil count.

Abbreviation: Cum, cumulative.

Figure 6 Overall survival in relation to neutrophil count.

Abbreviation: Cum, cumulative.

Figure 7 Disease-free survival in relation to lymphocyte count.

Abbreviation: Cum, cumulative.

Figure 8 Overall survival in relation to lymphocyte count.

Abbreviation: Cum, cumulative.

Table 4 Clinical and laboratory characteristics as well as disease-free survival and overall survival of the 91 patients with gastric cancer

Parameters	Patients cases	Disease free survival, monthsa	χ^2	P-valueb	Overall survival, monthsa	χ^2	P-valueb
Neutrophil count			0.720	0.396	–	0.388	0.534
<3.70	44 (48.4%)	26.87 (17.95–35.79)	–	–	29.37 (24.31–34.43)	–	–
≥3.70	47 (51.6%)	22.33 (11.98–32.68)	–	–	24.43 (14.45–34.41)	–	–
Lymphocyte count			0.241	0.624		0.300	0.584
<1.68	43 (47.3%)	21.03 (13.75–28.31)	–	–	26.37 (19.15–33.59)	–	–
≥1.68	48 (52.7%)	26.87 (9.89–43.86)	–	–	27.93 (12.21–43.65)	–	–
NLR			1.077	0.299		0.695	0.405
<2.17	45 (49.5%)	26.87 (16.27–37.47)	–	–	29.73 (17.02–42.44)	–	–
≥2.17	46 (50.5%)	19.97 (11.28–28.66)	–	–	25.83 (19.02–32.64)	–	–

Notes:

a The disease-free survival and overall survival data are presented as median survival with the 95% confidence interval (CI) in parentheses.

b Kaplan–Meier survival analysis.

Abbreviation: NLR, neutrophil-to-lymphocyte ratio.

Table 5 Clinical and laboratory characteristics as well as disease-free survival of the 91 patients with gastric cancer by NLR

Parameters	N	Low NLR <2.17	N	High NLR ≥2.17	χ^2	P-value
Neutrophil count					0.706	0.401
<3.70	34 (77.3%)	26.87 (8.29–45.45)	10 (22.7%)	19.97 (6.60–33.34)
≥3.70	11 (23.4%)	24.87 (15.11–34.64)	36 (76.6%)	18.30 (8.89–27.71)
Lymphocyte count					1.432	0.231
<1.68	15 (34.9%)	19.30 (11.56–27.04)	28 (65.1%)	22.33 (12.36–32.30)
≥1.68	30 (62.5%)	36.93 (17.02–56.84)	18 (37.5%)	10.67 (2.90–18.44)

Abbreviation: NLR, neutrophil-to-lymphocyte ratio.

Table 6 Clinical and laboratory characteristics as well as overall survival of the 91 patients with gastric cancer by NLR

Parameters	N	Low NLR <2.17	N	High NLR ≥2.17	χ^2	P-value
Neutrophil count					0.457	0.499
<3.70	34 (77.3%)	29.73 (18.34–41.12)	10 (22.7%)	25.83 (16.27–35.39)
≥3.70	11 (23.4%)	28.94 (18.84–39.04)	36 (76.6%)	24.43 (13.16–35.70)
Lymphocyte count					1.084	0.298
<1.68	15 (34.9%)	21.03 (6.01–36.05)	28 (65.1%)	29.37 (7.55–51.19)
≥1.68	30 (62.5%)	39.33 (8.53–70.13)	18 (37.5%)	15.90 (8.33–23.47)

Abbreviation: NLR, neutrophil-to-lymphocyte ratio.

Table 7 One-year, 3-year, and 5-year DFS and OS rates of the 91 patients with gastric cancer

Parameters	N	DFS			OS
		1-year	3-year	5-year	1-year	3-year	5-year
Low NLR <2.17	45	82.2% (37/45)	26.7% (12/45)	8.9% (4/45)	91.1% (41/45)	28.9% (13/45)	13.3% (6/45)
High NLR ≥2.17	46	69.6% (32/46)	19.6% (9/46)	6.5% (3/46)	84.8% (39/46)	23.9% (11/46)	8.7% (4/46)
Total	91	75.8% (69/91)	23.1% (21/91)	7.7% (7/91)	87.9% (80/91)	26.4% (24/91)	11.0% (10/91)

Abbreviations: DFS, disease-free survival; NLR, neutrophil-to-lymphocyte ratio; OS, overall survival.

Table 8 Main toxicities according to NCI-CTC scale of the 91 patients with gastric cancer

Toxicity	N	Anemia			Leukopenia
		Grade 0	Grades 1–2	Grades 3–4	Grade 0	Grades 1–2	Grades 3–4
Low NLR <2.17	45	32 (71.1%)	13 (28.9%)	0 (0%)	35 (77.8%)	10 (22.2%)	0 (0%)
High NLR ≥2.17	46	26 (56.5%)	20 (43.5%)	0 (0%)	38 (82.6%)	8 (17.4%)	0 (0%)
Total	91	58 (63.7%)	33 (36.3%)	0 (0%)	73 (80.2%)	18 (19.8%)	0 (0%)

Abbreviations: NCI-CTC, National Cancer Institute Common Toxicity Criteria; NLR, neutrophil-to-lymphocyte ratio.

Table 9 Main toxicities according to NCI-CTC scale of the 91 patients with gastric cancer

Toxicity	N	Neutropenia			Thrombocytopenia
		Grade 0	Grades 1–2	Grades 3–4	Grade 0	Grades 1–2	Grades 3–4
Low NLR <2.17	45	31 (68.9%)	12 (26.7%)	2 (4.4%)	43 (95.6%)	2 (4.4%)	0 (0%)
High NLR ≥2.17	46	36 (78.3%)	9 (19.6%)	1 (2.2%)	44 (95.7%)	2 (4.3%)	0 (0%)
Total	91	67 (73.6%)	21 (23.1%)	3 (3.3%)	87 (95.6%)	4 (4.4%)	0 (0%)

Abbreviations: NCI-CTC, National Cancer Institute Common Toxicity Criteria; NLR, neutrophil-to-lymphocyte ratio.