Monocyte to lymphocyte ratio predicts survival in patients with advanced gastric cancer undergoing neoadjuvant chemotherapy

Figures & data

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

Parameters	Patients	Low-MLR <0.27	High-MLR ≥0.27	χ^2	P-value
Age (years)				1.846	0.174
<57	45 (49.5%)	24 (57.1%)	21 (42.9%)
≥57	46 (50.5%)	18 (42.9%)	28 (57.1%)
Gender				4.622	0.032
Male	70 (76.9%)	28 (66.7%)	42 (85.7%)
Female	21 (23.1%)	14 (33.3%)	7 (14.3%)
BMI (kg/m^2)				1.357	0.244
<22.32	45 (49.5%)	18 (42.9%)	27 (55.1%)
≥22.32	46 (50.5%)	24 (57.1%)	22 (44.9%)
ABO blood type				2.797	0.473#
A	23 (25.3%)	12 (28.6%)	11 (22.4%)
B	32 (35.2%)	14 (33.3%)	18 (36.7%)
O	27 (29.7%)	10 (23.8%)	17 (34.7%)
AB	9 (9.9%)	6 (14.3%)	3 (6.1%)
Chemotherapy regimen				1.858	0.173
SOX	35 (38.5%)	13 (31.0%)	22 (44.9%)
XELOX	56 (61.5%)	29 (69.0%)	27 (55.1%)
Radical resection				2.460	0.292
R0	51 (56.0%)	24 (57.1%)	27 (55.1%)
R1	21 (23.1%)	7 (16.7%)	14 (28.6%)
R2	19 (20.9%)	11 (26.2%)	8 (16.3%)
Type of surgery				2.802	0.330#
Distal gastrectomy	52 (57.1%)	27 (64.3%)	25 (51.0%)
Proximal gastrectomy	6 (6.6%)	1 (2.4%)	5 (10.2%)
Total gastrectomy	33 (36.3%)	14 (33.3%)	19 (38.8%)
Differentiation				1.927	0.462#
Poorly differentiated	54 (59.3%)	24 (57.1%)	30 (61.2%)
Moderately differentiated	32 (35.2%)	17 (40.5%)	15 (30.6%)
Well differentiated	5 (5.5%)	1 (2.4%)	4 (8.2%)
Primary tumor site				8.078	0.011#
Upper 1/3	11 (12.1%)	2 (4.8%)	9 (18.4%)
Middle 1/3	31 (34.1%)	11 (26.2%)	20 (40.8%)
Low 1/3	49 (53.8%)	29 (69.0%)	20 (40.8%)
Pathology				1.600	0.714#
Adenocarcinoma	64 (70.3%)	31 (73.8%)	33 (67.3%)
Mucinous carcinoma	10 (11.0%)	5 (11.9%)	5 (10.2%)
Signet ring cell carcinoma	12 (13.2%)	5 (11.9%)	7 (14.3%)
Others	5 (5.5%)	1 (2.4%)	4 (8.2%)
Clinical TNM classification
T stage				0.038	1.000
T3	6 (6.6%)	3 (7.1%)	3 (6.1%)
T4	85 (93.4%)	39 (92.9%)	46 (93.9%)
N stage				0.055	0.973
N0	24 (26.4%)	11 (26.2%)	13 (26.5%)
N1	51 (56.0%)	24 (57.1%)	27 (55.1%)
N2	16 (17.6%)	7 (16.7%)	9 (18.4%)
TNM stage				–	1.000#
II	2 (2.2%)	1 (2.4%)	1 (2.0%)
III	89 (97.8%)	41 (97.6%)	48 (98.0%)
Pathological TNM classification
T stage				5.895	0.176#
T0	5 (5.5%)	1 (2.4%)	4 (8.2%)
T1	7 (7.7%)	4 (9.5%)	3 (6.1%)
T2	14 (15.4%)	10 (23.8%)	4 (8.2%)
T3	43 (47.3%)	17 (40.5%)	26 (53.1%)
T4	22 (24.2%)	10 (23.8%)	12 (24.5%)
N stage				0.121	0.989
N0	24 (26.4%)	11 (26.2%)	13 (26.5%)
N1	23 (25.3%)	10 (23.8%)	13 (26.5%)
N2	15 (16.5%)	7 (16.7%)	8 (16.3%)
N3	29 (31.9%)	14 (33.3%)	15 (30.6%)
TNM stage				3.039	0.547#
Tis	5 (5.5%)	1 (2.4%)	4 (8.2%)
I	9 (9.9%)	6 (14.3%)	3 (6.1%)
II	29 (31.9%)	13 (31.0%)	16 (32.7%)
III	45 (49.5%)	21 (50.0%)	24 (49.0%)
IV	3 (3.3%)	1 (2.4%)	2 (4.1%)
Total lymph nodes				0.554	0.457
<27	45 (49.5%)	19 (45.2%)	26 (53.1%)
≥27	46 (50.5%)	23 (54.8%)	23 (46.9%)
Positive lymph nodes				0.017	0.897
<3	44 (48.4%)	20 (47.6%)	24 (49.0%)
≥3	47 (51.6%)	22 (52.4%)	25 (51.0%)
HER-2				0.791	0.374
0 or +	54 (59.3%)	27 (64.3%)	27 (55.1%)
++ or +++	37 (40.7%)	15 (35.7%)	22 (44.95)
Monocyte				15.072	<0.001
<0.44×10^9/L	45 (49.5%)	30 (71.4%)	15 (30.6%)
≥0.44×10^9/L	46 (50.5%)	12 (28.6%)	34 (69.4%)
Lymphocyte				8.315	0.004
<1.68×10^9/L	43 (47.3%)	13 (31.0%)	30 (61.2%)
≥1.68×10^9/L	48 (52.7%)	29 (69.0%)	19 (38.8%)
Response				3.971	0.275#
CR	5 (5.5%)	1 (2.4%)	4 (8.2%)
PR	65 (71.4%)	34 (81.0%)	31 (63.3%)
SD	7 (7.7%)	3 (7.1%)	4 (8.2%)
PD	14 (15.4%)	4 (9.5%)	10 (20.4%)

Note:

# Performed using the Fisher’s exact test.

Abbreviations: MLR, monocyte to lymphocyte ratio; BMI, body mass index; SOX, S-1 plus oxaliplatin; XELOX, oxaliplatin and capecitabine; TNM, tumor-node-metastasis; CR, complete response; PR, partial response; SD, stable disease; PD, progression of disease; Tis, tumor in situ.

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

Figure 2 Overall survival of 91 patients with advanced gastric cancer.

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

Parameters	Univariate analysis		Multivariate analysis
	Hazard ratio (95% CI)	P-value	Hazard ratio (95% CI)	P-value
Age (<57 vs ≥57 years)	1.024 (0.984–1.066)	0.241
Gender (male vs female)	0.799 (0.335–1.909)	0.614
BMI (<22.32 vs ≥22.32 kg/m^2)	0.632 (0.327–1.219)	0.171
ABO blood type (A vs B vs O vs AB)	1.390 (0.899–2.149)	0.138
Chemotherapy regimen (SOX vs XELOX)	1.072 (0.508–2.260)	0.856
Radical resection (R0 vs R1 vs R2)	2.199 (1.365–3.544)	0.001	2.059 (1.445–2.932)	<0.001
Type of surgery (distal vs proximal vs total gastrectomy)	0.755 (0.470–1.213)	0.245
Differentiation (poorly vs moderately vs well differentiated)	0.701 (0.375–1.312)	0.267
Primary tumor site (upper vs middle vs low 1/3)	0.443 (0.218–0.899)	0.024
Pathology (adenocarcinoma vs mucinous vs signet ring	1.366 (0.935–1.995)	0.107
cell carcinoma vs others)
Clinical T stage (T3 vs T4)	3.627 (0.382–34.475)	0.262
Clinical N stage (N0 vs N1 vs N2)	1.122 (0.660–1.906)	0.671
Clinical TNM stage (II vs III)	0.183 (0.008–4.259)	0.290
Pathological T stage (T0 vs T1 vs T2 vs T3 vs T4)	1.076 (0.620–1.868)	0.794
Pathological N stage (N0 vs N1 vs N2 vs N3)	1.265 (0.677–2.363)	0.461
Pathological TNM stage (Tis vs I vs II vs III vs IV)	2.747 (1.156–6.526)	0.022	2.782 (1.829–4.233)	<0.001
Total lymph nodes (<27 vs ≥27)	0.688 (0.348–1.361)	0.283
Positive lymph nodes (<3 vs ≥3)	1.402 (0.296–6.640)	0.671
HER-2 (0 – + vs ++ – +++)	1.773 (0.946–3.323)	0.074
Monocyte (<0.44 vs ≥0.44×10^9/L)	0.665 (0.275–1.608)	0.365
Lymphocyte (<1.68 vs ≥1.68×10^9/L)	1.621 (0.725–3.627)	0.240
MLR (<0.27 vs ≥0.27)	0.969 (0.434–2.165)	0.938
Response (CR vs PR vs SD vs PD)	0.962 (0.563–1.644)	0.887

Abbreviations: CI, confidence interval; BMI, body mass index; SOX, S-1 plus oxaliplatin; XELOX, oxaliplatin and capecitabine; TNM, tumor-node-metastasis; MLR, monocyte to lymphocyte ratio; CR, complete response; PR, partial response; SD, stable disease; PD, progression of disease; Tis, tumor in situ.

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

Parameters	Univariate analysis		Multivariate analysis
	Hazard ratio (95% CI)	P-value	Hazard ratio (95% CI)	P-value
Age (<57 vs ≥57 years)	1.021 (0.980–1.064)	0.312
Gender (male vs female)	1.053 (0.447–2.483)	0.906
BMI (<22.32 vs ≥22.32)	0.523 (0.263–1.042)	0.065
ABO blood type (A vs B vs O vs AB)	1.069 (0.718–1.592)	0.743
Chemotherapy regimen (SOX vs XELOX)	1.362 (0.630–2.946)	0.432
Radical resection (R0 vs R1 vs R2)	3.072 (1.886–5.005)	<0.001	2.494 (1.730–3.595)	<0.001
Type of surgery (distal vs proximal vs total gastrectomy)	0.673 (0.413–1.096)	0.112
Differentiation (poorly vs moderately vs well differentiated)	0.940 (0.503–1.759)	0.847
Primary tumor site (upper vs middle vs low 1/3)	0.536 (0.259–1.110)	0.093
Pathology (adenocarcinoma vs mucinous vs signet ring cell carcinoma vs others)	1.292 (0.862–1.937)	0.215
Clinical T stage (T3 vs T4)	3.538 (0.342–36.638)	0.289
Clinical N stage (N0 vs N1 vs N2)	1.065 (0.618–1.836)	0.821
Clinical TNM stage (II vs III)	0.139 (0.006–3.504)	0.231
Pathological T stage (T0 vs T1 vs T2 vs T3 vs T4)	1.091 (0.631–1.884)	0.756
Pathological N stage (N0 vs N1 vs N2 vs N3)	1.189 (0.640–2.208)	0.581
Pathological TNM stage (Tis vs I vs II vs III vs IV)	2.598 (1.057–6.385)	0.037	3.041 (1.949–4.746)	<0.001
Total lymph nodes (<27 vs ≥27)	0.566 (0.287–1.115)	0.100
Positive lymph nodes (<3 vs ≥3)	1.799 (0.369–8.782)	0.468
HER-2 (0 – + vs ++ – +++)	1.565 (0.852–2.873)	0.149
Monocyte (<0.44 vs ≥0.44×10^9/L)	0.191 (0.216–1.357)	0.191
Lymphocyte (<1.68 vs ≥1.68×10^9/L)	1.683 (0.743–3.812)	0.212
MLR (<0.27 vs ≥0.27)	1.054 (0.448–2.484)	0.904
Response (CR vs PR vs SD vs PD)	1.038 (0.601–1.793)	0.893

Abbreviations: CI, confidence interval; BMI, body mass index; SOX, S-1 plus oxaliplatin; XELOX, oxaliplatin and capecitabine; TNM, tumor-node-metastasis; MLR, monocyte to lymphocyte ratio; CR, complete response; PR, partial response; SD, stable disease; PD, progression of disease; Tis, tumor in situ.

Figure 3 Disease free survival in relation to MLR.

Abbreviation: MLR, monocyte to lymphocyte ratio.

Figure 4 Overall survival in relation to MLR.

Abbreviation: MLR, monocyte to lymphocyte ratio.

Figure 5 Disease free survival in relation to monocyte count.

Figure 6 Overall survival in relation to monocyte count.

Figure 7 Disease free survival in relation to lymphocyte count.

Figure 8 Overall survival in relation to lymphocyte count.

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

Parameters	Patient cases (%)	Disease free survival (months)a	χ^2	P-valueb	Overall survival (months)a	χ^2	P-valueb
Monocyte			0.212	0.645		0.437	0.509
<0.44×10^9/L	45 (49.5%)	30.23 (11.40–49.06)			37.97 (23.90–52.04)
≥0.44×10^9/L	46 (50.5%)	21.03 (11.42–30.64)			25.83 (19.08–32.58)
Lymphocyte			0.241	0.624		0.300	0.584
<1.68×10^9/L	43 (47.3%)	21.03 (13.75–28.31)			26.37 (19.15–33.58)
≥1.68×10^9/L	48 (52.7%)	26.87 (9.89–43.86)			27.93 (12.21–43.65)
MLR			0.202	0.653		0.059	0.807
<0.27	42 (46.2%)	26.80 (17.57–36.04)			27.93 (20.99–34.87)
≥0.27	49 (53.8%)	23.73 (17.23–30.23)			26.87 (16.88–36.86)

Notes:

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

b Kaplan–Meier survival analysis.

Abbreviation: MLR, monocyte to lymphocyte ratio.

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

Parameters	Na	Low-MLR <0.27	Na	High-MLR ≥0.27	χ^2	P-value
Monocyte					0.785	0.376
<0.44×10^9/L	30 (71.4%)	36.30 (23.65–48.95)	15 (30.6%)	33.05 (19.42–46.68)
≥0.44×10^9/L	12 (28.6%)	31.47 (22.85–40.09)	34 (69.4%)	33.75 (22.47–45.02)
Lymphocyte					0.164	0.686
<1.68×10^9/L	13 (31.0%)	18.40 (7.29–29.51)	30 (61.2%)	22.33 (12.94–31.72)
≥1.68×10^9/L	29 (69.0%)	36.93 (8.52–65.34)	19 (38.8%)	23.73 (15.04–32.42)

Note:

a The values are based on the MLR, monocyte count, and lymphocyte count by the the optimal cutoff value by receiver operating characteristic.

Abbreviation: MLR, monocyte to lymphocyte ratio.

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

Parameters	Na	Low-MLR <0.27	Na	High-MLR ≥0.27	χ^2	P-value
Monocyte					0.703	0.402
<0.44×10^9/L	30 (71.4%)	48.21 (31.22–65.21)	15 (30.6%)	34.66 (20.97–48.35)
≥0.44×10^9/L	12 (28.6%)	39.14 (27.24–51.03)	34 (69.4%)	38.16 (27.04–49.28)
Lymphocyte					0.101	0.751
<1.68×10^9/L	13 (31.0%)	25.83 (8.45–43.21)	30 (61.2%)	29.37 (4.41–54.34)
≥1.68×10^9/L	29 (69.0%)	39.93 (0–77.04)	19 (38.8%)	27.93 (15.01–40.86)

Note:

a The values are based on the MLR, monocyte count, and lymphocyte count by the optimal cutoff value by receiver operating characteristic.

Abbreviation: MLR, monocyte to lymphocyte ratio.

Table 7 The 1-year, 3-year, and 5-year DFS and OS rates of the 91 patients with advanced gastric cancer

Parameters	Patients (n)	DFS			OS
		1-year	3-year	5-year	1-year	3-year	5-year
Low-MLR <0.27	42	71.4% (30/42)	26.2% (11/42)	9.5% (4/42)	85.7% (36/42)	26.2% (11/42)	14.3% (6/42)
High-MLR ≥0.27	49	79.6% (39/49)	20.4% (10/49)	6.1% (3/49)	89.8% (44/49)	26.5% (13/49)	8.2% (4/49)
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; OS, overall survival; MLR, monocyte to lymphocyte ratio.

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

Toxicity	Patients (n)	Anemia			Leucopenia
		Grade 0 (%)	Grade 1–2 (%)	Grade 3–4 (%)	Grade 0 (%)	Grade 1–2 (%)	Grade 3–4 (%)
Low-MLR <0.27	42	27 (64.3%)	15 (35.7%)	0 (0%)	30 (71.4%)	12 (28.6%)	0 (0%)
High-MLR ≥0.27	49	31 (63.3%)	18 (36.7%)	0 (0%)	43 (87.6%)	6 (12.4%)	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; MLR, monocyte to lymphocyte ratio.

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

Toxicity	Patients (n)	Neutropenia			Thrombocytopenia
		Grade 0 (%)	Grade 1–2 (%)	Grade 3–4 (%)	Grade 0 (%)	Grade 1–2 (%)	Grade 3–4 (%)
Low-MLR <0.27	42	26 (61.9%)	14 (33.3%)	2 (4.8%)	41 (97.6%)	1 (2.4%)	0 (0%)
High-MLR ≥0.27	49	41 (83.7%)	7 (14.3%)	1 (2.0%)	46 (93.9%)	3 (6.1%)	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; MLR, monocyte to lymphocyte ratio.