Neutrophile-to-lymphocyte, lymphocyte-to-monocyte, and platelet-to-lymphocyte ratios as prognostic and response biomarkers for resectable locally advanced gastric cancer

Table 1 Patients’ demographics

	All, n = 295
Age at diagnosis in yr, mean (min-max)	63.7 (31-84)
Male, n (%)	176 (59.7%)
Primary tumor site, n (%)
Stomach
Body	139 (47.1%)
Antrum	100 (33.9%)
Cardia	33 (11.2%)
Lower esophagus	3 (1%)
Gastroesophageal junction	20 (6.8%)
Lauren classification1, n (%)
Diffuse	61 (21.6%)
Intestinal or mixed	152 (53.9%)
NOS	69 (24.5%)
Differentiation degree2, n (%)
Well differentiated	26 (11.7%)
Moderately differentiated	75 (33.8%)
Poorly differentiated	121 (54.5%)
Blood cell count and blood ratios serum quantification, mean ± SD
Neutrophiles	6103 ± 3354
Lymphocytes	1890 ± 1014
Platelets	268658 ± 92373
Monocytes	585 ± 407
NLR	4.66 ± 7.1
LMR	5.29 ± 9.2
PLR	182.91 ± 148.19
Clinical/imagiological T stage3, n (%)
T1	12 (4.3%)
T2	67 (23.8%)
T3	130 (46.3%)
T4	72 (25.6%)
Clinical/imagiological N stage4, n (%)
Nx	14 (4.8%)
N0	43 (14.7%)
N1	66 (22.5%)
N2	62 (21.2%)
N3	7 (2.4%)
N+	101 34.5%)
PreFLOT cycles, median (min-max)	4 (1-12)
Progressive disease under preFLOT, n (%)	24 (8.1%)
Suspension of preFLOT due to toxicity, n (%)	22 (7.5%)
Waiting time to surgery in wk, median (min-max)	12 (6-33)
Patients submitted to surgery5, n (%)	271 (91.9%)
Total gastrectomy	129 (49%)
Subtotal gastrectomy	121 (46%)
Distal gastrectomy	2 (0.8%)
Esophagectomy	11 (4.1%)
Lymphadenectomy6, n (%)
D1	9 (4%)
D1+	24 (10.6%)
D2	193 (85.4%)
Resection margin7, n (%)
0	249 (95%)
1	13 (5%)
Pathological T stage4, n (%)
T0	40 (14.7%)
Tis	2 (0.7%)
T1	52 (19%)
T2	39 (14.3%)
T3	96 (35.2%)
T4	44 (16.1%)
Pathological N stage4, n (%)
N0	147 (53.8%)
N1	36 (13.2)
N2	48 (17.6%)
N3	42 (15.4%)
Pathological stage regression, n (%)
T stage regression8	126 (46.5%)
N stage regression9	156 (57.6%)
Post-surgery tumor staging status, n (%)
Tumor downstaging	161 (61%)
No response	53 (20.1%)
Tumor upstaging	50 (18.9%)
TRG10, n (%)
Complete tumor regression	48 (20.1%)
Partial/incomplete tumor regression	111 (46.4%)
No evidence of regression	80 (33.5%)
Mortality status at the end of study time, n (%)
Dead	62 (21%)
Alive	233 (79%)

¹13 missing data.

²73 missing data.

³14 missing data.

⁴22 missing data.

⁵8 missing data.

⁶45 missing data.

⁷9 missing data.

⁸17 missing data.

⁹9 missing data.

¹⁰56 missing data.

FLOT: Fluorouracil plus leucovorin, oxaliplatin, and docetaxel; LMR: Lymphocyte-to-monocyte ratio; NLR: Neutrophile-to-lymphocyte ratio; NOS: Nitric oxide synthase; PLR: Platelet-to-lymphocyte ratio; preFLOT: Preoperative fluorouracil plus leucovorin, oxaliplatin, and docetaxel; SD: Standard deviation; TRG: Tumor regression grade.

Table 2 Relationship between neutrophil-to-lymphocyte, lymphocyte-to-monocyte, and platelet-to-lymphocyte ratios and clinicopathological variables in patients with resectable locally advanced gastroesophageal cancer

	NLR, mean ± SD	P value	LMR, mean ± SD	P value	PLR, mean ± SD	P value
Age		0.37		0.323		0.335
< 75 yr (n = 262)	4.72 ± 7.24		5.37 ± 9.66		178.88 ± 129.45
≥ 75 yr (n = 33)	4.21 ± 5.94		4.69 ± 4.06		214.98 ± 252.77
Sex		0.073		0.435		0.177
Male (n = 176)	4.19 ± 4.33		5.12 ± 4.9		169.61 ± 120.07
Female (n = 119)	5.37 ± 9.84		5.55 ± 13.24		202.6 ± 146.38
Treatment suspension due to toxicity		0.336		0.818		0.144
Yes (n = 22)	5.32 ± 5.5		5.05 ± 3.89		208.26 ± 136.91
No (n = 273)	4.61 ± 7.22		5.31 ± 9.5		180.87 ± 149.11
Systemic progression under preFLOT		0.935		0.287		0.022
Yes (n = 24)	4.66 ± 4.48		3.78 ± 2.9		251.94 ± 173.3
No (n = 271)	4.66 ± 7.29		5.43 ± 9.55		176.8 ± 144.54
T stage regression		0.743		0.021		0.62
Yes (n = 126)	4.14 ± 3.94		4.38 ± 3.64		168.23 ± 117.2
No (n = 138)	4.73 ± 8.97		6.5 ± 12.84		177.73 ± 145.62
N stage regression		0.119		0.635		0.157
Yes (n = 156)	5.04 ± 8.81		5.76 ± 12.04		184.45 ± 140.76
No (n = 115)	4.06 ± 4.56		4.91 ± 4.29		166.13 ± 150.31
Tumor downstaging		0.081		0.873		0.82
Yes (n = 161)	5.07 ± 8.58		4.7 ± 4.27		180.13 ± 139.93
No (n = 103)	4.02 ± 4.74		6.58 ± 14.42		197.79 ± 154.23
TRG		0.9		0.99		0.305
Partial/incomplete or complete regression (n = 161)	4.87 ± 8.45		5.17 ± 11.49		180.4 ± 139.45
No evidence of regression (n = 86)	4.77 ± 5.3		4.45 ± 3.63		189.73 ± 157.16
Pathological complete response		0.511		0.472		0.832
Yes (n = 48)	4.32 ± 3.73		4.62 ± 4.1		177 ± 138.81
No (n = 191)	5 ± 8.23		5.09 ± 10.54		183.87 ± 151.46
Mortality status at the end of study time		0.082		0.14		0.013
Alive (n = 233)	4.47 ± 7.45		5.6 ± 10.18		175.64 ± 149.02
Dead (n = 62)	5.38 ± 5.57		4.15 ± 3.45		210.27 ± 142.87

FLOT: Fluorouracil plus leucovorin, oxaliplatin, and docetaxel; LMR: Lymphocyte-to-monocyte ratio; NLR: Neutrophile-to-lymphocyte ratio; PLR: Platelet-to-lymphocyte ratio; preFLOT: Preoperative fluorouracil plus leucovorin, oxaliplatin, and docetaxel; SD: Standard deviation; TRG: Tumor regression grade.

Table 3 Univariate regressions of significant predictive or prognostic factors in resectable locally advanced gastroesophageal cancer patients

Poisson regression	Relative risk (95%CI)	Hazard ratio (95%CI)	P value
T stage regression between LMR groups
> 3.56/≤ 3.56	1.42 (1.01-1.99)		0.043
Progression between PLR groups
> 141/≤ 141	2.17 (0.89-5.26)		0.088
Mortality between PLR groups
> 144/≤ 144	1.53 (0.92-2.55)		0.103
Cox regression
NLR		1 (0.97-1.0)	0.972
Patients without pCR		2.1 (0.8-5.2)	0.129
Patients without (pathological) tumor regression		2.8 (1.6-5)	< 0.001
Patients without T stage regression		2.1 (1.1-3.9)	0.017

CI: Confidence interval; FLOT: Fluorouracil plus leucovorin, oxaliplatin, and docetaxel; LMR: Lymphocyte-to-monocyte ratio; NLR: Neutrophile-to-lymphocyte ratio; pCR: Pathological complete response; PLR: Platelet-to-lymphocyte ratio; preFLOT: Preoperative fluorouracil plus leucovorin, oxaliplatin, and docetaxel; TRG: Tumor regression grade.