Peripheral blood marker changes predict response and prognosis in locally advanced gastric cancer with neoadjuvant sintilimab plus XELOX

Table 1 Baseline clinical and pathological characteristics of patients (n = 39)

Characteristic	Median (range) or n (%)
Age (years)	64 (35-77)
Gender
Male	25 (64.1)
Female	14 (35.9)
Tumor differentiation
Poor	25 (64.1)
Moderate	14 (35.9)
Histological type
PC	15 (38.5)
Non-PC	24 (61.5)
Tumor location
Cardia	9 (23.1)
Gastric antrum	16 (41.0)
Gastric body	14 (35.9)
Lauren classification
Intestinal	18 (46.2)
Diffuse	21 (53.8)
cT
cT3	16 (41.0)
cT4	23 (59.0)
cN
cN0	5 (12.8)
cN1	17 (43.6)
cN2	9 (23.1)
cN3	8 (20.5)
pT
pT0	6 (15.4)
pT1	4 (10.3)
pT2	8 (20.5)
pT3	11 (28.2)
pT4	10 (25.6)
pN
pN0	21 (53.8)
pN1	7 (17.9)
pN2	1 (2.6)
pN3	10 (25.6)
TRG
Grade 0	6 (15.4)
Grade 1	8 (20.5)
Grade 2	22 (56.4)
Grade 3	3 (7.7)

PC: Poorly cohesive gastric adenocarcinoma; TRG: Tumor regression grade.

Table 2 Changes in peripheral blood parameters at baseline and post-treatment, median (range)

	Baseline	Post-treatment	P value
Laboratory examination
Neutrophil count (× 109/L)	3.25 (2.70, 4.22)	3.21 (2.60, 4.22)	0.653
Lymphocyte count (× 109/L)	1.44 (1.14, 1.91)	1.18 (0.88, 1.68)	0.000
Monocyte count (× 109/L)	0.39 (0.29, 0.46)	0.51 (0.42, 0.65)	0.000
Blood platelet count (× 109/L)	245.00 (204.00, 315.00)	168.00 (111.00, 202.00)	0.000
T lymphocyte subsets
CD3+ T lymphocytes (%)	72.00 (64.00, 80.40)	80.50 (72.60, 84.10)	0.000
CD4+ T lymphocytes (%)	41.60 (33.50, 46.10)	41.30 (34.90, 50.50)	0.171
CD8+ T lymphocytes (%)	28.70 (19.10, 35.80)	32.70 (21.60, 41.50)	0.002
Inflammatory indicators
NLR	2.35 (1.79, 3.17)	2.68 (2.11, 4.02)	0.070
MLR	0.28 (0.21, 0.35)	0.43 (0.32, 0.64)	0.000
PLR	182.05 (131.82, 207.24)	121.05 (92.19, 211.97)	0.005

NLR: Neutrophil-to-lymphocyte ratio; PLR: Platelet-to-lymphocyte ratio; MLR: Monocyte-to-lymphocyte ratio.

Table 3 Univariate analysis of factors associated with treatment response

	MPR (n = 14)	Non-MPR (n = 25)	χ2/Z	P value
Sex			1.987	0.187
Male	11 (78.6)	14 (56.0)
Female	3 (21.4)	11 (44.0)
Age			0.223	0.733
≤ 60 years	4 (28.6)	9 (36.0)
> 60 years	10 (71.4)	16 (64.0)
Tumor differentiation			1.888	0.297
Poor	7 (50.0)	18 (64.1)
Moderate	7 (50.0)	7 (35.9)
Histological type			5.393	0.038
PC	2 (14.3)	13 (52.0)
Non-PC	12 (85.7)	12 (48.0)
Tumor location			1.988	0.370
Cardia	5 (35.7)	4 (16.0)
Gastric body	4 (28.6)	10 (40.0)
Gastric antrum	5 (35.7)	11 (44.0)
Lauren classification			2.889	0.108
Intestinal	9 (64.3)	9 (36.0)
Diffuse	5 (35.7)	16 (64.0)
cT			2.345	0.179
cT3	8 (57.1)	8 (32.0)
cT4	6 (42.9)	17 (68.0)
cN			10.242	0.003
cN0	5 (35.7)	0 (0)
cN1-3	9 (64.3)	25 (100.0)
pT			19.168	0.000
pT0-2	13 (92.9)	5 (20.0)
pT3-4	1 (7.1)	20 (80.0)
pT			13.374	0.000
pN0	13 (92.9)	8 (32.0)
pN1-3	1 (7.1)	17 (68.0)
Baseline CD3+ T lymphocytes (%)	66.05 (51.98, 79.23)	73.80 (70.30, 80.45)	-2.255	0.024
Baseline CD4+ T lymphocytes (%)	34.00 (32.60, 42.28)	42.70 (35.55, 48.15)	-2.108	0.035
Baseline CD8+ T lymphocytes (%)	29.05 (16.55, 36.53)	28.40 (21.15, 35.70)	-0.293	0.770
Baseline NLR	2.53 (1.84, 3.13)	2.30 (1.78, 3.41)	-0.088	0.930
Baseline PLR	189.27 (109.94, 209.08)	181.48 (132.58, 202.99)	-0.263	0.792
Baseline MLR	0.29 (0.22, 0.33)	0.27 (0.20, 0.35)	-0.234	0.815
Post-treatment CD3+ T lymphocytes (%)	78.15 (67.43, 83.53)	82.00 (73.00, 85.25)	-1.098	0.272
Post-treatment CD4+ T lymphocytes (%)	40.90 (31.60, 52.88)	43.40 (35.55, 50.10)	-0.381	0.703
Post-treatment CD8+ T lymphocytes (%)	31.00 (15.90, 42.50)	32.70 (23.40, 41.50)	-0.454	0.650
Post-treatment NLR	2.62 (2.31, 4.18)	2.68 (1.89, 3.96)	-0.351	0.725
Post-treatment PLR	185.07 (90.05, 194.27)	124.14 (89.37, 220.30)	-0.263	0.792
Post-treatment MLR	0.57 (0.42, 0.74)	0.39 (0.29, 0.54)	-2.196	0.028
ΔCD3+ T cell (%)	11.41 (5.37, 23.05)	5.06 (-4.09, 12.32)	-2.108	0.035
ΔCD4+ T cell (%)	5.96 (-8.10, 42.41)	2.16 (-8.62, 16.26)	-0.908	0.364
ΔCD8+ T cell (%)	15.79 (-6.19, 38.67)	9.44 (-1.57, 23.01)	-0.351	0.725
ΔNLR (%)	38.16 (-17.95, 64.18)	29.48 (-28.99, 55.18)	-0.716	0.447
ΔPLR (%)	-18.50 (-38.86, 10.81)	-30.63 (-47.68, -6.89)	-0.732	0.464
ΔMLR (%)	114.43 (50.51, 170.73)	57.53 (17.98, 89.64)	-2.576	0.010
ΔCD3+ T cell (%)	6.65 (3.05, 13.50)	3.70 (-3.10, 8.95)	-1.874	0.061
ΔCD4+ T cell (%)	1.70 (-3.10, 17.40)	1.00 (-4.15, 6.50)	-0.952	0.341
ΔCD8+ T cell (%)	3.30 (-1.85, 7.00)	2.90 (-0.45, 6.65)	-0.132	0.895
ΔNLR	0.68 (-0.54, 1.44)	0.65 (-0.61, 1.13)	-0.322	0.747
ΔPLR	-27.31 (-90.98, 10.66)	-51.53 (-117.17, -7.75)	0.878	0.380
ΔMLR	0.27 (0.14, 0.48)	0.11 (0.04, 0.22)	-2.752	0.006

NLR: Neutrophil-to-lymphocyte ratio; PLR: Platelet-to-lymphocyte ratio; MLR: Monocyte-to-lymphocyte ratio; PC: Poorly cohesive gastric adenocarcinoma; MPR: Major pathological response.

Table 4 Multivariate logistic regression analysis of predictors of treatment response

	OR	P value	95%CI
cT stage (cT4 vs cT3)	0.425	0.283	0.089-2.028
Histological type (non-PC vs PC)	8.522	0.036	1.146-63.374
Post-treatment MLR	2.479	0.035	1.064-5.788

OR: Odds ratio; CI: Confidence interval; PC: Poorly cohesive gastric adenocarcinoma; MLR: Monocyte-to-lymphocyte ratio.

Table 5 Univariate and multivariate Cox regression analyses of prognostic factors for progression-free survival

	HR (95%CI)	P value	HR (95%CI)	P value
Sex
Male
Female	0.871 (0.268-2.830)	0.818
Age
≤ 60 years
> 60 years	0.696 (0.228-2.131)	0.526
Tumor differentiation
Poor
Moderate	0.267 (0.059-1.206)	0.086
Histological type
PC
Non-PC	0.653 (0.219-1.945)	0.444
Tumor location
Cardia
Gastric body	2.425 (0.489-12.034)	0.279
Gastric antrum	1.484 (0.288-7.650)	0.637
Lauren classification
Intestinal
Diffuse	6.284 (1.389-28.431)	0.017	5.545 (0.568-12.955)	0.011
cT
cT3
cT4	4.854 (1.074-21.936)	0.040
cN
cN0
cN1-3	1.951 (0.254-15.009)	0.521
pT
pT0-2
pT3-4	3.756 (1.030-13.688)	0.045
pT
pN0
pN1-3	3.333 (1.025-10.839)	0.045
Baseline CD3+ T lymphocytes (%)	1.008 (0.959-1.059)	0.753
Baseline CD4+ T lymphocytes (%)	0.990 (0.930-1.055)	0.764
Baseline CD8+ T lymphocytes (%)	1.017 (0.961-1.075)	0.561
Baseline NLR	1.035 (0.722-1.485)	0.852
Baseline PLR	1.002 (0.995-1.008)	0.622
Baseline MLR	0.679 (0.152-3.201)	0.642
Post-treatment CD3+ T lymphocytes (%)	0.977 (0.928-1.028)	0.373
Post-treatment CD4+ T lymphocytes (%)	1.003 (0.959-1.049)	0.894
Post-treatment CD8+ T lymphocytes (%)	0.982 (0.939-1.026)	0.408
Post-treatment NLR	0.975 (0.754-1.261)	0.847
Post-treatment PLR	1.001 (0.994-1.009)	0.760
Post-treatment MLR	1.000 (0.076-13.126)	1.000
ΔCD3+ T cell (%)	0.971 (0.928-1.017)	0.216
ΔCD4+ T cell (%)	1.817 (0.270-12.233)	0.540
ΔCD8+ T cell (%)	0.971 (0.946-0.998)	0.032	0.970 (0.934-0.998)	0.024
ΔNLR (%)	0.976 (0.584-1.629)	0.925
ΔPLR (%)	0.961 (0.320-2.888)	0.944
ΔMLR (%)	1.000 (0.991-1.009)	0.948
ΔCD3+ T cell (%)	0.960 (0.901-1.023)	0.205
ΔCD4+ T cell (%)	1.012 (0.959-1.069)	0.659
ΔCD8+ T cell (%)	0.906 (0.830-0.981)	0.016
ΔNLR	0.965 (0.760-1.225)	0.770
ΔPLR	0.999 (0.993-1.005)	0.842
ΔMLR	1.535 (0.302-7.801)	0.606

HR: Hazard ratio; CI: Confidence interval; NLR: Neutrophil-to-lymphocyte ratio; PLR: Platelet-to-lymphocyte ratio; MLR: Monocyte-to-lymphocyte ratio; ΔCD8+ T cells: Relative change in CD8+ T-cell proportion; PC: Poorly cohesive gastric adenocarcinoma.