Survival prognosis in advanced HER-2 negative gastric cancer treated with immunochemotherapy: A novel model

Table 1 Baseline characteristics, n (%)

Characteristics	Total (n = 200)	Text (n = 60)	Train (n = 140)	Statistic	P value
Sex				χ2 = 0.63	0.426
Male	75 (37.50)	25 (41.67)	50 (35.71)
Female	125 (62.50)	35 (58.33)	90 (64.29)
Age				χ2 =0.02	0.899
< 60	78 (39.00)	23 (38.33)	55 (39.29)
≥ 60	122 (61.00)	37 (61.67)	85 (60.71)
BMI, kg/m2				χ2 =0.11	0.742
< 25	166 (83.00)	49 (81.67)	117 (83.57)
≥ 25	34 (17.00)	11 (18.33)	23 (16.43)
CEA, ng/mL				χ2 =0.01	0.925
< 3	121 (60.50)	36 (60.00)	85 (60.71)
≥ 3	79 (39.50)	24 (40.00)	55 (39.29)
CA199, U/mL				χ2 =0.60	0.440
< 37	128 (64.00)	36 (60.00)	92 (65.71)
≥ 37	72 (36.00)	24 (40.00)	48 (34.29)
ECOG PS				χ2 =0.20	0.653
0	72 (36.00)	23 (39.33)	49 (35.00)
1	128 (64.00)	37 (61.67)	91 (65.00)
Staging				χ2 =0.28	0.598
3	89 (44.50)	25 (41.67)	64 (45.71)
4	111 (55.50)	35 (58.33)	76 (54.29)
Site				χ2 =0.23	0.634
Stomach	142 (71.00)	98 (70.00)	44 (73.33)
Gastric and esophageal binding	58 (29.00)	72 (30.00)	16 (26.67)
Differentiation				χ2 =1.06	0.304
Low	180 (90.00)	56 (93.33)	124 (88.57)
Medium-high differentiation	20 (10.00)	4 (6.67)	16 (11.43)
Peritoneal metastasis				χ2 =0.81	0.367
No	113 (56.50)	31 (51.67)	82 (58.57)
Yes	87 (43.50)	29 (48.33)	58 (41.43)
Liver metastasis				χ2 =2.15	0.143
No	157 (78.50)	51 (85.00)	106 (75.71)
Yes	43 (21.50)	9 (15.00)	34 (24.29)
EBV status				χ2 =0.06	0.802
No-infect	187 (93.50)	57 (95.00)	130 (92.86)
Infect	13 (6.50)	3 (5.00)	10 (7.14)
PD-L1 expression				χ2 =0.65	0.419
CPS < 5	88 (44.00)	29 (48.33)	59 (42.14)
CPS ≥ 5	112 (56.00)	31 (51.67)	81 (57.86)
MMR status				χ2 =0.31	0.579
pMMR	169 (84.50)	52 (86.67)	117 (83.57)
dMMR	31 (15.50)	8 (13.33)	23 (16.43)
CALLY index, median (Q1, Q3)	1.13 (0.18, 4.99)	1.25 (0.17, 3.15)	1.03 (0.18, 5.19)	Z = -0.42	0.674
NLR, median (Q1, Q3)	2.58 (1.81, 4.17)	2.61 (1.88, 4.04)	2.57 (1.72, 4.30)	Z = -0.30	0.762
SII, median (Q1, Q3)	627.11 (339.65, 939.08)	661.80 (361.13, 883.91)	613.29 (325.57, 998.95)	Z = -0.53	0.598

BMI: Body mass index; CEA: Carcinoembryonic antigen; CA199: Carbohydrate antigen 199; ECOG PS: Eastern Cooperative Oncology Group performance status; EBV: Epstein-Barr virus; PD-L1: Programmed cell death ligand 1; CPS: Combined positive score; MMR: Mismatch repair; pMMR: Proficient mismatch repair; dMMR: Deficient mismatch repair; NLR: Neutrophil-to-lymphocyte ratio; CALLY: C-reactive protein-albumin-lymphocyte; SII: Systemic immune inflammation.

Table 2 Evaluation of efficacy, n (%)

Parameter
Over best response	CR	1 (0.5)
	PR	32 (16.0)
	SD	59 (29.5)
	PD	108 (54.0)
ORR	CR + PR	33 (16.5)
DCR	CR + PR + SD	92 (46.0)

CR: Complete response; PR: Partial response; SD: Stable disease; PD: Progression disease; ORR: Objective responds rates; DCR: Disease control rates.

Table 3 Univariate and multivariate analyses of prognostic factors for progression-free survival

Factors	Univariate		Multivariate
	HR (95%CI)	P value	HR (95%CI)	P value
Sex (female vs male)	1.08 (0.67-1.74)	0.757
Age (< 60 vs ≥ 60), years	0.89 (0.56-1.42)	0.629
BMI (≥ 25 vs < 25), kg/m2	1.28 (0.73-2.26)	0.386
CEA (< 3 vs ≥ 3), ng/mL	1.45 (0.92-2.29)	0.107
CA199 (< 37 vs ≥ 37), U/mL	1.29 (0.81-2.06)	0.278
ECOG (0 vs 1)	1.62 (0.97-2.68)	0.063
Staging (3 vs 4)	4.68 (2.71-8.11)	< 0.001	4.61 (2.53-8.41)	< 0.001
Differentiation (low vs medium-high)	0.14 (0.03-0.56)	0.006	0.20 (0.05-0.83)	0.027
Site (stomach vs gastric and esophageal binding)	1.36 (0.81-2.28)	0.252
Liver metastasis (no vs yes)	1.61 (0.98-2.66)	0.060
Peritoneal metastasis (no vs yes)	1.51 (0.96-2.37)	0.076
PD-L1 expression (CPS < 5 vs CPS ≥ 5)	0.17 (0.10-0.29)	< 0.001	0.37 (0.22-0.64)	< 0.001
MMR status (dMMR vs pMMR)	0.12 (0.04-0.37)	< 0.001	0.28 (0.08-0.94)	0.040
EBV status (infect vs no-infect)	0.57 (0.21-1.56)	0.274
CALLY index	0.88 (0.82-0.94)	< 0.01	0.91 (0.85-0.99)	0.020
NLR	1.14 (1.08-1.22)	< 0.001	1.13 (1.05-1.22)	< 0.001
SII	1.07 (1.00-1.14)	0.052

BMI: Body mass index; CEA: Carcinoembryonic antigen; CA199: Carbohydrate antigen 199; ECOG: Eastern Cooperative Oncology Group; PD-L1: Programmed cell death ligand 1; CPS: Combined positive score; MMR: Mismatch repair; dMMR: Deficient mismatch repair; pMMR: Proficient mismatch repair; EBV: Epstein-Barr virus; CALLY: C-reactive protein-albumin-lymphocyte; NLR: Neutrophil-to-lymphocyte ratio; SII: Systemic immune inflammation.

Table 4 Univariate and multivariate analyses of prognostic factors for overall survival

Factors	Univariate		Multivariate
	HR (95%CI)	P value	HR (95%CI)	P value
Sex (female vs male)	1.10 (0.68-1.77)	0.704
Age (< 60 vs ≥ 60), years	0.90 (0.57-1.43)	0.663
BMI (≥ 25 vs < 25), kg/m2	1.17 (0.66-2.06)	0.586
CEA (< 3 vs ≥ 3), ng/mL	1.39 (0.88-2.20)	0.152
CA199 (< 37 vs ≥ 37), U/mL	1.43 (0.89-2.27)	0.136
ECOG PS (0 vs 1)	1.63 (0.98-2.71)	0.059
Staging (3 vs 4)	4.12 (2.38-7.13)	< 0.001	3.73 (2.05-6.81)	< 0.001
Differentiation (low vs medium-high)	0.13 (0.03-0.54)	0.005	0.18 (0.04-0.74)	0.018
Site (stomach vs gastric and esophageal binding)	1.30 (0.77-2.18)	0.326
Liver metastasis (no vs yes)	1.58 (0.96-2.61)	0.072
Peritoneal metastasis (no vs yes)	1.41 (0.90-2.22)	0.136
PD-L1 expression (CPS < 5 vs CPS ≥ 5)	0.18 (0.11-0.31)	< 0.001	0.45 (0.26-0.76)	0.003
MMR status (dMMR vs pMMR)	0.10 (0.03-0.32)	< 0.001	0.20 (0.06-0.73)	0.015
EBV status (infect vs no-infect)	0.57 (0.21-1.57)	0.279
CALLY index	0.86 (0.79-0.92)	< 0.001	0.88 (0.81-0.95)	0.002
NLR	1.18 (1.11-1.26)	< 0.001	1.16 (1.08-1.25)	< 0.001
SII	1.04 (0.97-1.11)	0.275

BMI: Body mass index; CEA: Carcinoembryonic antigen; CA199: Carbohydrate antigen 199; ECOG PS: Eastern Cooperative Oncology Group performance status; PD-L1: Programmed cell death ligand 1; CPS: Combined positive score; MMR: Mismatch repair; dMMR: Deficient mismatch repair; pMMR: Proficient mismatch repair; EBV: Epstein-Barr virus; CALLY: C-reactive protein-albumin-lymphocyte; NLR: Neutrophil-to-lymphocyte ratio; SII: Systemic immune inflammation.

Table 5 Univariate and multivariate logistic regression for objective responds rates

Factors	Univariate		Multivariate
	HR (95%CI)	P value	HR (95%CI)	P value
Sex (female vs male)	0.62 (0.24-1.55)	0.302
Age (< 60 vs ≥ 60), years	0.74 (0.30-1.85)	0.520
BMI (≥ 25 vs < 25), kg/m2	0.77 (0.21-2.87)	0.701
CEA (< 3 vs ≥ 3), ng/mL	1.68 (0.67-4.20)	0.266
CA199 (< 37 vs ≥ 37), U/mL	1.31 (0.55-3.11)	0.543
ECOG PS (0 vs 1)	1.42 (0.54-3.74)	0.480
Staging (3 vs 4)	2.49 (1.15-5.40)	0.021	0.61 (0.15-2.45)	0.483
Differentiation (low vs medium-high)	0.08 (0.03-0.22)	< 0.001	0.11 (0.03-0.40)	< 0.001
Site (stomach vs gastric and esophageal binding)	1.14 (0.50-2.58)	0.760
Liver metastasis (no vs yes)	1.54 (0.59-3.98)	0.376
Peritoneal metastasis (no vs yes)	2.66 (1.13-6.26)	0.025	2.13 (0.54-8.44)	0.284
PD-L1 expression (CPS < 5 vs CPS ≥ 5)	0.07 (0.02-0.28)	< 0.001	0.13 (0.02-0.66)	0.014
MMR status (dMMR vs pMMR)	0.11 (0.04-0.31)	< 0.001	0.15 (0.04-0.61)	0.008
EBV status (infect vs no-infect)	0.27 (0.08-0.89)	0.031	0.32 (0.05-2.14)	0.242
CALLY index	0.86 (0.79-0.92)	< 0.001	0.88 (0.81-0.95)	0.002
NLR	1.16 (0.95-1.41)	0.144
SII	1.28 (1.10-1.48)	0.001	1.33 (1.05-1.69)	0.017

BMI: Body mass index; CEA: Carcinoembryonic antigen; CA199: Carbohydrate antigen 199; ECOG PS: Eastern Cooperative Oncology Group performance status; PD-L1: Programmed cell death ligand 1; CPS: Combined positive score; MMR: Mismatch repair; dMMR: Deficient mismatch repair; pMMR: Proficient mismatch repair; EBV: Epstein-Barr virus; CALLY: C-reactive protein-albumin-lymphocyte; NLR: Neutrophil-to-lymphocyte ratio; SII: Systemic immune inflammation.