Neoadjuvant intra-arterial chemoembolization improves tumor pathological regression and survival in Borrmann type IV gastric cancer

Table 1 Comparison of patients’ clinical characteristics between before and after intra-arterial chemoembolization

Characteristics	Pre-IAC	Post-IAC	P value
Age (years)	66.0 (52.8-70.0)
Sex
Male	51 (72.9)
Female	19 (27.1)
ECOG PS
0	60 (85.7)
1	10 (14.3)
BMI (kg/m2)	21.8 ± 3.4	21.9 ± 3.5	0.712
Smoking	38 (54.3)
Drinking	35 (50.0)
Hypertension	14 (20.0)
T2DM	9 (12.9)
Hemoglobin (g/L)	113.6 ± 28.3	104.6 ± 25.5	P < 0.05a
Albumin (g/L)	37.9 ± 4.3	36.2 ± 5.0	P < 0.05a
CEA (ng/mL)	2.2 (1.3-4.8)	3.1 (2.1-5.0)	P < 0.05a
CA 19-9 (U/mL)	9.1 (6.6-15.8)	9.5 (6.7-14.4)	0.089
Tumor location
Fundus	23 (32.9)
Body	24 (34.3)
Antrum	18 (25.7)
Whole stomach	5 (7.1)
Degree of differentiation
Poor	49 (70)
Well	21 (30)
Tumor stage			P < 0.05a
cT3	18 (25.7)	19 (27.1)
cT4a	36 (51.4)	41 (58.6)
cT4b	16 (22.9)	10 (14.3)
Node stage			P < 0.05a
cN0	8 (11.4)	11 (15.7)
cN1	14 (20.0)	28 (40.0)
cN2	31 (44.3)	25 (35.7)
cN3	17 (24.3)	6 (8.6)
TNM stage			P < 0.05a
IIa	6 (8.6)	8 (11.4)
IIb	4 (5.7)	14 (20.0)
IIIa	29 (41.4)	31 (44.3)
IIIb	19 (27.1)	13 (18.6)
IIIc	12 (17.1)	4 (5.7)
IAC regimen
DOS	23 (32.9)
Nab-P-SOX	47 (67.1)
Number of IAC
1	48 (68.6)
≥ 2	22 (31.4)

^aP < 0.05.

Continuous variables are expressed as mean ± SD if normally distributed, or median and interquartile range if non-normally distributed; categorical variables as n (%). IAC: Intra-arterial chemoembolization; ECOG PS: Eastern Cooperative Oncology Group performance status; BMI: Body mass index; T2DM: Type 2 diabetes mellitus; CEA: Carcinoembryonic antigen; CA 19-9: Carbohydrate antigen 19-9; TNM: Tumor-node-metastasis; DOS: Docetaxel, oxaliplatin, and S-1; Nab-P-SOX: Nanoparticle albumin-bound paclitaxel, oxaliplatin, and S-1.

Table 2 Adverse events of intra-arterial chemoembolization plus chemotherapy

Side effects	G1	G2	G3	G4	≥ G3 (%)
Leukocytopenia	36	24	1	1	2.9
Anemia	42	7	1	0	1.4
Neutropenia	36	5	2	1	4.3
Platelets	35	0	0	0	0
Total bilirubin	14	0	0	0	0
AST	23	1	0	0	0
ALT	25	1	0	0	0
Creatinine	20	0	0	0	0
Nausea	70	0	0	0	0
Vomiting	65	0	0	0	0
Anorexia	66	1	0	0	0
Diarrhea	10	0	0	0	0
Abdominal pain	45	2	0	0	0
Fatigue	65	1	0	0	0
Thrombosis	2	0	0	0	0

AST: Aspartate aminotransferase; ALT: Alanine aminotransferase.

Table 3 Clinical and postoperative pathological findings, n (%)

	Clinical	Postoperative	P value
T			P < 0.05a
T0		14 (20.0)
T1		6 (8.6)
T2		8 (11.4)
T3	18 (25.7)	6 (8.6)
T4	52 (74.3)	36 (51.4)
N			P < 0.05a
N0	8 (11.4)	37 (52.9)
N1	14 (20.0)	9 (12.9)
N2	31 (44.3)	11 (15.7)
N3	17 (24.3)	13 (18.6)
M
M0	70 (100)	68 (97.1)
M1		2 (2.9)
TNM			P < 0.05a
0		14 (20.0)
I		8 (11.4)
II	10 (14.3)	18 (25.7)
III	60 (85.7)	28 (40.0)
IV		2 (2.9)
Pathological response
CR		14 (20.0)
PR		14 (20.0)
SD		40 (57.1)
PD		2 (2.9)

^aP < 0.05.

TNM: Tumor-node-metastasis; CR: Complete response; PR: Partial response; SD: Stable disease; PD: Progressive disease.

Table 4 Comparison of patients’ clinical characteristics between complete response/partial response and stable disease/progressive disease, n (%)/mean ± SD

Characteristics	CR/PR (n = 28)	SD/PD (n = 42)	P value
Age (years)	63.9 ± 13.6	56.3 ± 13.3	P < 0.05a
Sex			0.249
Female	5 (17.9)	14 (33.3)
Male	23 (82.1)	28 (66.7)
BMI (kg/m2), median (range)	22.2 (17.0-30.0)	20.8 (17.0-28.8)	P < 0.05a
Smoking	17 (60.7)	18 (42.9)	0.223
Hemoglobin (g/L)	103.8 ± 22.6	101.7 ± 26.7	0.824
Albumin (g/L)	35.5 ± 3.8	36.6 ± 5.8	0.403
CEA (ng/L)	3.0 ± 1.3	6.9 ± 21.1	0.101
CA 19-9 (ng/L)	12.0 ± 9.3	12.4 ± 9.9	0.881
Tumor location			0.268
Fundus	10 (35.7)	8 (19.0)
Body	7 (25.0)	17 (40.5)
Antrum	10 (35.7)	13 (31.0)
Whole stomach	1 (3.6)	4 (9.5)
T stage			0.077
T3	9 (32.1)	5 (11.9)
T4	19 (67.9)	37 (88.1)
N stage			0.267
N0	3 (10.7)	2 (4.8)
N1	10 (35.7)	8 (19.0)
N2	10 (35.7)	22 (52.4)
N3	5 (17.9)	10 (23.8)
TNM stage			0.077
II	7 (25.0)	3 (7.1)
III	21 (75.0)	39 (92.9)
Degree of differentiation			0.621
Poor	19 (67.9)	32 (76.2)
Well	9 (32.1)	10 (23.8)
Number of IAC			0.227
1	22 (78.6)	26 (61.9)
≥ 2	6 (21.4)	16 (38.1)
Procedures			0.517
TG	15 (53.6)	27 (64.3)
SG	13 (46.4)	15 (35.7)
Reconstruction methods			0.560
B-I and B-II	2 (7.1)	1 (2.4)
R-Y	26 (92.9)	41 (97.6)
Operation time (minutes)	254.8 ± 74.3	230.0 ± 73.1	0.115
Intraoperative blood loss (mL)	162.5 ± 147.4	117.9 ± 134.4	0.032
Postoperative complications	8 (28.6)	7 (16.7)	0.372

^aP < 0.05.

For continuous variables, the independent samples t-test was used when data followed a normal distribution and homogeneity of variance was met; otherwise, the Mann-Whitney U test was applied. For categorical variables, Pearson’s χ² test was used when all expected frequencies were ≥ 5; otherwise, Fisher’s exact test was applied. For data that followed a normal distribution, the paired t-test was used; for data that did not follow a normal distribution, the Wilcoxon signed-rank test was applied. For comparisons involving multicategorical variables, the paired Wilcoxon signed-rank test was employed. CR: Complete response; PR: Partial response; SD: Stable disease; PD: Progressive disease; BMI: Body mass index; CEA: Carcinoembryonic antigen; CA 19-9: Carbohydrate antigen 19-9; TNM: Tumor-node-metastasis; IAC: Intra-arterial chemotherapy; TG: Total gastrectomy; SG: Subtotal gastrectomy; B-I: Billroth I reconstruction; B-II: Billroth II reconstruction; R-Y: Roux-en-Y reconstruction.

Table 5 Univariable and multivariable analysis of overall survival

Risk factors	Univariate analysis		Multivariate analysis
	HR (95%CI)	P value	HR (95%CI)	P value
Age (per 10 years)	0.949 (0.738-1.221)	0.684	0.949 (0.727-1.237)	0.697
Sex (male/female)	1.040 (0.481-2.251)	0.919	-
BMI (kg/m2)	0.978 (0.873-1.096)	0.697	-
Smoking (yes/no)	1.052 (0.526-2.106)	0.886	-
Hemoglobin (g/L)	0.995 (0.983-1.007)	0.422	-
Degree of differentiation (poor/well)	1.488 (0.663-3.337)	0.335	-
Clinical tumor stage (III/II)	1.181 (0.412-3.384)	0.757	-
Number of IAC	0.643 (0.268-1.547)	0.324	-	-
Surgery type (TG/SG)	1.388 (0.678-2.842)	0.369	-
T-stage regression (yes/no)	0.532 (0.264-1.069)	0.076	0.512 (0.232-1.131)	0.098
N-stage regression (yes/no)	0.314 (0.155-0.636)	P < 0.05a	0.301 (0.138-0.655)	P < 0.05a
Tumor regression (CR and PR/SD and PD)	0.470 (0.217-1.016)	0.055	-	-
Complications (yes/no)	1.807 (0.851-3.836)	0.123	3.123 (1.283-7.597)	P < 0.05a

^aP < 0.05.

HR: Hazard ratio; CI: Confidence interval; BMI: Body mass index; IAC: Intra-arterial chemoembolization; TG: Total gastrectomy; SG: Subtotal gastrectomy; CR: Complete response; PR: Partial response; SD: Stable disease; PD: Progressive disease.

Table 6 Univariable and multivariable analysis of disease-free survival

Risk factors	Univariable analysis		Multivariate analysis
	HR (95%CI)	P value	HR (95%CI)	P value
Age (per 10 years)	0.917 (0.717-1.173)	0.490	0.919 (0.712-1.187)	0.518
Sex (male/female)	1.091 (0.507-2.350)	0.823	-
BMI (kg/m2)	0.953 (0.851-1.068)	0.407	-
Smoking (yes/no)	1.168 (0.590-2.315)	0.626	-
Hemoglobin (g/L)	0.993 (0.980-1.005)	0.234	-
Degree of differentiation (poor/well)	1.358 (0.609-3.026)	0.454	-
Clinical tumor stage (III/II)	1.166 (0.572-2.377)	0.672	-
Number of IAC	0.692 (0.305-1.571)	0.379	-
Surgery type (TG/SG)	1.508 (0.741-3.069)	0.257	-
T-stage regression (yes/no)	0.599 (0.301-1.191)	0.144	0.623 (0.289-1.344)	0.228
N-stage regression (yes/no)	0.313 (0.157-0.627)	P < 0.05a	0.314 (0.147-0.669)	P < 0.05a
Tumor regression (CR and PR/SD and PD)	0.446 (0.207-0.961)	P < 0.05a	-	-
Complications (yes/no)	1.996 (0.946-4.212)	0.070	3.189 (1.335-7.621)	P < 0.05a

^aP < 0.05.

HR: Hazard ratio; CI: Confidence interval; BMI: Body mass index; IAC: Intra-arterial chemoembolization; TG: Total gastrectomy; SG: Subtotal gastrectomy; CR: Complete response; PR: Partial response; SD: Stable disease; PD: Progressive disease.