Safety and efficacy of a programmed cell death 1 inhibitor combined with oxaliplatin plus S-1 in patients with Borrmann large type III and IV gastric cancers

doi:10.4251/wjgo.v16.i4.1281

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World Journal of Gastrointestinal Oncology

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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World J Gastrointest Oncol. Apr 15, 2024; 16(4): 1281-1295
Published online Apr 15, 2024. doi: 10.4251/wjgo.v16.i4.1281

Table 1 Demographic data before surgery

Baseline variable	P-SOX group (n = 28)	SOX group (n = 61)	χ²	P value
Gender			0.080	0.777
Male	21 (75%)	44 (72.58%)
Female	7 (25%)	17 (27.42%)
Age			0.107	0.743
< 60	10 (35.71%)	24 (38.71%)
≥ 60	18 (64.29%)	37 (61.29%)
BMI			1.684	0.431
< 18.5	4 (14.29%)	10 (16.39%)
18.5-23	19 (67.86%)	33 (54.10%)
≥ 23	5 (17.86%)	18 (29.51%)
Tumor location			2.101	0.350
Upper	6 (21.43%)	15 (24.59%)
Middle	12 (42.86%)	33 (54.10%)
Lower	10 (35.71%)	13 (21.31%)
cT stage			0.297	0.586
T1/T2	5 (8.06%)	14 (22.58%)
T3/T4	23 (37.10%)	47 (77.42%)
cN stage			1.099	0.295
N0	3 (10.71%)	12 (19.67%)
N1-N3	25 (89.29%)	49 (80.32%)
cM stage			0.670	0.413
0	23 (82.14%)	54 (88.91%)
1	5 (17.86%)	7 (11.29%)
cTNM stage			0.351	0.554
I and II	7 (11.29%)	19 (32.26%)
III and IV	21 (33.87%)	42 (67.74%)
Neoadjuvant cycle			0.053	0.817
≤ 3	20 (71.43%)	45 (72.58%)
> 3	8 (28.57%)	16 (27.42%)
Operation mode			0.149	0.700
Open surgery	25 (89.29%)	56 (91.94%)
Laparoscopy	3 (10.71%)	5 (8.06%)
Adverse chemotherapy reaction			0.610	0.435
Yes	6 (21.43%)	9 (14.52%)
No	22 (78.57%)	52 (85.24%)
Differentiation			1.140	0.286
Well and middle	5 (17.86%)	6 (9.84%)
Poor and under-differentiated	23 (82.14%)	55 (90.16%)
Borrmann type			0.279	0.597
Big III	15 (53.58%)	29 (47.54%)
IV	13 (46.43%)	32 (52.46%)
AFP¹ (ng/mL)			0.566	0.452
≤ 8.1	20 (71.43%)	43 (70.49%)
> 8.1	2 (7.14%)	8 (13.11%)
Unknown	6 (21.43%)	10 (16.39%)
CEA¹ (ng/mL)			0.123	0.726
≤ 5	16 (57.14%)	35 (57.38%)
> 5	6 (21.43%)	16 (26.23%)
Unknown	6 (21.43%)	10 (16.39%)
CA199¹ (U/mL)			0.123	0.726
≤ 37	16 (57.14%)	35 (57.38%)
> 37	6 (21.43%)	16 (26.23%)
Unknown	6 (21.43%)	10 (16.39%)
CA724¹ (U/mL)			0.432	0.511
≤ 6.9	12 (42.86%)	32 (52.46%)
> 6.9	10 (35.71%)	19 (31.15%)
Unknown	6 (21.43%)	10 (16.39%)
CA125¹ (U/mL)			4.477	0.034^a
≤ 35	13 (46.43%)	42 (68.85%)
> 35	9 (32.14%)	9 (14.75%)
Unknown	6 (21.43%)	10 (16.39%)
CA50¹ (U/mL)			0.003	0.956
≤ 25	18 (64.29%)	42 (68.85%)
> 25	4 (14.29%)	9 (14.75%)
Unknown	6 (21.43%)	10 (16.39%)
Leukemia¹			0.228	0.892
≤ 3.5	1 (3.57%)	3 (4.92%)
3.5-9.5	19 (67.86%)	43 (70.49%)
> 9.5	3 (10.71%)	5 (8.20%)
Unknown	5 (8.20%)	10 (16.39%)
HGB¹			0.473	0.492
≤ 130	18 (64.29%)	36 (59.02%)
130-175	5 (8.20%)	15 (24.59%)
> 175	0	0
Unknown	5 (8.20%)	10 (16.39%)
Platelets¹			0.806	0.668
≤ 125	2 (7.14%)	2 (3.28%)
125-350	16 (57.14%)	39 (63.93%)
> 350	5 (8.20%)	10 (16.39%)
Unknown	5 (8.20%)	10 (16.39%)
Neutrophils¹			0.667	0.716
≤ 1.8	1 (3.57%)	4 (6.56%)
1.8-6.3	18 (64.29%)	41 (67.21%)
> 6.3	4 (14.29%)	6 (9.84%)
Unknown	5 (8.20%)	10 (16.39%)
Lymphocytes¹			0.084	0.772
≤ 1.1	8 (28.57%)	16 (26.23%)
1.1-3.2	15 (53.57%)	35 (57.38%)
> 3.2	0	0
Unknown	5 (8.20%)	10 (16.39%)
AFP² (ng/mL)			0.078	0.781
≤ 8.1	20 (71.43%)	46 (75.41%)
> 8.1	4 (14.29%)	11 (18.03%)
Unknown	4 (14.29%)	4 (6.56%)
CEA² (ng/mL)			2.806	0.094
≤ 5	22 (78.57%)	43 (70.49%)
> 5	2 (7.14%)	14 (22.95%)
Unknown	4 (14.29%)	4 (6.56%)
CA199² (U/mL)			0.507	0.476
≤ 37	22 (78.57%)	49 (80.33%)
> 37	2 (7.14%)	8 (13.11%)
Unknown	4 (14.29%)	4 (6.56%)
CA724² (U/mL)			2.034	0.154
≤ 6.9	18 (64.29%)	32 (52.46%)
> 6.9	6 (21.43%)	23 (37.70%)
Unknown	4 (14.29%)	6 (9.84%)
CA125² (U/mL)			0.043	0.835
≤ 35	23 (82.14%)	54 (88.52%)
> 35	1 (3.57%)	3 (4.92%)
Unknown	4 (14.29%)	4 (6.56%)
CA50² (U/mL)			0.583	0.445
≤ 25	22 (78.57%)	47 (77.05%)
> 25	2 (7.14%)	8 (13.11%)
Unknown	4 (14.29%)	6 (9.84%)
Leukemia²			1.181	0.554
≤ 3.5	7 (25%)	12 (19.67%)
3.5-9.5	16 (57.14%)	43 (70.49%)
> 9.5	3 (10.71%)	4 (6.56%)
Unknown	2 (7.14%)	2 (3.28%)
HGB²			0.662	0.416
≤ 130	23 (82.14%)	48 (78.69%)
130-175	3 (10.71%)	11 (18.03%)
Unknown	2 (7.14%)	2 (3.28%)
Platelets²			0.614	0.433
≤ 125	7 (25%)	21 (34.43%)
> 125	19 (67.86%)	38 (62.30%)
Unknown	2 (7.14%)	2 (3.23%)
Neutrophils²			0.730	0.673
≤ 1.8	6 (21.43%)	13 (21.31%)
1.8-6.3	17 (60.71%)	42 (68.85%)
> 6.3	3 (10.71%)	4 (6.56%)
Unknown	2 (7.14%)	2 (3.23%)

¹Tumor markers at first diagnosis.

²Preoperative tumor markers.

^aStatistically significant (P < 0.05).

SOX: S-1 + oxaliplatin; P-SOX: Programmed cell death 1 + S-1 + oxaliplatin; BMI: Body mass index; AFP: Alpha-fetoprotein; CEA: Carcinoembryonic antigen; CA199: Carbohydrate antigen199; HGB: Hemoglobin; cTNM: Clinical tumor node metastasis.

Table 2 Differences in response among the two groups

Baseline variable	P-SOX group (n = 28)	SOX group (n = 61)	P value
TRG			0.038
TRG0	4 (14.29%)	3 (4.92%)
TRG1	8 (28.57%)	8 (13.11%)
TRG2	13 (46.43%)	30 (49.18%)
TRG3	3 (10.71%)	20 (32.79%)
Subgroup analysis			0.013^a
TRG0/TRG1	12 (42.86%)	11 (18.03%)
TRG2/TRG3	16 (57.14%)	50 (81.97%)
ypT stage			0.272
0	4 (14.29%)	2 (3.23%)
1	1 (3.57%)	3 (4.92%)
2	6 (21.43%)	8 (13.11%)
3	2 (7.14%)	5 (8.20%)
4	15 (53.57%)	43 (70.49%)
ypN stage			0.130
0	11 (39.29%)	12 (19.67%)
1	5 (8.20%)	7 (11.48%)
2	5 (8.20%)	15 (24.59%)
3	7 (25%)	27 (44.26%)
ypM stage			0.099
	26 (92.86%)	48 (78.69%)
	2 (7.14%)	13 (21.31%)
ypTNM stage			0.196
pCR	4 (14.29%)	3 (4.92%)
I	4 (14.29%)	3 (4.92%)
II	4 (14.29%)	12 (19.67%)
III	13 (46.43%)	29 (47.54%)
IV	3 (10.71%)	14 (22.95%)
ypT stage			0.055
T0	4 (14.29%)	2 (3.28%)
T1-T4	24 (85.71%)	59 (96.72%)
ypN stage			0.05^a
N0	11 (39.29%)	12 (19.67%)
N1-N3	17 (60.71%)	49 (80.33%)
ypTNM stage			0.130
pCR	4 (14.29%)	3 (4.92%)
I-IV	24 (85.71%)	58 (95.08%)

^aStatistically significant (P < 0.05).

SOX: S-1 + oxaliplatin; P-SOX: Programmed cell death 1 + S-1 + oxaliplatin; pCR: Pathological complete response; TRG: Tumor regression grade.

Table 3 Clinicopathological results after surgery

Baseline variable	P-SOX group (n = 28)	SOX group (n = 61)	χ²	P value
Surgical approach			0.149	0.700
Laparoscopy	25 (89.29%)	56 (91.80%)
Open	3 (10.71%)	5 (8.20%)
Extent of resection			0.041	0.840
R0	23 (82.14%)	49 (80.33%)
R1	5 (17.86%)	12 (19.67%)
Nerve invasion			0.634	0.426
No	14 (50%)	25 (40.98%)
Yes	14 (50%)	36 (59.01%)
Vessel invasion			0.214	0.644
No	12 (42.86%)	23 (37.70%)
Yes	16 (57.14%)	38 (62.30%)
Harvested lymph nodes				0.354
Median	27.85 ± 10.27	31.45 ± 12.48
Positive lymph nodes				0.254
Median	4.71 ± 5.52	7.04 ± 8.84

SOX: S-1 + oxaliplatin; P-SOX: Programmed cell death 1 + S-1 + oxaliplatin.

Table 4 Postoperative complications

Baseline variable	P-SOX group (n = 28)	SOX group (n = 61)	P value
Total	5 (17.86%)	4 (6.56%)	0.101
Clavien-Dindo grading
Grade I-II	4	3	0.127
Fever	2	1	0.182
Lung infection	2	1	0.182
Pancreatic leakage	0	1	> 0.99
Cardiac insufficiency	0	1	> 0.99
Grade III	1	1	> 0.99
Anastomotic leakage	1	1	0.568
Grade IV	0	0	NA
Grade V	0	0	NA
Postoperative bleeding	94.82 ± 70.91	136.97 ± 119.59	0.020^a
Postoperative hospital stay	11.42 ± 5.67	11.20 ± 4.57	0.964

^aStatistically significant (P < 0.05).

SOX: S-1 + oxaliplatin; P-SOX: Programmed cell death 1 + S-1 + oxaliplatin; NA: Not available.

Table 5 Neoadjuvant treatment adverse effects

Baseline variable	P-SOX group (n = 28)	SOX group (n = 61)	χ²	P value
WHO grading
0	7 (25%)	16 (26.23%)	0.015	0.902
I	8 (28.57%)	21 (34.43%)	0.299	0.584
II	9 (32.14%)	15 (24.59%)	0.566	0.456
III	4 (14.29%)	9 (14.75%)	0.003	0.954
IV	0	0
WBC decreased			0.023	0.881
Grade 0, 1	24 (85.71%)	53 (86.88%)
Grade 2, 3, 4	4 (14.29%)	8 (13.11%)
HGB decreased			0.026	0.873
Grade 0, 1	22 (78.57%)	47 (77.05%)
Grade 2, 3, 4	6 (21.43%)	14 (22.95%)
Platelet count decreased			2.324	0.127
Grade 0, 1	24 (85.71%)	58 (95.08%)
Grade 2, 3, 4	4 (14.29%)	3 (4.92%)
Neutrophil count decreased			0.140	0.708
Grade 0, 1	24 (85.71%)	54 (88.52%)
Grade 2, 3, 4	4 (14.29%)	7 (11.48%)
Other adverse effects			0.458	0.499
Grade 0, 1	25 (89.29%)	59 (96.72%)
Grade 2, 3, 4	3 (10.71%)	2 (3.28%)

SOX: S-1 + oxaliplatin; P-SOX: Programmed cell death 1 + S-1 + oxaliplatin; WBC: White blood count; HGB: Hemoglobin.

Table 6 Comparison of tumor indexes between programmed cell death 1 + S-1 + oxaliplatin group and S-1 + oxaliplatin group before and after chemotherapy

	P-SOX group (n = 28)			SOX group (n = 61)
	First diagnosed	Preoperative	P value	First diagnosed	Preoperative	P value
AFP (ng/mL)			0.019^a			0.002^a
≤ 8.1	20 (71.43%)	20 (71.43%)		43 (70.49%)	46 (75.41%)
> 8.1	2 (7.14%)	4 (14.29%)		8 (13.11%)	11 (18.03%)
Unknown	6 (21.43%)	4 (14.29%)		10 (16.39%)	4 (6.56%)
CEA (ng/mL)			0.211			0.405
≤ 5	16 (57.14%)	22 (57.14%)		35 (57.38%)	43 (70.49%)
> 5	6 (21.43%)	2 (21.43%)		16 (26.23%)	14 (22.95%)
Unknown	6 (21.43%)	4 (14.29%)		10 (16.39%)	4 (6.56%)
CA199 (U/mL)			0.232			0.181
≤ 37	16 (57.14%)	22 (57.14%)		36 (59.02%)	49 (80.33%)
> 37	6 (21.43%)	2 (21.43%)		15 (24.59%)	8 (13.11%)
Unknown	6 (21.43%)	4 (14.29%)		10 (16.39%)	4 (6.56%)
CA724 (U/mL)			0.356			0.552
≤ 6.9	12 (42.86%)	18 (42.86%)		32 (52.46%)	32 (52.46%)
> 6.9	10 (35.71%)	6 (35.71%)		19 (31.15%)	23 (37.70%)
Unknown	6 (21.43%)	4 (14.29%)		10 (16.39%)	6 (9.84%)
CA125 (U/mL)			0.005^a			0.023^a
≤ 35	13 (46.43%)	23 (82.14%)		42 (68.85%)	54 (88.52%)
> 35	9 (32.14%)	1 (3.57%)		9 (14.75%)	3 (4.92%)
Unknown	6 (21.43%)	4 (14.29%)		10 (16.39%)	4 (6.56%)
CA50 (U/mL)			0.301			0.915
≤ 25	18 (64.29%)	22 (64.29%)		42 (68.85%)	47 (77.05%)
> 25	4 (14.29%)	2 (14.29%)		9 (14.75%)	8 (13.11%)
Unknown	6 (21.43%)	4 (14.29%)		10 (16.39%)	6 (9.84%)
Leukemia			0.366			0.005^a
≤ 3.5	1 (3.57%)	7 (25%)		3 (4.92%)	12 (19.67%)
3.5-9.5	19 (67.86%)	16 (57.14%)		43 (70.49%)	43 (70.49%)
> 9.5	3 (10.71%)	3 (10.71%)		5 (8.20%)	4 (6.56%)
Unknown	5 (8.20%)	2 (7.14%)		10 (16.39%)	2 (3.28%)
HGB			0.094			0.045^a
≤ 130	18 (64.29%)	23 (82.14%)		36 (59.02%)	48 (78.69%)
130-175	5 (8.20%)	3 (10.71%)		15 (24.59%)	11 (18.03%)
> 175	0	0		0	0
Unknown	5 (8.20%)	2 (7.14%)		10 (16.39%)	2 (3.28%)
Platelets			0.001^a			0.001^a
≤ 125	2 (7.14%)	7 (25%)		2 (3.28%)	21 (34.43%)
125-350	16 (57.14%)	19 (67.86%)		39 (63.93%)	35 (57.38%)
> 350	5 (8.20%)	0		10 (16.39%)	3 (4.92%)
Unknown	5 (8.20%)	2 (7.14%)		10 (16.39%)	2 (3.28%)
Neutrophils			0.077			0.005^a
≤ 1.8	1 (3.57%)	6 (21.43%)		4 (6.56%)	13 (21.31%)
1.9-6.3	18 (64.29%)	17 (60.71%)		41 (67.21%)	42 (68.85%)
> 6.3	4 (14.29%)	3 (10.71%)		6 (9.84%)	4 (6.56%)
Unknown	5 (8.20%)	2 (7.14%)		10 (16.39%)	2 (3.28%)

^aStatistically significant (P < 0.05).

SOX: S-1 + oxaliplatin; P-SOX: Programmed cell death 1 + S-1 + oxaliplatin; AFP: Alpha-fetoprotein; CEA: Carcinoembryonic antigen; CA199: Carbohydrate antigen199; HGB: Hemoglobin.

Citation: Bao ZH, Hu C, Zhang YQ, Yu PC, Wang Y, Xu ZY, Fu HY, Cheng XD. Safety and efficacy of a programmed cell death 1 inhibitor combined with oxaliplatin plus S-1 in patients with Borrmann large type III and IV gastric cancers. World J Gastrointest Oncol 2024; 16(4): 1281-1295
URL: https://www.wjgnet.com/1948-5204/full/v16/i4/1281.htm
DOI: https://dx.doi.org/10.4251/wjgo.v16.i4.1281