Adjuvant chemotherapy with S-1 plus oxaliplatin improves survival of patients with gastric cancer after D2 gastrectomy: A multicenter propensity score-matched study

Table 1 Clinicopathologic features of the study population undergoing surgery alone and receiving adjuvant S-1 plus oxaliplatin chemotherapy before and after propensity score-matching n (%)

Variable	Before PSM (n = 807)			After PSM (n = 351)
	Surgery alone(n = 683)	Adjuvant SOX(n = 124)	P value	Surgery alone(n = 234)	Adjuvant SOX(n = 117)	P value
Age at diagnosis (yr)			0.099			0.443
< 35	9 (1.32)	3 (2.42)		3 (1.28)	0 (0.00)
35-60	303 (44.36)	66 (53.23)		118 (50.43)	62 (52.99)
> 60	371 (54.32)	55 (44.35)		113 (48.29)	55 (47.01)
Gender			0.83			1
Female	177 (25.92)	31 (25.00)		60 (25.64)	30 (25.64)
Male	506 (74.08)	93 (75.00)		174 (74.36)	87 (74.36)
Tumor location			0.063			0.424
None-Cardia cancer	425 (62.23)	88 (70.97)		152 (64.96)	81 (69.23)
Cardia cancer	258 (37.77)	36 (29.03)		82 (35.04)	36 (30.77)
Tumor grade			0.006			0.725
Moderate to well	50 (7.32)	4 (3.23)		14 (5.98)	4 (3.42)
Moderate	171 (25.04)	21 (16.94)		36 (15.38)	21 (17.95)
Poor to moderate	427 (62.52)	97 (78.23)		180 (76.92)	90 (76.92)
Early cancer or not reported	35 (5.12)	2 (1.61)		4 (1.71)	2 (1.71)
Pathological stage			< 0.001			0.604
IB1	302 (44.22)	8 (6.45)		20 (8.55)	8 (6.84)
II	127 (18.59)	29 (23.39)		48 (20.51)	29 (24.79)
III	254 (37.19)	87 (70.16)		166 (70.94)	80 (68.38)
Lymphatic and venous invasion			< 0.001			0.574
No	573 (83.89)	86 (69.35)		155 (66.24)	81 (69.23)
Yes	110 (16.11)	38 (30.65)		79 (33.76)	36 (30.77)
Perineural invasion			0.437			0.754
No	606 (88.73)	107 (86.29)		197 (84.19)	100 (85.47)
Yes	77 (11.27)	17 (13.71)		37 (15.81)	17 (14.53)

¹Patients of stage IB (pT2N0M0) without high-risk features including poorly differentiated or higher grade cancer, lymphovascular invasion, neural invasion, or < 50 years of age were not included. SOX: S-1 plus oxaliplatin; PSM: Propensity score-matching.

Table 2 Clinicopathologic features of the study population in adjuvant S-1 plus oxaliplatin group and adjuvant capecitabine plus oxaliplatin group before and after propensity score-matching n (%)

Variable	Before PSM (n = 184)			After PSM (n = 114)
	Adjuvant SOX(n = 124)	Adjuvant XELOX(n = 60)	P value	Adjuvant SOX(n = 57)	Adjuvant XELOX(n = 57)	P value
Age at diagnosis (yr)			0.322			0.848
≤ 60	69 (55.65)	38 (63.33)		34 (59.65)	35 (61.40)
> 60	55 (44.35)	22 (36.67)		23 (40.35)	22 (38.60)
Gender			1			0.404
Female	31 (25.00)	15 (25.00)		18 (31.58)	14 (24.56)
Male	93 (75.00)	45 (75.00)		39 (68.42)	43 (75.44)
Tumor location			0.567			1
None-Cardia cancer	88 (70.97)	45 (75.00)		42 (73.68)	42 (73.68)
Cardia cancer	36 (29.03)	15 (25.00)		15 (26.32)	15 (26.32)
Tumor grade			0.521			0.233
Moderate to well	4 (3.23)	1 (1.67)		4 (7.02)	1 (1.75)
Moderate	21 (16.94)	14 (23.33)		13 (22.81)	12 (21.05)
Poor to moderate	97 (78.23)	45 (75.00)		38 (66.67)	44 (77.19)
Early cancer or not reported	2 (1.61)	0 (0.00)		2 (3.51)	0 (0.00)
Pathological stage			0.038			0.708
IB1	8 (6.45)	11 (18.33)		7 (12.28)	9 (15.79)
II	29 (23.39)	10 (16.67)		12 (21.05)	9 (15.79)
III	87 (70.16)	39 (65.00)		38 (66.67)	39 (68.42)
Lymphatic and venous invasion			0.929			0.839
No	86 (69.35)	42 (70.00)		39 (68.42)	40 (70.18)
Yes	38 (30.65)	18 (30.00)		18 (31.58)	17 (29.82)
Perineural invasion			0.102			1
No	107 (86.29)	46 (76.67)		46 (80.70)	46 (80.70)
Yes	17 (13.71)	14 (23.33)		11 (19.30)	11 (19.30)

¹Patients of stage IB (pT2N0M0) without high-risk features including poorly differentiated or higher grade cancer, lymphovascular invasion, neural invasion, or < 50 years of age were not included. SOX: S-1 plus oxaliplatin; XELOX: Capecitabine plus oxaliplatin; PSM: Propensity score-matching.

Table 3 Prognostic factors of overall survival in 351 matched patients with gastric cancer after D2 dissection

Variable	Hazard ratio	95%CI	P value
Age at diagnosis (yr)
≤ 60	1
> 60	1.629	(1.155-2.297)	0.005
Gender
Female	1
Male	1.073	(0.731-1.576)	0.718
Tumor location
None-Cardia cancer	1
Cardia cancer	0.862	(0.605-1.227)	0.409
Tumor grade			0.888
Moderate to well	1
Moderate	1.37	(0.558-3.363)	0.492
Poor to moderate	1.283	(0.551-2.983)	0.563
Early cancer or not reported	1.972	(0.205-18.948)	0.557
Pathological stage			< 0.001
IB1	1
II	4.691	(0.994-22.128)	0.051
III	9.857	(2.174-44.686)	0.003
Lymphatic and venous invasion
No	1
Yes	0.963	(0.670-1.384)	0.837
Perineural invasion
No	1
Yes	1.679	(1.091-2.585)	0.019
Adjuvant chemotherapy
Surgery alone	1
SOX	0.475	(0.326-0.693)	< 0.001

¹Patients of stage IB (pT2N0M0) without high-risk features including poorly differentiated or higher grade cancer, lymphovascular invasion, neural invasion, or < 50 years of age were not included. SOX: S-1 plus oxaliplatin.

Table 4 Adverse events reported by ≥ 10% of patients who received adjuvant S-1 plus oxaliplatin chemotherapy

Event	Adjuvant SOX (n = 124)
	Grade 1	Grade 2	Grade 3	Grade 4	All grade	Grade 3 or 4
	No. of patients				%
Leukopenia	46	18	8	3	60.5	8.9
Neutropenia	34	31	19	9	75	22.6
Anemia	35	3	1	1	32.3	1.6
Thrombocytopenia	22	18	7	0	37.9	5.6
Elevated total serum bilirubin level	23	2	1	0	21	0.8
Elevated AST/ALT level	53	5	1	1	48.4	1.6
Elevated ALP level	12	3	1	0	12.9	0.8
Nausea	41	19	4	-	51.6	3.2
Vomiting	17	16	4	0	29.8	3.2
Diarrhea	33	7	1	0	33.1	0.8
Peripheral sensory neuropathy	61	4	0	-	52.4	0

Grades of adverse events were defined according to the Common Terminology Criteria for Adverse Events (Version 4.0). SOX: S-1 plus oxaliplatin; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; ALP: Alkaline phosphatase; -: Not available.