Neoadjuvant chemotherapy vs upfront surgery for gastric signet ring cell carcinoma: A retrospective, propensity score-matched study

Table 1 Demographic and clinical characteristics of patients, n (%)

Variable	All patients		P value	Matched patients		P value
	NAC and surgery (n = 36)	Surgery first (n = 108)		NAC and surgery (n = 36)	Surgery first (n = 36)
Age, yr (mean ± SD)	52 ± 11	57 ± 12	< 0.05	51.6 ± 11.4	49.9 ± 12.2	0.531
Sex			0.307			1
Male	21 (58.3)	75 (69.4)		21 (58.3)	21 (58.3)
Female	15 (41.7)	33 (30.6)		15 (41.7)	15 (41.7)
BMI, kg/m2 (mean ± SD)	24.1 ± 50	23.7 ± 3.4	0.527	24.1 ± 5.0	23.6 ± 3.4	0.649
ASA			0.731			1
I-II	34 (94.4)	99 (91.7)		34 (94.4)	33 (91.7)
III-IV	2 (5.6)	9 (8.3)		2 (5.6)	3 (8.3)
Comorbidity			0.152			1
Absent	28 (77.8)	68 (63.0)		28 (77.8)	27 (75.0)
Present	8 (22.2)	40 (37.0)		8 (22.2)	9 (25.0)
Tumor location			0.069			0.896
Upper	4 (11.1)	32 (29.6)		4 (11.1)	5 (13.9)
Middle	13 (36.1)	36 (33.3)		13 (36.1)	14 (38.9)
Lower	19 (52.8)	40 (37.0)		19 (52.8)	17 (47.2)
Clinical T stage			1			0.462
3	15 (41.7)	46 (42.6)		15 (41.7)	11 (30.6)
4	21 (58.3)	62 (57.4)		21 (58.3)	25 (69.4)
Clinical N stage			< 0.05			0.514
0	4 (11.1)	35 (32.4)		4 (11.1)	7 (19.4)
1-3	32 (88.9)	73 (67.6)		32 (88.9)	29 (80.6)
Clinical TNM stage			0.181			0.829
IIB	4 (11.1)	27 (25.0)		4 (11.1)	6 (16.7)
III	29 (80.6)	70 (64.8)		29 (80.6)	28 (77.8)
IVA	3 (8.3)	11 (10.2)		3 (8.3)	2 (5.6)

NAC: Neoadjuvant chemotherapy; BMI: Body mass index; ASA: American Society of Anesthesiologists.

Table 2 Neoadjuvant therapy and response, n (%)

Neoadjuvant therapy	n = 36
Clinical response
PR	18 (50)
SD	18 (50)
Mandard grade
1	3 (8.3)
2	4 (11.1)
3	4 (11.1)
4	3 (8.3)
5	22 (61.1)

PR: Partial remission; SD: Stable disease.

Table 3 Toxicity occurring during neoadjuvant chemotherapy, n (%)

Adverse event	Total	Grade 3/4
Leukopenia/neutropenia	9 (25.0)	6 (16.7)
Nausea/vomiting	6 (16.7)	3 (8.3)
Thrombocytopenia	2 (5.6)	1 (2.8)
Diarrhea	2 (5.6)	0
Hand-foot skin reaction	1 (2.8)	0
Allergy	1 (2.8)	0
Alopecia	1 (2.8)	0
Liver dysfunction	3 (8.3)	0

Table 4 Comparison of operative and postoperative parameters between neoadjuvant chemotherapy and surgery-first groups, n (%)

Variable	All patients		P value	Matched patients		P value
	NAC and surgery (n = 36)	Surgery first (n = 108)		NAC and surgery (n = 36)	Surgery first (n = 36)
Type of surgery			0.109			0.430
Total gastrectomy	24 (66.7)	87 (80.6)		24 (66.7)	28 (77.8)
Subtotal gastrectomy	12 (33.3)	21 (19.4)		12 (33.3)	8 (22.2)
Combined resection			1.000			1.000
Yes	1 (2.8)	4 (3.7)		1 (2.8)	2 (5.6)
No	35 (97.2)	104 (96.3)		35 (97.2)	34 (94.4)
Resection			1.000			1.000
R0	32 (88.9)	96 (88.9)		32 (88.9)	31 (86.1)
R1/R2	4 (11.1)	12 (11.1)		4 (11.1)	5 (13.9)
Operation time (min)	196 ± 54	197 ± 56	0.961	196 ± 54	190 ± 49	0.600
Blood loss (mL)	144 ± 139	127 ± 140	0.527	144 ± 139	129 ± 122	0.628
Blood transfusion			0.495			1.000
Yes	32 (88.9)	100 (92.6)		4 (11.1)	4 (11.1)
No	4 (11.1)	8 (7.4)		32 (88.9)	32 (88.9)
Morbidity			0.563			0.478
Yes	3 (8.3)	14 (13.0)		3 (8.3)	6 (16.7)
No	33 (91.7)	94 (87.0)		33 (91.7)	30 (83.3)
Postoperative hospital stay (d)	13.3 ± 4.9	13.9 ± 13.2	0.821	13.3 ± 4.9	14.2 ± 14.0	0.743
Borrmann type			0.082			0.450
I	3 (8.3)	10 (9.3)		3 (8.3)	1 (2.8)
II	10 (27.8)	11 (10.2)		10 (27.8)	6 (16.7)
III	17 (47.2)	69 (63.9)		17 (47.2)	22 (61.1)
IV	6 (16.7)	18 (16.7)		6 (16.7)	7 (19.4)
Tumor size (cm)	5.9 ± 3.3	5.9 ± 2.9	0.995	5.9 ± 3.2	6.0 ± 3.5	0.927
Neural invasion			0.700			0.474
Yes	18 (50.0)	74 (68.5)		17 (47.2)	13 (36.1)
No	18 (50.0)	34 (31.5)		19 (52.8)	23 (63.9)
Lymphovascular invasion			0.848			0.341
Yes	17 (47.2)	55 (50.9)		18 (50.0)	23 (63.9)
No	19 (52.8)	53 (49.1)		18 (50.0)	13 (36.1)
Pathological tumor classification			0.001			0.039
(y)pT0-1	5 (13.9)	0 (0)		5 (13.9)	0 (0)
(y)pT2	0 (0)	1 (0.9)		0 (0)	1 (2.8)
(y)pT3	9 (25.0)	40 (37.0)		9 (25.0)	15 (41.7)
(y)pT4a/4b	22 (61.1)	67 (62.0)		22 (61.1)	20 (55.6)
Pathologic nodal classification			0.09			0.671
(y)pN0	12 (34.3)	15 (13.9)		12 (34.3)	8 (22.2)
(y)pN1	3 (8.6)	12 (11.1)		3 (8.6)	3 (8.3)
(y)pN2	7 (20.0)	28 (25.9)		7 (20.0)	7 (19.4)
(y)pN3	13 (37.1)	53 (49.1)		13 (37.1)	18 (50.0)
Adjuvant chemotherapy			1.000			0.396
Yes	26 (72.2)	77 (71.3)		26 (72.2)	30 (83.3)
No	10 (27.8)	31 (28.7)		10 (27.8)	6 (16.7)

NAC: Neoadjuvant chemotherapy.

Table 5 Univariate analysis of overall survival before and after propensity score matching

Variable	All patients (n = 144)		Matched patients (n = 72)
	Hazard ratio	P value	Hazard ratio	P value
Age: < 60 yr vs ≥ 60 yr	1.248 (0.669-2.330)	0.486	0.778 (0.308-1.965)	0.595
Sex: Male vs female	0.991 (0.525-1.869)	0.977	0.974 (0.432-2.194)	0.949
Comorbidity: Present vs absent	1.228 (0.664-2.271)	0.513	1.830 (0.782-4.281)	0.163
NAC: Yes vs No	1.466 (0.777-2.768)	0.235	1.709 (0.756-3.816)	0.192
Extent of gastrectomy: Subtotal vs total	1.394 (0.966-1.883)	0.079	1.282 (0.479-3.435)	0.621
Tumor location: Lower vs upper	1.128 (0.507-2.514)	0.767	0.676 (0.218-2.522)	0.676
Tumor location: Middle vs upper	1.750 (0.758-3.832)	0.197	0.758 (0.228-2.522)	0.651
Tumor size: > 5 cm vs ≤ 5 cm	2.429 (1.282-4.603)	0.006	4.765 (1.886-12.038)	0.001
cT stage: T4a/4b vs T3	0.834 (0.461-1.570)	0.548	1.347 (0.575-3.153)	0.492
cN stage: N1-3 vs N0	1.748 (0.839-3.641)	0.136	0.971 (0.332-2.844)	0.957
Lymphovascular invasion: Yes vs No	2.291 (1.233-4.256)	0.009	2.600 (1.141-5.928)	0.023
Neural invasion: Yes vs No	1.390 (0.736-2.652)	0.310	2.304 (0.953-5.567)	0.064
Adjuvant chemotherapy: Yes vs No	0.673 (0.357-1.270)	0.222	0.654 (0.271-1.581)	0.346

NAC: Neoadjuvant chemotherapy.