Unnecessity of lymph node regression evaluation for predicting gastric adenocarcinoma outcome after neoadjuvant chemotherapy

Table 1 Classification of lymph node regression and residual tumor status

Group	Description
A	True negative LNs with no evidence of a preoperative therapy effect
B	No residual metastasis but presence of regression change in LNs
C	Residual metastasis with regression change in LNs
D	Metastasis with minimal or no regression change in LNs

LNs: Lymph nodes.

Table 2 Relationship between regression changes and residual tumor groups in lymph nodes and clinicopathological characteristics

Characteristics	n (%)	Lymph node regression groups				P value
		A, n (%)	B, n (%)	C, n (%)	D, n (%)
Total	192	30	24	98	40
Gender						0.162
Male	139 (72.4)	26 (86.7)	18 (75)	70 (71.4)	25 (62.5)
Female	53 (27.6)	4 (13.3)	6 (25)	28 (28.6)	15 (37.5)
Age, yr						0.869
< 55	89 (46.4)	12 (40)	11 (45.8)	46 (46.9)	20 (50)
≥ 55	103 (53.6)	18 (60)	13 (54.2)	52 (53.1)	20 (50)
Location						0.876
Esophagogastric junction	44 (22.9)	6 (20)	5 (20.8)	23 (23.5)	10 (25)
Proximal gastric	71 (37)	13 (43.3)	9 (37.5)	32 (32.7)	17 (42.5)
Distal gastric	77 (40.1)	11 (36.7)	10 (41.7)	43 (43.9)	13 (32.5)
Maximal diameter of tumor bed						0.259
< 4.5 cm	108 (56.2)	22 (73.3)	15 (62.5)	50 (51)	21 (52.5)
4.5-8 cm	64 (33.3)	8 (26.7)	7 (29.2)	34 (34.7)	15 (37.5)
> 8 cm	20 (10.4)	0 (0)	2 (8.3)	14 (14.3)	4 (10)
Histological differentiation						0.044
Well-moderately differentiated	45 (23.4)	12 (40)	8 (33.3)	18 (18.4)	7 (17.5)
Poorly differentiated	147 (76.6)	18 (60)	16 (66.7)	80 (81.6)	33 (82.5)
Laurén classification						0.336
Intestinal	77 (40.1)	17 (56.7)	11 (45.8)	37 (37.8)	12 (30)
Diffuse	73 (38)	8 (26.7)	10 (41.7)	37 (37.8)	18 (45)
Mixed	42 (21.9)	5 (16.7)	3 (12.5)	24 (24.5)	10 (25)
LVI						< 0.001
Negative	94 (49)	21 (70)	20 (83.3)	37 (37.8)	16 (40)
Positive	98 (51)	9 (30)	4 (16.7)	61 (62.2)	24 (60)
PNI						< 0.001
Negative	76 (39.6)	17 (56.7)	20 (83.3)	32 (32.7)	7 (17.5)
Positive	116 (60.4)	13 (43.3)	4 (16.7)	66 (67.3)	33 (82.5)
AJCC ypT category						< 0.001
0	11 (5.7)	3 (10)	6 (25)	2 (2)	0 (0)
1	20 (10.4)	5 (16.7)	6 (25)	6 (6.1)	3 (7.5)
2	23 (12)	5 (16.7)	5 (20.8)	10 (10.2)	3 (7.5)
3	57 (29.7)	13 (43.3)	4 (16.7)	32 (32.7)	8 (20)
4	81 (42.2)	4 (13.3)	3 (12.5)	48 (49)	26 (65)
AJCC ypN category						< 0.001
0	54 (28.1)	30 (100)	24 (100)	0 (0)	0 (0)
1	35 (18.2)	0 (0)	0 (0)	25 (25.5)	10 (25)
2	52 (27.1)	0 (0)	0 (0)	40 (40.8)	12 (30)
3	51 (26.6)	0 (0)	0 (0)	33 (33.7)	18 (45)
AJCC ypTNM stage						< 0.001
0	9 (4.7)	3 (10)	6 (25)	0 (0)	0 (0)
1	24 (12.5)	9 (0)	11 (58.3)	4 (29.2)	0 (0)
2	53 (27.6)	18 (60)	6 (25)	20 (20.4)	9 (22.5)
3	106 (55.2)	0 (0)	1 (4.2)	74 (75.5)	31 (77.5)
R0 resection						0.029
Yes	159 (82.8)	28 (93.3)	23 (95.8)	74 (75.5)	34 (85)
No	33 (17.2)	2 (6.7)	1 (4.2)	24 (24.5)	6 (15)
Mandard-TRG						< 0.001
1	11 (5.7)	3 (10)	6 (25)	2 (2)	0 (0)
2	23 (12)	7 (23.3)	5 (20.8)	11 (11.2)	0 (0)
3	40 (20.8)	8 (26.7)	9 (37.5)	21 (21.4)	2 (5)
4	78 (40.6)	6 (20)	4 (16.7)	47 (48)	21 (52.5)
5	40 (20.8)	6 (20)	0 (0)	17 (17.3)	17 (42.5)

A: True negative lymph nodes (LNs) with no evidence of a preoperative therapy effect; B: No residual metastasis but presence of regression change in LNs; C: Residual metastasis with regression change in LNs; D: Metastasis with minimal or no regression change in LNs; LVI: Lymph-vascular invasion; PNI: Perineural invasion; AJCC: American Joint Committee on Cancer; ypT: Pathological T category after therapy; ypN: Pathological N category after therapy.

Table 3 Histopathological regression change in lymph nodes, n (%)

Residual metastatic status in LNs	LNs with histopathological regression
	Total	Fibrosis	Foamy cells	Mucin pools
Yes, n = 1087	314	259 (82.5)	69 (22)	78 (24.8)
No, n = 3777	281	217 (77.2)	89 (31.7)	73 (26)
Total, n = 4864	595	476 (80)	158 (26.6)	151 (25.4)

LNs: Lymph nodes.

Table 4 Comparison of overall survival among groups created based on regression change and residual tumor in lymph nodes

Groups based on regression change in LNs	Kaplan-Meier analysis		Univariate Cox proportional hazards analysis
	5-year OS rate, %	P value1	HR	95% CI	P value
A	67.5	< 0.01	0.276	0.103-0.739	0.01
B	67.4		0.356	0.133-0.955	0.04
C	28.2		1.506	0.890-2.548	0.127
D	39.5		1

¹Groups A + B vs Groups C + D. A: True negative lymph nodes (LNs) with no evidence of a preoperative therapy effect; B: No residual metastasis but presence of regression change in LNs; C: Residual metastasis with regression change in LNs; D: Metastasis with minimal or no regression change in LNs; OS: Overall survival; LNs: Lymph nodes; HR: Hazard ratio.

Table 5 Comparison of progression-free survival among groups created based on regression change and residual tumor in lymph nodes

Groups based on regression change in LNs	Kaplan-Meier analysis		Univariate Cox proportional hazards analysis
	5-year PFS rate, %	P value1	HR	95% CI	P value
A	64.8	< 0.01	0.293	0.126-0.684	0.005
B	60.7		0.423	0.189-0.947	0.036
C	27.4		1.215	0.751-1.965	0.427
D	34.1		1

¹Groups A + B vs Groups C + D. A: True negative lymph nodes (LNs) with no evidence of a preoperative therapy effect; B: No residual metastasis but presence of regression change in LNs; C: Residual metastasis with regression change in LNs; D: Metastasis with minimal or no regression change in LNs; PFS: Progression-free survival; LNs: Lymph nodes; HR: Hazard ratio.