Prognostic impact of histopathological features and serum inflammatory markers in patients with gastric cancer undergoing neoadjuvant therapy

Table 1 Characteristics of patient, n (%)

Characteristics	Patients (n = 177)
Age, median	63 (33-80)
Gender
Male	125 (70.6)
Female	52 (29.4)
ECOG
0	107 (60.5)
1	70 (39.5)
Body mass index
< 25	85 (48.0)
≥ 25	89 (50.3)
Unknown	3 (1.7)
Location
Cardia	93 (52.5)
Corpus	52 (29.4)
Antrum	32 (18.1)
Histological type
Adeno	141 (79.7)
Signet-ring cell	36 (20.3)
c-T stage
1-2	29 (16.4)
3-4	148 (83.6)
c-stage
1-2	47 (26.6)
3	130 (73.4)
c-N stage
N0	24 (13.6)
N+	153 (86.4)
Grade
1-2	87 (49.2)
3	90 (50.8)
Neoadjuvant FLOT	177 (100)
Interval between surgery and last chemotherapy, days	43.3 (10-158)
Radiological response
CR	12 (6.8)
PR	91 (51.4)
SD	71 (40.1)
PD	3 (1.7)
CEA (ng/L)
> 5 ng/L	45 (25.4)
< 5 ng/L	113 (63.8)
Missing	19 (10.7)
HER-2 status
Negative	158 (89.3)
Positive	9 (5.1)
Missing	10 (5.6)
MSI
Low	142 (80.2)
High	13 (7.3)
Missing	22 (12.4)
Surgery
Total gastrectomy	145 (81.9)
Distal	27 (15.3)
Proximal	5 (2.8)
Surgery
R0	157 (88.7)
R1	20 (11.3)
p-T stage
0-2	64 (36.2)
3-4	113 (63.8)
p-N stage
N0-1	100 (56.5)
N2-3	77 (43.5)
yp stage
0	22 (12.4)
1	29 (16.4)
2	44 (24.9)
3	82 (46.3)
Total lymph node
Positive	115 (64.3)
Negative	64 (35.7)
Lymphovascular invasion
Yes	107 (60.5)
No	70 (39.5)
Perineural invasion
Yes	87 (49.2)
No	90 (50.8)
Pathological response score
CR /near CR (1)	42 (23.7)
PR (2)	76 (42.9)
Poor/unresponsive (3)	59 (33.3)
Adjuvant
Yes	150 (84.7)
No	27 (15.3)
Chemotherapy regimen (n = 150)
FLOT, median 4 (4-8)	122 (81.3)
FOLFOX	16 (10.7)
FOLFIRI	3 (2.0)
FUFA	9 (6.0)
Post operative radiotherapy
Yes	62 (35.0)
No	115 (65.0)
Relapse
No	102 (57.6)
Yes	75 (42.4)
Dead	59 (33.3)
Alive	118 (66.7)
Hb mean g/dL (anemia)
Yes	106 (59.9)
No	71 (40.1)
NLR, median	2.06 (0.76-30.0)
Low	84 (47.5)
High	91 (51.4)
PLR, median	128.4 (43.9-572)
Low	87 (49.1)
High	88 (49.7)

ECOG: Eastern Cooperative Oncology Group; FLOT: 5-fluorouracil, leucovorin, oxaliplatin and docetaxel chemotherapy; c-T: Clinic tumor stage; c-N: Clinic lymph node stage; CR: Complete response; PR: Partial response; SD: Stable disease; PD: Progressive disease; MSI: Microsatellite instability; pT: Pathological tumor stage; pN: Pathological node stage; yp stage: Post neoadjuvant therapy stage; NLR: Neutrophil-to-lymphocyte count; PLR: Platelet-to-lymphocyte count; CEA: Carcinoembryonic antigen.

Table 2 Univariate analysis of disease-free survival by patient and tumor characteristics, n (%)

Population characteristics	Relapse (n = 75)	No relapse (n = 102)	P value	Univariate analysis of DFS, months	P value	Multivariate analysis P value
Age, years			0.41		0.080	HR: 1.64, P = 0.04, CI: 1.019-2.652
< 65	38 (50.7)	58 (56.9)		27.9
≥ 65	37 (49.3)	44 (43.1)		18.5
Gender			0.32		0.110
Male	50 (66.7)	75 (73.5)		33.4
Female	25 (33.3)	27 (26.5)		19.0
ECOG PS			0.04		0.070
0	39 (52.0)	68 (66.7)		33.4
1	36 (48.0)	34 (33.3)		19.9
Body mass index			< 0.001		< 0.001
≥ 25	25 (33.3)	64 (64.6)		NA
< 25	50 (66.7)	35 (35.4)		18.5
Histological type			< 0.001		< 0.001
Adeno	49 (65.3)	92 (90.2)		37.3
Signet ring cell	26 (34.7)	10 (9.8)		15.9
c-T stage			< 0.001		< 0.001
1-2	2 (2.7)	27 (26.5)		NA
3-4	73 (97.3)	75 (73.5)		20.9
c-N stage			0.006		0.011
Negative	4 (5.3)	20 (19.6)		NA
Positive	71 (94.7)	82 (80.4)		22.7
c-stage			< 0.001		< 0.001
1-2	6 (8.0)	41 (40.2)		NA
3	69 (92.0)	61 (59.8)		18.8
Grade			< 0.001		< 0.001
I-II	24 (32.0)	63 (61.8)		NA
III	51 (68.0)	39 (38.2)		17.7
HER-2 status			0.50		0.330
Negative	67 (93.1)	91 (95.8)		27.0
Positive	5 (6.9)	4 (4.2)		15.4
MSI			0.44		0.660
Low	59 (93.7)	83 (90.2)		24.0
High	4 (6.3)	9 (9.8)		20.9
pT stage			< 0.001		< 0.001
0-2	11 (14.7)	53 (52.0)		NA
3-4	64 (85.3)	49 (48.0)		18.8
pN stage			< 0.001		< 0.001
N0-1	21 (28.0)	79 (77.5)		NA
N2-3	54 (72.0)	23 (22.5)		14.0
yp stage			< 0.001		< 0.001
0-1	6 (8.0)	45 (44.1)		NA
2-3	69 (92.0)	57 (55.9)		18.8
Lymphovascular invasion						HR: 4.20, P < 0.001, CI: 2.000-8.860
No	10 (13.3)	60 (58.8)	< 0.001	NA	< 0.001
Yes	65 (86.7)	42 (41.2)		16.6
Perineural invasion			< 0.001		< 0.001	HR: 1.87, P = 0.03, CI: 1.043-3.374
No	19 (25.3)	71 (69.6)		NA
Yes	56 (74.7)	31 (30.4)		16.7
Surgery			< 000.1		< 0.001
R0	59 (78.7)	98 (96.1)		33.4
R1	16 (21.3)	4 (3.9)		13.0
Becker regression score			< 0.001		< 0.001
1	6 (8.0)	36 (35.3)		NA
2-3	69 (92.0)	66 (64.7)		20.9
Adjuvant therapy			0.001		< 0.001	HR: 3.58, P < 0.001, CI: 2.004-6.409
Yes	56 (74.7)	94 (92.2)		36.0
No	19 (25.3)	8 (7.8)		8.3
Post operative radiotherapy			0.014		0.120
No	41 (54.7)	74 (72.5)		44.9
Yes	34 (45.3)	28 (27.5)		19.0
NLR (median = 2.06)			0.350		0.300
Low	32 (43.8)	52 (51.0)		26.9
High	41 (56.2)	50 (49.0)		27.0
PLR (median = 128.4)			0.310		0.240
Low	33 (45.2)	54 (52.9)		36.0
High	40 (54.8)	48 (47.1)		27.0
Anemia, Hb < 12 g/dL			0.360		0.500
No	33 (44.0)	38 (37.3)		24.0
Yes	42 (56.0)	64 (62.7)		33.4
Albumin, 3.5 g/L			0.016		0.014	HR: 2.73, P = 0.01, CI: 1.278-5.858
High	64 (87.7)	98 (97.0)		27.9
Low	9 (12.3)	3 (3.0)		12.5
CEA			0.69		0.51
< 5 ngr/L	49 (73.1)	64 (70.3)		26.9
> 5 ngr/L	18 (26.9)	27 (29.7)		33.4

DFS: Disease-free survival; HR: Hazard ratio; CI: Confidence interval; ECOG PS: Eastern Cooperative Oncology Group performance status; c-T: Clinic tumor stage; c-N: Clinic lymph node stage; MSI: Microsatellite instability; pT: Pathological tumor stage; pN: Pathological node stage; yp stage: Post neoadjuvant therapy stage; NLR: Neutrophil-to-lymphocyte count; PLR: Platelet-to-lymphocyte count; CEA: Carcinoembryonic antigen; NA: Not available.

Table 3 Multivariate analysis of overall survival by patient and tumor characteristics, n (%)

Population characteristics	Alive, 118 (66.7)	Dead, 59 (33.3)	P value	Univariate analysis of OS, months	P value	Multivariate analysis, P value
Age, years			0.33		0.14
< 65	67 (56.8)	29 (49.2)		NA
≥ 65	51 (43.2)	27 (50.8)		33.6
Gender			0.35		0.12
Male	86 (72.9)	39 (66.1)		26.9
Female	32 (27.1)	20 (33.9)		45.9
ECOG PS			0.06		0.21
0	77 (65.3)	30 (50.8)		NA
1	41 (34.7)	29 (49.2)		29.0
Body mass index			0.003		0.04
≥ 25	68 (59.1)	21 (35.6)		NA
< 25	47 (40.9)	38 (64.4)		27.6
Histological type			< 0.001		< 0.001
Adeno	104 (88.1)	37 (62.7)		45.9
Signet ring cell	14 (11.9)	22 (37.3)		21.5
c-T stage			< 0001		0.001
1-2	28 (23.7)	1 (1.7)		NA
3-4	90 (76.3)	58 (98.3)		28.7
c-N stage			0.06		0.07
Negative	20 (16.9)	4 (6.8)		NA
Positive	98 (83.1)	55 (93.2)		33.4
c-stage			< 0.001		< 0.001
1-2	42 (35.6)	5 (8.5)		NA
3	76 (64.4)	54 (91.5)		27.6
Grade			0.001		< 0.001
I-II	68 (57.6)	19 (32.2)		NA
III	50 (42.4)	40 (67.8)		23.6
HER-2 status			0.990		0.850
Negative	105 (94.6)	53 (94.6)		36.0
Positive	6 (5.4)	3 (5.4)		15.7
MSI			0.34		0.340
Low	96 (89.7)	46 (95.8)		37.3
High	11 (10.3)	2 (4.2)		NA
pT stage			< 0.001		< 0.001
0-2	55 (46.6)	9 (15.3)		NA
3-4	63 (53.4)	50 (84.7)		26.9
pN stage			< 0.001		0.001
N0-1	84 (71.2)	16 (27.1)		NA
N2-3	34 (28.8)	43 (72.9)		21.5
yp stage			< 0.001		< 0.001
0-1	47 (39.8)	4 (6.8)		NA
2-3	71 (60.2)	55 (93.2)		26.9
Lymphovascular invasion			< 0.001		< 0.001	HR: 3.68, P < 0.003, CI: 1.536-8.829
No	63 (53.4)	7 (11.9)		NA
Yes	55 (46.6)	52 (88.1)		26.3
Perineural invasion			< 0.001		< 0.001
No	74 (62.7)	16 (27.1)		NA
Yes	44 (37.3)	43 (72.9)		26.3
Surgery			< 0.001		< 0.001	HR: 2.37, P = 0.01, CI: 1.219-4.634
R0	112 (94.9)	45 (76.3)		37.3
R1	6 (5.1)	14 (23.7)		14.8
Regression score			< 0.001		0.001
1	38 (32.2)	4 (6.8)		NA
2-3	80 (67.8)	55 (93.2)		27.6
Adjuvant			< 0.001		< 0.001	HR: 3.99, P < 0.001, CI: 2.253-7.097
Yes	110 (93.2)	40 (67.8)		NA
No	8 (6.8)	19 (32.2)		11.0
Postoperative radiotherapy			0.03		0.14
No	35 (29.7)	27 (45.8)		NA
Yes	83 (70.3)	32 (54.2)		26.3
NLR (median = 2.06)			0.27		0.33
Low	60 (50.8)	24 (42.1)		37.3
High	58 (49.2)	33 (57.9)		33.4
PLR (median = 128.4)			0.04		0.05
Low	65 (55.1)	22 (38.6)		NA
High	53 (44.9)	35 (61.4)		29.0
Anemia, < 12 g/dL			0.44		0.35
No	45 (38.1)	26 (44.1)		27.2
Yes	73 (61.9)	33 (55.9)		36.0
Albumin, 3.5 g/dL			0.001		0.01	HR: 2.50, P = 0.01, CI: 1.198-5.215
High	114 (97.4)	48 (84.2)		45.9
Low	3 (2.6)	9 (15.8)		15.9
CEA			0.85		0.94
< 5 ngr/L	77 (72.0)	36 (70.6)		36.0
> 5 ngr/L	30 (28.0)	15 (29.4)		37.3

OS: Overall survival; HR: Hazard ratio; CI: Confidence interval; ECOG PS: Eastern Cooperative Oncology Group performance status; c-T: Clinic tumor stage; c-N: Clinic lymph node stage; MSI: Microsatellite instability; pT: Pathological tumor stage; pN: Pathological node stage; yp stage: Post neoadjuvant therapy stage; NLR: Neutrophil-to-lymphocyte count; PLR: Platelet-to-lymphocyte count; CEA: Carcinoembryonic antigen; NA: Not available.