Nomogram for predicting pathological complete response to neoadjuvant chemotherapy in patients with advanced gastric cancer

Table 1 Patient characteristics and P value of univariate analysis

Characteristics	Total	Non-pCR	pCR	P value
Number of patients	208	181	27
Sex
Male	161	138	23	0.3
Female	47	43	4
Age	59 (50-64)	59 (50-64)	59 (51-63)	0.631
BMI	22 ± 2.9	22 ± 2.9	22 ± 3.4	0.226
Location
Esophago-gastric junction	61	53	8	0.1
Upper third	25	20	5
Middle third	43	42	1
Lower third	79	66	13
Tumor differentiation
Well differentiated	8	5	3	0.025
Moderately differentiated	56	46	10
Moderately-poorly differentiated	28	22	6
Poorly differentiated	94	87	7
Signet ring cell	22	21	1
Clinical T staging
T3	103	88	15	0.725
T4a	84	75	9
T4b	21	18	3
Clinical N staging
N0	4	4	0	0.435
N+	204	177	27
Regimen
mFLOT	122	102	20	0.217
SOX/FOLFOX/XELOX	75	69	6
other	11	10	1
Cycles	4 (4-5)	4 (4-5)	4 (4-4)	0.766
WBC, 109/L)	6.47 ± 1.89	6.51 ± 1.93	5.80 ± 1.48	0.061
RBC, 1012/L	4.39 (3.84-4.72)	4.42 (3.9-4.73)	4.23 (3.69-4.55)	0.263
NEU, 109/L	3.76 (2.82-4.9)	3.86 (2.89-4.97)	3.05 (2.61-3.58)	0.589
NEUR	0.61 ± 0.1	0.62 ± 0.11	0.57 ± 0.07	0.2
LYM, 109/L	1.62 (1.26-2.07)	1.6 (1.22-2.08)	1.71 (1.42-2.07)	0.107
LYMR	0.26 (0.2-0.33)	0.24 (0.2-0.33)	0.32 (0.28-0.35)	0.001
MONO, 109/L	0.5 (0.4-0.64)	0.51 (0.41-0.64)	0.44 (0.31-0.57)	0.017
MONOR	0.08 (0.07-0.1)	0.08 (0.07-0.1)	0.08 (0.06-0.09)	0.211
EOS, 109/L	0.13 (0.08-0.21)	0.13 (0.08-0.21)	0.15 (0.08-0.22)	0.428
EOSR	0.02 (0.01-0.03)	0.02 (0.01-0.03)	0.03 (0.02-0.05)	0.071
BASO, 109/L	0.03 (0.02-0.04)	0.03 (0.02-0.04)	0.04 (0.01-0.05)	0.513
BASOR	0.01 (0-0.01)	0.01 (0-0.01)	0.01 (0-0.01)	0.299
HGB, g/L	123 (97.18-137)	123 (99-137)	118 (81-134.1)	0.373
PLT, 109/L	262.5 (211.7-330)	262 (212.8-328)	263 (197-358)	0.809
UA, μmol/L	348.7 (274-420.8)	342 (263.9-413.3)	407.3 (341-481.6)	0.003
Cr, μmol/L	78.4 (66.4-89.1)	77.3 (64.92-89)	81.09 (75.5-89.5)	0.176
ALT, U/L	13.8 (9.86-18.98)	13.79 (9.91-19)	14 (9.69-18)	0.958
AST, U/L	18.2 (14.8-22.1)	18.5 (14.84-22.11)	17.02 (13.39-22.1)	0.37
r-GT, U/L	18.8 (14.8-30.4)	18.8 (14.61-30.28)	18.51 (15-34.71)	0.672
TP, g/L	68.2 ± 6.53	67.86 ± 6.52	70.37 ± 6.3	0.89
Alb, g/L	39.81 ± 4.39	39.59 ± 4.47	41.23 ± 3.53	0.1
AKP, U/L	84.6 (68.1-100.5)	85.61 (70-101.55)	77.44 (58.97-91)	0.156
PA, g/L	0.2 ± 0.06	0.2 ± 0.06	0.21 ± 0.05	0.59
TBIL, μmol/L	11 (8.67-14.45)	11.12 (8.85-14.39)	10.48 (6.92-16.24)	0.421
DBIL, μmol/L	2.21 (1.68-3.08)	2.25 (1.68-3.08)	2.05 (1.46-2.99)	0.29
LD, U/L	167 (147.9-194.7)	167 (147.8-191.4)	168 (149.5-197.3)	0.548
CH, mmol/L	4.79 ± 1.1	4.73 ± 1.1	5.15 ± 1	0.26
TG, mmol/L	1.06 (0.83-1.38)	1.03 (0.83-1.38)	1.15 (0.81-1.47)	0.588
HDL, mmol/L	1.15 (0.95-1.32)	1.14 (0.95-1.3)	1.24 (1.06-1.41)	0.088
LDL, mmol/L	3.06 (2.52-3.50)	2.95 (2.47-3.51)	3.25 (2.92-3.50)	0.08
CRP, mg/L	2.36 (0.91-9.09)	2.37 (0.91-9.78)	2.17 (0.83-5.85)	0.593
CA125, U/mL	14.95 (9.4-23.55)	15.1 (9.5-24.4)	12.5 (7.6-20)	0.375
CEA, ng/mL	2.8 (1.43-5.92)	2.51 (1.38-4.88)	8.04 (2.36-26.2)	0.002
CA199, U/mL	9.71 (2.86-40.35)	8.87 (2.4-47.64)	15.32 (4.46-34.15)	0.303
CA-153, U/mL	7.5 (5.38-11)	7.4 (5.3-10.8)	8.3 (6.2-11.9)	0.289
AFP, ng/mL	2.7 (1.97-4.28)	2.67 (1.94-4.19)	2.78 (2.06-10.96)	0.551
Blood type
Type O	75	72	3	0.005
Type A	61	46	15
Type B	50	43	7
Type AB	22	20	2

WBC: White blood cell; RBC: Red blood cell; NEU: Neutrophil cell; NEUR: Neutrophil cell ratio; LYM: Lymphocyte; LYMR: Lymphocyte ratio; MONO: Monocyte; MONOR: Monocyte ratio; EOS: Eosinophil; EOSR: Eosinophil ratio; BASO: Basophil; BASOR: Basophil ratio; HGB: Hemoglobin; PLT: Platelets; UA: Uric acid; Cr: Creatinine; ALT: Alanine transaminase; AST: Aspartate transaminase; r-GT: Gamma-glutamyl transpeptidase; TP: Total protein; Alb: Albumin; AKP: Alkaline phosphatase; PA: Prealbumin; TBIL: Total bilirubin; DBIL: Direct bilirubin; LD: Lactate dehydrogenase; CH: Cholesterol; TG: Triglyceride; HDL: High density lipoprotein; LDL: Low density lipoprotein; CRP: C-reactive protein; CA125: Carbohydrate antigen 125; CEA: Carcinoembryonic antigen; CA199: Carbohydrate antigen 199; CA-153: Carbohydrate antigen 153; AFP: Alpha fetoprotein; BMI: Body mass index.

Table 2 Hematological toxicity of neoadjuvant chemotherapy, n (%)

Items	mFLOT, n = 122		FOLFOX, SOX/XELOX, n = 75		Other1, n = 11
Grade	3	4	3	4	3	4
Anemia	41 (33.6)	15 (12.3)	18 (24)	9 (12)	6 (54.5)	3 (27.3)
Neutropenia	24 (19.7)	26 (21.3)	25 (33.3)	5 (6.7)	5 (45.5)	1 (9.1)
Febrile-neutropenia	6 (4.9)	0	1 (1.3)	0	0	0
Thrombocytopenia	8 (6.6)	4 (3.3)	8 (10.7)	0	0	5 (45.5)

¹Other regimen includes 10 cases of Docetaxel plus fluorouracil and 1 case of docetaxel monotherapy. mFLOT means Docetaxel 50-60 mg/m² + Oxaliplatin 85 mg/m² + Fluorouracil 2800 mg/m² intravenous injection over 48 h; every 2 wk. SOX means Oxaliplatin 130 mg/m² intravenous injection + Tegafur Gimeracil Oteracil Potassium Capsule 40-60 mg bid D1-D14; every 3 wk. XELOX means Oxaliplatin 130 mg/m² + Capecitabine 1000 mg/m² bid D1-D14; every 3 wk. FOLFOX means Oxaliplatin 85 mg/m² + Fluorouracil 2800 mg/m² continuous intravenous injection over 48 h; every 2 wk.

Table 3 Postoperative complication and mortality, n (%)

Items	Total, n = 208	Non-pCR, n = 181	pCR, n = 27	P value
Any complication	44 (21.2)	41 (22.7)	3 (11.1)	0.25
Abdominal abscess	31 (14.9)	28 (15.5)	3 (11.1)	0.60
Anastomotic leakage	10 (4.8)	9 (5)	1 (3.7)	0.08
Duodenal stump leakage	2 (1)	1 (0.6)	1 (3.7)	0.13
Other leakage1	8 (3.8)	7 (3.9)	1 (3.7)	0.97
Bleeding	4 (1.9)	4 (2.2)	0	0.44
Intra-abdominal bleeding	3 (1.4)	3 (1.7)	0	0.50
Anastomotic bleeding	1 (0.5)	1 (0.6)	0	0.70
Pneumonia	12 (5.8)	10 (5.5)	2 (7.4)	0.13
Pancreatic fistula	3 (1.4)	2 (1.1)	1 (3.7)	0.30
Obstruction or ileus	3 (1.4)	2 (1.1)	1 (3.7)	0.30
Diarrhea	2 (1)	2 (1.1)	0	0.59
Diabetes	1 (0.5)	0	1 (3.7)	0.01
Reoperation	2 (1)	1 (0.6)	1 (3.7)	0.13
Death before discharge	1 (0.5)	1 (0.6)	0	0.70

¹Other leakage: Includes esophagojejunal anastomotic leakage, gastrojejunal anastomotic leakage and intestinal anastomotic leakage. pCR: Pathological complete response.

Table 4 Postoperative adjuvant chemotherapy

Adjuvant chemotherapy	n = 208	%
Platin-based doublet regimen
FOLFOX	75	36.1
SOX	48	23.1
XELOX	3	1.4
Taxanes contained regimen
mFLOT	15	7.2
Docetaxel plus fluorouracil	25	12.0
Docetaxel plus S-1 capsule	2	1.0
Monotherapy
S-1 capsule	13	6.3
Capecitabine	9	4.3
No adjuvant chemotherapy	18	8.7

mFLOT means Docetaxel 50-60 mg/m² + Oxaliplatin 85 mg/m² + Fluorouracil 2800 mg/m² intravenous injection over 48 h; every 2 wk. SOX means Oxaliplatin 130 mg/m² intravenous injection + Tegafur Gimeracil Oteracil Potassium Capsule 40-60 mg bid D1-D14; every 3 wk. XELOX means Oxaliplatin 130 mg/m² + Capecitabine 1000 mg/m² bid D1-D14; every 3 wk. FOLFOX means Oxaliplatin 85 mg/m² + Fluorouracil 2800 mg/m² continuous intravenous injection over 48 h; every 2 wk.

Table 5 Result of multivariate analysis

Items	OR	95%CI	P value
UA, μmol/L	1.48	1.48-2.2	0.052
Blood type	1.2	1.2-1.92	0.45
Tumor differentiation	0.65	0.65-1	0.048
MONO, 109/L	0.73	0.73-0.98	0.038
CEA, ng/mL	1.57	1.57-2.01	< 0.01
LYMR	1.08	1.08-1.14	< 0.01

UA: Uric acid; MONO: Monocyte; CEA: Carcinoembryonic antigen; LYMR: Lymphocyte ratio; OR: Odd ratio; CI: Confidence interval.