Prognostic factors and efficacy of postoperative chemotherapy in patients with gastric cancer with positive peritoneal cytology after gastrectomy

Table 1 Characteristics of patients with peritoneal lavage cytology-positive who underwent gastrectomy

Variables	All (n = 82)
Age	74.3 (42-96)
Sex
Male	56
Female	26
Performance status (ECOG)
0	56
1	20
2	6
Macroscopic type
Non-type 4	60
Type 4	22
Preoperative CEA
> ULN	21
≤ ULN	60
Unknown	1
Preoperative CA19-9	1
> ULN	25
≤ ULN	55
Unknown	2
Pathological T factor
T3	16
T4a	59
T4b	7
Pathological N factor
N0	1
N1-2	35
N3	46
Histology
Intestinal	31
Diffuse	51
HER2 status
Positive	14
Negative	46
Unknown	22
Surgery
Distal gastrectomy	43
Total gastrectomy	37
Proximal gastrectomy	2
Lymph node dissection
< D2	21
D2	48
D2+	13
Postoperative complication1
Yes (grade III)	22 (5)
No	60
Postoperative CTx
Yes	42
No	40

¹Clavien-Dindo classification.

ECOG: Eastern Cooperative Oncology Group; CEA: Carcinoembryonic antigen; ULN: Upper limit of normal; CA19-9: Carbohydrate antigen 19-9; HER2: Human epidermal growth factor receptor 2; CTx: Chemotherapy.

Table 2 Univariate and multivariate analysis of overall survival in patients with peritoneal lavage cytology-positive who underwent gastrectomy

Variables	n	Univariate analysis		Multivariate analysis
		HR (95%CI)	P value	HR (95%CI)	P value
Age (years)
≤ 75	41	Reference		Reference
> 75	41	2.20 (1.25-3.87)	0.006	1.81 (0.98-3.34)	0.057
Gender
Male	56	Reference		Reference
Female	26	1.79 (1.01-3.21)	0.048	1.45 (0.79-2.69)	0.233
Performance status (ECOG)
0, 1	76	Reference
2	6	1.03 (0.32-3.33)	0.955
BMI (kg/m2)
< 25	73	Reference
≥ 25	8	1.06 (0.42-2.67)	0.900
Preoperative CEA
≤ ULN	60	Reference
> ULN	21	1.50 (0.81-2.80)	0.201
Preoperative CA19-9
≤ ULN	55	Reference
> ULN	25	0.81 (0.42-1.56)	0.527
Surgery
DG, PG	45	Reference
TG	37	1.21 (0.70-2.10)	0.504
Lymph node dissection
≥ D2	61	Reference
< D2	21	1.36 (0.71-2.62)	0.354
Postoperative complication
No	60	Reference
Yes	22	1.47 (0.82-2.63)	0.200
Macroscopic type
Non-type 4	60	Reference
Type 4	22	1.63 (0.90-2.95)	0.107
Histology
Intestinal	31	Reference		Reference
Diffuse	51	1.89 (1.05-3.39)	0.034	2.65 (1.43-4.92)	0.002
pT
T3	16	Reference
T4	66	1.14 (0.53-2.42)	0.743
pN
N0-2	36	Reference
N3	46	1.08 (0.62-1.88)	0.785
Postoperative CTx
Yes	42	Reference		Reference
No	40	3.24 (1.82-5.78)	0.001	3.26 (1.75-6.08)	0.001

HR: Hazard ratio; CI: Confidence interval; ECOG: Eastern Cooperative Oncology Group; BMI: Body mass index; CEA: Carcinoembryonic antigen; ULN: Upper limit of normal; CA19-9: Carbohydrate antigen 19-9; DG: Distal gastrectomy; PG: Proximal gastrectomy; TG: Total gastrectomy; CTx: Chemotherapy.

Table 3 Characteristics of patients with peritoneal lavage cytology-positive who undergo gastrectomy followed by postoperative chemotherapy, n (%)

	Conventional chemotherapy1 (n = 25)	New combination chemotherapy2 (n = 17)	P value
Age (years)	72 (42-87)	66.2 (45-76)	0.073
Gender			0.589
Male	20 (80)	14 (82)
Female	5 (20)	3 (18)
Performance status (ECOG)			0.595
0, 1	24 (96)	17 (100)
2	1 (4)	0 (0)
Preoperative BMI (kg/m2)	21.1 (17.5-27.7)	21.7 (17.3-27.5)	0.531
CEA			0.437
≤ ULN	20 (83)	13 (76)
> ULN	4 (7)	4 (24)
CA19-9			0.565
≤ ULN	19 (79)	13 (76)
> ULN	5 (21)	4 (24)
Surgery			0.175
DG, PG	17 (68)	8 (47)
TG	8 (32)	9 (53)
Lymph node dissection			0.397
≥ D2	20 (80)	15 (88)
< D2	5 (20)	2 (12)
Postoperative complication			0.589
No	20 (80)	14 (82)
Yes	5 (20)	3 (18)
Macroscopic type			0.173
Non-type 4	9 (36)	3 (18)
Type 4	16 (64)	14 (82)
Histology			0.542
Intestinal	8 (32)	7 (41)
Diffuse	17 (68)	10 (59)
pT			0.463
T3	6 (24)	3 (18)
T4	19 (76)	14 (82)
pN			0.845
N0-2	11 (44)	8 (47)
N3	14 (56)	9 (53)
HER2 status			0.346
Positive	16	8
Negative	6	4
Unknown	3	5
BW decrease rate3			0.465
< 10%	18 (81)	15 (88)
≥ 10%	4 (19)	2 (12)
Pre-chemotherapy BMI (kg/m2)	19.9 (15.1-26.3)	20.7 (16.0-25.5)	0.377
Ccr (mL/minute)			0.174
< 60	14 (56)	13 (82)
≥ 60	11 (44)	4 (18)
Pre-chemotherapy CEA			0.534
≤ ULN	21 (84)	15 (88)
> ULN	4 (16)	2 (12)
Pre-chemotherapy CA19-9			0.630
≤ ULN	22 (92)	16 (94)
> ULN	2 (8)	1 (6)

¹Conventional chemotherapy includes S1 monotherapy or combination therapy with fluoropyrimidine + cisplatin.

²Novel chemotherapy include fluoropyrimidine + oxaliplatin or fluoropyrimidine + docetaxel.

³BW decrease rate represents the rate of weight loss from the time of surgery to the initiation of chemotherapy.

ECOG: Eastern Cooperative Oncology Group; BMI: Body mass index; CEA: Carcinoembryonic antigen; ULN: Upper limit of normal; CA19-9: Carbohydrate antigen 19-9; DG: Distal gastrectomy; PG: Proximal gastrectomy; TG: Total gastrectomy; HER2: Human epidermal growth factor receptor 2; BW: Body weight; Ccr: Creatineine clearance.

Table 4 Univariate and multivariate analysis of overall survival in patients with peritoneal lavage cytology-positive who underwent postoperative chemotherapy

Variables	n	Univariate analysis		Multivariate analysis
		HR (95%CI)	P value	HR (95%CI)	P value
Age (years)
≤ 75	29	Reference
> 75	13	1.39 (0.58-3.33)	0.460
Gender
Male	34	Reference
Female	8	1.55 (0.57-4.21)	0.395
Performance status (ECOG)
0, 1	41	Reference
2	1	1.82 (0.24-13.69)	0.562
Pre-chemotherapy BMI (kg/m2)
≥ 25	2	Reference
< 25	37	1.21 (0.16-9.04)	0.854
Pre-chemotherapy CEA
≤ ULN	36	Reference
> ULN	6	1.46 (0.49-4.30)	0.498
Pre-chemotherapy CA19-9
≤ ULN	38	Reference
> ULN	3	1.53 (0.36-6.60)	0.566
Surgery
DG, PG	25	Reference
TG	17	1.21 (0.52-2.82)	0.667
Lymph node dissection
≥ D2	35	Reference
< D2	7	1.09(0.37-3.22)	0.883
Postoperative complication
No	34	Reference
Yes	8	1.18 (0.43-3.21)	0.746
Macroscopic type
Non-type 4	14	Reference		Reference
Type 4	28	2.17 (0.92-5.09)	0.076	5.00 (1.76-14.25)	0.003
Histology
Intestinal	15	Reference
Diffuse	27	1.78 (0.72-4.38)	0.210
pT
T3	9	Reference
T4	33	1.86 (0.55-6.33)	0.318
pN
N0-2	19	Reference
N3	23	0.98 (0.42-2.27)	0.964
HER2 status
Positive	10	Reference
Negative	24	2.09 (0.69-6.39)	0.194
Postoperative CTx
New combination chemotherapy	17	Reference		Reference
Conventional chemotherapy	25	5.34 (1.77-16.14)	0.003	9.53 (2.54-35.79)	< 0.001
Duration of postoperative CTx
≥ 1 year	16	Reference		Reference
< 1 year	26	12.75 (2.98-55.55)	< 0.001	18.98 (3.68-97.93)	< 0.001
Ccr (mL/minute)
≥ 60	27	Reference
< 60	15	1.08 (0.45-2.61)	0.862
Grade III adverse event1
No	22	Reference
Yes	20	0.64 (0.27-1.55)	0.326

¹Common Terminology Criteria for Adverse Event v5.0.

HR: Hazard ratio; CI: Confidence interval; ECOG: Eastern Cooperative Oncology Group; BMI: Body mass index; CEA: Carcinoembryonic antigen; ULN: Upper limit of normal; CA19-9: Carbohydrate antigen 19-9; DG: Distal gastrectomy; PG: Proximal gastrectomy; TG: Total gastrectomy; HER2: Human epidermal growth factor receptor 2; CTx: Chemotherapy; Ccr: Creatineine clearance.

Table 5 Details of chemotherapy

	Conventional chemotherapy (n = 25)	New combination chemotherapy (n = 17)	P value
TI until the postoperative CTx (week)1	5.1 (1.9-9.1)	5.1 (1.4-10.6)	0.908
TTF (months)
Oral drug	12.6(1.6-49.0)	17.0 (3.0-45.8)	0.129
Intravenous	5.3 (1.2-8.6)	5.4 (2.1-11.4)	0.946
Course: Median (range)
Intravenous	3.6 (1-5)	6.2 (2-15)	0.098
RDI: Median (%)
Intravenous	74.5 (54.5-100)	82.1 (60.9-100)	0.276
< 80%: > 80%	4:2	7:10	0.001
Adverse event (grade III)2	8 (32%)	17 (71%)	0.014
Reason for CTx discontinuation
Recurrence: Adverse events, etc.3	15:4:6	4:4:9	0.051
Subsequent CTx after recurrence	10/15 (67%)	2/4 (50%)	0.475

¹Time interval until the postoperative chemotherapy refers to the period between surgery and the initiation of chemotherapy.

²Common Terminology Criteria for Adverse Event v5.0.

³Includes planned cessation, long-term administration, and ongoing treatment.

TI: Time interval; CTx: Chemotherapy; TTF: Time to failure; RDI: Relative dose intensity.