Role of D2 gastrectomy in gastric cancer with clinical para-aortic lymph node metastasis

Table 1 Characteristics of the patients at baseline

Variable	≥ 60 yr old	< 60 yr old
Gender
Male	21 (91.3)	18 (72.0)
Female	2 (8.7)	7 (28.0)
Tumor location
Lower	2 (8.7)	4 (16.0)
Middle	9 (39.1)	12 (48.0)
Upper	12 (52.2)	9 (36.0)
Clinical tumor stage
T4	22 (95.7)	23 (92.0)
T3	1 (4.3)	2 (8.0)
Clinical nodal stage
N2-3	18 (78.3)	21 (84.0)
N0-1	5 (21.7)	4 (16.0)
Macroscopic type
4	4 (17.4)	3 (12.0)
1-3 or 5	19 (82.6)	22 (88.0)
Differentiation
Poorly differentiated	18 (78.3)	23 (92.0)
Well differentiated	5 (21.7)	2 (8.0)
Performance status
0	6 (26.1)	11 (44.0)
1	17 (73.9)	14 (56.0)

Table 2 Adverse events of preoperative chemotherapy

	Grade					Total	Grade ≥ 3 (%)
Toxicity	1	2	3	4	5
Diarrhea	4	2	2	0	0	8	4.2
Malaise	9	1	0	0	0	10	0.0
Anorexia	22	10	1	0	0	33	2.1
Nausea	20	11	2	0	0	33	4.2
Vomiting	6	4	0	0	0	10	0.0
Peripheral sensory neuropathy	13	4	0	0	0	17	0.0
Rash	1	0	1	0	0	2	2.1
Thromboembolic event	0	0	0	0	1	1	2.1
Anemia	11	2	3	0	0	16	6.3
Thrombocytopenia	7	6	4	1	0	18	10.4
Leukopenia	11	14	3	1	0	29	8.3
Neutropenia	7	5	9	4	0	25	27.1
Febrile neutropenia	4	0	0	0	0	4	0.0

Table 3 Lymph node information at baseline and after chemotherapy

Variable	No. of patients (%)
At baselinePAN station involved number
1-2	35 (72.9)
3-4	13 (27.1)
PAN station involved
n16a1	8 (16.7)
n16a2	24 (50.0)
n16b1	34 (70.8)
n16b2	9 (18.8)
Clinical response after chemotherapy
Overall (RECIST)
Target lesions
CR	2 (4.2)
PR	16 (33.3)
SD	6 (12.5)
PD	2 (4.2)
Non-target lesions only
CR	1 (2.1)
Non-CR/Non-PD	19 (39.6)
PD	2 (4.2)
Primary lesions (JGCA)
CR	3 (6.3)
PR	22 (45.8)
SD	19 (39.6)
PD	4 (8.3)
Metastatic lesions
CR	24 (50.0)
Non-CR	24 (50.0)

PAN: Para-aortic node; CR: Complete response; PR: Partial response; SD: Stable disease; PD: Progressive disease; NE: Not evaluable; RECIST: Response Evaluation Criteria in Solid Tumors (version 1.1); JGCA: Japanese Gastric Cancer Association.

Table 4 Demographic characteristics and response of para-aortic nodes

Variable	n	Response of PAN		P-value	Treatment		P-value
		Complete response	Residual tumor		With D2 resection	Without D2 resection
Tumor location				0.5647			0.0931
Upper	21	10 (41.7)	11 (45.8)		7 (31.8)	14 (53.8)
Middle	21	12 (50.0)	9 (37.5)		10 (45.5)	11 (42.3)
Lower	6	2 (8.3)	4 (16.7)		5 (22.7)	1 (3.8)
Clinical tumor stage				0.5510			0.4545
T3	3	2 (8.3)	1 (4.2)		2 (9.1)	1 (3.8)
T4	45	22 (91.7)	23 (95.8)		20 (90.9)	25 (96.2)
Clinical nodal stage				0.2673			0.1640
N0-1	9	6 (25.0)	3 (12.5)		6 (27.3)	3 (11.5)
N2-3	39	18 (75.0)	21 (87.5)		16 (72.7)	23 (88.5)
Macroscopic type				0.2199			0.5158
1-3 or 5	41	22 (91.7)	19 (79.2)		18 (81.8)	23 (88.5)
4	7	2 (8.3)	5 (20.8)		4 (18.2)	3 (11.5)
No. of PAN stations involved				0.1044			0.0012
1-2	35	20 (83.3)	15 (62.5)		21 (95.5)	14 (53.8)
3-4	13	4 (16.7)	9 (37.5)		1 (4.5)	12 (46.2)
Largest PAN in short-axis				0.0822			0.0899
< 10 mm	22	14 (58.3)	8 (33.3)		13 (59.1)	9 (34.6)
≥ 10 mm	26	10 (41.7)	16 (66.7)		9 (40.9)	17 (65.4)
Largest PAN in short-axis				0.0455			0.0026
< 15 mm	36	21 (87.5)	15 (62.5)		21 (95.5)	15 (57.7)
≥ 15 mm	12	3 (12.5)	9 (37.5)		1 (4.5)	11 (42.3)
Overall (RECIST)				0.0109			0.1405
CR + PR	19	10 (41.7)	9 (37.5)		7 (31.8)	12 (46.2)
SD + PD	10	1 (4.2)	9 (37.5)		3 (13.6)	7 (26.9)
NE	19	13 (54.2)	6 (25.0)		12 (54.5)	7 (26.9)
Primary lesions (JGCA)				0.0431			0.1405
CR + PR	25	16 (66.7)	9 (37.5)		14 (63.6)	11 (42.3)
SD + PD	23	8 (33.3)	15 (62.5)		8 (36.4)	15 (57.7)

PAN: Para-aortic node; CR: Complete response; PR: Partial response; SD: Stable disease; PD: Progressive disease; NE: Not evaluable; RECIST: Response Evaluation Criteria in Solid Tumors (version 1.1); JGCA: Japanese Gastric Cancer Association.

Table 5 Surgical and pathological findings

Variable	Chemotherapy plus surgery
Residual tumor
R0	14 (63.6)
R1-R2	8 (36.4)
Surgery approach
Laparoscopy	8 (36.4)
Open	14 (63.6)
Extent of gastric resection
Distal	11 (50.0)
Proximal	3 (13.6)
Total	7 (31.8)
Multiple organ resection	1 (4.5)
Macroscopic type
1-3 or 5	18 (81.8)
4	4 (18.2)
Histological type
Intestinal or mixed	11 (50.0)
Diffuse	11 (50.0)
Mandard grade
1-2	2 (9.1)
3	13 (59.1)
4-5	7 (31.8)
Tumor depth
ypT0	2 (9.1)
ypT1a	1 (4.5)
ypT1b	1 (4.5)
ypT2	1 (4.5)
ypT3	6 (27.3)
ypT4a	10 (45.5)
ypT4b	1 (4.5)
Lymph node metastases
ypN0	7 (31.8)
ypN1	5 (22.7)
ypN2	2 (9.1)
ypN3a	5 (22.7)
ypN3b	3 (13.6)

Table 6 Long-term survivors (more than 3 years)

Therapy	PAN			Response				Survival
	Target	SN		Overall	Primary	PAN		SR	OS	PFS	Status
C+S+C	NT	1		NE	PR	CR			65.1	65.1	Alive
C+S+C	NT	1		PR	PR	CR			72.4	72.4	Alive
C+S+C	NT	1		NE	PR	CR			62.1	62.1	Alive
C+S+C	NT	2		CR	CR	CR		L	52.8	16.8	Alive
C+S+CRT	NT	2		NE	SD	NN			70.1	70.1	Alive
C+S+CRT	NT	2		PR	PR	CR		PAN	50.7	16.2	Dead
C	T	3		CR	CR	CR		NA	37.8	20.9	Alive
C	T	3		PR	PR	NN		NA	36.3	36.3	Alive

C: Chemotherapy; S: D2 gastrectomy; CRT: Chemoradiotherapy; PAN: Para-aortic node; NT: Non-target lesions; SN: Para-aortic node station involved number; CR: Complete response; PR: Partial response; SD: Stable disease; PD: Progressive disease; NE: Not evaluable; NC: Non-complete response; SR: Sites of recurrence; L: Lung; OS: Overall survival; PFS: Progression-free survival.