Survival in gastric cancer in relation to postoperative adjuvant therapy and determinants

Table 1 Demographic and clinicopathologic characteristics of patients n (%)

	Follow up (yr)		Total (n = 201)	P value
	Before 2008 (n = 127)	2008-2010 (n = 74)
Demographics
Age (yr), mean ± SD	56.7 ± 12.7	54.7 ± 10.3	56.0 ± 11.9	0.2701
Gender
Female	36 (28.3)	25 (33.8)	61 (30.3)	0.4192
Male	91 (71.7)	49 (66.8)	140 (69.7)
Clinicopathologic characteristics
Pathological type
AdenoCa	92 (72.4)	39 (52.7)	131 (65.2)	0.0012
Signet ring	33 (26.0)	31 (41.9)	64 (31.8)
Squamous	2 (1.6)	0	0
Mucinous	0	4 (5.4)	4 (2.0)
Tumor size
< 5 cm	49 (43.0)	28 (47.5)	77 (44.5)	0.0552
5-10 cm	60 (52.6)	23 (39.0)	83 (48.0)
> 10 cm	5 (4.4)	8 (13.6)	13 (7.5)
Tumor location
Antrum	56 (44.8)	37 (51.4)	93 (47.2)	0.2492
Cardia	29 (23.2)	15 (20.8)	44 (22.3)
Corpus	37 (29.6)	15 (20.8)	52 (26.4)
> 1 region	3 (2.4)	5 (6.9)	8 (4.1)
Differentiation
Well	2 (1.7)	1 (1.8)	3 (1.7)	0.8852
Moderate	41 (35.3)	18 (31.6)	59 (34.1)
Poor	73 (62.9)	38 (66.7)	111 (64.2)
Surgery type
Total gastrectomy	64 (50.4)	37 (50.0)	101 (50.2)	0.9572
Subtotal gastrectomy	63 (49.6)	37 (50.0)	100 (49.8)
Surgical margin
Negative	114 (89.8)	61 (82.4)	175 (87.1)	0.1352
Positive	13 (10.2)	13 (17.6)	26 (12.9)
Vascular involvement	81 (64.8)	58 (80.6)	139 (70.6)	0.0333
Perineural involvement	80 (64.0)	52 (72.2)	132 (68.4)	0.4263
TM stage
T1T2	40 (31.5)	23 (31.1)	63 (31.3)	0.9512
T3T4	87 (68.5)	51 (68.9)	138 (68.7)
Nodal stage
N0	30 (24.2)	12 (16.7)	42 (21.4)	0.2542
N1	55 (44.4)	26 (36.1)	81 (41.3)
N2	26 (21.0)	24 (33.3)	50 (25.5)
N3	13 (10.5)	10 (13.9)	23 (11.7)
AJCC 2002 nodal stage
N0	32 (25.2)	14 (18.9)	46 (22.9)	0.3642
N1	62 (48.8)	35 (47.3)	97 (48.3)
N2	26 (20.5)	15 (20.3)	41 (20.4)
N3	6 (4.7)	8 (10.8)	14 (7.0)
NX	1 (0.8)	2 (2.7)	3 (1.5)
AJCC 2010 nodal stage
N0	32 (25.2)	14 (18.9)	46 (22.9)	0.2312
N1	32 (25.2)	12 (16.2)	44 (21.9)
N2	31 (24.4)	23 (31.1)	54 (26.9)
N3a	25 (19.7)	15 (20.3)	40 (19.9)
N3b	6 (4.7)	8 (10.8)	14 (7.0)
Nx	1 (0.8)	2 (2.7)	3 (1.5)
Dissected lymph nodes, median (IQR)	15 (13.0)	17.5 (13.0)	16 (14.0)	0.2164
LN1
< 15	66 (52.4)	30 (40.5)	96 (48.0)	0.1062
≥ 16	60 (47.6)	44 (59.5)	104 (52.0)
LN2
< 10	38 (30.2)	18 (24.3)	56 (28.0)	0.3752
≥ 11	88 (69.8)	56 (75.7)	144 (72.0)
Involved lymph nodes, median (IQR)	2 (6.0)	4 (7.0)	3 (6.0)	0.0734

¹Student-t test;

²χ² test;

³Fisher-Exact test;

⁴Mann-Whitney U test. AJCC: American Joint Committee on Cancer.

Table 2 Postoperative adjuvant treatment protocols n (%)

Treatment	Follow up (yr)		Total (n = 201)	P value1
	Before 2008 (n = 127)	2008-2010 (n = 74)
Chemoradiotherapy	84 (66.1)	63 (85.1)	147 (73.1)	0.023
Chemotherapy	19 (15.0)	6 (8.1)	25 (12.4)
Supportive treatment	10 (7.9)	2 (2.7)	12 (6.0)
None (follow up)	14 (11.0)	3 (4.1)	17 (8.5)
Radiotherapy				0.003
No	43 (33.9)	11 (14.9)	54 (26.9)
Yes	84 (66.1)	63 (85.1)	147 (73.1)
Chemotherapy protocol				< 0.001
FUFA	70 (55.1)	42 (56.8)	112 (55.7)
CEF	9 (7.1)	21 (28.3)	30 (14.9)
None	14 (11.0)	3 (4.1)	17 (8.5)
UFT	23 (18.1)	1 (1.4)	24 (11.9)
TCF	1 (0.8)	5 (6.8)	6 (3.0)
Supportive	10 (7.9)	2 (2.7)	12 (6.0)
Type of radiotherapy device				< 0.001
Co60	21 (25.3)	0 (0.0)	21 (14.4)
Linak	58 (69.9)	7 (11.1)	65 (44.5)
Varian-Siemens	4 (4.8)	56 (88.9)	60 (41.1)
Simulator planning				< 0.001
2 dimensional	79 (62.7)	7 (9.5)	86 (43.0)
3 dimensional	4 (3.2)	56 (75.7)	60 (30.0)
No radiotherapy	43 (34.1)	11 (14.9)	54 (27.0)

¹χ² test. FUFA: 5-fluorouracil and leucovorin-folinic acid; CEF: Cyclophosphamide, epirubicin, and fluorouracil; UFT: Uracil/tegafur; TCF: Docetaxel, cisplatin, and fluorouracil.

Table 3 Median survival (mo) in study groups according to variables

	Total (n = 201)			Before 2008 (n = 127)			2008-2010 (n = 74)
	LFS	DFS	OS	LFS	DFS	OS	LFS	DFS	OS
Treatment protocols
Chemoradiotherapy	31.9	24.1	31.9	37.8	24.1	37.8	11.7	19.2	11.7
Chemotherapy	25.9	20.6	27.1	43.6	22.3	51.7	15.0	18.2	15.3
P value1	0.793	0.834	0.597	0.792	0.656	0.630	0.959	0.848	0.715
Chemotherapy protocolsa
FUFA	29.9	23.8	31.9
UFT	42.5	20.6	53.0
CEF	13.3	16.0	13.3
TCF	15.0	1.6	15.0
P value (FUFA-UFT)1	0.036	0.6	0.477
Surgical margin2
Positive	20.6	21.4	22.4	43.8	20.5	52.2	15.0	19.1	15.0
Negative	26.0	19.2	27.7	41.5	48.2	50.9	15.0	18.3	15.3
P value1	0.509	0.511	0.016	0.239	0.126	0.053	0.519	0.699	0.185
RT simulator planningb
2 dimensional	42.4	23.1	50.4
3 dimensional	14.1	16.0	14.1
P value3	NA	NA	NA
Time of RT initiation
< 4 mo	36.3	20.6	40.9
≥ 4 mo	39.8	16.8	39.8
P value	0.0581	NA	0.3704

¹Kaplan Meier-Log rank test;

²Based on patients on chemoradiotherapy;

³Not calculated to exclude potential bias since mean follow up duration was significantly longer in the 2 dimensional simulator planning group. Analysis was performed in the overall population, since

^aOnly 1 patient recevied FUFA in the “after 2008” group;

^b2-dimensional planning was the leading option before 2008 and 3 dimensional planning after 2008;

⁴Breslow test. FUFA: 5-fluorouracil and leucovorin-folinic acid; CEF: Cyclophosphamide, epirubicin, and fluorouracil; UFT: Uracil/tegafur; TCF: Docetaxel, cisplatin, and fluorouracil; RT: Radiation therapy; NA: Not available; OS: Overall survival; PFS: Progression-free survival; DFS: Disease-free survival.

Table 4 Univariate analysis for the correlates of median local recurrence free, distant metastasis free and overall survival

	Local recurrence free survival (mo)			Distant metastasis free survival (mo)			Overall survival (mo)
	Before 2008 (n = 127)	2008-2010 (n = 74)	Total (n = 201)	Before 2008 (n = 127)	2008-2010 (n = 74)	Total (n= 201)	Before 2008 (n = 127)	2008-2010 (n = 74)	Total (n = 201)
Age
≤ 50 yr	44.1	20.6	49.8	14.0	23.1	14.0	28.7	20.6	33.7
> 50 yr	39.1	26.0	43.6	15.9	18.3	15.9	26.0	22.2	26.7
P value	0.066	0.471	0.312	0.747	0.925	0.48	0.044	0.65	0.181
Type of treatment
Chemoradiotherapy	37.8	24.1	37.8	11.7	19.2	11.7	31.9	24.1	31.9
Chemotherapy	43.6	22.3	51.7	15.0	18.2	15.3	25.9	20.6	27.1
P value	0.792	0.656	0.63	0.959	0.848	0.715	0.793	0.834	0.597
Type of gastrectomy surgery
Total	39.8	15.9	26.7	29.8	18.3	24.0	43.9	15.9	29.1
Subtotal	43.3	13.8	25.9	14.9	19.1	16.0	46.9	13.8	28.5
P value	0.885	0.122	0.888	0.395	0.636	0.393	0.318	0.1	0.092
Vascular involvement
No	49.7	11.5	39.7	26.0	-	26.0	49.8	11.5	43.9
Yes	35.0	16.0	23.5	24.0	18.3	21.4	37.8	16.2	24.0
P value	0.697	0.005	0.594	0.858	-	0.81	< 0.001	0.795	< 0.001
Perineural involvement
No	45.9	14.9	31.3	24.0	-	24.0	48.6	14.9	32.5
Yes	41.2	15.0	25.0	22.4	16.0	20.5	43.6	15.2	25.9
P value	0.706	0.353	0.822	0.609	-	0.999	0.122	0.275	0.058
T stage
T1	55.4	20.2	48.6	27.6	-	27.6	55.4	20.2	48.6
T2	54.4	16.4	28.3	29.4	30.2	29.8	54.4	16.9	32.4
T3	37.0	14.1	25.1	24.1	18.3	22.1	41.1	14.1	26.0
T4	30.9	24.4	24.4	18.6	12.6	16.6	31.8	30.6	30.6
P value	0.054	0.959	0.128	0.668	0.223	0.353	0.04	0.28	0.002
Nodal stage
N0	54.9	13.7	45.7	41.1	22.2	41.1	54.9	14.8	47.8
N1	46.9	14.6	29.1	30.6	21.0	27.7	53.7	14.8	37.0
N2	23.2	16.0	19.2	16.6	18.3	16.6	24.1	16.0	19.2
N3	27.1	13.4	16.6	16.1	12.6	15.0	35.0	13.4	20.7
P value	0.515	0.504	0.647	0.02	0.887	0.014	< 0.001	0.439	< 0.001
Nodal stage (AJCC 2002)
N0	54.9	11.3	42.1	41.1	22.2	41.1	54.9	11.3	45.7
N1	42.4	16.9	28.3	30.6	20.5	26.0	49.2	16.9	29.1
N2	19.3	15.5	16.1	14.2	13.8	14.2	20.1	15.5	19.1
N3	31.0	10.7	15.0	19.5	19.8	19.8	31.0	10.7	15.0
P value	0.057	0.283	0.024	0.011	0.817	0.001	< 0.001	0.224	< 0.001
LN1
< 15	40.5	14.9	30.5	24.0	19.1	23.1	45.7	14.9	33.2
> 16	42.7	15.0	25.4	24.0	18.3	20.5	44.9	15.2	25.7
P value	0.181	0.768	0.423	0.309	0.742	0.664	0.724	0.461	0.523
LN2
< 10	34.0	15.9	25.4	20.9	22.2	22.2	40.5	16.2	31.0
> 11	46.4	14.6	26.8	24.1	16.0	22.2	47.8	14.6	28.0
P value	0.169	0.768	0.373	0.204	0.742	0.349	0.985	0.464	0.822
Nodal stage (AJCC 2010)
N0	54.9	11.3	42.1	41.1	22.2	41.1	54.9	11.3	45.7
N1	51.0	16.9	39.1	29.4	36.8	33.1	53.8	16.9	44.9
N2	32.5	16.0	25.8	28.0	18.3	22.3	37.8	17.0	25.9
N3a	19.6	15.0	16.1	15.4	13.8	14.6	20.7	15.0	17.7
N3b	31.0	15.0	16.3	19.5	19.8	19.8	31.0	15.0	16.3
P value	0.131	0.402	0.057	0.06	0.849	0.039	< 0.001	0.098	< 0.001
Involved lymph nodes (n)
≤ 5	48.6	35.5	52.2	15.9	24.1	16.2	35.5	31.9	38.3
> 5	20.7	16.9	26.0	15.0	16.0	15.2	16.1	16.3	16.6
P value	0.002	0.564	< 0.001	0.036	0.191	0.218	0.23	0.001	< 0.001

AJCC: American Joint Commission on Cancer; LN: Lymph nodes.

Table 5 Multivariate Cox regression analysis for the correlates of local recurrence free, distant metastasis free and overall survival

	Local recurrence free survival						Distant metastasis free survival						Overall survival
	Before 2008		2008-2010		Overall		Before 2008		2008-2010		Overall		Before 2008		2008-2010		Overall
	Sig.	Exp(B)	Sig.	Exp(B)	Sig.	Exp(B)	Sig.	Exp(B)	Sig.	Exp(B)	Sig.	Exp(B)	Sig.	Exp(B)	Sig.	Exp(B)	Sig.	Exp(B)
Age (yr)
< 50 vs > 50	0.748	1.191			0.387	1.468							0.122	1.742
Operaton type
Total vs subtotal			0.118	0.284											0.147	0.426
Vascular involvement
Yes vs No			0.748	0.707									0.099	2.375			0.085	2.106
Perinueral involvement
Yes vs No													0.656	0.820			0.326	0.707
T stage	0.772				0.318								0.781				0.762
T1	0.938	10856.260			0.936	18774.638							0.995	0.995			0.967	0.967
T2	0.934	21845.678			0.935	23091.062							0.674	1.425			0.651	1.447
T3	0.933	24325.273			0.928	62667.340							0.969	0.962			0.734	1.369
LN1
< 15 vs > 16	0.458	2.278					0.722	0.863
LN2
< 10 vs > 11	0.073	0.146
Nodal stage (AJCC 2010)	0.782				0.167		0.994				0.052		0.033				0.104
N1	0.255	3.526			0.217	2.748	0.754	1.196			0.831	1.118	0.404	1.624			0.162	2.184
N2	0.232	3.853			0.0421	4.959	0.969	1.025			0.313	1.614	0.122	2.439			0.0091	4.056
N3a	0.452	3.407			0.786	1.380	0.814	1.266			0.014	3.218	0.0061	5.132			0.059	4.733
N3b	0.344	5.380			0.502	2.330	0.761	1.471			0.060	3.446	0.0271	5.263			0.098	4.292
İnvolved lymph nodes (n)
≤ 5 vs > 5	0.464	2.322			0.242	2.573	0.283	2.677	0.207	2.245					0.303	1.742	0.726	1.245
Significance of the model	P = 0.053		P = 0.218		P = 0.017		P = 0.153		P = 0.196		P = 0.054		P = 0.001		P = 0.151		P < 0.0011

¹Indicate statistical significance at α = 0.05 level. Only the variables with P < 0.2 significance in the univariate analysis were included into the Cox-regression model on the basis of Hosmer-Lemeshow method. Since both American Joint Commission on Cancer (AJCC) 2002 and 2010 nodal staging variables met the criteria to be included in the multivariate analysis, only AJCC 2010 nodal staging was included.