Development of a novel staging classification for Siewert II adenocarcinoma of the esophagogastric junction after neoadjuvant chemotherapy

Table 1 Clinicopathological characteristics of Siewert type II adenocarcinoma of the esophagogastric junction underwent radical gastrectomy with neoadjuvant chemotherapy

Characteristics	n (%)/mean ± SD
Age, (yr)
< 65	468 (64.6)
≥ 65	257 (35.4)
Sex
Male	623 (85.9)
Female	102 (14.1)
Marital status
Married	502 (69.2)
Divorced or separated	79 (10.9)
Single (never married)	91 (12.6)
Widowed	30 (4.1)
Others	23 (3.2)
Race
White	647 (89.2)
Others	78 (10.8)
Year of operation
2004-2009	230 (31.7)
2010-2015	495 (68.3)
Type of surgery
Subtotal gastrectomy	418 (57.7)
Total gastrectomy	156 (21.5)
Unknown	151 (20.8)
Tumor size
< 50 mm	387 (53.4)
≥ 50 mm	200 (27.6)
Unknown	138 (19.0)
The number of examined lymph nodes	17.4 ± 10.9
yp T stage
T1	82 (11.3)
T2	108 (14.9)
T3	441 (60.8)
T4	94 (13.0)
yp N stage
N0	218 (30.1)
N1	223 (30.8)
N2	186 (25.7)
N3	98 (13.5)
Grade
Well differentiated	35 (4.8)
Moderate differentiated	253 (34.9)
Low differentiated	400 (55.2)
The tumor grade cannot be identified	37 (5.1)
Adjuvant chemotherapy
No	530 (73.1)
Yes	139 (19.2)
Unknown	56 (7.7)

Table 2 Univariate and multivariate analysis of overall survival for Siewert type II adenocarcinoma of the esophagogastric junction underwent radical gastrectomy with neoadjuvant chemotherapy

	Univariate analysis			Multivariate analysis
	HR	95%CI	P value	HR	95%CI	P value
Age
< 65 yr	1
≥ 65 yr	1.11	0.93-1.33	0.259
Sex
Male	1			1
Female	0.81	0.62-1.06	0.120	0.74	0.57-0.98	0.035
Marital status
Married	1			1
Divorced or separated	1.38	1.05-1.8	0.019	1.51	1.15-1.99	0.003
Single (never married)	1.11	0.85-1.46	0.435	1.07	0.81-1.4	0.642
Widowed	1.40	0.91-2.15	0.130	1.34	0.86-2.08	0.198
Others	0.77	0.43-1.37	0.368	0.74	0.41-1.31	0.302
Race
White	1			1
Others	0.81	0.6-1.1	0.173	0.8	0.59-1.08	0.148
Year of diagnosis
2004-2009	1
2010-2015	1.01	0.84-1.22	0.910
Type of surgery
Subtotal gastrectomy	1
Total gastrectomy	1.04	0.83-1.3	0.762
Tumor size
< 50 mm	1
≥ 50 mm	1.08	0.88-1.32	0.477
The number of examined lymph nodes	1	0.99-1	0.379
yp T stage
T1	1			1
T2	1.42	0.96-2.1	0.082	1.25	0.84-1.87	0.265
T3	1.89	1.36-2.63	< 0.001	1.43	1.01-2.02	0.043
T4a	2.66	1.82-3.88	< 0.001	1.85	1.24-2.75	0.003
yp N stage
N0	1			1
N1	1.40	1.1-1.78	0.006	1.37	1.07-1.76	0.012
N2	1.90	1.49-2.42	< 0.001	1.84	1.42-2.38	< 0.001
N3	3.13	2.37-4.12	< 0.001	3.11	2.31-4.18	< 0.001
Grade
Well differentiated	1
Moderate differentiated	0.87	0.56-1.35	0.539
Low differentiated	1.31	0.86-2	0.211
Gx	1.01	0.58-1.77	0.976
Adjuvant chemotherapy
No	1			1
Yes	0.80	0.63-1.02	0.067	0.67	0.52-0.85	0.001

HR: Hazard ratio.

Table 3 Univariate and multivariate analysis of disease-specific survival for Siewert type II adenocarcinoma of the esophagogastric junction underwent radical gastrectomy with neoadjuvant chemotherapy

	Univariate analysis			Multivariate analysis
	HR	95%CI	P value	HR	95%CI	P value
Age
< 65 yr old	1
≥ 65 yr old	1.01	0.83-1.24	0.895
Sex
Male	1			1
Female	0.75	0.56-1.01	0.060	0.75	0.55-1.01	0.056
Marital status
Married	1
Divorced or separated	1.23	0.9-1.67	0.197
Single (never married)	1.23	0.93-1.63	0.150
Widowed	1.18	0.71-1.96	0.516
Others	0.84	0.46-1.54	0.579
Race
White	1			1
Others	0.78	0.55-1.09	0.142	0.72	0.51-1.01	0.054
Year of diagnosis
2004-2009	1
2010-2015	0.96	0.78-1.18	0.699
Type of surgery
Subtotal gastrectomy	1
Total gastrectomy	1	0.78-1.28	0.985
Tumor size
< 50 mm	1
≥ 50 mm	1.08	0.86-1.35	0.504
The number of examined lymph nodes	1	0.99-1.01	0.516
yp T stage
T1	1			1
T2	1.44	0.9-2.3	0.125	1.25	0.78-2.01	0.347
T3	2.29	1.55-3.38	< 0.001	1.69	1.13-2.54	0.010
T4a	3.19	2.06-4.94	< 0.001	2.18	1.38-3.44	0.001
yp N stage
N0	1			1
N1	1.56	1.19-2.05	0.001	1.43	1.08-1.88	0.012
N2	2.22	1.7-2.92	< 0.001	1.93	1.45-2.56	< 0.001
N3	3.7	2.73-5.02	< 0.001	3.17	2.31-4.35	< 0.001
Grade
Well differentiated	1
Moderate differentiated	0.93	0.56-1.55	0.795
Low differentiated	1.53	0.93-2.49	0.091
Gx	1.11	0.58-2.1	0.759
Adjuvant chemotherapy
No	1
Yes	0.88	0.68-1.12	0.301

HR: Hazard ratio.

Table 4 Model evaluation

Models	Harrell's C-index	AIC	Log likelihood	P value
OS
Novel nomogram	0.635 (0.609-0.662)	-2923.6	5875.2	Ref.
8th AJCC EC ypTNM staging system	0.610 (0.583-0.636)	-2940.6	5889.1	0.004
8th AJCC GC ypTNM staging system	0.593 (0.568-0.619)	-2948.4	5900.7	< 0.001
DSS
Novel nomogram	0.635 (0.607-0.664)	-2451.9	4927.7	Ref.
8th AJCC EC ypTNM staging system	0.627 (0.600-0.655)	-2458.9	4925.8	0.218
8th AJCC GC ypTNM staging system	0.609 (0.582-0.636)	-2467.2	4938.4	< 0.001

OS: Overall survival; DSS: Disease-specific survival; AIC: Akaike information criterion; AJCC: American Joint Committee on Cancer; EC: Esophageal cancer; GC: Gastric cancer; ypTNM: Y-pathologic-TNM.