Nomogram for overall survival in ampullary adenocarcinoma using the surveillance, epidemiology, and end results database and external validation

Table 1 Patient baseline characteristics, n (%)

Characteristics	Training cohort (n = 1406)	Internal validation cohort (n = 603)	External validation cohort (n = 257)
Age
< 50	109 (7.8)	56 (9.3)	24 (9.3)
50-59	267 (19.0)	127 (21.1)	80 (31.1)
60-69	381 (27.1)	153 (25.4)	78 (30.4)
70-79	358 (25.5)	172 (28.5)	61 (23.7)
≥ 80	291 (20.7)	95 (15.8)	14 (5.4)
Sex
Female	626 (44.5)	274 (45.4)	110 (42.8)
Male	780 (55.5)	329 (54.6)	147 (57.2)
Race
White	1075 (76.5)	465 (77.1)	0 (0)
Black	107 (7.6)	53 (8.8)	0 (0)
Unknown	224 (15.9)	85 (14.1)	257 (100)
SEER stage
Localized	207 (14.7)	79 (13.1)	91 (35.4)
Regional	795 (56.5)	371 (61.5)	57 (22.2)
Distant	357 (25.4)	130 (21.6)	84 (32.7)
Unknown	47 (3.3)	23 (3.8)	25 (9.7)
Surgery
No	373 (26.5)	155 (25.7)	38 (14.8)
Surgical removal of primary site	412 (29.3)	201 (33.3)	154 (59.9)
Radical surgery	621 (44.2)	247 (41.0)	65 (25.3)
Radiation
No	1123 (79.8)	478 (79.3)	249 (96.9)
Yes	283 (20.1)	125 (20.7)	8 (3.1)
Chemotherapy
No	762 (54.2)	325 (53.9)	167 (65.0)
Yes	644 (45.8)	278 (46.1)	90 (35.0)
Bone metastasis
No	1404 (99.9)	598 (99.2)	254 (98.8)
Yes	2 (0.1)	5 (0.8)	3 (1.2)
Brain metastasis
No	1402 (99.7)	601 (99.7)	257 (100)
Yes	4 (0.3)	2 (0.3)	0 (0)
Liver metastasis
No	1309 (93.1)	557 (92.4)	226 (87.9)
Yes	97 (6.9)	46 (7.6)	31 (12.1)
Lung metastasis
No	1378 (98.0)	591 (98.0)	250 (97.3)
Yes	28 (2.0)	12 (2.0)	7 (2.7)
Tumor size
< 2 cm	452 (32.1)	185 (30.7)	82 (31.9)
> 2 cm	698 (49.6)	322 (53.4)	117 (45.5)
Unknown	256 (18.2)	96 (15.9)	58 (22.6)
LNR
0	468 (33.3)	198 (32.8)	175 (68.1)
0-0.5	468 (33.3)	220 (36.5)	14 (5.4)
0.5-1	61 (4.3)	20 (3.3)	25 (9.7)
Unknown	409 (29.1)	165 (27.4)	43 (16.7)
Marital status
Single	235 (16.7)	110 (18.2)	3 (1.2)
Divorced	127 (9.0)	48 (8.0)	6 (2.3)
Married	769 (54.7)	341 (56.6)	237 (92.2)
Widowed	220 (15.6)	71 (11.8)	11 (4.3)
Unknow	55 (3.9)	33 (5.5)	0 (0)
Stage T
T1	276 (19.6)	107 (17.7)	27 (10.5)
T2	366 (26.0)	171 (28.4)	96 (37.4)
T3	334 (23.8)	152 (25.2)	37 (14.4)
T4	351 (25.0)	140 (23.2)	57 (22.2)
Unknown	79 (5.6)	33 (5.5)	40 (15.6)
Stage N
N0	775 (55.1)	322 (53.4)	135 (52.5)
N1	583 (41.5)	264 (43.8)	50 (19.5)
Unknown	48 (3.4)	17 (2.8)	72 (28.0)
Stage M
M0	1251 (89.0)	543 (90.0)	223 (86.8)
M1	155 (11.0)	60 (10.0)	34 (13.2)
Extension
Localized	131 (9.3)	54 (9.0)	40 (15.6)
Duodenal wall	554 (39.4)	244 (40.5)	95 (40.0)
Pancreas	346 (24.6)	157 (26.0)	52 (20.2)
Common bile duct	88 (6.3)	43 (7.1)	27 (10.5)
Invasive tumor confined	208 (14.8)	72 (11.9)	33 (12.8)
Extension to other adjacent organs	79 (5.6)	33 (5.5)	10 (3.9)
Tumor differentiation
Well differentiated	138 (9.8)	65 (10.8)	20 (7.8)
Moderately differentiated	668 (47.5)	288 (47.8)	105 (40.9)
Poorly differentiated	377 (26.8)	160 (26.5)	77 (30.0)
Undifferentiated	16 (1.1)	2 (0.3)	27 (10.5)
Unknown	207 (14.7)	88 (14.6)	28 (10.9)

LNR: Lymph node ratio; SEER: Surveillance, epidemiology, and end results.

Table 2 Univariate and multivariate Cox analyses for overall survival in the training group

Variable	Univariate analysis			Multivariate analysis
	HR	95%CI	P value	HR	95%CI	P value
Age
< 50	Reference
50-59	1.25	0.91-1.71	0.17	1.19	0.86-1.64	0.30
60-69	1.44	1.07-1.953	< 0.05	1.10	0.81-1.50	0.55
70-79	1.93	1.43-2.61	< 0.05	1.62	1.19-2.20	< 0.05
≥ 80	3.35	2.48-4.53	< 0.05	1.83	1.31-2.56	< 0.05
Sex
Female	Reference
Male	1.08	0.95-1.23	0.23	1.20	1.03-1.38	< 0.05
Race
White	Reference
Black	1.09	0.86-1.38	0.46	1.28	1.00-1.65	< 0.05
Unknown	0.71	0.59-0.86	< 0.05	0.90	0.74-1.09	0.29
SEER stage
Localized	Reference
Regional	0.98	0.80-1.19	0.81	1.30	0.89-1.90	0.18
Distant	2.17	1.76-2.68	< 0.05	1.80	0.82-3.94	0.14
Unknown	3.01	2.12-4.28	< 0.05	1.49	0.82-2.71	0.19
Surgical modality
None	Reference
Surgical removal of primary site	0.21	0.18-0.25	< 0.05	0.35	0.25-0.50	< 0.05
Radical surgery	0.22	0.19-0.26	< 0.05	0.38	0.26-0.54	< 0.05
Radiation
No	Reference
Yes	0.89	0.76-1.05	0.16
Chemotherapy
No	Reference
Yes	0.81	0.71-0.92	< 0.05	0.61	0.52-0.71	< 0.05
Bone metastasis
No	Reference
Yes	2.86	0.71-11.46	0.14
Brain metastasis
No	Reference
Yes	6.57	2.46-17.58	< 0.05	4.18	1.42-12.33	< 0.05
Liver metastasis
No	Reference
Yes	3.55	2.86-4.42	< 0.05	1.01	0.68-1.51	0.96
Lung metastasis
No	Reference
Yes	3.27	2.23-4.80	< 0.05	0.63	0.38-1.06	0.08
Tumor size
< 2 cm	Reference
> 2 cm	1.40	1.20-1.63	< 0.05	1.04	0.88-1.23	0.63
Unknown	3.12	2.61-3.74	< 0.05	1.28	1.02-1.63	< 0.05
LNR
0	Reference
0-0.5	2.04	1.71-2.42	< 0.05	1.49	1.02-2.19	< 0.05
0.5-1	5.11	3.79-6.89	< 0.05	2.99	1.90-4.72	< 0.05
Unknown	6.02	5.05-7.18	< 0.05	2.22	1.55-3.17	< 0.05
Marital status
Single	Reference
Divorced	1.15	0.89-1.50	0.28	1.03	0.79-1.34	0.85
Married	0.96	0.80-1.15	0.66	0.97	0.80-1.17	0.74
Widowed	1.66	1.33-2.06	< 0.05	1.08	0.84-1.38	0.55
Unknown	1.02	0.70-1.48	0.91	0.88	0.60-1.29	0.52
T stage
T1	Reference
T2	0.64	0.52-0.78	< 0.05	0.97	0.67-1.39	0.87
T3	0.98	0.80-1.19	0.83	1.72	0.79-3.73	0.17
T4	1.44	1.19-1.74	< 0.05	1.77	1.11-2.81	< 0.05
Unknown	2.65	2.01-3.49	< 0.05	0.73	0.44-1.22	0.23
N stage
N0	Reference
N1	1.25	1.10-1.43	< 0.05	1.23	0.87-1.74	0.24
Unknown	3.14	2.30-4.29	< 0.05	1.12	0.79-1.59	0.53
M stage
M0	Reference
M1	3.89	3.24-4.66	< 0.05	1.46	0.71-3.00	0.31
Extension
Localized	Reference
Duodenal wall	0.36	0.29-0.44	< 0.05	1.02	0.74-1.40	0.92
Pancreas	0.53	0.42-0.66	< 0.05	0.87	0.45-1.69	0.68
Common bile duct	0.78	0.58-1.07	0.12	0.53	0.36-0.80	< 0.05
Invasive tumor confined	0.66	0.52-0.84	< 0.05	0.83	0.39-1.77	0.63
Extension to other adjacent organs	1.39	1.03-1.87	< 0.05
Tumor differentiation
Well-differentiated	Reference
Moderately differentiated	1.19	0.93-1.52	0.16	1.07	0.83-1.38	0.59
Poorly differentiated	1.81	1.41-2.34	< 0.05	1.65	1.26-2.15	< 0.05
Undifferentiated	1.62	0.86-3.04	0.14	0.98	0.51-1.86	0.94
Unknown	2.54	1.94-3.33	< 0.05	1.03	0.77-1.38	0.83

CI: Confidence interval; HR: Hazard ratio; LNR: Lymph node ratio (refers to the ratio of regional nodes that were positive vs those examined); SEER: Surveillance, epidemiology, and end results.

Table 3 Univariate and multivariate Cox analyses for cancer-specific survival in the training group

Variable	Univariate analysis			Multivariate analysis
	HR	95%CI	P value	HR	95%CI	P value
Age
< 50	Reference
50-59	1.37	1.02-1.85	< 0.05	1.19	0.88-1.61	0.26
60-69	1.49	1.12-1.98	< 0.05	1.52	0.86-1.55	0.35
70-79	2.11	1.59-2.80	< 0.05	1.60	1.19-2.14	< 0.05
≥ 80	3.57	2.68-4.75	< 0.05	1.98	1.43-2.73	< 0.05
Sex
Female	Reference
Male	1.08	0.95-1.23	0.23	1.20	1.03-1.38	< 0.02
Race
White	Reference
Black	1.09	0.86-1.38	0.46	1.28	1.00-1.65	< 0.05
Unknown	0.71	0.59-0.86	< 0.05	0.90	0.74-1.09	0.29
SEER stage
Localized	Reference
Regional	0.98	0.80-1.19	0.81	1.30	0.89-1.90	0.18
Distant	2.17	1.76-2.68	< 0.05	1.80	0.82-3.94	0.14
Unknown	3.01	2.12-4.28	< 0.05	1.49	0.82-2.71	0.19
Surgical modality
None	Reference
surgical removal of primary site	0.21	0.18-0.25	< 0.05	0.35	0.25-0.50	< 0.05
Radical surgery	0.22	0.19-0.26	< 0.05	0.38	0.26-0.54	< 0.05
Radiation
No	Reference
Yes	0.89	0.76-1.05	0.16
Chemotherapy
No	Reference
Yes	0.81	0.71-0.92	< 0.05	0.61	0.52-0.71	< 0.05
Bone metastasis
No	Reference
Yes	2.86	0.71-11.46	0.14
Brain metastasis
No	Reference
Yes	6.57	2.46-17.58	< 0.05	4.18	1.42-12.33	< 0.05
Liver metastasis
No	Reference
Yes	3.55	2.86-4.42	< 0.05	1.01	0.68-1.51	0.96
Lung metastasis
No	Reference
Yes	3.27	2.23-4.80	< 0.05	0.63	0.38-1.06	0.08
Tumor size
< 2 cm	Reference
> 2 cm	1.40	1.20-1.63	< 0.05	1.04	0.88-1.23	0.63
Unknown	3.12	2.61-3.74	< 0.05	1.28	1.02-1.61	< 0.05
LNR
0	Reference
0-0.5	2.04	1.71-2.43	< 0.05	1.49	1.02-2.19	< 0.05
0.5-1	5.11	3.79-6.89	< 0.05	2.99	1.89-4.72	< 0.05
Unknown	6.02	5.048-7.182	< 0.05	2.22	1.55-3.17	< 0.05
Marital status
Single	Reference
Divorced	1.15	0.89-1.50	0.28	1.03	0.77-1.34	0.85
Married	0.96	0.80-1.15	0.66	0.97	0.80-1.17	0.74
Widowed	1.66	1.33-2.06	< 0.05	1.08	0.84-1.38	0.55
Unknown	1.02	0.70-1.48	0.91	0.88	0.60-1.29	0.52
T stage
T1	Reference
T2	0.64	0.52-0.78	< 0.05	0.97	0.67-1.39	0.87
T3	0.98	0.80-1.19	< 0.05	1.72	0.79-3.73	0.17
T4	1.44	1.19-1.74	< 0.05	1.77	1.11-2.81	< 0.05
Unknown	2.65	2.01-3.49	< 0.05	0.73	0.44-1.22	0.23
N stage
N0	Reference
N1	1.25	1.10-1.43	< 0.05	1.23	0.87-1.74	0.24
Unknown	3.14	2.30-4.29	< 0.05	1.12	0.79-1.59	0.53
M stage
M0	Reference
M1	3.89	3.24-4.66	< 0.05	1.46	0.71-3.00	0.31
Extension
Localized	Reference
Duodenal wall	0.36	0.29-0.44	< 0.05	1.02	0.74-1.40	0.92
Pancreas	0.53	0.42-0.66	< 0.05	0.87	0.45-1.69	0.68
Common bile duct	0.78	0.58-1.07	0.12	0.53	0.36-0.80	< 0.05
Invasive tumor confined	0.66	0.52-0.84	< 0.05	0.83	0.39-1.77	0.63
Extension to other adjacent organs	1.39	1.03-1.87	< 0.05
Tumor differentiation
Well differentiated	Reference
Moderately differentiated	1.19	0.93-1.52	0.16	1.07	0.83-1.38	0.59
Poorly differentiated	1.81	1.41-2.34	< 0.05	1.65	1.26-2.15	< 0.05
Undifferentiated	1.62	0.86-3.04	0.14	0.98	0.51-1.86	0.94
Unknown	2.54	1.94-3.33	< 0.05	1.03	0.77-1.38	0.83

CI: Confidence interval; HR: Hazard ratio; LNR: Lymph node ratio (refers to the ratio of regional nodes that were positive vs those examined); SEER: Surveillance, epidemiology, and end results.