Risk factors, prognostic predictors, and nomograms for pancreatic cancer patients with initially diagnosed synchronous liver metastasis

Table 1 Clinical characteristics for patients diagnosed with pancreatic cancer with and without liver metastasis in Surveillance, Epidemiology, and End Result database (2010-2015), n (%)

Variable	Levels	Total (n = 33459)	With LM (n = 11458	Without LM (n = 22001)	P value1
Age at diagnosis (yr)	≤ 70	20680 (61.8)	7552 (65.9)	13128 (59.7)	< 0.001
	> 70	12779 (38.2)	3906 (34.1)	8873 (40.3)
Sex	Female	16390 (49.0)	5195 (45.3)	11195 (50.9)	< 0.001
	Male	17069 (51.0)	6263 (54.7)	10806 (49.1)
Race	White	26459 (79.1)	9048 (79)	17411 (79.1)	< 0.001
	Black	4139 (12.4)	1533 (13.4)	2606 (11.8)
	Other	2861 (8.6)	877 (7.7)	1984 (9)
Primary site	Head	17950 (53.6)	4441 (38.8)	13509 (61.4)	< 0.001
	Body/tail	10200 (30.5)	4762 (41.5)	5438 (24.7)
	Other	5309 (15.9)	2255 (19.7)	3054 (13.9)
Histology	Adenocarcinoma	22948 (68.6)	8746 (76.3)	14202 (64.6)	< 0.001
	Neuroendocrine carcinoma	1585 (4.7)	615 (5.4)	970 (4.4)
	Other	8926 (26.7)	2097 (18.3)	6829 (31)
Pathological grade	Well/moderate	8293 (24.8)	1185 (10.3)	7108 (32.3)	< 0.001
	Poor/anaplastic	5105 (15.3)	1367 (11.9)	3738 (17)
	Unspecific	20061 (60.0)	8906 (77.7)	11155 (50.7)
T stage	T1	2063 (6.2)	362 (3.2)	1701 (7.7)	< 0.001
	T2	8383 (25.1)	3934 (34.3)	4449 (20.2)
	T3	14526 (43.4)	3541 (30.9)	10985 (49.9)
	T4	6635 (19.8)	2116 (18.5)	4519 (20.5)
	TX	1852 (5.5)	1505 (13.1)	347 (1.6)
LN metastasis	No	18469 (55.2)	6044 (52.7)	12425 (56.5)	< 0.001
	Yes	14990 (44.8)	5414 (47.3)	9576 (43.5)
Tumor size (cm)	< 2	3617 (10.8)	664 (5.8)	2953 (13.4)	< 0.001
	2-4	14644 (43.8)	4338 (37.9)	10306 (46.8)
	> 4	15198 (45.4)	6456 (56.3)	8742 (39.7)
Surg prim	No	24100 (72.0)	11054 (96.5)	13046 (59.3)	< 0.001
	Yes	9359 (28.0)	404 (3.5)	8955 (40.7)
Surg dis	No	32408 (96.9)	11102 (96.9)	21306 (96.8)	0.822
	Yes	1051 (3.1)	356 (3.1)	695 (3.2)
Radiation	No	27483 (82.1)	10909 (95.2)	16574 (75.3)	< 0.001
	Yes	5976 (17.9)	549 (4.8)	5427 (24.7)
Chemotherapy	No	13156 (39.3)	4298 (37.5)	8858 (40.3)	< 0.001
	Yes	20303 (60.7)	7160 (62.5)	13143 (59.7)
Bone metastasis	No	32524 (97.2)	10812 (94.4)	21712 (98.7)	< 0.001
	Yes	935 (2.8)	646 (5.6)	289 (1.3)
Brain metastasis	No	33365 (99.7)	11405 (99.5)	21960 (99.8)	< 0.001
	Yes	94 (0.3)	53 (0.5)	41 (0.2)
Lung metastasis	No	30546 (91.3)	9701 (84.7)	20845 (94.7)	< 0.001
	Yes	2913 (8.7)	1757 (15.3)	1156 (5.3)
Vital status	Alive	6025 (18.0)	804 (7)	5221 (23.7)	< 0.001
	Dead	27434 (82.0)	10654 (93)	16780 (76.3)

¹Statistical differences between pancreatic cancer with liver metastasis (LM) and without LM groups.

LN: Lymph node; LM: Liver metastasis; Surg prim: Surgical treatments of the primary site; Surg dis: Surgical treatments of the distant site.

Table 2 Univariate and multivariate logistic analyses of liver metastasis in pancreatic cancer patients, n (%)

Variable	Levels	Without LM (n = 14608)	With LM (n = 7698)	Univariate analysis (OR, 95%CI)	Multivariate analysis (OR, 95%CI)
Age at diagnosis (yr)	≤ 70	8783 (60.1)	5032 (65.4)
	> 70	5825 (39.9)	2666 (34.6)	0.80 (0.75-0.85, P < 0.001)	0.72 (0.68-0.77, P < 0.001)
Sex	Female	7393 (50.6)	3485 (45.3)
	Male	7215 (49.4)	4213 (54.7)	1.24 (1.17-1.31, P < 0.001)	1.16 (0.89-1.23, P = 0.056)
Race	White	11590 (79.3)	6048 (78.6)
	Black	1730 (11.8)	1047 (13.6)	1.16 (1.07-1.26, P < 0.001)	1.07 (0.97-1.17, P = 0.186)
	Other	1288 (8.8)	603 (7.8)	0.90 (0.81-0.99, P = 0.036)	0.93 (0.83-1.04, P = 0.228)
Primary site	Head	8939 (61.2)	3003 (39)
	Body/tail	3604 (24.7)	3212 (41.7)	2.65 (2.49-2.83, P < 0.001)	2.30 (2.14-2.47, P < 0.001)
	Other	2065 (14.1)	1483 (19.3)	2.14 (1.98-2.31, P < 0.001)	1.76 (1.61-1.92, P < 0.001)
Histology	Adenocarcinoma	9394 (64.3)	5867 (76.2)
	Neuroendocrine carcinoma	640 (4.4)	411 (5.3)	1.03 (0.90-1.17, P = 0.670)	1.28 (1.10-1.49, P = 0.001)
	Other	4574 (31.3)	1420 (18.4)	0.50 (0.46-0.53, P < 0.001)	0.61 (0.56-0.66, P < 0.001)
Pathological grade	Well/moderate	4727 (32.4)	799 (10.4)
	Poor/anaplastic	2476 (16.9)	919 (11.9)	2.20 (1.97-2.44, P < 0.001)	2.26 (2.01-2.53, P < 0.001)
	Unspecific	7405 (50.7)	5980 (77.7)	4.78 (4.40-5.19, P < 0.001)	4.23 (3.86-4.64, P < 0.001)
T stage	T1	1131 (7.7)	245 (3.2)
	T2	2901 (19.9)	2653 (34.5)	4.22 (3.65-4.90, P < 0.001)	1.53 (0.89-1.86, P = 0.080)
	T3	7325 (50.1)	2402 (31.2)	1.51 (1.31-1.75, P < 0.001)	0.81 (0.64-1.02, P = 0.054)
	T4	3019 (20.7)	1411 (18.3)	2.16 (1.86-2.52, P < 0.001)	0.72 (0.56-1.01, P = 0.051)
	TX	232 (1.6)	987 (12.8)	9.4 (6.4-9.7, P < 0.001)	7.18 (5.52-9.35, P < 0.001)
LN metastasis	No	8213 (56.2)	4046 (52.6)
	Yes	6395 (43.8)	3652 (47.4)	1.16 (1.10-1.23, P < 0.001)	1.38 (1.30-1.47, P < 0.001)
Tumor size (cm)	< 2	1966 (13.5)	460 (6)
	2-4	6800 (46.5)	2939 (38.2)	1.85 (1.66-2.06, P < 0.001)	1.29 (1.08-1.55, P = 0.006)
	> 4	5842 (40)	4299 (55.8)	3.15 (2.82-3.51, P < 0.001)	2.05 (1.71-2.46, P < 0.001)

OR: Odds ratio; CI: Confidence interval; LN: Lymph node; LM: Liver metastasis.

Table 3 Multivariate Cox analysis of the training cohort based on the results of least absolute shrinkage and selection operator regression, n (%)

Variable	Levels	All	Multivariate analysis (HR, 95%CI)
Age at diagnosis (yr)	≤ 70	4812 (62.5)
	> 70	2886 (37.5)	1.29 (1.23-1.36, P < 0.001)
Histology	Adenocarcinoma	5867 (76.2)
	Neuroendocrine carcinoma	411 (5.3)	0.31 (0.28-0.35, P < 0.001)
	Other	1420 (18.4)	0.79 (0.75-0.85, P < 0.001)
Pathological grade	Well/moderate	799 (10.4)
	Poor/anaplastic	919 (11.9)	1.72 (1.55-1.91, P < 0.001)
	Unspecific	5980 (77.7)	1.48 (1.36-1.61, P < 0.001)
Surg prim	No	7429 (96.5)
	Yes	269 (3.5)	0.37 (0.31-0.43, P < 0.001)
Surg dis	No	7450 (96.8)
	Yes	248 (3.2)	0.80 (0.69-0.93, P = 0.004)
Chemotherapy	No	2934 (38.1)
	Yes	4764 (61.9)	0.43 (0.41-0.45, P < 0.001)
Lung metastasis	No	6510 (84.6)
	Yes	1188 (15.4)	1.35 (1.27-1.44, P < 0.001)

HR: Hazard ratio; CI: Confidence interval; Surg prim: Surgical treatments of the primary site; Surg dis: Surgical treatments of the distant site.