Nomograms predicting long-term survival in patients with invasive intraductal papillary mucinous neoplasms of the pancreas: A population-based study

Table 1 Patient demographics and clinical characteristics (n = 1219)

Characteristics	Training cohort (n = 853)		Validation cohort (n = 366)
	Number of patients	Percent (%)	Number of patients	Percent (%)
Age (yr)
≤ 60	218	25.6	70	19.1
60-69	276	32.4	127	34.7
70-79	281	32.8	131	35.8
≥ 80	78	9.2	38	10.4
Sex
Male	470	55.1	201	54.9
Female	383	44.9	165	45.1
Race
White	694	81.4	316	86.3
Others1	159	18.6	50	13.7
Marital status
Married	558	65.4	233	63.7
Unmarried2	295	34.6	133	36.3
Grade
Well differentiated	187	21.9	66	18.0
Moderately differentiated	320	37.5	157	42.9
Poorly differentiated/Undifferentiated	162	19.0	73	19.9
Unknown	184	21.6	70	19.1
Tumor location
Head	181	21.2	232	63.4
Body/tail	553	64.8	75	20.5
Other3	119	14.0	59	16.1
T stage
T1	124	14.5	57	15.6
T2	206	24.2	71	19.4
T3	468	54.9	207	56.5
T4	55	6.4	31	8.5
N stage
N0	497	58.3	209	57.1
N1	356	41.7	157	42.9
M stage
M0	800	93.8	346	94.5
M1	53	6.2	20	5.5
Clinical stage
I	267	31.3	95	26.0
II	500	58.6	231	63.0
III	33	3.9	20	5.5
IV	53	6.2	20	5.5
Tumor size
< 3 cm	302	35.4	146	39.9
3-6 cm	417	48.9	168	45.9
> 6 cm	134	15.7	52	14.2
Surgical type
Partial/localized pancreatectomy	152	17.8	65	17.8
Total pancreatectomy	122	14.3	45	12.3
Extensive pancreatoduodenectomy	579	67.9	256	69.9
Radiation
None	609	71.4	248	67.8
Adjuvant radiotherapy solely	222	26.0	107	29.2
Others4	22	2.6	11	3.0
Chemotherapy
No/unknown	435	51.0	180	49.2
Yes	418	49.0	186	50.8

¹Including Black, Asian, Pacific Islander, American Indian, and Alaska Native;

²Including single (never married), widowed, and divorced;

³Including pancreatic duct, overlapping lesion of the pancreas, and other specified parts of the pancreas;

⁴Including neoadjuvant radiotherapy, and radiotherapy before and after surgery.

Table 2 Univariate and multivariate survival analyses of overall and cancer-specific survival in the training cohort

Variables	OS				CSS
	Univariate analysis		Multivariate analysis		Univariate analysis		Multivariate analysis
	HR (95%CI)	P value	HR (95%CI)	P value	HR (95%CI)	P value	HR (95%CI)	P value
Age (yr)
≤ 60	Reference		Reference		Reference		Reference
60-69	1.33 (1.06-1.67)	0.014	1.41 (1.12-1.79)	0.003	1.10 (0.83-1.46)	0.525	1.10 (0.82-1.47)	0.512
70-79	1.74 (1.39-2.16)	< 0.001	1.68 (1.33-2.12)	< 0.001	1.22 (0.91-1.62)	0.181	1.16 (0.86-1.56)	0.344
≥ 80	2.47 (1.81-3.35)	< 0.001	2.82 (2.04-3.91)	< 0.001	1.52 (1.20-2.21)	0.007	1.81 (1.14-2.87)	0.012
Sex
Male	Reference		Reference		Reference		Reference
Female	1.12 (0.95-1.32)	0.168	1.10 (0.92-1.31)	0. 300	1.23 (0.98-1.52)	0.068	1.27 (0.99-1.60)	0. 051
Race
White	Reference		Reference		Reference		Reference
Others1	0.77 (0.61-0.96)	0.018	0.84 (0.67-1.06)	0.142	0.73 (0.54-0.98)	0.040	0.80 (0.59-1.08)	0.143
Marital status
Married	Reference		Reference		Reference		Reference
Unmarried2	1.31 (1.10-1.55)	0.002	1.31 (1.10-1.57)	0.003	1.23 (1.05-1.54)	0.004	1.34 (1.05-1.71)	0.017
Grade
Well differentiated	Reference		Reference		Reference		Reference
Moderately differentiated	1.58 (1.25-1.99)	< 0.001	1.36 (1.08-1.72)	0.001	1.77 (1.29-2.43)	< 0.001	1.39 (1.01-1.92)	0.047
Poorly differentiated/undifferentiated	2.46 (1.90-3.18)	< 0.001	1.73 (1.32-2.28)	< 0.001	2.71 (1.90-3.86)	< 0.001	1.70 (1.16-2.48)	0.006
Unknown	1.08 (0.82-1.40)	0.598	1.17 (0.89-1.55)	0.253	1.08 (0.74-1.57)	0.707	1.51 (1.02-2.23)	0.040
Tumor location
Head	Reference		Reference		Reference		Reference
Body/tail	1.06 (0.86-1.29)	0.605	1.10 (0.83-1.45)	0.524	0.97 (0.74-1.29)	0.853	0.93 (0.62-1.37)	0.700
Others3	0.81 (0.63-1.03)	0.088	0.91 (0.69-1.20)	0.503	0.80 (0.58-1.11)	0.184	0.86 (0.60-1.24)	0.424
T stage
T1	Reference		Reference		Reference		Reference
T2	1.70 (1.23-2.34)	0.001	1.49 (1.03-2.14)	0.033	2.35 (1.36-4.05)	0.002	1.97 (1.09-3.56)	0.026
T3	2.84 (2.12-3.80)	< 0.001	1.94 (1.36-2.76)	< 0.001	5.38 (3.28-8.82)	< 0.001	2.63 (1.36-5.09)	0.004
T4	4.94 (3.36-7.28)	< 0.001	3.19 (2.01-5.07)	< 0.001	8.03 (5.70-12.61)	< 0.001	5.56 (2.17-14.22)	< 0.001
N stage
N0	Reference		Reference		Reference		Reference
N1	2.51 (2.13-2.96)	< 0.001	2.06 (1.69-2.50)	< 0.001	3.33 (2.66-4.18)	< 0.001	2.29 (1.72-3.04)	< 0.001
M stage
M0	Reference		Reference		Reference		Reference
M1	2.35 (1.75-3.15)	< 0.001	1.47 (1.03-2.08)	0.032	2.77 (1.93-3.98)	< 0.001	2.65 (1.29-5.44)	0.008
Clinical stage
I	Reference		Reference		Reference		Reference
II	2.37 (1.94-2.89)	< 0.001	1.13 (0.90-1.41)	0.377	2.72 (1.79-3.96)	< 0.001	1.66 (0.96-2.88)	0.071
III	3.55 (2.38-5.29)	< 0.001	1.59 (0.74-3.42)	0.235	3.79 (2.53-7.49)	< 0.001	1.78 (0.66-4.81)	0.253
IV	4.28 (3.08-5.96)	< 0.001	1.72 (0.85-3.81)	0.176	4.99 (3.58-9.68)	< 0.001	1.89 (0.82-4.63)	0.155
Tumor size
< 3 cm	Reference		Reference		Reference		Reference
3-6 cm	1.66 (1.38-2.00)	< 0.001	1.13 (0.91-1.40)	0.261	1.80 (1.40-2.31)	< 0.001	1.07 (0.81-1.41)	0.645
> 6 cm	1.25 (1.04-1.74)	0.023	1.03 (0.77-1.37)	0.848	1.43 (1.01-2.00)	0.041	1.06 (0.74-1.54)	0.741
Surgical type
Partial/localized pancreatectomy	Reference		Reference		Reference		Reference
Total pancreatectomy	0.90 (0.67-1.21)	0.496	0.97 (0.69-1.35)	0.846	0.78 (0.53-1.16)	0.224	0.75 (0.48-1.17)	0.201
Extensive pancreatoduodenectomy	0.96 (0.77-1.19)	0.716	0.96 (0.71-1.29)	0.767	0.97 (0.73-1.29)	0.815	0.95 (0.64-1.42)	0.809
Radiotherapy
None	Reference		Reference		Reference		Reference
Adjuvant radiotherapy solely	1.25 (1.04-1.50)	0.015	1.13 (0.90-1.42)	0.303	1.45 (1.14-1.83)	0.002	1.14 (0.86-1.52)	0.430
Others4	0.75 (0.44-1.28)	0.290	0.78 (0.44-1.36)	0.376	1.01 (0.52-1.98)	0.966	0.76 (0.37-1.53)	0.440
Chemotherapy
No/unknown	Reference		Reference		Reference		Reference
Yes	0.64 (0.55-0.76)	< 0.001	0.72 (0.58-0.89)	0.002	1.27 (1.02-1.58)	0.036	0.70 (0.53-0.92)	0.012

¹Including Black, Asian, Pacific Islander, American Indian, and Alaska Native;

²Including single (never married), widowed, and divorced;

³Including pancreatic duct, overlapping lesion of the pancreas, and other specified parts of the pancreas;

⁴Including neoadjuvant radiotherapy, and radiotherapy before and after surgery. OS: Overall survival; CSS: Cancer-specific survival; HR: Hazard ratio; CI: Confidence interval.

Table 3 The net reclassification improvement and integrated discrimination improvement of the nomogram compared to the American Joint Committee on Cancer 7^th staging system

Category	NRI (95%CI)	P value	IDI (95%CI)	P value
OS
Training set
3-yr OS	0.564 (0.413-0.731)	< 0.001	0.106	< 0.001
5-yr OS	0.467 (0.292-0.653)	< 0.001	0.104	< 0.001
10-yr OS	0.458 (0.323-0.715)	< 0.001	0.091	< 0.001
Validation set
3-yr OS	0.526 (0.344-0.714)	< 0.001	0.095	< 0.001
5-yr OS	0.455 (0.225-0.697)	< 0.001	0.092	< 0.001
10-yr OS	0.529 (0.234-0.764)	< 0.001	0.076	< 0.001
CSS
Training set
3-yr OS	0.570 (0.293-0.763)	< 0.001	0.076	< 0.001
5-yr OS	0.376 (0.225-0.673)	< 0.001	0.072	< 0.001
10-yr OS	0.421 (0.174-0.662)	< 0.001	0.068	< 0.001
Validation set
3-yr OS	0.461 (0.246-0.752)	< 0.001	0.065	< 0.001
5-yr OS	0.368 (0.197-0.680)	< 0.001	0.060	< 0.001
10-yr OS	0.436 (0.188-0.711)	< 0.001	0.059	< 0.001

OS: Overall survival; CSS: Cancer-specific survival; NRI: Net reclassification improvement; IDI: Integrated discrimination improvement; CI: Confidence interval.