Background
Methods
Patients
Statistical analyses
Nomogram construction and validation
Results
Patient characteristics
Variable | Category | The US | Belgium | The Netherlands | Slovenia | Norway |
---|---|---|---|---|---|---|
Incidence (per 100,000)2 | Male | 8.6 | 7.4 | 7.4 | 9.3 | 7.8 |
Female | 6.5 | 5.6 | 6.1 | 6.5 | 6.5 | |
Years of diagnosis | 2004–2015 | 2004–2013 | 2003–2014 | 2003–2013 | 2003–2014 | |
n
| 9519 | 1105 | 982 | 118 | 113 | |
Diagnosis in 2010 or later | Yes | 5635 (59) | 579 (52) | 747 (76) | 67 (57) | 79 (70) |
Sex | Female | 4671 (49) | 522 (47) | 483 (49) | 50 (42) | 58 (51) |
Age (years) | Median (interquartile range) | 65 (58–72) | 65 (58–71) | 64 (57–69) | 61 (54–68) | 63 (59–70) |
Mean ± standard deviation | 65 ± 10 | 64 ± 10 | 62 ± 9 | 61 ± 9 | 64 ± 8 | |
< 50 | 706 (7) | 90 (8) | 92 (9) | 11 (9) | 4 (4) | |
50–59 | 2101 (22) | 264 (24) | 235 (24) | 38 (32) | 29 (26) | |
60–69 | 3464 (36) | 406 (37) | 417 (42) | 46 (39) | 50 (44) | |
≥ 70 | 3248 (34) | 345 (31) | 238 (24) | 23 (19) | 30 (27) | |
Tumor location3 | Pancreas head | 7314 (83) | 658 (82) | 820 (90) | 97 (92) | 91 (88) |
Pancreas body | 622 (7) | 58 (7) | 31 (3) | 5 (5) | 4 (4) | |
Pancreas tail | 845 (10) | 86 (11) | 63 (7) | 3 (3) | 8 (8) | |
Other | 738 (8) | 303 (27) | 68 (7) | 13 (11) | 10 (9) | |
T stage4 | T1 | 494 (5) | 56 (5) | 72 (7) | 0 (0) | 8 (8) |
T2 | 1192 (13) | 185 (17) | 182 (19) | 8 (7) | 28 (26) | |
T3 | 7815 (82) | 860 (78) | 727 (74) | 108 (93) | 70 (66) | |
N stage5 | N1 | 6339 (67) | 805 (73) | 703 (72) | 97 (84) | 60 (55) |
Differentiation6 | Well | 858 (10) | 149 (15) | 91 (11) | 12 (11) | 3 (3) |
Intermediate | 4540 (52) | 511 (52) | 423 (51) | 44 (40) | 64 (63) | |
Poor/undifferentiated | 3266 (38) | 326 (33) | 319 (38) | 55 (50) | 35 (34) |
Survival outcomes
Survival | The US | Belgium | The Netherlands | Slovenia | Norway |
---|---|---|---|---|---|
OS (95% CI)1 | OS (95% CI) | OS (95% CI) | OS (95% CI) | OS (95% CI) | |
Short-term survival | |||||
6-month | 94 (94–95) | 95 (94–96) | 97 (96–98) | 95 (89–98) | 96 (91–99) |
9-month | 87 (86–87) | 86 (84–88) | 89 (87–91) | 79 (70–85) | 90 (83–94) |
Long-term survival | |||||
1-year | 77 (76–78) | 77 (74–79) | 79 (77–82) | 69 (60–77) | 77 (67–83) |
2-year | 47 (46–48) | 46 (43–49) | 44 (40–47) | 39 (30–47) | 46 (36–55) |
3-year | 31 (30–32) | 29 (26–32) | 29 (25–32) | 21 (14–29) | 27 (18–36) |
5-year | 19 (18–20) | 17 (14–20) | 20 (16–23) | 10 (5–17) | 21 (12–31) |
Survival-associated factors
Variable | Category | The US | The US (white) | Belgium | The Netherlands | Slovenia | Norway |
---|---|---|---|---|---|---|---|
Used no. | 8657 | 7170 | 979 | 833 | 109 | 96 | |
HR (95% CI)1 | HR (95% CI) | HR (95% CI) | HR (95% CI) | HR (95% CI) | HR (95% CI) | ||
Year of diagnosis | Per year; continuous | 0.97 (0.96–0.98) | 0.97 (0.96–0.98) | 0.98 (0.95–1.01) | 0.99 (0.95–1.03) | 0.96 (0.89–1.03) | 0.80 (0.69–0.93) |
Age | Per year; continuous | 1.01 (1.01–1.01) | 1.01 (1.01–1.01) | 1.02 (1.01–1.02) | 1.00 (0.99–1.01) | 1.01 (0.99–1.04) | 1.04 (1.00–1.08) |
Sex | Female | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) |
Male | 1.10 (1.05–1.16) | 1.12 (1.06–1.18) | 0.93 (0.80–1.07) | 1.08 (0.91–1.29) | 1.49 (0.96–2.32) | 1.14 (0.67–1.95) | |
Tumor location | Pancreas head | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) |
Pancreas body | 1.03 (0.92–1.15) | 1.04 (0.92–1.17) | 1.34 (0.99–1.82) | 1.19 (0.69–2.04) | 1.33 (0.47–3.81) | 0.40 (0.05–2.98) | |
Pancreas tail | 1.02 (0.93–1.12) | 1.03 (0.93–1.14) | 1.00 (0.76–1.30) | 0.85 (0.57–1.26) | 0.39 (0.09–1.66) | 2.67 (1.09–6.53) | |
Other2 | 1.02 (0.93–1.13) | 1.03 (0.93–1.15) | 0.95 (0.80–1.12) | 0.92 (0.65–1.38) | 0.83 (0.37–1.84) | 0.89 (0.30–2.65) | |
T stage | T1 | 0.66 (0.57–0.75) | 0.70 (0.61–0.81) | 0.68 (0.47–0.97) | 0.48 (0.33–0.71) | – | 0.17 (0.04–0.72) |
T2 | 0.86 (0.79–0.93) | 0.88 (0.81–0.97) | 0.89 (0.74–1.08) | 1.02 (0.82–1.26) | 0.70 (0.29–1.67) | 0.89 (0.49–1.61) | |
T3 | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | |
N stage | N0 | 0.65 (0.61–0.69) | 0.65 (0.61–0.69) | 0.78 (0.66–0.92) |
0.51 (0.41–0.64)
| 0.77 (0.40–1.51) | 0.71 (0.39–1.29) |
N1 | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | |
Differentiation | Well | 0.60 (0.55–0.66) | 0.59 (0.53–0.65) | 0.68 (0.55–0.85) | 0.48 (0.35–0.67) | 0.57 (0.27–1.22) | 0.31 (0.04–2.58) |
Intermediate | 0.77 (0.73–0.81) | 0.78 (0.73–0.82) | 0.81 (0.69–0.94) | 0.61 (0.50–0.73) | 0.82 (0.51–1.32) | 0.93 (0.54–1.61) | |
Poor/undifferentiated | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) |
Variable | The US | Belgium | The Netherlands | Slovenia | ||||
---|---|---|---|---|---|---|---|---|
n | HR (95% CI) | n | HR (95% CI) | n | HR (95% CI) |
n
| HR (95% CI) | |
Resection margin | ||||||||
Negative | – | – | – | – | 637 | 1.00 (reference) | 51 | 1.00 (reference) |
Positive | – | – | – | – | 291 | 1.36 (1.12–1.65) | 34 | 1.54 (0.82–2.88) |
Hospital type | ||||||||
Non-academic | – | – | 497 | 1.00 (reference) | 510 | 1.00 (reference) | – | – |
Academic | – | – | 608 | 0.89 (0.77–1.03) | 472 | 0.79 (0.66–0.94) | – | – |
Tumor size | ||||||||
≤ 2 cm | 1490 | 1.00 (reference) | – | – | – | – | – | – |
2–3 cm | 3146 | 1.23 (1.12–1.35) | – | – | – | – | – | – |
3–4 cm | 2487 | 1.38 (1.25–1.52) | – | – | – | – | – | – |
4–5 cm | 1229 | 1.60 (1.44–1.78) | – | – | – | – | – | – |
> 5 cm | 938 | 1.56 (1.39–1.75) | – | – | – | – | – | – |
T stage (8th version) | ||||||||
T1 | 1490 | 0.62 (0.57–0.68) | – | – | – | – | – | – |
T2 | 5633 | 0.81 (0.76–0.87) | – | – | – | – | – | – |
T3 | 2167 | 1.00 (reference) | – | – | – | – | – | – |
Positive LN number (continuous) | 9426 | 1.05 (1.04–1.06) | – | – | 974 | 1.07 (1.04–1.10) | – | – |
N stage (8th version) | ||||||||
N0 (0 positive LNs) | 3180 | 1.00 (reference) | – | – | 280 | 1.00 (reference) | – | – |
N1 (1–3 positive LNs) | 3885 | 1.42 (1.33–1.51) | – | – | 416 | 1.68 (1.33–2.13) | – | – |
N2 (≥ 4 positive LNs) | 2244 | 1.84 (1.72–1.98) | – | – | 278 | 2.43 (1.89–3.12) | – | – |
Harvested LN number (continuous) | 9484 | 0.99 (0.99–0.99) | – | – | 959 | 0.99 (0.98–1.00) | – | – |
LN ratio (continuous) | 9138 | 2.60 (2.26–3.00) | – | – | 945 | 3.15 (2.05–4.84) | – | – |
ECOG score | ||||||||
0 | – | – | 140 | 1.00 (reference) | – | – | – | – |
1 | – | – | 662 | 0.96 (0.76–1.20) | – | – | – | – |
≥ 2 | – | – | 63 | 1.04 (0.73–1.47) | – | – | – | – |
Resection type | ||||||||
Pancreatoduodenectomy | 7108 | 1.00 (reference) | – | – | 877 | 1.00 (reference) | – | – |
Distal pancreatectomy | 1142 | 1.02 (0.92–1.14) | – | – | 88 | 1.33 (0.61–2.91) | – | – |
Total pancreatectomy | 1102 | 1.07 (0.99–1.15) | – | – | 10 | 0.98 (0.36–2.65) | – | – |
Comorbidity | ||||||||
Cardiovascular disease (yes v no) | – | – | – | – | 30/119 | 1.33 (0.69–2.57) | – | – |
Hypertension (yes v no) | – | – | – | – | 39/110 | 1.01 (0.59–1.75) | – | – |
Diabetes (yes v no) | – | – | – | – | 33/116 | 1.34 (0.76–2.38) | – | – |
Pulmonary disease (yes v no) | – | – | – | – | 14/135 | 1.96 (0.88–4.36) | – | – |
Number of comorbidities | ||||||||
0 | – | – | – | – | 52 | 1.00 (reference) | – | – |
1 | – | – | – | – | 48 | 1.48 (0.84–2.62) | – | – |
≥ 2 | – | – | – | – | 49 | 1.86 (1.00–3.46) | – | – |
Prognostic nomogram
Construction
Prognostic factors | ||
Variable | Category | Score |
Sex | Female | 0 |
Male | 18 | |
Age (years) | 25 | 42 |
30 | 34 | |
35 | 27 | |
40 | 19 | |
45 | 11 | |
50 | 4 | |
55 | 0 | |
60 | 5 | |
65 | 18 | |
70 | 24 | |
75 | 33 | |
80 | 46 | |
85 | 59 | |
90 | 73 | |
95 | 86 | |
100 | 100 | |
T stage | T1 | 0 |
T2 | 53 | |
T3 | 78 | |
N stage | N0 | 0 |
N1 | 82 | |
Differentiation | Well | 0 |
Intermediate | 47 | |
Poor/undifferentiated | 97 | |
Median survival | ||
Total score | Median survival (months) | |
251 | 20 | |
152 | 30 | |
99 | 40 | |
64 | 50 | |
43 | 60 | |
27 | 70 | |
13 | 80 | |
0 | 90 | |
1-year survival | ||
Total score | 1-year survival probability | |
345 | 0.60 | |
313 | 0.65 | |
277 | 0.70 | |
236 | 0.75 | |
187 | 0.80 | |
126 | 0.85 | |
44 | 0.90 | |
2-year survival | ||
Total score | 2-year survival probability | |
358 | 0.20 | |
329 | 0.25 | |
302 | 0.30 | |
276 | 0.35 | |
250 | 0.40 | |
224 | 0.45 | |
197 | 0.50 | |
169 | 0.55 | |
138 | 0.60 | |
106 | 0.65 | |
70 | 0.70 | |
29 | 0.75 | |
3-year survival | ||
Total score | 3-year survival probability | |
342 | 0.10 | |
305 | 0.15 | |
273 | 0.20 | |
245 | 0.25 | |
218 | 0.30 | |
192 | 0.35 | |
166 | 0.40 | |
139 | 0.45 | |
112 | 0.50 | |
84 | 0.55 | |
54 | 0.60 | |
21 | 0.65 | |
5-year survival | ||
Total score | 5-year survival probability | |
323 | 0.05 | |
272 | 0.10 | |
235 | 0.15 | |
204 | 0.20 | |
175 | 0.25 | |
148 | 0.30 | |
122 | 0.35 | |
96 | 0.40 | |
70 | 0.45 | |
43 | 0.50 | |
15 | 0.55 |
An example of use
Calibration and validation
Model modification/subgroup | Concordance index | 95% confidence interval |
---|---|---|
Training cohort | ||
The US, our nomogram | 0.60 | 0.59–0.61 |
The US, model based on both T and N stages | 0.56 | 0.56–0.57 |
Validation cohorts | ||
Belgium, our nomogram | 0.58 | 0.55–0.60 |
Belgium, model based on both T and N stages | 0.54 | 0.52–0.56 |
The Netherlands, our nomogram | 0.62 | 0.59–0.65 |
The Netherlands, model based on both T and N stages | 0.56 | 0.54–0.59 |
Slovenia, our nomogram | 0.58 | 0.51–0.65 |
Slovenia, model based on both T and N stages | 0.52 | 0.47–0.57 |
Norway, our nomogram | 0.63 | 0.55–0.71 |
Norway, model based on both T and N stages | 0.61 | 0.54–0.68 |
Sensitivity analyses for the training US cohort | ||
Replacement | ||
Age group in place of continuous age | 0.59 | 0.59–0.60 |
Metastatic lymph node number in place of N stage | 0.60 | 0.59–0.61 |
Lymph node ratio in place of N stage |
0.61
| 0.61–0.62 |
The 8th version of T stage in place of the original stage |
0.61
| 0.60–0.61 |
The 8th version of N stage in place of the original stage | 0.60 | 0.59–0.61 |
The 8th version of T & N stages in place of the original stages |
0.61
| 0.60–0.62 |
Addition | ||
Harvested lymph node added | 0.60 | 0.60–0.61 |
Tumor size added |
0.61
| 0.60–0.61 |
Harvested lymph node & tumor size added |
0.61
| 0.60–0.62 |
Subgroup | ||
Diagnosis after 2009 | 0.60 | 0.59–0.61 |
White ethnicity | 0.60 | 0.59–0.61 |
Pancreas head | 0.60 | 0.59–0.61 |
Pancreas body & tail |
0.61
| 0.59–0.63 |