TABLE 3.
Models of PanNET Survival
| Independent Variables | Hazard Ratio | 95% Confidence Interval | P |
|---|---|---|---|
| Univariate analysis | |||
| 1. Independent variables | |||
| Size, cm | |||
| (0,2] vs (2,4] | 2.74 | 1.07–7.00 | 0.035* |
| (2,4] vs > 4 | 1.52 | 0.98–2.36 | 0.060 |
| (0,2] vs > 4 | 4.17 | 1.65–10.53 | 0.003* |
| Tumor location† | |||
| Head | 1.34 | 0.88–2.05 | 0.170 |
| Body | 0.87 | 0.48–1.58 | 0.653 |
| Tail | 1.08 | 0.71–1.65 | 0.711 |
| Uncinate process | 0.63 | 0.09–4.52 | 0.644 |
| Focality† | 0.38 | 0.09–1.55 | 0.176 |
| Extent of spread† | 2.84 | 1.82–4.44 | <0.001* |
| Grade† | |||
| Grade II (vs I) | 1.91 | 1.17–3.12 | 0.010* |
| Grade III (vs I) | 15.67 | 8.07–30.44 | <0.001* |
| Large vessel invasion† | 1.86 | 1.06–3.27 | 0.030* |
| Small vessel invasion† | 3.14 | 2.02–4.90 | <0.001* |
| Race† | 2.03 | 0.82–5.02 | 0.124 |
| Positive margins | 2.53 | 1.59–4.02 | <0.001* |
| Positive lymph nodes | 2.17 | 1.40–3.37 | 0.001* |
| Distant metastases | 3.18 | 2.00–5.03 | <0.001* |
| Necrosis present | 2.65 | 1.72–4.09 | <0.001* |
| Perineural invasion | 1.99 | 1.30–3.04 | 0.002* |
| Age‡ | 1.02 | 1.01–1.04 | 0.004* |
| Sex (male) | 1.68 | 1.09–2.58 | 0.019* |
| 2. AJCC staging system, 2010§ (HCI = 0.68) | |||
| AJCC Ib (vs Ia) | 1.17 | 0.40–3.38 | 0.775 |
| AJCC IIa (vs Ia) | 4.42 | 1.73–11.25 | 0.002* |
| AJCC IIb (vs Ia) | 3.91 | 1.61–9.50 | 0.003* |
| AJCC IV (vs Ia) | 8.41 | 3.45–20.51 | <0.001* |
| AJCC IIa (vs Ib) | 3.78 | 1.63–8.78 | 0.002* |
| AJCC IIb (vs Ib) | 3.35 | 1.53–7.36 | 0.003* |
| AJCC IV (vs Ib) | 7.20 | 3.24–16.00 | <0.001* |
| AJCC IIb (vs IIa) | 0.89 | 0.48–1.62 | 0.696 |
| AJCC IV (vs IIa) | 1.91 | 1.03–3.53 | 0.041* |
| AJCC IV (vs IIb) | 2.15 | 1.27–3.63 | 0.004* |
| 3. ENETS staging system, 2006§ (HCI = 0.68) | |||
| ENETS II (vs I) | 2.14 | 0.74–6.19 | 0.161 |
| ENETS III (vs I) | 4.45 | 1.57–12.63 | 0.005* |
| ENETS IV (vs I) | 9.04 | 3.16–25.84 | <0.001* |
| ENETS III (vs II) | 2.08 | 1.21–3.56 | 0.008* |
| ENETS IV (vs II) | 4.22 | 2.40–7.44 | <0.001* |
| ENETS IV (vs III) | 2.03 | 1.22–3.39 | 0.007* |
| Multivariate analyses | |||
| 1. Multivariate AJCC reduced model¶ (HCI = 0.76) | |||
| AJCC II (vs I) | 1.68 | 0.86–3.30 | 0.13 |
| AJCC IV (vs I) | 3.46 | 1.67–7.16 | 0.001* |
| AJCC IV (vs II) | 2.06 | 1.22–3.46 | 0.007* |
| Log grade‖ | 1.83 | 1.47–2.29 | <0.001* |
| Positive margins | 1.28 | 0.76–2.17 | 0.354 |
| Sex (male) | 1.65 | 1.03–2.63 | 0.037* |
| Age† | 1.03 | 1.02–1.05 | <0.001* |
| 2. Multivariate ENETS reduced model** (HCI = 0.76) | |||
| ENETS II (vs I) | 1.10 | 0.36–3.34 | 0.867 |
| ENETS III (vs I) | 1.82 | 0.62–5.30 | 0.274 |
| ENETS IV (vs I) | 3.20 | 1.07–9.58 | 0.037* |
| ENETS III (vs II) | 1.65 | 0.91–3.00 | 0.097 |
| ENETS IV (vs II) | 2.91 | 1.59–5.32 | 0.001* |
| ENETS IV (vs III) | 1.76 | 0.99–3.12 | 0.053 |
| Log grade* | 1.94 | 1.55–2.42 | <0.001* |
| Positive margins | 1.33 | 0.80–2.23 | 0.273 |
| Sex (male) | 1.76 | 1.10–2.79 | 0.017* |
| Age† | 1.03 | 1.01–1.05 | 0.001* |
| 3. Multivariate nonstaged reduced model† (HCI = 0.74) | |||
| Size, cm | |||
| (0,2] vs (2,4] | 1.14 | 0.42–3.09 | 0.795 |
| (0,2] vs >4 | 1.21 | 0.43–3.39 | 0.723 |
| Positive lymph nodes | 1.23 | 0.71–2.13 | 0.453 |
| Distant metastasis | 1.95 | 1.06–3.58 | 0.031* |
| Log grade‖ | 1.88 | 1.50–2.36 | <0.001* |
| Positive margins | 1.28 | 0.73–2.23 | 0.396 |
| Sex (male) | 1.85 | 1.12–3.03 | 0.015* |
| Age† | 1.03 | 1.01–1.05 | <0.001* |
| 4. “Grade Only” model‡ (HCI = 0.74) | |||
| Log grade‖ | 2.10 | 1.71–2.57 | <0.001* |
| Sex (male) | 1.61 | 1.02–2.55 | 0.041* |
| Age† | 1.03 | 1.01–1.05 | <0.001* |
| 5. AJCC staging system corrected for age and sex§ (HCI = 0.72) | |||
| AJCC II (vs I) | 3.51 | 1.91–6.45 | <0.001* |
| AJCC IV (vs I) | 8.47 | 4.39–16.36 | <0.001* |
| AJCC IV (vs II) | 2.42 | 1.47–3.96 | <0.001* |
| Sex (male) | 1.51 | 0.97–2.36 | 0.067 |
| Age† | 1.03 | 1.01–1.04 | 0.001* |
| 6. ENETS staging system corrected for age and sex§ (HCI = 0.70) | |||
| ENETS II (vs I) | 2.26 | 0.78–6.56 | 0.132 |
| ENETS III (vs I) | 4.12 | 1.45–11.75 | 0.008* |
| ENETS IV (vs I) | 10.22 | 3.56–29.33 | <0.001* |
| ENETS III (vs II) | 1.82 | 1.06–3.12 | 0.029* |
| ENETS IV (vs II) | 4.51 | 2.55–7.98 | <0.001* |
| ENETS IV (vs III) | 2.48 | 1.46–4.21 | 0.001* |
| Sex (male) | 1.66 | 1.07–2.57 | 0.024* |
| Age† | 1.02 | 1.01–1.04 | 0.004* |
| 7. “Grade Only” plus distant metastases model‡ (HCI = 0.75) | |||
| Log grade‖ | 1.97 | 1.59–2.44 | <0.001* |
| Sex (male) | 1.73 | 1.09–2.76 | 0.020* |
| Age† | 1.03 | 1.01–1.05 | <0.001* |
| Distant metastases | 2.32 | 1.40–3.84 | 0.001* |
| 8. Proposed model‡ (HCI = 0.74) | |||
| Log grade‖ | 2.00 | 1.65–2.42 | <0.001* |
| Sex (male) | 1.52 | 0.96–2.42 | 0.074 |
| Age > 63 | 1.82 | 1.13–2.95 | 0.014* |
Statistically significant at α < 0.05.
Tumor location: head, body, tail, and uncinate process (each category compared to the rest); focality: uni- vs multifocal; extent of spread: contained to the pancreas or extending to peripancreatic soft tissue/adjacent organs; grade: categorical Ki-67 index of (0%–3%], (3, 20%] and >20%; large vessel invasion: celiac axis or superior mesenteric artery invasion; small vessel invasion: any vessel invasion other than large vessel invasion; race: white vs nonwhite.
Age is compared with the age of the previous year so that a change in age by X years would be associated with a change in the hazard of death by a factor of (1.02)X.
If ln(hazard ratio) = 0.51, a change in Ki-67% by a factor of X will be associated with a change in the hazard of death by a factor of X0.51.
Complete case analysis, n = 320; number of events = 89; P value from log-rank test of equality of survival curves < 0.001.
Complete case analysis, n = 271; number of events = 81; P value from likelihood ratio test of stage terms = 0.002.
Complete case analysis, n = 271; number of events = 81; P value from likelihood ratio test of stage terms = 0.003.
Complete case analysis, n = 256; number of events = 77.
Complete case analysis, n = 271; number of events = 81.
Complete case analysis, n = 320; number of events = 89; P value from likelihood ratio test of stage terms < 0.001.