Table 3b. Correlation of serial biomarker levels with OS.
|
Overall survival | ||||||||
|---|---|---|---|---|---|---|---|---|
| Time (days) | Median OS (months) (CI) | P (log rank) | Hazard ratio (CI) | P (Cox) | C index (CI) | Hazard ratio (CI) (adjusted for KPS) | P (Cox) | C index (CI) |
|
d0 | ||||||||
| CYFRA 21-1 |
|
<0.001 |
|
|
0.693 (0.637–0.748) |
|
|
0.746 (0.694–0.799) |
| <2.7 | 14.8 (8.4–23.7) | |||||||
| 2.7–10 | 7.1 (5.4–9.5) | 2.9 (1.6–5.4) | 0.001 | 3.1 (1.6–5.8) | 0.001 | |||
| >10 |
4.8 (3.2–6.3) |
|
5.0 (2.6–9.5) |
<0.001 |
|
5.5 (2.9–10.8) |
<0.001 |
|
| CEA |
|
<0.001 |
|
|
0.618 (0.553–0.684) |
|
|
0.693 (0.624–0.761) |
| <2.9 | 12.9 (8.2–23.7) | |||||||
| 2.9–15 | 7.1 (4.4–8.4) | 2.6 (1.4–4.7) | 0.002 | 3.1 (1.7–5.8) | <0.001 | |||
| >15 |
6.3 (4.6–8.2) |
|
3.0 (1.6–5.7) |
0.001 |
|
3.1 (1.6–5.9) |
0.001 |
|
| CA 19-9 |
|
<0.001 |
|
|
0.660 (0.589–0.731) |
|
|
0.709 (0.647–0.772) |
| <200 | 14.2 (9.4–24.3) | |||||||
| 200–6600 | 7.1 (5.8–8.3) | 3.0 (1.6–5.7) | 0.001 | 3.1 (1.6–6.0) | 0.001 | |||
| >6600 |
5.2 (2.9–7.7) |
|
3.6 (1.9–6.9) |
<0.001 |
|
4.3 (2.2–8.5) |
<0.001 |
|
|
d7 | ||||||||
| CYFRA 21-1 |
|
<0.001 |
|
|
0.683 (0.623–0.744) |
|
|
0.713 (0.647–0.780) |
| <2.5 | 14.2 (8.4–23.3) | |||||||
| 2.5–6 | 9.4 (6.6–10.3) | 2.2 (1.1–4.1) | 0.021 | 2.1 (1.1–4.1) | 0.028 | |||
| >6 |
5.0 (3.2–7.6) |
|
4.6 (2.3–9.0) |
<0.001 |
|
4.8 (2.4–9.6) |
<0.001 |
|
| CEA |
|
0.021 |
|
|
0.607 (0.535–0.680) |
|
|
0.679 (0.607–0.750) |
| <2.6 | 11.9 (8.2–19.0) | |||||||
| 2.6–14 | 8.3 (7.1–10.8) | 1.4 (0.8–2.5) | 0.296 | 1.8 (0.9–3.3) | 0.084 | |||
| >14 |
6.4 (4.7–8.2) |
|
2.4 (1.3–4.6) |
0.007 |
|
3.0 (1.5–5.9) |
0.001 |
|
| CA 19-9 |
|
<0.001 |
|
|
0.658 (0.585–0.731) |
|
|
0.705 (0.641–0.769) |
| <200 | 14.8 (9.4–24.3) | |||||||
| 200–6400 | 7.7 (6.4–11.9) | 2.1 (1.1–4.0) | 0.028 | 2.6 (1.3–5.1) | 0.006 | |||
| >6400 |
6.0 (3.0–9.5) |
|
3.9 (1.9–8.0) |
<0.001 |
|
4.2 (2.1–8.7) |
<0.001 |
|
|
d14 | ||||||||
| CYFRA 21-1 |
|
<0.001 |
|
|
0.677 (0.610–0.745) |
|
|
0.687 (0.615–0.759) |
| <1.9 | 16.1 (8.4–23.3) | |||||||
| 1.9–6 | 10.1 (6.2–14.8) | 1.6 (0.8–3.1) | 0.197 | 1.9 (0.9–3.8) | 0.084 | |||
| >6 |
5.9 (3.5–7.6) |
|
4.4 (2.1–9.2) |
<0.001 |
|
4.8 (2.3–10.4) |
<0.001 |
|
| CEA |
|
0.0223 |
|
|
0.609 (0.531–0.686) |
|
|
0.650 (0.575–0.725) |
| <2.1 | 12.9 (7.0–19.0) | |||||||
| 2.1–11 | 9.4 (7.1–17.9) | 1.1 (0.6–2.2) | 0.787 | 1.3 (0.6–2.7) | 0.455 | |||
| >11 |
6.4 (4.7–8.3) |
|
2.4 (1.2–4.9) |
0.013 |
|
2.6 (1.3–5.4) |
0.008 |
|
| CA 19-9 |
|
0.0032 |
|
|
0.648 (0.572–0.724) |
|
|
0.671 (0.593–0.749) |
| <150 | 15.5(8.2–25.0) | |||||||
| 150–4000 | 10.3 (6.8–13.9) | 1.9 (0.9–3.8) | 0.090 | 1.9 (0.9–3.9) | 0.078 | |||
| >4000 |
6.4 (3.6–8.3) |
|
3.5 (1.6–7.4) |
0.001 |
|
3.5 (1.6–7.4) |
0.002 |
|
|
d21 | ||||||||
| CYFRA 21-1 |
|
<0.001 |
|
|
0.684 (0.621–0.748) |
|
|
0.733 (0.671–0.795) |
| <2.1 | 11.9 (7.1–19.0) | |||||||
| 2.1–6 | 7.1 (5.4–10.0) | 1.5 (0.8–2.9) | 0.251 | 1.4 (0.7–2.8) | 0.291 | |||
| >6 |
4.6 (2.0–5.8) |
|
4.2 (2.1–8.6) |
<0.001 |
|
3.5 (1.7–7.3) |
0.001 |
|
| CEA |
|
0.1853 |
|
|
0.581 (0.510–0.653) |
|
|
0.701 (0.637–0.766) |
| <2.5 | 10.2 (5.6–16.1) | |||||||
| 2.5–9 | 7.1 (3.0–10.8) | 1.3 (0.7–2.5) | 0.464 | 1.2 (0.6–2.4) | 0.514 | |||
| >9 |
5.9 (3.6–8.2) |
|
1.9 (0.9–3.7) |
0.073 |
|
2.0 (1.0–3.9) |
0.050 |
|
| CA 19-9 |
|
0.0104 |
|
|
0.644 (0.569–0.720) |
|
|
0.722 (0.656–0.787) |
| <310 | 11.4(7.1–19.0) | |||||||
| 310–4000 | 7.0 (4.6–10.2) | 2.0 (1.0–4.1) | 0.046 | 1.9 (1.0–3.9) | 0.066 | |||
| >4000 |
5.8 (3.0–6.6) |
|
2.9 (1.4–5.9) |
0.004 |
|
2.4 (1.2–5.0) |
0.020 |
|
|
d28 | ||||||||
| CYFRA 21-1 |
|
0.0096 |
|
|
0.637 (0.552–0.722) |
|
|
0.651 (0.564–0.739) |
| <2.1 | 11.9 (6.8–19.0) | |||||||
| 2.1–3.8 | 8.3 (6.2–11.3) | 1.2 (0.6–2.4) | 0.663 | 1.3 (0.6–2.6) | 0.499 | |||
| >3.8 |
5.8 (3.0–7.7) |
|
2.8 (1.3–5.8) |
0.006 |
|
2.9 (1.4–6.1) |
0.005 |
|
| CEA |
|
0.2343 |
|
|
0.545 (0.446–0.644) |
|
|
0.621 (0.571–0.725) |
| <2.0 | 9.4 (5.4–11.9) | |||||||
| 2.0–6 | 9.25 (4.6–23.3) | 0.7 (0.3–1.4) | 0.264 | 0.6 (0.3–1.2) | 0.161 | |||
| >6 |
6.8 (5.8–8.4) |
|
1.3 (0.6–2.6) |
0.537 |
|
1.2 (0.6–2.4) |
0.665 |
|
| CA 19-9 |
|
0.0487 |
|
|
0.616 (0.526–0.705) |
|
|
0.662 (0.585–0.738) |
| <100 | 13.3 (5.6–24.3) | |||||||
| 100–2500 | 7.4 (4.7–10.8) | 1.7 (0.8–3.6) | 0.143 | 1.9 (0.9–4.0) | 0.091 | |||
| >2500 |
6.4 (4.6–7.7) |
|
2.5 (1.2–5.5) |
0.017 |
|
2.5 (1.1–5.4) |
0.021 |
|
|
d56 | ||||||||
| CYFRA 21-1 |
|
<0.001 |
|
|
0.681 (0.620–0.743) |
|
|
0.714 (0.648–0.779) |
| <1.7 | 10.8 (8.2–17.9) | |||||||
| 1.7–5 | 9.8 (6.3–11.9) | 1.2 (0.7–2.3) | 0.492 | 1.4 (0.8–2.7) | 0.259 | |||
| >5 |
4.7 (2.0–6.0) |
|
3.7 (1.9–6.9) |
<0.001 |
|
3.3 (1.7–6.3) |
<0.001 |
|
| CEA |
|
0.0075 |
|
|
0.630 (0.562–0.699) |
|
|
0.731 (0.666–0.795) |
| <2.5 | 12.9 (8.2–19.0) | |||||||
| 2.5–13 | 7.7 (4.7–10.3) | 1.9 (1.0–3.5) | 0.037 | 1.6 (0.8–3.0) | 0.156 | |||
| >13 |
6.3 (3.6–7.7) |
|
2.7 (1.4–5.2) |
0.003 |
|
2.3 (1.2–4.5) |
0.012 |
|
| CA 19-9 |
|
<0.001 |
|
|
0.699 (0.638–0.760) |
|
|
0.742 (0.679–0.805) |
| <120 | 14.5 (8.2–24.3) | |||||||
| 120–3960 | 7.6 (5.8–10.8) | 2.5 (1.3–5.0) | 0.009 | 2.8 (1.4–5.6) | 0.004 | |||
| >3960 | 5.8 (2.0–6.8) | 5.3 (2.5–11.0) | <0.001 | 5.0 (2.4–10.6) | <0.001 | |||
Abbreviations: CA 19-9=Carbohydrate antigen 19-9; CEA=carcinoembryonic antigen; CI=95% confidence interval; d=day; KPS=Karnofsky performance status; OS=overall survival. The bold entries indicate the highest C index (assessed at each specific time point for all 3 markers).