Table 3a. Correlation of serial biomarker levels with TTP.
|
Time to progression | ||||||||
|---|---|---|---|---|---|---|---|---|
| Time (days) | Median TTP (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 |
|
|
0.652 (0.592–0.712) |
|
|
0.713 (0.658–0.767) |
| <2.7 | 9.8 (6.0–19.0) | |||||||
| 2.7–10 | 2.2 (1.6–3.9) | 3.0 (1.7–5.5) | <0.001 | 3.4 (1.9–6.2) | <0.001 | |||
| >10 |
2.7 (1.6–4.6) |
|
3.3 (1.8–6.0) |
<0.001 |
|
3.6 (1.9–6.7) |
<0.001 |
|
| CEA |
|
<0.001 |
|
|
0.633 (0.571–0.694) |
|
|
0.695 (0.635 0.755) |
| <2.9 | 6.5 (3.9–17.9) | |||||||
| 2.9–15 | 3.8 (2.0–6.2) | 1.9 (1.1–3.4) | 0.026 | 2.4 (1.3–4.3) | 0.005 | |||
| >15 |
2.1 (1.8–3.6) |
|
3.0 (1.6–5.5) |
<0.001 |
|
3.3 (1.8–6.2) |
<0.001 |
|
| CA 19-9 |
|
0.016 |
|
|
0.625 (0.555–0.696) |
|
|
0.675 (0.614–0.736) |
| <200 | 6.0 (3.9–17.9) | |||||||
| 200– 6600 | 3.7 (2.0–6.9) | 1.8 (1.0–3.3) | 0.05 | 2.0 (1.1–3.7) | 0.022 | |||
| >6600 |
2.1 (1.5–3.9) |
|
2.3 (1.3–4.3) |
0.006 |
|
2.6 (1.4–4.8) |
0.003 |
|
|
d7 | ||||||||
| CYFRA 21-1 |
|
0.0046 |
|
|
0.623 (0.553–0.694) |
|
|
0.651 (0.574–0.727) |
| <2.5 | 7.1 (4.1–17.9) | |||||||
| 2.5–6 | 3.9 (2.0–6.9) | 1.8 (1.0–3.3) | 0.061 | 1.8 (0.9–3.3) | 0.075 | |||
| >6 |
3.0 (1.6–5.0) |
|
2.8 (1.5–5.3) |
0.002 |
|
2.8 (1.5–5.4) |
0.002 |
|
| CEA |
|
0.0183 |
|
|
0.610 (0.535–0.684) |
|
|
0.657 (0.590–0.724) |
| <2.6 | 6.9 (3.9–17.9) | |||||||
| 2.6–14 | 4.1 (3.0–6.2) | 1.3 (0.7–2.5) | 0.344 | 1.7 (0.9–3.1) | 0.122 | |||
| >14 |
2.1 (1.8–5.0) |
|
2.4 (1.3–4.4) |
0.007 |
|
2.7 (1.4–5.1) |
0.002 |
|
| CA 19-9 |
|
0.0021 |
|
|
0.639 (0.564–0.713) |
|
|
0.670 (0.609–0.731) |
| <200 | 6.2 (3.9–19.0) | |||||||
| 200–6400 | 5.2 (2.7–7.6) | 1.6 (0.8–3.0) | 0.167 | 1.8 (0.9–3.5) | 0.072 | |||
| >6400 |
2.1 (1.6–3.9) |
|
3.1 (1.6–6.1) |
0.001 |
|
3.4 (1.7–6.7) |
0.001 |
|
|
d14 | ||||||||
| CYFRA 21-1 |
|
0.0081 |
|
|
0.646 (0.575–0.718) |
|
|
0.655 (0.579–0.732) |
| <1.9 | 10.3 (4.6–21.4) | |||||||
| 1.9–6 | 3.9 (1.6–6.2) | 1.9 (1.0–3.7) | 0.055 | 2.3 (1.2–4.7) | 0.018 | |||
| >6 |
2.8 (1.2–5.3) |
|
2.9 (1.4–5.9) |
0.003 |
|
3.2 (1.6–6.7) |
0.001 |
|
| CEA |
|
0.0017 |
|
|
0.626 (0.549–0.703) |
|
|
0.658 (0.583–0.733) |
| <2.1 | 8.0 (3.4–17.9) | |||||||
| 2.1–11 | 6.1 (3.7–9.7) | 0.9 (0.5–1.8) | 0.80 | 1.1 (0.5–2.2) | 0.849 | |||
| >11 |
1.8 (1.3–3.6) |
|
2.7 (1.4–5.4) |
0.003 |
|
3.0 (1.5–6.1) |
0.002 |
|
| CA 19-9 |
|
0.0232 |
|
|
0.636 (0.556–0.717) |
|
|
0.650 (0.572–0.728) |
| <150 | 6.1 (3.7–19.0) | |||||||
| 150–4000 | 5.6 (1.9–9.7) | 1.4 (0.7–2.8) | 0.346 | 1.4 (0.7–2.7) | 0.387 | |||
| >4000 |
1.9 (1.2–3.9) |
|
2.6 (1.3–5.2) |
0.009 |
|
2.5 (1.2–5.2) |
0.011 |
|
|
d21 | ||||||||
| CYFRA 21-1 |
|
<0.001 |
|
|
0.674 (0.605–0.743) |
|
|
0.716 (0.652–0.780) |
| <2.1 | 9.7 (4.6–19.0) | |||||||
| 2.1–6 | 3.4 (2.0–4.6) | 2.7 (1.3–5.4) | 0.005 | 2.7 (1.3–5.5) | 0.005 | |||
| >6 |
2.1 (1.4–4.6) |
|
4.7 (2.2–9.9) |
<0.001 |
|
3.9 (1.8–8.3) |
0.001 |
|
| CEA |
|
0.1314 |
|
|
0.578 (0.501–0.654) |
|
|
0.685 (0.623–0.748) |
| <2.5 | 5.3 (2.5–11.9) | |||||||
| 2.5–9 | 4.0 (1.5–6.9) | 1.1 (0.6–2.2) | 0.742 | 1.1 (0.6–2.1) | 0.778 | |||
| >9 |
2.2 (1.8–5.0) |
|
1.9 (1.0–3.6) |
0.064 |
|
1.7 (0.9–3.3) |
0.132 |
|
| CA 19-9 |
|
0.0492 |
|
|
0.615 (0.529–0.70) |
|
|
0.687 (0.626–0.748) |
| <310 | 5.9 (3.4–11.9) | |||||||
| 310–4000 | 3.9 (1.8–5.3) | 1.9 (0.9–3.7) | 0.071 | 1.6 (0.8–3.2) | 0.200 | |||
| >4000 |
2.1 (1.6–4.6) |
|
2.3 (1.1–4.5) |
0.022 |
|
1.8 (0.9–3.7) |
0.120 |
|
|
d28 | ||||||||
| CYFRA 21-1 |
|
0.0674 |
|
|
0.623 (0.544–0.703) |
|
|
0.637 (0.554–0.719) |
| <2.1 | 6.2 (3.7–19.0) | |||||||
| 2.1–3.8 | 3.9 (1.6–5.8) | 1.6 (0.8–3.3) | 0.169 | 1.9 (0.9–4.0) | 0.077 | |||
| >3.8 |
2.3 (1.6–5.3) |
|
2.3 (1.1–4.6) |
0.025 |
|
2.3 (1.1–4.7) |
0.024 |
|
| CEA |
|
0.1012 |
|
|
0.574 (0.485–0.662) |
|
|
0.639 (0.552–0.726) |
| <2.0 | 5.3 (1.6–9.7) | |||||||
| 2.0–6 | 5.0 (2.3–11.5) | 0.7 (0.3–1.5) | 0.378 | 0.6 (0.3–1.4) | 0.235 | |||
| >6 |
2.3 (1.8–5.1) |
|
1.6 (0.8–3.2) |
0.216 |
|
1.5 (0.7–3.1) |
0.265 |
|
| CA 19-9 |
|
0.0961 |
|
|
0.621 (0.532–0.710) |
|
|
0.661 (0.582–0.741) |
| <100 | 5.9 (3.4–19.0) | |||||||
| 100–2500 | 5.0 (2.3–7.1) | 1.6 (0.8–3.3) | 0.217 | 1.7 (0.8–3.6) | 0.150 | |||
| >2500 |
2.1 (1.6–3.9) |
|
2.2 (1.1–4.6) |
0.035 |
|
2.4 (1.1–5.1) |
0.024 |
|
|
d56 | ||||||||
| CYFRA 21-1 |
|
<0.001 |
|
|
0.672 (0.613–0.731) |
|
|
0.697 (0.636–0.759) |
| <1.7 | 7.1 (6.0–12.0) | |||||||
| 1.7–5 | 2.6 (1.8–5.8) | 2.0 (1.1–3.7) | 0.024 | 2.4 (1.3–4.4) | 0.007 | |||
| >5 |
2.1 (1.4–3.6) |
|
3.2 (1.7–6.1) |
<0.001 |
|
3.0 (1.6–5.7) |
0.001 |
|
| CEA |
|
<0.001 |
|
|
0.641 (0.572–0.710) |
|
|
0.725 (0.664–0.786) |
| <2.5 | 7.0 (4.6–17.9) | |||||||
| 2.5–13 | 5.5 (2.7–7.6) | 1.5 (0.8–2.8) | 0.173 | 1.3 (0.7–2.4) | 0.394 | |||
| >13 |
2.0 (1.6–3.6) |
|
3.3 (1.7–6.3) |
<0.001 |
|
2.9 (1.5–5.7) |
0.002 |
|
| CA 19-9 |
|
<0.001 |
|
|
0.688 (0.625–0.751) |
|
|
0.719 (0.663–0.776) |
| <120 | 8.4 (3.7–19.0) | |||||||
| 120–3960 | 5.8 (2.7–7.7) | 1.5 (0.8–2.9) | 0.205 | 1.6 (0.8–3.1) | 0.144 | |||
| >3960 | 1.9 (1.4–2.1) | 4.6 (2.3–9.3) | <0.001 | 4.4 (2.1–8.9) | <0.001 | |||
Abbreviations: CA 19-9=Carbohydrate antigen 19-9; CEA=carcinoembryonic antigen; CI=95% confidence interval; d=day; KPS=Karnofsky performance status; TTP=time to progression. The bold entries indicate the highest C index (assessed at each specific time point for all 3 markers.