Table 4. Cox proportional hazards regression models, n=556 patients, 520 deaths.
| Variable | χ 2 | P-value | HR (95% CI) | |
|---|---|---|---|---|
| (a) Model 1 – ‘Linear’ covariates | ||||
|
Full model
| ||||
| AIC=5558.4 | ||||
| Stratification factors | Trial | 7.3 | 0.007 | 0.76 (0.63, 0.93) |
| Cancer stagea | 0.0001 | 0.99 | 1.00 (0.69, 1.44) | |
| Sex | 3.8 | 0.050 | 0.82 (0.68, 1.00) | |
| TRT | 2.6 | 0.11 | 1.17 (0.97, 1.42) | |
| Independent factors | Age | 3.0 | 0.081 | 1.01 (1.00, 1.02) |
| Albumin | 22.9 | <0.001 | 0.94 (0.92, 0.96) | |
| Alkaline phosphatase | 24.3 | <0.001 | 1.00 (1.00, 1.00) | |
| AST | 5.3 | 0.022 | 1.00 (0.99, 1.00) | |
| Bilirubin | 0.7 | 0.40 | 1.00 (1.00, 1.01) | |
| BUN | 2.3 | 0.13 | 1.02 (0.99, 1.05) | |
| CA19/9 | 0.9 | 0.34 | 1.00 (1.00, 1.00) | |
| Ethnic | 0.0009 | 0.98 | 1.01 (0.74, 1.36) | |
| Haemoglobin | 0.01 | 0.91 | 1.00 (0.94, 1.08) | |
| LDH | 19.3 | <0.001 | 1.00 (1.00, 1.00) | |
| METSb | 8.5 | 0.004 | 1.50 (1.14, 1.96) | |
| Nodesb | 0.4 | 0.51 | 1.08 (0.86, 1.37) | |
| Tumour stageb | 0.03 | 0.86 | 1.02 (0.84, 1.23) | |
| WBC | 10.2 | 0.001 | 1.04 (1.02, 1.07) | |
|
Final model
| ||||
| AIC=5557.1 | ||||
| Stratification factors | Trial | 8.1 | 0.005 | 0.76 (0.63, 0.92) |
| Cancer stagea | 0.008 | 0.93 | 1.01 (0.74, 1.38) | |
| Sex | 3.8 | 0.051 | 0.84 (0.70, 1.00) | |
| TRT | 3.2 | 0.073 | 1.19 (0.98, 1.44) | |
| Independent factors | Albumin | 41.0 | <0.001 | 0.94 (0.92, 0.96) |
| LDH | 13.3 | <0.001 | 1.00 (1.00, 1.00) | |
| METSb | 10.5 | 0.001 | 1.50 (1.17, 1.92) | |
| WBC | 11.7 | <0.001 | 1.04 (1.02, 1.07) | |
| Alkaline phosphatase | 21.1 | <0.001 | 1.00 (1.00, 1.00) | |
| (b) Model 2 – ‘Categorical’ covariates | ||||
|
Full model
| ||||
| AIC=5582.3 | ||||
| Stratification factors | Trial | 5.8 | 0.016 | 0.79 (0.65, 0.96) |
| Cancer stagea | 0.0001 | 0.99 | 1.00 (0.70, 1.44) | |
| Sex | 2.1 | 0.14 | 0.87 (0.72, 1.05) | |
| TRT | 3.3 | 0.07 | 1.19 (0.99, 1.44) | |
| Independent factors | Age | 2.2 | 0.13 | 1.15 (0.96, 1.39) |
| Albumin | 17.6 | <0.001 | 2.08 (1.48, 2.93) | |
| Alkaline phosphatase | 0.3 | 0.57 | 1.07 (0.85, 1.34) | |
| AST | 1.5 | 0.22 | 1.20 (0.90, 1.59) | |
| Bilirubin | 5.0 | 0.025 | 1.28 (1.03, 1.58) | |
| BUN | 1.9 | 0.17 | 1.14 (0.94, 1.39) | |
| CA19/9 | 7.8 | 0.005 | 1.43 (1.11, 1.85) | |
| Ethnic | 0.5 | 0.48 | 0.89 (0.66, 1.22) | |
| Haemoglobin | 2.2 | 0.14 | 0.82 (0.62, 1.07) | |
| LDH | 22.8 | <0.001 | 2.07 (1.54, 2.79) | |
| METSb | 13.3 | <0.001 | 1.64 (1.26, 2.14) | |
| Nodesb | 2.3 | 0.13 | 1.20 (0.95, 1.51) | |
| T stageb | 0.06 | 0.80 | 0.98 (0.81, 1.18) | |
| WBC | 9.2 | 0.002 | 1.42 (1.13, 1.78) | |
|
Final model
| ||||
| AIC=5583.2 | ||||
| Stratification factors | Trial | 7.0 | 0.008 | 0.77 (0.64, 0.94) |
| Cancer stagea | 0.9 | 0.36 | 1.16 (0.85, 1.58) | |
| Sex | 1.8 | 0.18 | 0.89 (0.74, 1.06) | |
| TRT | 3.4 | 0.065 | 1.19 (0.99, 1.44) | |
| Independent factors | Albumin | 24.2 | <0.001 | 2.30 (1.65, 3.21) |
| LDH | 25.1 | <0.001 | 2.05 (1.55, 2.72) | |
| METSb | 11.9 | <0.001 | 1.54 (1.21, 1.97) | |
| WBC | 10.3 | 0.001 | 1.44 (1.15, 1.79) | |
| Bilirubin | 8 .4 | 0 .004 | 1.34 (1.10, 1.64) | |
| CA199 | 9 .4 | 0 .002 | 1.48 (1.15, 1.89) | |
| (c) Model 3–‘Transformed’ covariates | ||||
|
Full model
| ||||
| AIC=5509.6 | ||||
| Stratification factors | Trial | 12.5 | <0.001 | 0.70 (0.57, 0.85) |
| Cancer stagea | 0.2 | 0.68 | 0.93 (0.64, 1.33) | |
| Sex | 4.3 | 0.038 | 0.82 (0.67, 0.99) | |
| TRT | 3.0 | 0.082 | 1.19 (0.98, 1.44) | |
| Independent factors | ||||
| Linear | Age | 2.3 | 0.13 | 1.01 (1.00, 1.02) |
| Linear | Albumin | 20.8 | <0.001 | 0.94 (0.92, 0.97) |
| Linear | Alkaline phosphatase | 11.3 | <0.001 | 1.00 (1.00, 1.00) |
| Linear | AST | 7.5 | 0.0062 | 1.00 (0.99, 1.00) |
| 1st degree FP | Log (bilirubin) | 3.0 | 0.083 | 1.16 (0.98, 1.37) |
| Linear | BUN | 3.2 | 0.075 | 1.02 (1.00, 1.05) |
| 2nd degree FP | CA1990.5 | 36.3 | <0.001 | 1.03 (1.02, 1.03) |
| 2nd degree FP | CA1990.5 × log(CA199) | 30.9 | <0.001 | 1.00 (1.00, 1.00) |
| Categorical | Ethnic | 0.1 | 0.74 | 0.95 (0.70, 1.29) |
| Linear | Haemoglobin | 0.3 | 0.61 | 0.98 (0.92, 1.05) |
| 1st degree FP | Log (LDH) | 12.3 | <0.001 | 1.72 (1.27, 2.32) |
| Categorical | METSb | 6.1 | 0.014 | 1.41 (1.07, 1.85) |
| Categorical | Nodesb | 1.4 | 0.24 | 1.15 (0.91, 1.46) |
| Categorical | Tumour stageb | 0.3 | 0.60 | 1.05 (0.87, 1.28) |
| Linear | WBC | 10.5 | 0.0012 | 1.05 (1.02, 1.07) |
|
Final model
| ||||
| AIC=5510.2 | ||||
| Stratification factors | Trial | 15.1 | <0.001 | 0.68 (0.56, 0.83) |
| Cancer stagea | 0.001 | 0.97 | 1.0 (0.73, 1.36) | |
| Sex | 3.5 | 0.061 | 0.84 (0.70, 1.01) | |
| TRT | 3.16 | 0.075 | 1.19 (0.98, 1.44) | |
| Independent factors | ||||
| Linear | Albumin | 41.4 | <0.001 | 0.94 (0.92, 0.95) |
| 1st degree FP | Log (LDH) | 12.8 | <0.001 | 1.70 (1.27, 2.27) |
| Categorical | METSb | 4.0 | 0.047 | 1.29 (1.00, 1.66) |
| Linear | WBC | 10.0 | 0.002 | 1.04 (1.02, 1.07) |
| Linear | Alkaline phosphatase | 14 .6 | <0 .001 | 1.00 (1.00, 1.00) |
| Linear | AST | 5 .2 | 0 .023 | 1.00 (0.99, 1.00) |
| Linear | BUN | 5 .0 | 0 .026 | 1.03 (1.00, 1.06) |
| 2nd degree FP | CA199 0.5 | 33 .3 | <0 .001 | 1.02 (1.02, 1.03) |
| 2nd degree FP | CA1990.5 × log(CA199) | 28.4 | <0.001 | 1.00 (1.00, 1.00) |
FP=fractional polynomial; HR=hazard ratio.
a
Stage (I/II vs III/IV).
b
Metastases (negative vs positive), Nodes (negative vs positive), Tumour stage (I/II vs III/IV): missing data included in analysis as a separate ‘dummy’ variable using lower level as the reference level.