Table 4.
Multivariable analysis of variable associated with PFS and OS in patients with HCC, iCCA, and cHCC-CCA
| Variables | Unadjusted HR/OR* (95% CI) | Unadjusted p value | Adjusted† HR/OR* (95% CI) | Adjusted†p value |
|---|---|---|---|---|
| PFS | ||||
| cHCC-CCA (reference) | Ref | Ref | Ref | |
| HCC | 1.06 (0.77–1.46) | 0.719 | 0.66 (0.37–1.20) | 0.172 |
| iCCA | 0.66 (0.47–0.92) | 0.014 | 0.63 (0.41–0.96) | 0.034 |
| Platinum-based (reference) | Ref | Ref | Ref | |
| TKI | 1.39 (1.07–1.80) | 0.013 | 1.54 (0.85–2.79) | 0.157 |
| Intrahepatic multiple nodules | 1.48 (1.06–2.05) | 0.021 | 1.63 (1.13–2.35) | 0.009 |
| Advanced fibrosis/cirrhosis | 1.37 (1.07–1.76) | 0.013 | 1.01 (0.74–1.38) | 0.941 |
| Metastasis | 1.07 (0.84–1.37) | 0.580 | 1.19 (0.86–1.66) | 0.293 |
| Macrovascular invasion | 1.06 (0.82–1.37) | 0.646 | 1.28 (0.95–1.73) | 0.102 |
| OS | ||||
| cHCC-CCA (reference) | Ref | Ref | ||
| HCC | 0.91 (0.68–1.22) | 0.521 | 0.67 (0.37–1.22) | 0.189 |
| iCCA | 0.73 (0.53–1.00) | 0.050 | 0.66 (0.43–1.02) | 0.064 |
| Platinum-based (reference) | Ref | Ref | ||
| TKI | 1.12 (0.87–1.43) | 0.382 | 1.12 (0.62–1.99) | 0.713 |
| Intrahepatic multiple nodules | 1.19 (0.85–1.65) | 0.312 | 1.29 (0.89–1.87) | 0.176 |
| Advanced fibrosis/cirrhosis | 1.58 (1.21–2.05) | <0.001 | 1.45 (1.04–2.01) | 0.028 |
| Metastasis | 1.12 (0.86–1.44) | 0.405 | 1.15 (0.89–1.61) | 0.401 |
| Macrovascular invasion | 1.31 (0.98–1.76) | 0.067 | 1.42 (1.05–1.92) | 0.025 |
| Objective response rate | ||||
| cHCC-CCA (reference) | Ref | Ref | ||
| HCC | 2.49 (0.51–12.18) | 0.261 | 1.34 (0.14–13.20) | 0.802 |
| iCCA | 4.05 (0.85–19.31) | 0.079 | 7.63 (0.83–69.84) | 0.072 |
| Platinum-based (reference) | ||||
| TKI | 0.87 (0.35–2.19) | 0.767 | 2.87 (0.16–51.14) | 0.473 |
| Intrahepatic multiple nodules | 0.90 (0.28–2.85) | 0.858 | 0.62 (0.18–2.11) | 0.442 |
| Advanced fibrosis/cirrhosis | 0.94 (0.37–2.36) | 0.888 | 1.35 (0.46–3.98) | 0.584 |
| Metastasis | 1.25 (0.48–3.28) | 0.645 | 0.99 (0.29–3.36) | 0.993 |
| Macrovascular invasion | 1.09 (0.41–2.85) | 0.868 | 0.96 (0.34–2.71) | 0.934 |
| DCR | ||||
| cHCC-CCA (reference) | Ref | Ref | ||
| HCC | 1.20 (0.61–2.38) | 0.593 | 1.43 (0.42–4.90) | 0.566 |
| iCCA | 1.74 (0.85–3.58) | 0.132 | 1.79 (0.74–4.33) | 0.199 |
| Platinum-based (reference) | Ref | |||
| TKI | 0.76 (0.44–1.30) | 0.308 | 0.78 (0.22–2.80) | 0.706 |
| Intrahepatic multiple nodules | 0.68 (0.33–1.38) | 0.284 | 0.62 (0.29–1.33) | 0.217 |
| Advanced fibrosis/cirrhosis | 0.58 (0.33–1.01) | 0.052 | 0.63 (0.34–1.18) | 0.148 |
| Metastasis | 0.75 (0.43–1.31) | 0.308 | 0.58 (0.29–1.14) | 0.114 |
| Macrovascular invasion | 1.26 (0.71–2.24) | 0.437 | 1.01 (0.54–1.88) | 0.971 |
cHCC-CCA, hepatocholangiocarcinoma; HCC, hepatocellular carcinoma; iCCA, intrahepatic cholangiocarcinoma.
*
Right-censored outcome (i.e., OS and PFS) regressions were Cox regressions (estimated effect sizes were expressed as HR with 95% CI) and binary outcome (i.e., ORR and DCR) regressions were logistic regressions (estimated effect sizes were expressed as OR with 95% CI).
†
Adjustment regarding unobserved heterogeneities between individuals was performed using frailty models (Cox or logistic regression), which included a frailty term (i.e., random effect) on everyone.