Table 1
Overview of patient baseline characteristics
| Characteristics | Number of patients (%) / median values |
|---|---|
| Total number of patients | 54 |
| Gender (male). | 24 (44%) |
| Median age in years at 1st THC (range) | 61 (26–81) |
| Prior systemic/liver-directed therapies | |
| Prior systemic therapy | 29 (53.7%) |
| Sorafenib | 25 (46.3) |
| MEK and PKC inhibitors | 3 (5.6%) |
| Ipilimumab | 1 (1.9%) |
| Conventional chemotherapy | 5 (9%) |
| Prior liver resection | 4 (7.4%) |
| Prior ablation | 1 (1.9%) |
| Further therapy after last transarterial chemoperfusion | 18 (33.3%) |
| Limited extrahepatic metastases at the time of 1st THC | 20 (37%) |
| Median maximal tumor size in cm (range) | 5.9 (1.3–19.8) |
| Lobar tumor involvement | |
| Bilobar | 54 (96.4%) |
| Unilobar | 2 (3.6%) |
| Hepatic tumor burden | |
| 0–25% | 23 (46%) |
| > 25–50% | 12 (24%) |
| > 50–75% | 9 (18%) |
| > 75% | 6 (12%) |
| ECOG | |
| 0 | 43 (80%) |
| 1 | 6 (11%) |
| 2 | 2 (4%) |
| Unknown | 3 (6%) |
| Karnofsky Index | |
| 100 | 4 (7%) |
| 90 | 33(61%) |
| 80 | 7 (13%) |
| < 80 | 3 (6%) |
| Unknown | 7 (13%) |
Figure 1
Overall survival of the entire study cohort. Estimated overall survival (OS) after diagnosis of primary, diagnosis of liver metastases, and after 1st transarterial chemoperfusion (THC).
Table 2
Uni- and multivariate analysis of overall survival (OS)
| Median (95OS % in CI) months | Univariate analysis | Multivariate analysis | ||||
|---|---|---|---|---|---|---|
| Subgroups | HR (95% CI) | p-value | HR (95% CI) | p-value | ||
| NLR | ≦ median (3.58) > median (3.58) | 11.1 (7.1–20.6) 6.3 (3.5–7.8) | 0.39 (0.2–0.75) 1 | 0.0045 | 0.73 (0.25–2.2) 1 | 0.57 |
| SII | ≦ median (1076) > median (1076) | 10.8 (7,2–20.6) 5.6 (3.4 – 7.7) | 0.33 (0.17 – 0.65) 1 | 0.0013 | 0.19 (0.11–0.7) 1 | 0.008 |
| PLR | ≦ median (203.8) > median (203.8) | 8.2 (5.6–15.8) 7.5 (4.7–11.1) | 0.69 (0.37–1.27) 1 | 0.23 | - - | - |
| CRP | normal > ULN | 13.5 (7.2–20.6) 5.3 (3.9–7.8) | 0.3 (0.15–0.6) 1 | 0.0005 | 0.29 (0.11–0.7) 1 | 0.005 |
| Neutrophils | normal > ULN | 8.2 (6.4–11.5) 6.3 (3.9–11.1) | 0.6 (0.3–1.28) 1 | 0.18 | - - | - |
| Thrombocytes | normal > ULN | 8.2 (63–11.1) 7.5 (0.64–13.5) | 0.8 (0.35–2.13) 1 | 0.62 | - - | |
| LDH | ≦ ULN >ULN | 12.8 (7.2–20.6) 7 (4.8–8.2) | 0.54 (0.23–1.11) 1 | 0.1 | - - | - |
| AST | ≦ ULN > ULN | 11.5 (7.2–20.6) 5.6 (4.5–8.2) | 0.45 (0.22–0.85) 1 | 0.015 | 0.34 (0.07–1.44) 1 | 0.15 |
| ALT | ≦ ULN > ULN | 11.5 (7.5–15.8) 5.6 (4.2–7.8) | 0.43 (0.2–0.8) 1 | 0.01 | 0.13 (0.02–0.63) 1 | 0.011 |
| GGT | ≦ ULN > ULN | 10.9 (7.2–15.8) 7.13 (5.3–10.2) | 0.94 (0.32–2.2) 1 | 0.9 | - - | - |
| AP | ≦ ULN > ULN | 10.94 (4.8–20.6) 6.3 (3.4–10.1) | 0.54 (0.22–1.26) 1 | 0.15 | – - | - |
| Hepatic tumor burden | 50% ≦ > 50% | 8.2 (7.12–11.5) 4.8 (1.2–7.8) | 0.36 (0.18–0.74) 1 | 0.007 | 0.5 (0.17–1.6) 1 | 0.24 |
| Prior systemic treatment | Yes No | 8.2 (7.5–11.5) 6.3 (4.5–11.1) | 0.78 (0.42–1.45) 1 | 0.43 | - - | - |
| Extrahepatic metastases | No Yes | 7.12 (4.6–10.1) 10.2 (6.3–11.1) | 1.1 (0.59–2.17) 1 | 0.75 | - - | - |
[i] ALT = alanine aminotransferase; AP = alkaline phosphatase; AST = aspartate aminotransferase; CRP = C-reactive protein; GGT = gamma-glutamyl transpeptidase; HR = hazard ratio; LDH = lactate dehydrogenase; NLR = neutrophil to lymphocyte ratio; PLR = platelet to lymphocyte ratio; SII = systemic immune-inflammation index; ULN = upper level of normal
Figure 2
Pretreatment inflammation-based markers predict overall survival. Overall survival is stratified for low (≦ median) vs. high (> median) neutrophil to lymphocyte ratio (NLR), systemic immune-inflammation index (SII), platelet to lymphocyte ratio (PLR), and C-reactive protein (CRP).
Figure 3
Scoring further improves overall survival estimation. Patients with zero to one elevated independent significant factors from multivariate analysis (C-reactive protein [CRP], systemic immune-inflammation index [SII], alanine aminotransferases [ALT]) had a significantly longer overall survival than patients with two or three elevated factors p < 0.0001.
Table 3
Scoring with significant independent factors from multivariate analysis. The number of elevated CRP, SII, ALT in patients further helps to predict median overall survival
| Group | Median OS in months (95% CI) | Hazard ratio (95% CI) | p-value |
|---|---|---|---|
| ≦ 1 elevated factor | 14.9 (10.1–0.0) | 0.08 (0.3–0.2) | - |
| 2 elevated factors | 6.7 (4.5–8.2) | 0.38 (0.17–0.86) | 0.0003 |
| 3 elevated factors | 3.9 (1.15–6.3) | 1 | < 0.0001* |