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Predictive impact of the inflammation-based indices in uveal melanoma liver metastases treated with transarterial hepatic chemoperfusion

Johannes M. Ludwig
Johannes M. Ludwig
, 
Johannes Haubold
Johannes Haubold
, 
Sebastian Bauer
Sebastian Bauer
, 
Heike Richly
Heike Richly
, 
Jens T. Siveke
Jens T. Siveke
, 
Julia Wimmer
Julia Wimmer
, 
Lale Umutlu
Lale Umutlu
, 
Benedikt M. Schaarschmidt
Benedikt M. Schaarschmidt
 und 
Jens M. Theysohn
Jens M. Theysohn
   | 31. Mai 2021
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Article Category: Research Article
Online veröffentlicht: 31. Mai 2021
Seitenbereich: 347 - 353
Eingereicht: 17. Jan. 2021
Akzeptiert: 12. Apr. 2021
DOI: https://doi.org/10.2478/raon-2021-0027
© 2021 Johannes M. Ludwig, Johannes Haubold, Sebastian Bauer, Heike Richly, Jens T. Siveke, Julia Wimmer, Lale Umutlu, Benedikt M. Schaarschmidt, Jens M. Theysohn, published by Sciendo
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

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).
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).

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).
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.
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.

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 - - -

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%)

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*
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