Introduction
Score | Included variables | Prognostic groups identified by the score | Median OS (months)b | References |
---|---|---|---|---|
BCLC (Biolato 2014) | ECOG score | A (early stage) | 18.3–76.2 | |
Number and diameter | B (intermediate stage) | 15.1–24 | ||
Vascular invasion and metastasis | C (advanced stage) | 9–13.7 | ||
Child–Pugh score | D (terminal stage) | 4–5.4 | ||
Okuda score | ||||
Serum albumin | A = 5–6 points | 18.3–104 | ||
INR | B = 7–9 points | 11.8–46 | ||
Ascites | C ≥ 10 points | 4–23.8 | ||
Encephalopathy | ||||
Total bilirubin | ||||
ART (Abbasi et al. 2017) | Child–Pugh score | Low risk < 2.5 points | 23.1–104 | |
Radiologic tumor response | High risk ≥ 2.5 points | 5.4–25 | ||
AST | ||||
HAP (Dhanasekaran et al. 2010) | AFP | A = 0 points | 25.5—n.r. | |
Serum albumin | B = 1 point | 18.1–55.0 | ||
Total bilirubin | C = 2 points | 8.9–46.0 | ||
Diameter | D ≥ points | 3.6–18 | ||
STATE (El Khaddari et al. 2002) | CRP | Low risk ≥ 18 points | 19.5–22.2 | |
Up-to-seven criteria | High risk < 18 points | 5.3–14.3 | ||
Serum albumin | ||||
Platelet count | ≤ 1.15a | (–) | ||
AST | > 1.15a | (–) | ||
ALBI | Total bilirubin | A1 ≤ − 2.6 | 28.9–38.9 | |
Serum albumin | A2 > − 2.6 ≤ − 1.39 | 10.2–22.4 | ||
A3 > − 1.39 | 6.05–15.3 | |||
SNACOR (Hucke et al. 2014b) | Number and Diameter | Low risk 0–2 points | 31.5–49.8 | |
AFP | Interm. risk 3–6 points | 19.9–30.7 | ||
Child–Pugh class | High risk 7–10 points | 9.2–12.4 | ||
Radiologic tumor response | ||||
CLIP (Kadalayil 2013) | AFP | 0 = 0 points | 31–68.7 | |
Portal vein thrombosis | 1 = 1 point | 27–43.8 | ||
Child–Pugh class | 2 = 2 points | 13–26.4 | ||
Number and diameter | 3 = 3 points | 8–15.0 | ||
4 ≥ 4 points | 2–3.3 | |||
Okuda (Kamath 2001) | Tumor size | I = 0 points | 27–45.5 | |
Ascites | II = 1–2 points | 10–21 | ||
Albumin | III = 3–4 points | 2–16 | ||
Bilirubin | ||||
INR | < 10 | (–) | ||
Creatinine | ≥ 10 | (–) | ||
Bilirubin |
Materials and methods
Study design
Subgroup definition
Calculation of scores
Statistics
Results
Patient characteristics and distribution of scores at TACE procedures
Patient characteristics at TACE procedures | Bridging dataset | Palliative dataset | p | ||
---|---|---|---|---|---|
N (%) | Total (N) | N (%) | Total (N) | ||
Number of all TACE procedures | 158 (100) | 334 (100) | |||
Age (years) (median, range) | 57 (28–70) | 158 | 71 (49–90) | 334 | < 0.001 |
Gender | |||||
Male | 127 (80.4) | 158 | 249 (74.6) | 334 | 0.155 |
Female | 31 (19.6) | 85 (25.4) | |||
Number of tumor nodules | |||||
Single tumor nodule | 61 (38.6) | 158 | 64 (19.2) | 334 | < 0.001 |
> 1 tumor nodule | 97 (61.4) | 270 (80.8) | |||
Max. diameter, cm (median, range) | 2.3 (0.9–5.0) | 158 | 4.6 (0.6–19.3) | 334 | < 0.001 |
Liver vein infiltration | 0 (0) | 158 | 7 (2.1) | 334 | 0.067 |
Portal vein infiltration | 0 (0) | 158 | 19 (5.7) | 334 | 0.002 |
Vena cava infiltration | 0 (0) | 158 | 3 (0.9) | 334 | 0.232 |
Extrahepatic tumor manifestation | 0 (0) | 158 | 40 (12.0) | 334 | < 0.001 |
Category of TACE treatment | |||||
DEB | 104 (65.8) | 158 | 244 (73.1) | 334 | 0.001 |
Conventional | 32 (20.3) | 28 (8.4) | |||
Biodegradable | 22 (13.9) | 62 (18.6) | |||
Additional therapy with sorafenib | 19 (12.0) | 158 | 16 (4.8) | 334 | 0.004 |
Number of therapy discontinuations (not discontinuations of TACE procedures) after TACE due to AE or death | 0 (0) | 158 | 73 (21.9) | 334 | < 0.001 |
Distribution of scores at TACE procedures | Bridging dataset | Palliative dataset | p | ||
---|---|---|---|---|---|
N (%) | Total (N) | N (%) | Total (N) | ||
BCLC stage | |||||
A | 103 (65.2) | 158 | 52 (15.6) | 334 | < 0.001 |
B | 29 (18.4) | 182 (54.5) | |||
C | 4 (2.5) | 70 (21.0) | |||
D | 22 (13.9) | 30 (9.0) | |||
Child–Pugh class | |||||
A | 69 (48.9) | 141 | 185 (64.9) | 285 | 0.005 |
B | 50 (35.5) | 75 (26.3) | |||
C | 22 (15.6) | 25 (8.8) | |||
STATE score | |||||
≥ 18 | 131 (92.9) | 141 | 200 (70.9) | 282 | < 0.001 |
< 18 | 10 (7.1) | 82 (29.1) | |||
HAP stage | |||||
A | 25 (18.0) | 139 | 68 (25.2) | 270 | < 0.001 |
B | 42 (30.2) | 81 (30.0) | |||
C | 71 (51.1) | 89 (33.0) | |||
D | 1 (0.7) | 32 (11.9) | |||
mSNACOR stage | |||||
Low risk | 21 (23.9) | 88 | 16 (8.2) | 195 | < 0.001 |
Interm. risk | 67 (76.1) | 146 (74.9) | |||
High risk | 0 (0) | 33 (16.9) | |||
SNACOR stage | |||||
Low risk | 11 (26.2) | 42 | 10 (19.6) | 51 | 0.026 |
Interm. risk | 31 (73.8) | 33 (64.7) | |||
High risk | 0 (0) | 8 (15.7) | |||
ALBI group | |||||
A1 | 34 (24.1) | 141 | 104 (36.7) | 283 | 0.003 |
A2 | 84 (59.6) | 157 (55.5) | |||
A3 | 23 (16.3) | 22 (7.8) | |||
CLIP group | |||||
0 | 19 (13.7) | 139 | 32 (11.9) | 270 | < 0.001 |
1 | 63 (45.3) | 72 (26.7) | |||
2 | 42 (30.2) | 88 (32.6) | |||
3 | 14 (10.1) | 47 (17.4) | |||
4 | 1 (0.7) | 31 (11.5) | |||
APRI score | |||||
< 1.15 | 58 (39.2) | 148 | 140 (47.5) | 295 | 0.099 |
> 1.15 | 90 (60.8) | 155 (52.5) | |||
mART score | |||||
≤ 1.5 | 42 (60.0) | 70 | 93 (65.5) | 142 | 0.434 |
> 2.5 | 28 (40.0) | 49 (34.5) | |||
ART score | |||||
≤ 1.5 | 22 (57.9) | 38 | 29 (61.7) | 47 | 0.722 |
≥ 2.5 | 16 (42.1) | 18 (38.3) | |||
Okuda stage | |||||
I | 75 (53.2) | 141 | 125 (43.9) | 285 | 0.112 |
II | 62 (44.0) | 143 (50.2) | |||
III | 4 (2.8) | 17 (6.0) | |||
MELD score | |||||
< 10 | 73 (49.3) | 148 | 190 (64.0) | 297 | 0.003 |
≥ 10 | 75 (50.7) | 107 (36.0) |
Performance of scores in the palliative dataset
Median overall survival (OS)
Score | Bridging dataset Median OS, months (SD; 95% CI) | p (u/m) | Palliative dataset Median OS, months (SD; 95% CI) | p (u/m) |
---|---|---|---|---|
CLIP group | ||||
0 | Not reached | 0.335/– | 37.4 (3.1; 31.4–43.4) | < 0.001/0.605 |
1 | Not reached | 38.0 (7.4; 23.5–52.4) | ||
2 | Not reached | 16.7 (2.3; 12.1–21.3) | ||
3 | Not reached | 12.6 (1.9; 8.8–16.3) | ||
4 | Not reached | 7.5 (1.9; 3.7–11.3) | ||
mART score | ||||
< 2.5 | Not reached | 0.472/– | 17.2 (3.9; 9.6–24.8) | 0.069/ |
≥ 2.5 | Not reached | 11.1 (2.6; 5.9–16.3) | ||
ART score | ||||
< 2.5 | Not reached | 0.110/– | 18.1 (5.0; 8.4–27.8) | 0.882/ |
≥ 2.5 | 39.0b | 33.1 (14.5; 4.7–61.6) | ||
ALBI group | ||||
A1 | Not reached | 0.360/– | 30.1 (3.4; 23.4–36.8) | < 0.001/0.372 |
A2 | Not reached | 16.9 (2.3; 12.3–21.5) | ||
A3 | Not reached | 5.1 (0.9; 3.3–6.8) | ||
APRI score | ||||
≤ 1.15 | Not reached | 0.396/– | 31.2 (3.5; 24.4–38.0) 14.5 (1.4; 11.8–17.2) | < 0.001/0.072 |
> 1.15 | Not reached | 31.2 (3.5; 24.4–38.0) 14.5 (1.4; 11.8–17.2) | ||
mSNACOR stage | ||||
Low risk | 51.8 (12.3; 27.6–75.9) | 0.371/– | 80.5b | < 0.001/0.006 |
Interm. risk | Not reached | 20.6 (4.7; 11.5–29.8) | ||
High risk | No cases | 10.4 (2.5; 5.4–15.3) | ||
SNACOR stage | ||||
Low risk | 39.0 (10.9; 17.6–60.4) | 0.380/– | 32.8b | 0.253/ |
Interm. risk | 60.8b | 28.0 (9.9; 8.6–47.4) | ||
High risk | No cases | 17.2 (8.6; 0.3–34.1) | ||
HAP stage | ||||
A | Not reached | 0.687/– | 35.2 (3.6; 28.1–42.2) | < 0.001/0.924 |
B | Not reached | 26.6 (4.8; 17.2–35.9) | ||
C | Not reached | 13.0 (2.0; 8.9–17.0) | ||
D | Not reached | 11.1 (1.8; 7.5–14.7) | ||
STATE score | ||||
≥ 18 | Not reached | 0.804/– | 24.1 (2.7; 18.8–29.3) | < 0.001/< 0.001 |
< 18 | 45.5 (23.8; 0–92.2) | 13.7 (0.9; 12.1–15.4) | ||
Child–Pugh class | ||||
A | Not reached | 0.473/– | 27.9 (3.2; 21.7–34.1) | < 0.001/< 0.001 |
B | Not reached | 11.2 (1.5; 8.2–14.1) | ||
C | Not reached | 4.2 (0.5; 3.2–5.3) | ||
BCLC stage | ||||
A | Not reached | 0.002/– | 32.8 (4.4; 24.2–41.5) | < 0.001/0.218 |
B | 45.5 (12.4; 21.1–69.8) | 21.6 (2.5; 16.7–26.6) | ||
C | Not reached | 21.8 (8.8; 4.6–39.1) | ||
D | Not reached | 4.2 (0.5; 3.3–5.2) | ||
Okuda stage | ||||
I | Not reached | 0.330/– | 36.3 (3.1; 30.2–42.4) | < 0.001/0.065 |
II | Not reached | 14.7 (1.0; 12.7–16.6) | ||
III | Not reached | 3.5 (1.1; 1.3–5.6) | ||
MELD | ||||
< 10 | Not reached | 0.213/– | 25.3 (2.5; 20.4–30.1) | 0.001/0.167 |
≥ 10 | 62.0 (8.8; 44.8–79.1) | 12.6 (1.7; 9.2–15.9) | ||
Totala | Not reached | 21.8 (2.7; 16.6–27.1) | < 0.001 |
Treatment discontinuation
3-years survival
Score | Bridging dataset AUC (sensitivity/1 − specificity) | p | Palliative dataset AUC (sensitivity/1 − specificity) | p |
---|---|---|---|---|
CLIP group (0–1 vs. 2–4) | 0.600 (0.567/0.367) | 0.095 | 0.646 (0.754/0.462) | < 0.001 |
mART score (< 2.5 vs. ≥ 2.5) | 0.542 (0.467/0.382) | 0.616 | 0.520 (0.364/0.323) | 0.678 |
ART score (< 2.5 vs. ≥ 2.5) | 0.588 (0.566/0.379) | 0.430 | 0.423 (0.304/0.458) | 0.366 |
ALBI group (A1 vs. A2 + A3) | 0.526 (0.800/0.748) | 0.661 | 0.560 (0.689/0.568) | 0.080 |
APRI score (≤ 1.15 vs. > 1.15) | 0.577 (0.727/0.574) | 0.180 | 0.585 (0.606/0.436) | 0.011 |
mSNACOR stage (low- and interm. risk vs. high risk) | – | – | 0.564 (0.232/0.104) | 0.122 |
SNACOR stage (low- and interm. risk vs. high risk) | – | – | 0.503 (0.160/0.154) | 0.970 |
mSNACOR stage (low risk vs. interm risk) | 0.484 (0.737/0.768) | 0.835 | – | – |
SNACOR stage (low risk vs. interm risk) | 0.455 (0.667/0.758) | 0.679 | – | – |
HAP stage (A + B vs. C + D) | 0.552 (0.600/0.495) | 0.381 | 0.607 (0.549/0.336) | 0.002 |
State score (≥ 18 vs. < 18) | 0.476 (0.033/0.081) | 0.689 | 0.553 (0.340/0.235) | 0.128 |
Child–Pugh class (A vs. B + C) | 0.557 (0.600/0.486) | 0.341 | 0.648 (0.490/0.194) | < 0.001 |
BCLC stage (A + B vs. C + D) | 0.470 (0.118/0.177) | 0.594 | 0.559 (0.357/0.239) | 0.063 |
Okuda stage (A vs. B + C) | 0.541 (0.533/0.487) | 0.487 | 0.657 (0.709/0.396) | < 0.001 |
MELD score (< 10 vs. ≥ 10) | 0.544 (0.576/0.487) | 0.438 | 0.573 (0.429/0.284) | 0.030 |
Performance of scores in the bridging dataset
Median overall survival (OS)
Treatment discontinuation
Score | Palliative dataset AUC (sensitivity/1 − specificity) | p |
---|---|---|
CLIP group (0–1 vs. 2–4) | 0.565 (0.712/0.583) | 0.113 |
mART score (< 2.5 vs. ≥ 2.5) | 0.596 (0.486/0.295) | 0.084 |
ART score (< 2.5 vs. ≥ 2.5) | 0.571 (0.500/0.359) | 0.533 |
ALBI group (A1 vs. A2 + A3) | 0.601 (0.788/0.585) | 0.013 |
APRI score (≤ 1.15 vs. > 1.15) | 0.549 (0.600/0.502) | 0.217 |
mSNACOR stage (low- and interm. risk vs. high risk) | 0.581 (0.292/0.129) | 0.091 |
SNACOR stage (low- and interm. risk vs. high risk) | 0.632 (0.364/0.100) | 0.184 |
HAP stage (A + B vs. C + D) | 0.630 (0.646/0.385) | 0.002 |
STATE score (≥ 18 vs. < 18) | 0.548 (0.364/0.269) | 0.242 |
Child–Pugh class (A vs. B + C) | 0.696 (0.652/0.260) | < 0.001 |
BCLC stage (A + B vs. C + D) | 0.536 (0.356/0.284) | 0.343 |
Okuda stage (A vs. B + C) | 0.588 (0.697/0.521) | 0.030 |
MELD score (< 10 vs. ≥ 10) | 0.633 (0.563/0.296) | 0.001 |
3-years survival
Discussion
Applicability of further parameters concerning the prediction of OS (Kaplan–Meier analysis) | Bridging dataset n = 61 Median OS (months) (SD; 95% CI) | p (u) | Palliative dataset n = 87 Median OS (months) (SD; 95% CI) | p (u) |
---|---|---|---|---|
< 2 | Not reached | 0.354 | 6.0 (8.4; 0.0–22.4) | < 0.001 |
2–4 | 62.0 | 16.0 (1.1; 13.8–18.2) | ||
> 4 | 51.1 (16.4; 19.0–83.2) | 41.7 (13.7; 14.8–68.6) |
ROC-analysis concerning 3-years survival | Palliative dataset Viral subgroup N = 120 (35.9%) | Palliative dataset Alcoholic subgroup N = 96 (28.7%) | Palliative dataset Cryptogenic/NASH subgroup N = 59 (17.7%) | |||
---|---|---|---|---|---|---|
AUC | p | AUC | p | AUC | p | |
CLIP group (0–1 vs. 2–4) | 0.729 | < 0.001 | 0.504 | 0.953 | 0.576 | 0.382 |
mART score (< 2.5 vs. ≥ 2.5) | 0.589 | 0.303 | 0.591 | 0.302 | 0.417 | 0.497 |
ART score (< 2.5 vs. ≥ 2.5) | 0.500 | 1.000 | 0.500 | 1.000 | 0.643 | 0.663 |
ALBI group (A1 vs. A2 + A3) | 0.617 | 0.043 | 0.463 | 0.549 | 0.654 | 0.064 |
APRI score (≤ 1.15 vs. > 1.15) | 0.584 | 0.136 | 0.552 | 0.400 | 0.542 | 0.610 |
mSNACOR stage (low- and interm. risk vs. high risk) | 0.661 | 0.021 | 0.545 | 0.547 | 0.569 | 0.759 |
SNACOR stage (low- and interm. risk vs. high risk) | 0.479 | 0.877 | 0.543 | 0.770 | 0.417 | 0.739 |
HAP stage (A + B vs. C + D) | 0.707 | < 0.001 | 0.503 | 0.968 | 0.693 | 0.027 |
STATE score (≥ 18 vs. < 18) | 0.564 | 0.271 | 0.656 | 0.012 | 0.481 | 0.821 |
Child–Pugh class (A vs. B + C) | 0.712 | < 0.001 | 0.602 | 0.098 | 0.674 | 0.034 |
Okuda stage (A vs. B + C) | 0.766 | < 0.001 | 0.552 | 0.396 | 0.551 | 0.533 |
MELD score (< 10 vs. ≥ 10) | 0.693 | 0.001 | 0.507 | 0.915 | 0.524 | 0.769 |
BCLC score (A + B vs. C + D | 0.614 | 0.032 | 0.591 | 0.126 | 0.395 | 0.169 |
ROC-analysis concerning therapy discontinuation | Palliative dataset Viral subgroup N = 120 (35.9%) | Palliative dataset Alcoholic subgroup N = 96 (28.7%) | Palliative dataset Cryptogenic/NASH subgroup N = 59 (17.7%) | |||
---|---|---|---|---|---|---|
AUC | p | AUC | p | AUC | p | |
CLIP group (0–1 vs. 2–4) | 0.710 | 0.002 | 0.503 | 0.968 | 0.750 | 0.037 |
mART score (< 2.5 vs. ≥ 2.5) | 0.600 | 0.251 | 0.624 | 0.240 | 0.685 | 0.251 |
ART score (< 2.5 vs. ≥ 2.5) | 0.546 | 0.767 | 0.596 | 0.671 | 0.643 | 0.663 |
ALBI group (A1 vs. A2 + A3) | 0.655 | 0.019 | 0.550 | 0.474 | 0.762 | 0.028 |
APRI score (≤ 1.15 vs. > 1.15) | 0.601 | 0.093 | 0.533 | 0.635 | 0.615 | 0.331 |
mSNACOR stage (low- and interm. risk vs. high risk) | 0.688 | 0.016 | 0.456 | 0.594 | 0.625 | 0.424 |
SNACOR stage (low- and interm. risk vs. high risk) | 0.567 | 0.663 | 0.617 | 0.461 | 1.000 | 0.127 |
HAP stage (A + B vs. C + D) | 0.691 | 0.005 | 0.504 | 0.953 | 0.895 | 0.001 |
STATE score (≥ 18 vs. < 18) | 0.587 | 0.187 | 0.486 | 0.842 | 0.709 | 0.077 |
Child–Pugh class (A vs. B + C) | 0.746 | < 0.001 | 0.643 | 0.039 | 0.838 | 0.004 |
Okuda stage (A vs. B + C) | 0.795 | < 0.001 | 0.453 | 0.500 | 0.690 | 0.109 |
MELD score (< 10 vs. ≥ 10) | 0.670 | 0.008 | 0.517 | 0.805 | 0.817 | 0.007 |
BCLC score (A + B vs. C + D | 0.552 | 0.398 | 0.504 | 0.953 | 0.532 | 0.787 |