Background
Methods
Patients
Evaluation of therapeutic response during sorafenib therapy
Procedure and effect comparisons of transarterial chemoembolization
Serological markers and liver biochemical assay methodology
Statistical analysis
Results
General distribution of overall and separate hepatocellular carcinoma groups
Demographics | Total cases (n = 156) | Group I (n = 52) | Group II (n = 58) | Group III (n = 46) |
---|---|---|---|---|
Age (yrs) (range) | 61.04 ± 12.76 (32.00–88.00) | 58.75 ± 13.33 (32.0–84.0) | 60.36 ± 12.45 (32.0–88.0) | 64.50 ± 12.02 (40.0–86.0) |
Sex (Male) (%) | 127 (81.41) | 46 (88.5) | 52 (89.66) | 29 (63.04) |
BMI (kgs/m2) (range) | 22.69 ± 3.88(14.10–34.82) | 23.05 ± 3.71 (15.24–34.82) | 21.92 ± 3.48 (14.10–32.86) | 23.26 ± 4.43 (15.56–33.75) |
Cirrhosis (+) (%) | 120 (76.92) | 32 (61.5) | 50 (86.21) | 38 (82.61) |
CPC, score 5 versus 6 (%) | 81 (51.92) versus 75 (48.08) | 30 (57.7) versus 22 (42.3) | 31 (53.45) versus 27 (46.55) | 20 (43.48) versus 26 (56.52) |
Biochemical values | ||||
Albumin (g/dL) (range) | 3.88 ± 0.50 (2.80–5.10) | 4.05 ± 0.42 (3.20–4.80) | 3.88 ± 0.51 (2.80–5.10) | 3.68 ± 0.51 (2.80–4.70) |
Bilirubin (mg/dL) (range) | 1.02 ± 0.46 (0.19–2.41) | 0.99 ± 0.41 (0.22–1.99) | 1.03 ± 0.48 (0.19–2.29) | 1.05 ± 0.51 (0.38–2.41) |
INR (range) | 1.14 ± 0.13 (0.89–1.63) | 1.13 ± 0.12 (0.90–1.63) | 1.15 ± 0.13 (0.90–1.48) | 1.15 ± 0.15 (0.89–1.63) |
AST (IU/L) (range) | 92.45 ± 105.98 (22.00–805.00) | 96.20 ± 102.12 (24.00–580.00) | 95.07 ± 136.90 (22.00–805.00) | 84.84 ± 53.33 (23.00–237.00) |
ALT (IU/L) (range) | 66.54 ± 102.12 (9.00–1156.00) | 65.73 ± 48.32 (15.00–251.00) | 76.86 ± 157.43 (9.00–1156.00) | 54.43 ± 39.91 (13.00–202.00) |
ALK-P (IU/L) (range) | 127.76 ± 93.34 (43.00–680.00) | 124.84 ± 81.74 (50.00–421.00) | 113.14 ± 93.05 (45.00–680.00) | 155.0 ± 104.82 (43.00–526.00) |
AFP (ng/mL) (range) | 9000.31 ± 17472.65 (0.91–54001.0) | 11769.7 ± 19836.59 (1.64–54001.0) | 6663.7 ± 14569.6 (0.91–54001.0) | 8815.86 ± 17910.81 (1.30–54001.0) |
Cr (mg/dL) (range) | 0.93 ± 0.35 (0.21–2.76) | 0.90 ± 0.30 (0.40–2.10) | 0.94 ± 0.32 (0.27–1.76) | 0.95 ± 0.43 (0.21–2.76) |
WBC (103/uL) (range) | 6.90 ± 3.71 (1.70–22.62) | 6.96 ± 3.33 (2.48–17.35) | 6.79 ± 3.66 (1.70–19.00) | 7.00 ± 4.23 (2.10–22.62) |
Hb (gm/dL) (range) | 12.48 ± 1.97 (7.90–17.10) | 12.63 ± 1.98 (7.90–16.00) | 12.64 ± 2.02 (7.90–17.10) | 12.11 ± 1.89 (8.10–15.10) |
Platelet (103/uL) (range) | 171.49 ± 110.79 (16.00–796.00) | 170.69 ± 82.45 (16.00–400.00) | 177.19 ± 145.22 (44.00–796.0) | 165.2 ± 88.18 (23.00–386.00) |
Virologic values | ||||
B or C or B + C (+) or NBNC (%) | 80 (51.28) or 50 (32.05) or 5 (3.21) or 21 (13.46) | 30 (57.7) or 9 (17.3) or 3 (5.8) or 10 (19.2) | 33 (56.9) or 18 (31.03) or 1 (1.72) or 6 (10.34) | 17 (36.96) or 23 (50.0) or 1 (2.17) or 5(10.87) |
Tumor characters | ||||
Tumor size (>5 cm) (%) | 74 (47.44) | 27 (51.9) | 25 (43.1) | 22 (47.83) |
Tumor number (>3) (%) | 91 (58.33) | 28 (53.8) | 32 (55.17) | 31 (67.39) |
Intra-hepatic vein (+) (%) | 61 (39.10) | 23 (44.2) | 18 (31.03) | 20 (43.48) |
Extra-hepatic metastases (%) | 75 (48.08) | 23 (44.2) | 31 (53.45) | 21 (45.65) |
Mixed type (vein and metastases) | 20 (12.82) | 6 (11.5) | 9 (15.52) | 5 (10.87) |
Survival analysis in overall and separate groups
Numbers |
P-value | Hazard Ratio (95 % CI) | ||
---|---|---|---|---|
Univariate | Multivariate | |||
Demographics | ||||
Age (yrs), ≤65 vs. >65 | 100 vs. 56 | 0.613 | ||
Gender, Female vs. Male | 29 vs. 127 | 0.863 | ||
BMI (kgs/m2), ≤22 (24) vs. >22 (24) | 102 vs. 54 | 0.798 | ||
Average dose (mg/kg), ≤35 vs. >35 | 97 vs. 59 | 0.848 | ||
Cirrhosis, (-) vs. (+) | 36 vs. 120 | 0.263 | ||
CPC, score 5 vs. 6 | 81 vs. 75 | 0.015* | 0.049* | 0.492 (0.213–1.137) |
AE, (-) vs. (+) | 57 vs. 99 | <0.001* | 0.015* | 3.423 (1.274–9.199) |
Biochemical values | ||||
Albumin (g/dL), ≤3.5 vs. >3.5 | 35 vs. 121 | 0.061 | ||
Bilirubin (mg/dL), ≤1.3 vs. > 1.3 | 118 vs. 38 | 0.466 | ||
INR, ≤1.2 vs. >1.2 | 116 vs. 40 | 0.321 | ||
AST (IU/L), ≤34 vs. >34 | 25 vs. 130 | 0.181 | ||
ALT (IU/L), ≤40 vs. >40 | 73 vs.83 | 0.036* | ||
Alk-p (IU/L), ≤126 vs. >126 | 87 vs.39 | 0.051 | ||
AFP (ng/mL), ≤9 vs. > 9 | 34 vs. 122 | <0.001* | 0.003* | 0.213 (0.078–0.583) |
Creatinine (mg/dL), ≤1.3 vs. > 1.3 | 138 vs. 18 | 0.188 | ||
WBC (103/dL), ≤105 vs. >105 | 136 vs.17 | 0.553 | ||
Hb (gm/dL), ≤12 vs. >12 | 62 vs.94 | 0.115 | ||
Platelet (103/uL), ≤130 vs. >130 | 61 vs. 95 | 0.207 | ||
Virologic values | ||||
HBV or HCV, (-) vs. (+) | 21 vs. 135 | 0.873 | ||
Tumor characters | ||||
Tumor size, ≤5 vs. >5 | 82 vs. 74 | 0.046* | ||
Tumor numbers, ≤3 vs. >3 | 65 vs. 91 | 0.001* | 0.009* | 0.313 (0.131–0.747) |
Intra-hepatic vein, (-) vs. (+) | 95 vs. 61 | 0.661 | ||
Extra-hepatic metastases, (-) vs. (+) | 81 vs. 75 | 0.388 | ||
Mixed type (vein and metastases), (-) vs. (+) | 136 vs. 20 | 0.517 | ||
Therapeutic response | ||||
Sorafenib duration, cycle ≤ 1 vs. >1 | 75vs. 81 | <0.001* | 0.004* | 3.694 (1.530–8.920) |
TACE (-) vs. (+) | 89 vs. 67 | 0.031* | 0.008* | 3.197 (1.353–7.553) |
Positive correlation between better sorafenib response and higher survival
TACE increases survival during and after sorafenib discontinuation
Sorafenib (+) TACE (+) vs. TACE (-) | Sorafenib (-) TACE (+) vs. TACE (-) | ||
---|---|---|---|
Subgroups | Subgroups | ||
Group I (n = 52) | 14/21 vs. 28/31 p = 0.002* | Group I (n = 38) | 6/10 vs. 24/28 p = 0.001* |
Group II (n = 58) | 13/21 vs. 23/37 p = 0.595 | Group II (n = 40) | 4/10 vs. 23/30 p = 0.034* |
Group III (n = 46) | 12/15 vs. 24/31 p = 0.074 | Group III (n = 31) | 3/6 vs. 20/25 p = 0.647 |
HCC-total Patients (N = 156) | 39/57 vs. 75/99 p = 0.002* | HCC-total Patients (N = 109) | 13/26 vs. 67/83 p = 0.001* |