Table 1.
Patient demographics, baseline characteristics, and therapeutic response
| Character | All (n = 110) | CRAFITY score 0 or 1 (n = 57) | CRAFITY score 2 (n = 53) | P value |
|---|---|---|---|---|
| Age (years) | 64.5 (54.6-72.4) | 65.0 (55.8-72.2) | 63.8 (51.0-74.1) | .475 |
| Sex (male), n (%) | 94 (85.5) | 49 (86.0) | 45 (84.9) | .875 |
| Body mass index (kg/m2) | 23.43 (20.96-26.72) | 23.54 (21.12-27.05) | 23.31 (20.71-26.50) | .647 |
| NLR | 5.34 (3.01-8.28) | 5.18 (2.70-7.80) | 5.34 (3.22-8.59) | .327 |
| Platelet count (× 109/L) | 174 (109-251) | 178 (105-256) | 168 (117-252) | .914 |
| AST (U/L) | 48 (32-92) | 41 (25-65) | 69 (39-118) | < .001 |
| ALT (U/L) | 35 (23-57) | 35 (19-55) | 43 (27-61) | .036 |
| Total bilirubin (mg/dL) | 0.97 (0.66-1.60) | 0.90 (0.67-1.20) | 1.28 (0.60-1.92) | .099 |
| Albumin (g/dL) | 3.6 (3.3-4.0) | 3.7 (3.3-4.1) | 3.5 (3.2-3.9) | .106 |
| INR | 1.06 (1.01-1.17) | 1.05 (0.99-1.18) | 1.07 (1.03-1.16) | .364 |
| Etiology | ||||
| Alcohol | 35 (31.8) | 16 (28.1) | 19 (35.8) | .384 |
| HBV | 62 (56.4) | 26 (45.6) | 36 (67.9) | .019 |
| HCV | 27 (24.5) | 17 (29.8) | 10 (18.9) | .184 |
| Diabetes mellitus | 29 (26.4) | 16 (28.1) | 13 (24.5) | .675 |
| Liver cirrhosis | 84 (76.4) | 40 (70.2) | 44 (83.0) | .115 |
| Child-Pugh score | 6 (5-7) | 5 (5-7) | 6 (5-8) | .007 |
| Child-Pugh class A | 72 (66.1) | 42 (73.7) | 30 (57.7) | |
| Child-Pugh class B | 37 (33.9) | 15 (26.3) | 22 (42.3) | |
| ALBI grade | .072 | |||
| 1 | 33 (30.6) | 20 (35.1) | 13 (25.5) | |
| 2 | 67 (62.0) | 36 (63.2) | 31 (60.8) | |
| 3 | 8 (7.4) | 1 (1.8) | 7 (13.7) | |
| AFP (ng/mL) | 126.48 (12.25-5056.0) | 13.42 (3.01-57.72) | 3406.0 (526.43-54000) | < .001 |
| BCLC stage | .481 | |||
| A | 6 (5.5) | 3 (5.3) | 3 (5.7) | |
| B | 16 (14.5) | 10 (17.5) | 6 (11.3) | |
| C | 88 (80.0) | 44 (77.2) | 44 (83.0) | |
| Max. tumor size (cm) | 4.7 (2.7-9.7) | 4.0 (2.3-8.2) | 6.83 (3.79-11.09) | .003 |
| Total tumor volume (cm3) | 740.4 (143.1-5339.6) | 382.5 (76.7-2378.2) | 2242.0 (426.2-6413.7) | .001 |
| MVIa | 65 (59.1) | 29 (50.9) | 36 (67.9) | .070 |
| VP3 | 24 (21.8) | 14 (24.6) | 10 (18.9) | |
| VP4 | 34 (30.9) | 12 (21.1) | 22 (41.5) | |
| Hepatic vein | 7 (6.4) | 3 (5.3) | 4 (7.5) | |
| EHMa | 61 (55.5) | 36 (63.2) | 33 (62.3) | .168 |
| Prior therapy | ||||
| Sorafenib | 63 (57.3) | 36 (63.2) | 27 (50.9) | |
| Lenvatinib | 19 (17.3) | 10 (17.5) | 9 (17.0) | |
| Surgery | 21 (19.1) | 10 (17.5) | 11 (20.8) | |
| PEI/RFA | 7 (6.4)/20 (18.2) | 5 (8.8)/14 (24.6) | 2 (3.8)/6 (11.3) | |
| TACEb/TARE | 66 (60.0)/3 (2.7) | 36 (63.2)/1 (1.8) | 30 (56.6)/2 (3.8) | |
| Radiotherapy | 3 (2.7) | 1 (1.8) | 2 (3.8) | |
| ICI duration (months) | 2.85 (1.67-6.63) | 3.40 (1.85-9.08) | 2.37 (1.55-4.65) | .053 |
| Nivolumabc | 100 (90.9) | 48 (84.2) | 52 (98.1) | |
| Nivolumab + ipilimumabc | 3 (2.7) | 0 (0) | 3 (5.7) | |
| Pembrolizumabc | 12 (10.9) | 11 (19.3) | 1 (1.9) | |
| Reduction > 25% | 59 (53.6) | 34 (59.6) | 25 (47.2) | |
| As 1st/2nd/3rd/4th-line systemic therapy | 35 (31.8)/53 (48.2) | 16 (28.1)/30 (52.6) | 19 (35.8)/23 (43.4) | |
| 16 (14.5)/6 (5.5) | 8 (14.0)/3 (5.3) | 8 (15.1)/3 (5.7) | ||
| Concurrent therapy | 87 (79.1) | 44 (77.2) | 43 (81.1) | .613 |
| Sorafenibd | 43 (39.1) | 21 (36.8) | 22 (41.5) | |
| Lenvatinibd | 32 (29.1) | 16 (28.1) | 16 (30.2) | |
| Regorafenibd | 17 (15.5) | 11 (19.3) | 6 (11.3) | |
| RFA | 3 (2.7) | 1 (1.8) | 2 (3.8) | |
| TACE | 14 (12.7) | 9 (15.8) | 5 (9.4) | |
| Liver radiotherapy | 20 (18.2) | 10 (17.5) | 10 (18.9) | |
| Therapeutic response | ||||
| Best Response | ||||
| Complete response | 7 (6.4) | 3 (5.3) | 4 (7.5) | |
| Partial response | 17 (15.5) | 12 (21.1) | 5 (9.4) | |
| Stable disease | 27 (24.5) | 15 (26.3) | 12 (22.6) | |
| Progressive disease | 59 (53.6) | 27 (47.4) | 32 (60.4) | |
| Not evaluable | ||||
| Death before evaluation | 13 (11.8) | 5 (8.8) | 8 (15.1) | |
| Lost to follow-upe | 4 (3.6) | 2 (3.5) | 2 (3.8) | |
| Objective response | 24 (21.8) | 15 (26.3) | 9 (17.0) | .238 |
| Disease control | 51 (46.4) | 30 (52.6) | 21 (39.6) | .174 |
| Progression-free survival (months)* | 2.87 (2.16-3.58) | 4.07 (1.54-6.59) | 2.47 (2.09-2.85) | .017 |
| Overall survival (months)* | 8.20 (4.23-12.17) | 15.73 (4.76-26.71) | 4.90 (2.64-7.16) | < .001 |
Data presented as median (first quartile-third quartile).
Data presented as median (95% confidence interval).
AFP, α-fetoprotein; ALBI, albumin-bilirubin; ALT, alanine aminotransferase; AST, aspartate aminotransferase; BCLC, Barcelona Clinic Liver Cancer; EHM, extrahepatic metastasis; HBV, hepatitis B virus; HCV, hepatitis C virus; ICI, immune checkpoint inhibitor; MVI, macrovascular invasion; NLR, neutrophil-lymphocyte ratio; TACE, transarterial chemoembolization; TARE, transarterial radioembolization; PEI, percutaneous ethanol injection; INR, international normalized ratio; RFA, radiofrequency ablation.
Thirty-eight patients with HCC had both macrovascular invasion and extrahepatic metastasis.
The median number of TACE sessions was 3 (2-5).
Five patients received sequential ICI therapy because of progressive disease: nivolumab→pembrolizumab→atezolizumab plus bevacizumab (n = 1), nivolumab→pembrolizumab→nivolumab (n = 2), nivolumab→atezolizumab plus bevacizumab→nivolumab plus ipilimumab (n = 1), and nivolumab plus ipilimumab→nivolumab plus sorafenib (n = 1).
Eighteen patients received sequential tyrosine kinase inhibitor therapy because of progressive disease: sorafenib→regorafenib (n = 8), sorafenib→lenvatinib (n = 3), sorafenib→regorafenib→lenvatinib (n = 1), lenvatinib→sorafenib (n = 2), lenvatinib→regorafenib (n = 1), sorafenib→ramucizumab (n = 1), and lenvatinib→cabozantinib (n = 2).
Four patients were lost to follow-up because of immune-related adverse events.