Demographic and clinical characteristics of the training cohort and validation cohort
| Variables | Training cohort (N=101) | P value | Validation cohort (N=50) | P value | ||
| Non-response (N=50) | Response (N=51) | Non-response (N=29) | Response (N=21) | |||
| Baseline characteristics | ||||||
| Age, year | 52.74±9.61 | 53.22±11.10 | 0.818 | 53.07±13.07 | 51.95±11.30 | 0.754 |
| Age group, year | 0.425 | 0.934 | ||||
| <65 | 44 (88.00) | 42 (82.35) | 22 (75.86) | 17 (80.95) | ||
| ≥65 | 6 (12.00) | 9 (17.65) | 7 (24.14) | 4 (19.05) | ||
| Sex | 1.000 | 0.171 | ||||
| Male | 48 (96.00) | 49 (96.08) | 29 (100.00) | 19 (90.48) | ||
| Female | 2 (4.00) | 2 (3.92) | 0 (0.00) | 2 (9.52) | ||
| Weight, kg | 64.95±10.57 | 63.80±12.45 | 0.616 | 63.62±11.89 | 64.73±10.77 | 0.736 |
| BMI, kg/m2 | 22.86±3.32 | 22.85±3.48 | 0.993 | 22.82±3.54 | 23.25±3.26 | 0.663 |
| ECOG PS score | 0.846 | 0.835 | ||||
| 0 | 40 (80.00) | 40 (78.43) | 23 (79.31) | 18 (85.71) | ||
| 1 | 10 (20.00) | 11 (21.57) | 6 (20.69) | 3 (14.29) | ||
| HBsAg | 0.015 | 1.000 | ||||
| Negative | 13 (26.00) | 4 (7.84) | 4 (13.79) | 3 (14.29) | ||
| Positive | 37 (74.00) | 47 (92.16) | 25 (86.21) | 18 (85.71) | ||
| Liver cirrhosis | 0.599 | 0.704 | ||||
| No | 31 (62.00) | 29 (56.86) | 15 (51.72) | 12 (57.14) | ||
| Yes | 19 (38.00) | 22 (43.14) | 14 (48.28) | 9 (42.86) | ||
| Laboratory examination | ||||||
| ALT, >50 U/L | 25 (50.00) | 25 (49.02) | 0.922 | 9 (31.03) | 7 (33.33) | 0.863 |
| AST, >40 U/L | 39 (78.00) | 42 (82.35) | 0.583 | 22 (75.86) | 15 (71.43) | 0.724 |
| AST/ALT, >1 | 41 (82.00) | 33 (64.71) | 0.050 | 24 (82.76) | 20 (95.24) | 0.368 |
| ALB, ≤35 g/L | 25 (50.00) | 20 (39.22) | 0.276 | 15 (51.72) | 12 (57.14) | 0.704 |
| TBIL, >22.2 µmol/L | 19 (38.00) | 19 (37.25) | 0.938 | 13 (44.83) | 13 (61.90) | 0.233 |
| PT, >14.4 s | 1 (2.00) | 3 (5.88) | 0.624 | 2 (6.90) | 2 (9.52) | 1.000 |
| AFP, ng/mL | 0.609 | 1.000 | ||||
| <7 | 5 (10.00) | 8 (15.69) | 4 (13.79) | 3 (14.29) | ||
| 7–400 | 17 (34.00) | 14 (27.45) | 5 (17.24) | 4 (19.05) | ||
| ≥400 | 28 (56.00) | 29 (56.86) | 20 (68.97) | 14 (66.67) | ||
| ALBI grade | 0.435 | 0.661 | ||||
| Grade 1 | 6 (12.00) | 6 (11.76) | 4 (13.79) | 4 (19.05) | ||
| Grade 2 | 40 (80.00) | 44 (86.27) | 24 (82.76) | 15 (71.43) | ||
| Grade 3 | 4 (8.00) | 1 (1.96) | 1 (3.45) | 2 (9.52) | ||
| Child-Pugh stage | 0.714 | 1.000 | ||||
| A | 44 (88.00) | 47 (92.16) | 26 (89.66) | 19 (90.48) | ||
| B | 6 (12.00) | 4 (7.84) | 3 (10.34) | 2 (9.52) | ||
| Tumor characteristics | ||||||
| Tumor diameter, cm | 8.61±4.07 | 10.29±4.67 | 0.057 | 11.10±5.47 | 11.86±3.66 | 0.595 |
| Tumor diameter group, cm | 0.556 | 0.849 | ||||
| <5 | 9 (18.00) | 7 (13.73) | 3 (10.34) | 1 (4.76) | ||
| ≥5 | 41 (82.00) | 44 (86.27) | 26 (89.66) | 20 (95.24) | ||
| Tumor number | 0.943 | 0.046 | ||||
| Single | 17 (34.00) | 17 (33.33) | 5 (17.24) | 9 (42.86) | ||
| Multiple | 33 (66.00) | 34 (66.67) | 24 (82.76) | 12 (57.14) | ||
| TBS | 8.83±3.95 | 10.48±4.56 | 0.102 | 11.30±5.38 | 11.98±3.62 | 0.616 |
| TBS group* | 0.037 | 0.095 | ||||
| <8.83 | 28 (56.00) | 18 (35.29) | 12 (41.38) | 4 (19.05) | ||
| ≥8.83 | 22 (44.00) | 33 (64.71) | 17 (58.62) | 17 (80.95) | ||
| Vascular invasion | 0.626 | 0.863 | ||||
| No | 21 (42.00) | 19 (37.25) | 9 (31.03) | 7 (33.33) | ||
| Yes | 29 (58.00) | 32 (62.75) | 20 (68.97) | 14 (66.67) | ||
| PVTT classification group | 0.089 | 0.890 | ||||
| <3 | 31 (62.00) | 23 (45.10) | 16 (55.17) | 12 (57.14) | ||
| ≥3 | 19 (38.00) | 28 (54.90) | 13 (44.83) | 9 (42.86) | ||
| HVTT classification group | 0.203 | 0.726 | ||||
| <2 | 39 (78.00) | 34 (66.67) | 18 (62.07) | 12 (57.14) | ||
| ≥2 | 11 (22.00) | 17 (33.33) | 11 (37.93) | 9 (42.86) | ||
| T stage | 0.593 | 0.568 | ||||
| I–II | 8 (16.00) | 11 (21.57) | 3 (10.34) | 4 (19.05) | ||
| III | 18 (36.00) | 14 (27.45) | 8 (27.59) | 7 (33.33) | ||
| IV | 24 (48.00) | 26 (50.98) | 18 (62.07) | 10 (47.62) | ||
| N stage | 0.320 | 0.485 | ||||
| N0 | 43 (86.00) | 40 (78.43) | 21 (72.41) | 17 (80.95) | ||
| N1 | 7 (14.00) | 11 (21.57) | 8 (27.59) | 4 (19.05) | ||
| M stage | 0.369 | 0.413 | ||||
| M0 | 29 (58.00) | 34 (66.67) | 16 (55.17) | 14 (66.67) | ||
| M1 | 21 (42.00) | 17 (33.33) | 13 (44.83) | 7 (33.33) | ||
| TNM stage | 0.659 | 0.586 | ||||
| I–II | 8 (16.00) | 10 (19.61) | 3 (10.34) | 4 (19.05) | ||
| III | 21 (42.00) | 24 (47.06) | 13 (44.83) | 10 (47.62) | ||
| IV | 21 (42.00) | 17 (33.33) | 13 (44.83) | 7 (33.33) | ||
| BCLC stage | 0.358 | 0.110 | ||||
| A | 2 (4.00) | 5 (9.80) | 0 (0.00) | 3 (14.29) | ||
| B | 14 (28.00) | 10 (19.61) | 7 (24.14) | 3 (14.29) | ||
| C | 34 (68.00) | 36 (70.59) | 22 (75.86) | 15 (71.43) | ||
| Treatment regimen | ||||||
| Immunotherapy | 0.657 | 0.114 | ||||
| Camrelizumab | 17 (34.00) | 21 (41.18) | 6 (20.69) | 4 (19.05) | ||
| Pembrolizumab | 15 (30.00) | 9 (17.65) | 9 (31.03) | 9 (42.86) | ||
| Sintilimab | 9 (18.00) | 12 (23.53) | 3 (10.34) | 6 (28.57) | ||
| Toripalimab | 2 (4.00) | 2 (3.92) | 2 (6.90) | 1 (4.76) | ||
| Tislelizumab | 7 (14.00) | 7 (13.73) | 9 (31.03) | 1 (4.76) | ||
| Interventional therapy | 0.228 | 0.109 | ||||
| TACE | 6 (12.00) | 9 (17.65) | 6 (20.69) | 1 (4.76) | ||
| HAIC | 28 (56.00) | 33 (64.71) | 15 (51.72) | 17 (80.95) | ||
| TACE+HAIC | 16 (32.00) | 9 (17.65) | 8 (27.59) | 3 (14.29) | ||
Note: Data are presented as number (percentage) and mean±SD.
*Value refers to the optimal threshold of TBS group using the maximum Youden Index method. TBS2=(maximum tumor diameter)2+(tumor number)2; ALBI=(log10 bilirubin×0.66)+ (–0.085×albumin), where bilirubin is in mol/L and albumin in g/L. The cut points of ALBI based on previous reports were as follows: ≤−2.60 (grade 1), more than −2.60 to −1.39 (grade 2) and more than −1.39 (grade 3).
AFP, alpha-fetoprotein; ALB, albumin; ALBI, albumin-bilirubin; ALT, alanine aminotransferase; AST, aspartate aminotransferase; BCLC, barcelona clinic liver cancer; BMI, body mass index; ECOG PS, Eastern Cooperative Oncology Group performance status; HAIC, hepatic artery infusion chemotherapy; HBsAg, hepatitis B surface antigen; HVTT, hepatic vein tumor thrombus; PT, prothrombin; PVTT, portal vein tumor thrombus; TACE, transcatheter arterial chemoembolization; TBIL, total bilirubin; TBS, Tumor Burden Score.