Table 2.
Clinical studies of thermal ablation combined with immunotherapy for patients with hepatocellular carcinoma
|
Ref.
|
Location
|
No. (combination group vs control group)
|
Tumor size (cm)
|
Number of tumor nodules (single/multiple)
|
Combination group
|
Control group
|
Follow-up period (mo)
|
Recurrence rates
|
OS, RFS, PFS or DFS
|
Adverse events in the combination group
|
| Weng et al[73], 2008 | China | 45 vs 40 | 2-13 | NR | RFA + TACE + CIK cells | RFA + TACE | 18 | 1-year (8.9% vs 30.0%), 18-mo (15.6% vs 40.0%) (both P < 0.05) | RFS rates: 68.9% (31/45) vs 20.0% (8/40) | A light feverand shiver (24.4%, 11/45) |
| Ma et al[75], 2010 | China | 7 | 1-3.5 | 6/1 | RFA + RAK cells | / | 7 | No recurrence | NR | A slight fever (14.3%, 1/7) |
| Huang et al[74], 2013 | China | 85 vs 89 | 1-26 | 41/44 vs 40/49 | RFA + TACE + CIK cells | RFA + TACE | median 78 (5–173) | NR | OS: 56 mo vs 31 mo (P = 0.001); PFS: 17 mo vs 10 mo (P = 0.001) | Fever (37.5–39.3℃) and chills (3.5%) |
| Cui et al[76], 2014 | China | 30 vs 32 | 2-8 | 12/18 vs 18/14 | RFA + CIT | RFA | Median 12 (10–28) | NR | OS rates: 1-year (100% vs 92.6%), 2-yr (100% vs 76.6%); PFS: not reached vs 12 mo (P < 0.0001) | Fever (38.5℃) (3.3%) |
| Bian et al[77] , 2014 | China | 62 vs 65 | BCLC stage 0-B | 35/27 | RFA + 131I metuximab | RFA | NR | 1-year (31.8% vs 56.3%), 2-year (58.5% vs 70.9%) | NR | No serious adverse events |
| Tu et al[78], 2015 | China | 12 vs 22 | < 5 (66.7%) | 10/2 vs 16/6 | RFA + 131I-chTNT | RFA | Median 31 (5–48) | 83.3% (10/12) vs 86.4% (19/22) | OS: 43 mo vs 35 mo (P = 0.052); PFS: 23 mo vs 7 mo (P = 0.047) | The counts of white blood cells increased |
| Yu et al[82], 2015 | China | 14 vs 15 | 2.4 ± 0.7 vs 2.5 ± 0.8 | NR | MWA + immunotherapy | MWA | 16 vs 19 | 7.1% vs 40% | OS rates: 100% vs 80% (P = 0.126); DFS rates: 92.86% vs 66.67% (P = 0.076) | Fever (< 39℃) (42.9%) |
| Duffy et al[72], 2017 | United States | 32 | BCLC stage C or B | NR | RFA + anti-CTLA-4 (tremelimumab) | / | NR | median time to tumor progression: 7.4 mo | Median OS: 12.3 mo; PFS rate: 6-m (57.1%), 12-mo (33.1%) | Pruritus |
| Huang et al[83] , 2020 | China | 43 vs 57 | Median 9 (5–26) | 19/24 vs 30/27 | TACE + MWA + CIK | TACE + MWA | Median 31 (1–163) | NR | OS: 41 mo vs 24 mo (P = 0.002); DFS: 17 mo vs 10 mo (P = 0.023) | No severe adverse events |
BCLC: Barcelona Clinic Liver Cancer; RFA: Radiofrequency ablation; TACE: transarterial chemo-embolization; MWA: Microwave ablation; CIK: Cytokine-induced killer; RAK: RetroNectin activated killer; CIT: Cellular immunotherapy; 131I-chTNT: Iodine-131-labeled chimeric tumor necrosis therapy; CTLA-4: Cytotoxic T-lymphocyte-associated protein 4; OS: Overall survival; RFS: Recurrence-free survival; PFS: Progression-free survival; DFS: Disease-free survival; NR: Not reported.