TABLE 2.
Selected randomised controlled trials identifying locoregional therapies in HCC.
| Trial | BCLC stage | Region | Arms | Endpoints | Outcomes |
|---|---|---|---|---|---|
| Local ablation | |||||
| Lencioni et al., 2003 | Early | Italy | RFA (n = 52) versus PEI (n = 50) | OS (2 years) | 98% versus 88%; HR 0.2 (95% CI 0.02–1.69); p = 0.13 |
| Lin et al., 2005 | Early | Chinese Taiwan | RFA (n = 62) versus PEI (n = 62) versus PAI (n = 63) | LR (3 years) | LR 14% versus 34% versus 31%, all p < 0.01; |
| OS (3 years) | OS 74% versus 51% versus 53%, all p < 0.01 | ||||
| Shiina et al., 2005 | Early | Japan | RFA (n = 118) versus PEI (n = 114) | OS (4 years) | 74% versus 57%; HR 0.54 (95% CI 0.33–0.89); p = 0.02 |
| Chen et al., 2006 | Early | China | RFA (n = 90) versus partial hepatectomy (n = 90) | OS (4 years) | OS 65.9% versus 51.6%; p = ns |
| Huang et al., 2010 | Early | China | RFA (n = 115) versus surgical resection (n = 115) | OS (5 years) | OS 54% versus 75%; p = 0.001 |
| RFS (5 years) | RFS 28% versus 51%; p = 0.017 | ||||
| Feng et al., 2012 | Early | China | RFA (n = 84) versus surgical resection (n = 84) | OS (3 years) | OS 67.2% versus 74.8%; p = 0.342 |
| Peng et al., 2013 | Early | China | RFA plus TACE (n = 94) versus RFA (n = 95) | OS (4 years) | OS 61.8 versus 45%; HR 0.52 (95% CI 0.33–0.88); p = 0.002 |
| RFS (4 years) | RFS 54.8% versus 38.9%; HR 0.57 (95% CI 0.37–0.89); p = 0.009 | ||||
| Chen et al., 2014 | Early | China | RFA plus iodine‐125 implantation (n = 68) versus RFA (n = 68) | TTR | TTR 93 versus 66.8 months; HR 0.50 (95% CI 0.31–0.81); p = 0.004 |
| OS | OS 95.8 versus 70.8 months; HR 0.50 (95% CI 0.31–0.80); p = 0.003 | ||||
| Wang et al., 2015 | Early/intermediate | China | RFA versus (n = 180) versus cryoablation (n = 180) | LTP (3 years) | LTP 11% versus 7%; p = 0.043 |
| OS (5 years) | OS 38% versus 50%; p = 0.747 | ||||
| Ng et al., 2017 | Early | China | Hepatic resection (n = 109) versus RFA (n = 109) | Recurrence | Overall recurrence 81.7% versus 71.3%; p = 0.09 |
| Yu et al., 2017 | Early | China | MWA (n = 203) versus RFA (n = 200) | LTP (5 years) | LTP 19.7% versus 11.4%; p = 0.11 |
| Vietti Violi et al., 2018 | Early | France, Switzerland | MWA (n = 76) versus RFA (n = 76) | LTP (2 years) | LTP 12% versus 6%; HR, 1.62 (95% CI 0.66–3.94); p = 0.27 |
| Tak et al., 2018 (HEAT study) | Early/intermediate | Global | RFA plus LTLD (n = 354) versus RFA (n = 347) | PFS | PFS 13.9 versus 13.9 months, HR 0.96 (95% CI 0.79–1.18), p = 0.71 |
| Xia et al., 2019 | Early (recurrent HCC) | China | Repeat hepatectomy (n = 120) versus RFA (n = 120) | OS | 37.5 versus 47.1 months; HR 1.26 (95% CI 0.91–1.76); p = 0.17 |
| Takayama et al., 2021 | Early | Japan | Surgery (n = 150) versus RFA (n = 151) | RFS | 3.5 versus 3.0 years; HR 0.92 (95% CI 0.67–1.25); p = 0.58 |
| TACE | |||||
| Llovet et al. (2002) | Intermediate/advanced | Spain | TAE (n = 37)/cTACE (n = 40) versus symptomatic treatment (n = 35) | OS | 25.3/28.7 versus 17.9 months; p = 0.009 (cTACE vs. control) |
| Lo et al. (2002) | Early/intermediate/advanced | Asian | cTACE (n = 40) versus symptomatic treatment (n = 39) | OS (3 years) | 26% versus 3%; HR 0.50 (95% CI 0.31–0.81), p = 0.005 |
| Okusaka et al., 2009 | Intermediate | Japan | TAI (n = 82) versus cTACE (n = 79) | OS | 22.6 versus 21.5 months; p = 0.383 |
| Lammer et al., 2010 (PRECISION V trial) | Early/intermediate/ | Europe | DEB‐TACE (n = 93) versus cTACE (n = 108) | 6‐month ORR | 51.6% versus 43.5%; p = 0.11 |
| Yu et al., 2014 | Early/intermediate | China | TEA (n = 49) versus cTACE (n = 49) | OS | 24.3 versus 20.1 months; p = 0.513 |
| Golfieri et al., 2014 (PRECISION ITALIA trial) | Early/intermediate/advanced | Italy | DEB‐TACE (n = 89) versus cTACE (n = 88) | 2‐year OS | 56.8% versus 55.4%; p = 0.949 |
| Ikeda et al., 2018 | Intermediate/advanced | Japan | cTACE with miriplatin (n = 129) versus cTACE with epirubicin (n = 128) | OS | 36.5 versus 37.1 months; HR 1.01 (95% CI 0.73–1.40); p = 0.946 |
| Ikeda et al. (2020) (JIVROSG‐1302 PRESIDENT trial) | Early/intermediate/advanced | Japan | DEB‐TACE (n = 99) versus cTACE (n = 101) | 3‐month CR rate | 27.6% versus 75.2%; p < 0.0001 |
| Zhu et al., 2022 | Early/intermediate | China | cTACE with dicycloplatin (n = 22, A1) versus cTACE with dicycloplatin plus epirubicin (n = 25, A2) versus cTACE with epirubicin (n = 24, B) | ORR | 50.0% versus 44.0% versus 29.17%; p = 0.093 (A1 vs. B); p = 0.338 (A2 vs. B) |
| HAIC | |||||
| Lyu et al., 2021 (FOHAIC‐1) | Advanced | China | HAIC (n = 130) versus sorafenib (n = 132) | OS | 13.9 versus 8.2 months; HR 0.408 (95% CI 0.301–0.552; p < 0.001) |
| Li et al., 2021 | Early/intermediate | China | HAIC (n = 159) versus TACE (n = 156) | OS | 23.1 versus 16.1 months; HR 0.58 (95% CI 0.4–0.75; p < 0.001) |
| Li et al., 2022 | Early/intermediate | China | Postoperative adjuvant HAIC (n = 157) versus routine follow‐up (n = 158) | DFS | 20.3 versus 10.0 months; HR 0.59 (95% CI 0.43–0.81); p = 0.001) |
| TARE | |||||
| Salem et al., 2016 | Early/intermediate | USA | TARE (n = 24) versus cTACE (n = 21) | TTP | >26 versus 6.8 months; HR 0.12 (95% CI 0.027–0.55); p = 0.001 |
| Vilgrain et al., 2017 (SARAH trial) | Advanced | France | TARE (n = 237) versus sorafenib (n = 222) | OS | 8 versus 9.9 months; HR 1.15 (95% CI 0.94–1.41); p = 0.18 |
| Chow et al., 2018 (SIRveNIB trial) | Advanced | Asia‐Pacific | TARE (n = 182) versus sorafenib (n = 178) | OS | 8.8 versus 10.0 months; HR 1.12 (95% CI 0.9–1.4); p = 0.36) |
Abbreviations: BCLC, Barcelona clinic liver cancer; CR, complete response; cTACE, conventional transarterial chemoembolization; DEB‐TACE, TACE with drug‐eluting beads; DFS, disease‐free survival; HAIC, hepatic arterial infusion chemotherapy; HR, hazard ratio; LR, local recurrence; LTLD, lyso‐thermosensitive liposomal doxorubicin; LTP, local tumour progression; MWA, microwave ablation; ORR, objective response rate; OS, overall survival; PAI, percutaneous acetic acid injection; PEI, percutaneous ethanol injection; RFA, radiofrequency ablation; RFS, recurrence‐free survival; TAE, transarterial embolisation; TAI, transarterial infusion chemotherapy; TARE, transarterial radioembolization; TEA, transarterial Ethanol Ablation; TTP, time to tumour progression; TTR, time to recurrence.