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©The Author(s) 2018.
World J Hepatol. Sep 27, 2018; 10(9): 571-584
Published online Sep 27, 2018. doi: 10.4254/wjh.v10.i9.571
Published online Sep 27, 2018. doi: 10.4254/wjh.v10.i9.571
Table 1 Guidelines for the clinical management of hepatocellular carcinoma
Publishing year | Guidelines | Drafted by | Treatment algorithm for advanced HCC(BCLC C) | Ref. | |
Asia | 2014 | JSH-LCSGJ | Japan Society of Hepatology and Liver Cancer Study Group of Japan | HAIC (Vp1-4), Sorafenib (Vp1-3), TACE (Vp1, 2), Resection (Vp1, 2) | [6] |
2014 | KLCSG-NCC | Korean Liver Cancer Study Group and National Cancer Center | TACE, Sorafenib | [7] | |
2014 | HKLC | Hong Kong Liver Cancer | Systemic therapy, Supportive care | [8] | |
2017 | APASL | Asian-Pacific Association for the Study of the Liver | Systemic therapy (sorafenib and regorafenib), TACE for patients with no extrahepatic metastasis | [9] | |
2017 | JSH | Japan Society of Hepatology | TACE, Resection, HAIC, Molecular targeted agents | [10] | |
Europe | 2018 | EASL | European Association for the Study of the Liver | Sorafenib (sorafenib, lenvatinib, regorafenib, and cabozantinib) | [11] |
2012 | ESMO-ESDO | European Society for Medical Oncology and European Society of Digestive Oncology | Sorafenib | [12] | |
United States | 2011 | AASLD | American Association for the Study of Liver Disease | Sorafenib | [13] |
Table 2 Serum and plasma biomarkers of sorafenib response and survival
Biomarkers | Ref. | Publishing year | Case number | Predictive factors for response | Predictive factors for survival | Others |
VEGF | Llovet et al[25] | 2012 | 299 | No predictive value | Not prognostic value | |
Miyahara et al[26] | 2013 | 120 | No predictive value | Not prognostic value | ||
Tsuchya et al[27] | 2014 | 63 | No predictive value | VEGF response (a > 5% decrease during 8 wk of treatment): Better OS | ||
Ang-2 | Llovet et al[25] | 2012 | 299 | No predictive value | Low Ang-2: Better OS | |
Miyahara et al[26] | 2013 | 120 | High Ang2: PD | Low Ang-2: Better OS | ||
Changes of AFP | Personeni et al[28] | 2012 | 85 | AFP response (a > 20% decrease during 8 wk of treatment): Better ORR, DCR | AFP response: Better OS | |
Yau et al[29] | 2011 | 94 | AFP response (a > 20% decrease during 6 wk of treatment): Better DCR | AFP response: Better PFS | ||
Kuzuya et al[30] | 2015 | 47 | - | High AFP ratio (a > 1.2 at 2 wk relative to baseline): Poor OS | High poor prognostic score (the absence of disapperance of arterial tumor enhancement on CE-CT, AFP ratio of > 1.2, and two or more increments in CP score after 2 wk of Treatment): Poor OS and DCR | |
Nakazawa et al[31] | 2013 | 59 | AFP increase (more than 20% from baseline during 4 wk of treatment): PD | AFP increase: Better OS and PFS | ||
AFP | Llovet et al[25] | 2012 | 299 | - | AFP > 200 ng/mL: Poor OS | |
Miyahara et al[26] | 2013 | 120 | - | Not prognostic value | ||
Kuzuya et al[30] | 2015 | 47 | - | Not prognostic value | ||
NLR | Zheng et al[32] | 2013 | 65 | - | High NLR (> 4): Poor OS and TTP | |
Howell et al[33] | 2017 | 175 | - | High NLR (> 2.52): Poor OS | ||
TEMs | Shoji et al[34] | 2017 | 25 | High ΔTEMs (changes in TEMs before and at 1 mo after therapy): PD | High ΔTEMs (changes in TEMs before and at 1 mo after therapy): Poor OS | |
MicroRNA | Stiuso et al[35] | 2015 | 39 | Upregulation of miR-423-5p after treatment: SD or PR | - | |
Yoon et al[36] | 2017 | 24 | - | Low miR-10b-3p: Poor OS | ||
Nishida et al[37] | 2017 | 53 | High miR-181a-5p: PR + SD | High miR-181a-5p: Better OS | ||
CTCs | Li et al[38] | 2016 | 59 | pERK+/pAkt- CTCs: Better DCR | pERK+/pAkt- CTCs: Better DCR |
Table 3 Tissue biomarkers of sorafenib response and survival
Biomarkers | Ref. | Publishing year | Case number | Predictive factors for response | Predictive factors for survival |
Expression of p-ERK | Abou-Alfa et al[39] | 2012 | 33 | - | High pERK: Longer TTP |
Chen et al[40] | 2013 | 54 | - | High pERK: Longer TTP | |
Negri et al[41] | 2015 | 77 | - | High pERK: Shorter OS and PFS | |
Expression of p-c-Jun | Hagiwara et al[42] | 2012 | 39 | High p-c-jun: Poor response | High p-c-jun: Shorter TTP and OS |
Expression of VEGFR-2 | Negri et al[41] | 2015 | 54 | - | High VEGFR-2: Shorter OS and PFS |
FGF3/FGF4 amplification | Arao et al[43] | 2013 | 48 | FGF3/FGF4 amplification: Responder | - |
Table 4 Regimens of hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma
Ref. | Publishing year | Case number | Vascular invasion (%) | Regimens | Response rate (%) | Median survival time (mo) |
Saeki et al[48] | 2015 | 90 | ND | Low-dose FP, including the combination of LV/IV or IV plus IFN | 34.4 | 10.6 |
Nouso et al[49] | 2013 | 476 | 44.1 | CDDP + 5-FU | 40.5 | 14.0 (341 patients) |
Monden et al[50] | 2012 | 34 | 90 | IFNα, 5-FU | 26.7 | 8.4 |
35 | 90.3 | Low-dose FP/CDDP | 25.8 | 11.8 | ||
Yamashita et al[52] | 2011 | 57 | 26.7 | IFNα, CDDP, 5-FU | 45.6 | 17.6 |
57 | 50 | IFNα, 5-FU | 24.6 | 10.5 | ||
Nagano et al[57] | 2011 | 102 | 100 | IFNα, 5-FU | 39.2 | 9 |
Obi et al[53] | 2006 | 116 | 100 | IFNα, 5-FU | 52 | 6.9 |
Ikeda et al[54] | 2013 | 25 | 100 | CDDP powder (IA call) | 28 | 7.6 |
Iwasa et al[55] | 2011 | 84 | 31 | CDDP powder (IA call) | 3.6 | 7.1 |
Kim et al[51] | 2011 | 41 | 83.3 | CDDP | 12.2 | 7.5 |
97 | CDDP, 5-FU | 27.8 | 12 | |||
Yoshikawa et al[56] | 2008 | 80 | 27.5 | CDDP powder (IA call) | 33.8 | ND |
Table 5 Predictive factors for response and survival of hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma
Ref. | Publishing year | Case number | Regimens | Poor predictive factors for response | Poor predictive factors for survival |
Saeki et al[48] | 2015 | 90 | Low-dose FP with/without LV, IV, or IV plus IFN | DCP reduction or increase of < 20% from baseline to 2 wk after HAIC | Child-Pugh B, AFP reduction or increase of < 20% from baseline to 2 wk after HAIC, DCP reduction or increase < 20% from baseline to 2 wk after HAIC |
Terashima et al[58] | 2015 | 266 | IFNα, 5-FU with/without CDDP | NLR ≥ 2.87 (cut-off, median value), presence of vascular invasion, presence of extrahepatic metastasis | NLR ≥ 2.87 (cut-off, median value), ECOG PS 1/2, Child-Pugh score 8-9, presence of extrahepatic metastasis, CRP ≥ 0.8 mg/dL, AFP ≥ 235.5 ng/mL |
Zaitsu et al[59] | 2014 | 44 | Low-dose FP with/without IV, or IV plus IFN | ND | Child-Pugh B, serum transferrin < 190 mg/dL |
Nouso et al[49] | 2013 | 476 | CDDP + 5-FU | ND | HBs antigen positive, Child-Pugh B, tumor number > 3, tumor size > 3 cm, presence of extrahepatic metastasis, Vp3/4, AFP > 400 ng/mL |
Niizeki et al[60] | 2012 | 71 | Low-dose FP | VEGF ≥ 100 pg/mL | Child-Pugh B, VEGF ≥ 100 pg/mL, therapeutic effect SD + PD |
Miyaki et al[61] | 2012 | 249 | Low-dose FP (106 patients); IFNα, 5-FU (143 patients) | HCV antibody negative, platelet count ≥ 15 × 104/μL | ECOG PS 1-2, Child-Pugh score 8-9, presence of extrahepatic metastasis, AFP ≥ 1000 ng/mL, abcence of additional therapy, theraputic effect SD + PD + DO |
Obi et al[53] | 2006 | 116 | IFNα, 5-FU | Not detect | Vp4, Total bilirubin ≥ 1.0 mg/dL, theraputic effect PR + SD + PD |
Table 6 Clinical characteristics of three advanced hepatocellular carcinoma patients with complete response who have survived over 10 years
Age diagnosed as HCC | Sex | Etiology | Child-Pugh | Tumor stage1 | Previous treatment | Maximum tumor size (mm) | Vascular invasion1 | Regimen | Therapeutic effect | AFP (ng/mL) | DCP (mAU/mL) | HCC recurrence | Prognosis | Cause of death |
67 | Male | HCV | A (5) | IVA | None | 110 | Vp4, Vv0 | Low-dose FP | CR | 120700 | 260 | 62 mo | 151 mo (dead) | Hepatic failure |
66 | Male | HCV | A (5) | III | None | 50 | Vp0, Vv0 | Low-dose FP + IV | CR | 6.4 | 2970 | None | 176 mo (dead) | Larynx cancer |
44 | Male | HBV | B (7) | III | None | 150 | Vp3, Vv3 | Low-dose FP + IV + Peg IFN | CR | 7145 | 233640 | None | 148 mo (alive2) | - |
- Citation: Saeki I, Yamasaki T, Maeda M, Hisanaga T, Iwamoto T, Fujisawa K, Matsumoto T, Hidaka I, Marumoto Y, Ishikawa T, Yamamoto N, Suehiro Y, Takami T, Sakaida I. Treatment strategies for advanced hepatocellular carcinoma: Sorafenib vs hepatic arterial infusion chemotherapy. World J Hepatol 2018; 10(9): 571-584
- URL: https://www.wjgnet.com/1948-5182/full/v10/i9/571.htm
- DOI: https://dx.doi.org/10.4254/wjh.v10.i9.571