scholarly journals Lenvatinib for Hepatocellular Carcinoma: A Literature Review

2021 ◽  
Vol 14 (1) ◽  
pp. 36
Author(s):  
Takeshi Hatanaka ◽  
Atsushi Naganuma ◽  
Satoru Kakizaki
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Liver Cancer ◽  
Liver Function ◽  
Adverse Events ◽  
Therapeutic Response ◽  
Objective Response ◽  
Intermediate Stage ◽  
Tumor Burden ◽  
Asia Pacific

Lenvatinib, which is an oral multikinase inhibitor, showed non-inferiority to the sorafenib in terms of overall survival (OS) and a higher objective response rate (ORR) and better progression-free survival (PFS) in patients with hepatocellular carcinoma (HCC). A good liver function and Barcelona Clinic Liver Cancer (BCLC) intermediate stage were the key factors in achieving therapeutic efficacy. The management of adverse events plays an important role in continuing lenvatinib treatment. While sequential therapies contributed to prolonging overall survival, effective molecular targeted agents for the administration after lenvatinib have not been established. Repeated transcatheter arterial chemoembolization (TACE) was associated with a decline in the liver function and poor therapeutic response in BCLC intermediate patients. Recently, the Asia-Pacific Primary Liver Cancer Expert (APPLE) Consensus Statement proposed the criteria for TACE unsuitability. Upfront systemic therapy may be better for the BCLC intermediate stage HCC patients with a high tumor burden, while selective TACE will be recommended for obtaining a curative response in patients with a low tumor burden. This article reviews the therapeutic response, management of adverse events, post-progression treatment after Lenvatinib, and treatment strategy for BCLC intermediate stage HCC.

scholarly journals Impact of Baseline ALBI Grade on the Outcomes of Hepatocellular Carcinoma Patients Treated with Lenvatinib: A Multicenter Study

Cancers ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 952 ◽  
Author(s):  
Kazuomi Ueshima ◽  
Naoshi Nishida ◽  
Satoru Hagiwara ◽  
Tomoko Aoki ◽  
Tomohiro Minami ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Function ◽  
Adverse Events ◽  
Objective Response Rate ◽  
Response Rate ◽  
Objective Response ◽  
Evaluation Criteria ◽  
Treatment Discontinuation ◽  
The Impact ◽  
Group 1

Background: This study investigated the impact of baseline liver function according to the Child–Pugh score and ALBI (albumin-bilirubin) grade on the outcomes of patients with unresectable hepatocellular carcinoma treated with lenvatinib. Methods: A total of 82 lenvatinib treated patients were included. The correlations of baseline liver function according to the Child–Pugh score and ALBI grade with treatment outcomes, including objective response rate per mRECIST (modified Response Evaluation Criteria in the Solid Tumor), time to treatment failure, treatment duration, and likelihood of treatment discontinuation due to adverse events, were assessed in patients with hepatocellular carcinoma treated with lenvatinib. Patients were divided into four groups: (1) Child–Pugh score 5 and ALBI grade 1 (group 1), (2) Child–Pugh score 5 and ALBI grade 2 (group 2), (3) Child–Pugh score 6 (group 3), and (4) Child–Pugh score ≥7 (group 4). Univariate and multivariate analyses were performed to identify the factors contributing to the objective response rate and likelihood of discontinuation due to adverse events. Results: Among the 82 patients analyzed, group 1 had the highest objective response rate (57.1%) and the lowest likelihood of treatment discontinuation because of adverse events (11.1%) among the four groups (p < 0.05 and p < 0.05). Multivariate analysis identified ALBI grade 1 and baseline AFP level <200 ng/mL as the significant predictors of a high objective response rate (p < 0.05 and p < 0.01), and confirmed that patients with ALBI grade 1 had the lowest probability of treatment discontinuation due to adverse events (p < 0.01). Conclusions: Patients with Child–Pugh score of 5 and ALBI grade 1 predicted a higher response rate and lower treatment discontinuation due to adverse events by lenvatinib treatment.

scholarly journals Lenvatinib as an Initial Treatment in Patients with Intermediate-stage Hepatocellular Carcinoma Beyond up-to-seven Criteria and Child-Pugh A Liver Function: A Proof-of-Concept Study

2019 ◽  
Author(s):  
Masatoshi Kudo ◽  
Kazuomi Ueshima ◽  
Stephan Chan ◽  
Tomohiro Minami ◽  
Hirokazu Chishina ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Propensity Score ◽  
Liver Function ◽  
Propensity Score Matching ◽  
Initial Treatment ◽  
Objective Response ◽  
Unmet Need ◽  
Intermediate Stage ◽  
Proof Of Concept ◽  
Concept Study

Background: Although transcatheter arterial chemoembolisation (TACE) is the standard of care for intermediate-stage hepatocellular carcinoma (HCC), this is a largely heterogeneous disease that includes a subgroup of patients who do not benefit from TACE. The treatment strategy for this subgroup of patients currently remains an unmet need in clinical practice. Here, we performed a proof-of-concept study that lenvatinib may be more favourable treatment option over TACE as an initial treatment in intermediate-stage HCC patients with large or multinodular tumours exceeding the up-to-seven criteria. Methods: This proof-of-concept study included 642 consecutive patients with HCC initially treated with lenvatinib or conventional TACE (cTACE) between January 2006 and December 2018. Of these patients, 176 who received lenvatinib or cTACE as an initial treatment and met the eligibility criteria [unresectable, beyond the up-to-seven criteria, no prior TACE/systemic therapy, no vascular invasion, no extrahepatic spread and Child-Pugh A liver function] were selected for the study. Propensity score matching was used to adjust for patient demographics. Results: After propensity-score matching, outcome of 30 patients prospectively treated with lenvatinib (14 in clinical trials, 1 in early access program and 15 in real world setting) and 60 patients treated with cTACE as the initial treatment was compared. The change of ALBI score from baseline to the end of treatment were -2.61 to -2.61 for 30 patients in lenvatinib group (p = 0.254) and -2.66 to -2.09 in cTACE group (p &lt; 0.01), respectively. The lenvatinib group showed a significantly higher objective response rate (73.3% vs. 33.3%; p &lt; 0.001) and significantly longer median progression-free survival than the cTACE group (16.0 vs. 3.0 months; p &lt; 0.001). Overall survival was significantly longer in the lenvatinib group than in the cTACE group (37.9 vs. 21.3 months; hazard ratio: 0.48, p &lt; 0.01). Conclusion: In patients with large or multinodular intermediate-stage HCC exceeding the up-to-seven criteria with Child-Pugh A liver function, who usually do not benefit from TACE, lenvatinib provides more favorable outcome than TACE.

Transarterial chemoembolization for pulmonary or mediastinal metastases from hepatocellular carcinoma

2020 ◽  
Vol 93 (1110) ◽  
pp. 20190407 ◽  
Author(s):  
Atsushi Hori ◽  
Ryosuke Ohira ◽  
Tomoyuki Nakamura ◽  
Yasushi Kimura ◽  
Shota Ueda ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Adverse Events ◽  
Objective Response ◽  
Evaluation Criteria ◽  
Reduction Rate ◽  
End Point ◽  
Promising Treatment ◽  
Grade 3 ◽  
Arterial Chemoembolization

Objective: To evaluate the feasibility, efficacy and safety of transcatheter arterial chemoembolization (TACE) with HepaSphere for patients with pulmonary or mediastinal metastases from hepatocellular carcinoma (HCC). Methods: Between June 2009 and January 2018, 14 patients with pulmonary or mediastinal metastases from HCC were treated with TACE with a combination of 1–3 chemotherapeutic drugs followed by HepaSphere embolization. As first end point, local tumor response and adverse events were evaluated after the first session of TACE, with Response Evaluation Criteria In Solid Tumors v. 1.1 and Common Terminology Criteria for Adverse Events v. 4 criteria, respectively. Overall survival was evaluated as secondary end point. TACE was repeated on-demand. Results: TACE with HepaSphere was well tolerated with acceptable safety profile and no 30 day mortality. 1 month objective response and disease control rate were calculated to be 7.1 and 100%, respectively. Mean tumor size reduction rate was 15.6±9.5% at the first month. Two Grade 3 cytopenia events were seen (14.3 %), however none of the Grade 2 or more post-embolization syndrome was observed. The median overall survival time was 15.0 months and the 1 year, 3 year and 5 year survival rate were, 57.1%, 28.6%, 19.1%, respectively. Conclusion: Early experience showed that the transarterial treatment with HepaSphere is safe and effective treatment for patients with pulmonary or mediastinal metastases from HCC. Advances in knowledge: Currently, the effects of molecular targeted drugs on HCC metastases are limited and side-effects are relatively frequent. In the present study, transarterial treatment might be a promising treatment for HCC metastasis.

scholarly journals Efficacy of Regorafenib in Hepatocellular Carcinoma Patients: A Systematic Review and Meta-Analysis

Cancers ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 36 ◽  
Author(s):  
Antonio Facciorusso ◽  
Mohamed A. Abd El Aziz ◽  
Rodolfo Sacco
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Adverse Events ◽  
Therapeutic Option ◽  
Controlled Trial ◽  
Meta Analysis ◽  
Objective Response ◽  
Progression Free Survival ◽  
Sensitivity Analyses ◽  
Free Survival

Regorafenib showed promising results as a second-line agent after sorafenib failure in hepatocellular carcinoma patients. The aim of this meta-analysis was to evaluate the efficacy and safety of regorafenib in hepatocarcinoma patients. A computerized bibliographic search was performed on the main databases. The primary outcome was overall survival. Secondary outcomes were progression-free survival, tumor response, and the adverse events rate. Outcomes were pooled through a random-effects model and summary estimates were expressed in terms of median and 95% confidence interval or rates, as appropriate. One randomized-controlled trial and seven non-randomized studies with 809 patients were included. The great majority of recruited patients were in Child-Pugh A and ECOG 0 stage. Median overall survival was 11.08 months (9.46–12.71) and sensitivity analyses confirmed this finding, with a median survival ranging from 10.2 to 13.8 months. Duration of regorafenib therapy was 3.58 months, whereas median progression-free survival was 3.24 months (2.68–3.86). The pooled objective response rate was 10.1% (7.8–12.5%) while the disease control rate was 65.5% (61.3–69.7%) with no evidence of heterogeneity (I2 = 0%; Diarrhea, fatigue, and hand-foot skin reaction were the most frequent adverse events. The current meta-analysis shows that regorafenib represents a valuable and relatively safe therapeutic option in intermediate/advanced hepatocellular carcinomapatients who progress on sorafenib.

scholarly journals ALBI and P-ALBI grade in Child-Pugh A patients treated with drug eluting embolic chemoembolization for hepatocellular carcinoma

2018 ◽  
Vol 60 (6) ◽  
pp. 702-709 ◽  
Author(s):  
Ulrik Carling ◽  
Bård Røsok ◽  
Pål-Dag Line ◽  
Eric J Dorenberg
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Function ◽  
Objective Response ◽  
Tumor Burden ◽  
Clinical Settings ◽  
Grading Systems ◽  
Significant Difference ◽  
Radiological Response ◽  
Drug Eluting ◽  
Pugh Class

Background Treatment outcome for hepatocellular carcinoma (HCC) is related to tumor burden and liver function. Grading systems assessing liver function need validation in different clinical settings. Purpose To evaluate drug-eluting embolic transarterial chemoembolization (DEE-TACE) in Child–Pugh A HCC with respect to albumin-bilirubin (ALBI) and platelet-albumin-bilirubin (P-ALBI) grade. Material and Methods Forty-nine patients with Child–Pugh class A, diagnosed with HCC and allocated to DEE-TACE treatment, were retrospectively analyzed regarding tumor and treatment characteristics, radiological response (mRECIST) one month post treatment, overall survival (OS), and adverse events (AEs; CTCAE, grades ≥3) with respect to ALBI and P-ALBI grade. Results There were 21 ALBI 1 patients, 29 P-ALBI 1 patients, and 19 patients were both ALBI and P-ALBI 1. Objective response rate was 74% with no statistically significant difference for ALBI (1 vs. 2; P = 0.08), or P-ALBI (1 vs. 2; P = 0.49). OS was 14.8 months (range = 1.7–62.0; ALBI 1 vs. 2: P = 0.08; P-ALBI 1 vs. 2: P = 0.003). OS in responders with ALBI 1 and 2 was 28.9 vs.10.2 months ( P = 0.02), and P-ALBI 1 and 2 was 26.7 vs. 8.6 months ( P < 0.001). In multivariate analyses, both ALBI 2 (HR = 2.4, P = 0.02) and P-ALBI 2 (HR = 3.3, P < 0.01) were negative prognostic factors for survival. There were 15 AEs in 13 patients, with hepatic failure only occurring in ALBI 2 and P-ALBI 2 patients. Conclusion P-ALBI grade 1 and 2 differentiated survival in Child–Pugh A patients treated with DEE-TACE. Both grading systems can differentiate survival in patients responding to treatment.

Treatment of Hepatocellular Carcinoma

2016 ◽  
Vol 34 (5) ◽  
pp. 597-602 ◽  
Author(s):  
Álvaro Díaz-González ◽  
María Reig ◽  
Jordi Bruix
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Liver Function ◽  
Primary Liver Cancer ◽  
Performance Status ◽  
Intermediate Stage ◽  
Extrahepatic Disease ◽  
Stage Migration ◽  
Advanced Stage ◽  
Tumour Burden

Hepatocellular carcinoma (HCC) represents the most frequent primary liver cancer. This disease usually arises as a result of a chronic liver disease, but may appear without any underlying disease. In most units, the staging and treatment decision in patients with HCC follows the Barcelona Clínic Liver Cancer (BCLC) strategy. Following this approach, patients diagnosed with HCC are classified according to tumour burden, liver function and ECOG-Performance Status (PS). This stratifies patients according to prognosis and links each stage with the evidence-based treatment approach to be first considered. Patients correspond to BCLC stage 0 (very early) when the tumour burden accounts for just one nodule and it measures 2 cm or less. BCLC stage A includes patients with just one nodule or 3 nodules under 3 cm. Both stages 0 and A gather patients with preserved liver function according to Child-Pugh score, being Child-Pugh A. Patients in BCLC B stage (intermediate stage) are patients with multinodular liver cancer confined to the liver, without extrahepatic disease, ECOG-PS 0 and preserved liver function (Child-Pugh A or B). Patients with portal venous invasion, extrahepatic disease or cancer-related symptoms measured by PS (1-2) and still with preserved liver function correspond to BCLC C (advanced) stage. Finally, patients classified in BCLC stage D are those with a severe alteration of liver function (Child-Pugh C) or severe cancer-related symptoms with PS above 2. In very early and early stages (BCLC 0 and A), treatment options include surgical treatment, ablation and liver transplantation. Intermediate stage (BCLC B) patients should be considered for transarterial chemoembolization. At advanced stage (BCLC C), the recommended treatment is sorafenib. Finally, at the end stage (BCLC D), symptomatic treatment is the suggested option. The treatment stage migration concept refers to patients who at first glance would be treated with the option that corresponds to their BCLC stage but, because of any coexisting comorbidity, technical issue or even treatment failure/progression but still within the original stage cannot be treated by the initial suggested treatment. These patients then move to the treatment that would correspond to the next stage/s.

scholarly journals CalliSpheres Drug-Eluting Bead Transcatheter Arterial Chemoembolization Presents With Better Efficacy and Equal Safety Compared to Conventional TACE in Treating Patients With Hepatocellular Carcinoma

2019 ◽  
Vol 18 ◽  
pp. 153303381983075 ◽  
Author(s):  
Hua Xiang ◽  
Lin Long ◽  
Yuanhui Yao ◽  
Zhiyong Fang ◽  
Zhiming Zhang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Liver Function ◽  
Transcatheter Arterial Chemoembolization ◽  
Response Rate ◽  
Objective Response ◽  
Progression Free Survival ◽  
Free Survival ◽  
Drug Eluting ◽  
Arterial Chemoembolization

The aim of this study was to compare the treatment response, survival, liver function, and adverse event incidence of drug-eluting bead transcatheter arterial chemoembolization using CalliSpheres microspheres with conventional transcatheter arterial chemoembolization in patients with hepatocellular carcinoma. Seventy-three patients with hepatocellular carcinoma who received drug-eluting bead transcatheter arterial chemoembolization (using CalliSpheres microspheres) or conventional transcatheter arterial chemoembolization treatment were consecutively enrolled. Treatment response was assessed by modified Response Evaluation Criteria in Solid Tumors at month 1/month 3/month 6; posttreatment, liver function indexes, and adverse events were recorded. Progression-free survival and overall survival were also calculated. Objective response rate of patients at months 1, 3, and 6, disease control rate of patients and objective response rate of nodules at month 3 were increased in drug-eluting bead transcatheter arterial chemoembolization group compared with conventional transcatheter arterial chemoembolization group. In addition, drug-eluting bead transcatheter arterial chemoembolization using CalliSpheres microspheres was an independent factor for predicting better objective response rate at month 1. Patients in drug-eluting bead transcatheter arterial chemoembolization group achieved longer progression-free survival and similar overall survival compared to those in conventional transcatheter arterial chemoembolization group; Cox proportional hazards regression model analyses revealed that drug-eluting bead transcatheter arterial chemoembolization using CalliSpheres microspheres was associated with better progression-free survival while it did not affect overall survival. Meanwhile, most of the occurrences of abnormal liver function indexes were similar between 2 groups, whereas drug-eluting bead transcatheter arterial chemoembolization group had a higher percentage of patients with total bile acid ≥2 upper limit of normal compared to conventional transcatheter arterial chemoembolization group at month 1. Moreover, the adverse event incidences between 2 groups were similar. In conclusion, drug-eluting bead transcatheter arterial chemoembolization using CalliSpheres microspheres achieves better treatment response and progression-free survival while equal safety compared to conventional transcatheter arterial chemoembolization in patients with hepatocellular carcinoma.

scholarly journals Brachytherapy with Iodine-125 seeds for treatment of portal vein-branch tumor thrombus in patients with hepatocellular carcinoma

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Duo Hong ◽  
Yi Zhou ◽  
Xiaoting Wan ◽  
Hongying Su ◽  
Haibo Shao
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Adverse Events ◽  
Portal Vein ◽  
Tumor Thrombus ◽  
Combined Treatment ◽  
Objective Response ◽  
Progression Free Survival ◽  
Portal Vein Branch ◽  
Iodine 125

Abstract Background There is currently no widely-accepted consensus for the management of hepatocellular carcinoma with portal vein tumor thrombus. We evaluate the safety and efficacy of ultrasound-guided percutaneous brachytherapy with iodine-125 seeds for the treatment of hepatocellular carcinoma with portal vein-branch tumor thrombus (PVBTT). Methods Sixty-nine hepatocellular carcinoma patients with PVBTT were enrolled; 34 received transarterial chemoembolization (TACE) combined with iodine-125 seeds implanted in the PVBTT; 35 were treated with TACE alone. Adverse events, objective response rate, disease control rate, progression-free survival, and overall survival were compared between the two groups. Tumor responses of PVBTT and intrahepatic tumor were correlated. Multivariate and subgroup analyses were conducted for overall survival. Results No grade 3 or 4 adverse events were recorded, and there was no difference in grade 1 or 2 adverse events between the two groups. Objective response rate and disease control rate for PVBTT were 58.9 and 91.2%, respectively, in the combined treatment group, which were significantly greater than the 5.7 and 54.3% rates, respectively, in the TACE-alone group (both p’s ≤ 0.001). Intrahepatic tumor response was positively correlated with the PVBTT response (γ = 0.782, p < 0.01). Survival outcomes were better in the combined treatment group than in the TACE-alone group: the median progression-free survival for PVBTT was 9 months versus 3 months (HR = 0.187 [95% CI: 0.101, 0.345], p < 0.001), and the median overall survival was 11 months versus 7 months (HR = 0.448 [95% CI: 0.265, 0.758], p = 0.003). Multivariate analysis revealed that application of brachytherapy and lower grade PVBTT (Vp1 + Vp2 vs. Vp3) were protective predictors of overall survival. In stratified analysis, the benefit of overall survival was more significant in the subgroup of PVBTT Vp1 + Vp2 rather than in Vp3. Conclusions The combination of iodine-125 seed brachytherapy guided by ultrasound and TACE is a convenient, safe, and effective treatment for patients with HCC and PVBTT, conferring a better survival benefit than TACE alone.

scholarly journals Tumor burden and liver function in HCC patient selection for selective internal radiation therapy: SARAH post-hoc study

2020 ◽  
Vol 16 (1) ◽  
pp. 4315-4325 ◽  
Author(s):  
Daniel H Palmer ◽  
Neil S Hawkins ◽  
Valérie Vilgrain ◽  
Helena Pereira ◽  
Gilles Chatellier ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Radiation Therapy ◽  
Liver Function ◽  
Tumor Burden ◽  
Selective Internal Radiation Therapy ◽  
Internal Radiation ◽  
Selective Internal Radiation ◽  
Internal Radiation Therapy ◽  
Post Hoc

Aim: To determine whether a liver tumor burden ≤25% and well-preserved liver function (albumin-bilirubin grade 1) are appropriate criteria for identifying patients with unresectable hepatocellular carcinoma who may benefit from selective internal radiation therapy (SIRT) using 90yttrium resin microspheres versus sorafenib. Patients & methods: Post-hoc analysis of patients in the intention-to-treat population of the SARAH trial (SIRT vs sorafenib) with ≤25% tumor burden and albumin-bilirubin grade 1. Primary end point: overall survival. Results: Median overall survival was 21.9 months (95% CI: 15.2–32.5, n = 37) with SIRT and 17.0 months (11.6–20.8, n = 48) with sorafenib (hazard ratios: 0.73; 95% CI: 0.44–1.21; p = 0.22). Conclusion: A combination of good liver function and low tumor burden may be relevant for selection of hepatocellular carcinoma patients for SIRT.

scholarly journals A Changing Paradigm for the Treatment of Intermediate-Stage Hepatocellular Carcinoma: Asia-Pacific Primary Liver Cancer Expert Consensus Statements

Liver Cancer ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 245-260 ◽  
Author(s):  
Masatoshi Kudo ◽  
Kwang-Hyub Han ◽  
Sheng-Long Ye ◽  
Jian Zhou ◽  
Yi-Hsiang Huang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Targeted Therapy ◽  
Liver Function ◽  
Primary Liver Cancer ◽  
Intermediate Stage ◽  
Asia Pacific ◽  
First Line ◽  
First Choice ◽  
Consensus Statements ◽  
Choice Of Treatment

The Asia-Pacific Primary Liver Cancer Expert (APPLE) Consensus Statement on the treatment strategy for patients with intermediate-stage hepatocellular carcinoma (HCC) was established on August 31, 2019, in Sapporo, Hokkaido during the 10th Annual APPLE Meeting. This manuscript summarizes the international consensus statements developed at APPLE 2019. Transarterial chemoembolization (TACE) is the only guideline-recommended global standard of care for intermediate-stage HCC. However, not all patients benefit from TACE because intermediate-stage HCC is a heterogeneous disease in terms of tumor burden and liver function. Ten important clinical questions regarding this stage of HCC were raised, and consensus statements were generated based on high-quality evidence. In intermediate-stage HCC, preservation of liver function is as important as achieving a high objective response (OR) because the treatment goal is to prolong overall survival. Superselective conventional TACE (cTACE) is recommended as the first choice of treatment in patients eligible for effective (curative) TACE, whereas in patients who are not eligible, systemic therapy is recommended as the first choice of treatment. TACE is not indicated as the first-line therapy in TACE-unsuitable patients. Another important statement is that TACE should not be continued in patients who develop TACE failure/refractoriness in order to preserve liver function. Targeted therapy is the recommended first-line treatment for TACE-unsuitable patients. Especially, the drug, which can have higher OR rate, is preferred. Immunotherapy, transarterial radioembolization, TACE + targeted therapy or other modalities may be considered alternative options in TACE-unsuitable patients who are not candidates for targeted therapy. Better liver function, such as albumin-bilirubin grade 1, is an important factor for maximizing the therapeutic effect of systemic therapy.

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