Treatment Options for Early-Stage Hepatocellular Carcinoma

AbstractPatients with early stage hepatocellular carcinoma have good prognosis and are treated with curative intent. Although this cohort of patients is generally defined by limited tumor burden, good liver function, and preserved functional status, there remains utility in further stratification to optimize overall survival and limit post-operative morbidity and mortality. Transplant, resection, ablation, transarterial radioembolization, and transarterial chemoembolization, either as monotherapy or in combination, may play a crucial role in treating this cohort of patients depending on a multitude of factors. In this section, we review each treatment modality and provide general guidelines for patient selection.

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Hepatocellular Carcinoma with Portal Vein Tumor Involvement: Best Management Strategies

Seminars in Liver Disease ◽

10.1055/s-0038-1666805 ◽

2018 ◽

Vol 38 (03) ◽

pp. 242-251 ◽

Cited By ~ 17

Author(s):

Po-Hong Liu ◽

Teh-Ia Huo ◽

Rebecca Miksad

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

Blood Flow ◽

Liver Function ◽

Portal Vein ◽

Complex Disease ◽

Treatment Options ◽

Management Strategies ◽

The United States ◽

Disease Entity

AbstractPortal vein tumor thrombosis (PVTT) commonly occurs in patients with hepatocellular carcinoma (HCC). Patients with PVTT usually have an aggressive disease course, decreased liver function reserve, limited treatment options, higher recurrence rates after treatment, and, therefore, worse overall survival. Among untreated HCC patients with PVTT, the median overall survival has been reported as low as 2 to 4 months. Historically, many aspects of PVTT have impacted the theoretical and practical safety and efficacy of treatment, for example, disordered blood flow and associated impairment of liver function, heat-sink effects of blood flow in the area of the PVTT, and risk of recurrence due to tumor location in the blood vessel. The current Barcelona Clinic Liver Cancer staging system categorizes HCC patients with PVTT as advanced stage, for which the standard of care is targeted therapy with sorafenib. However, sorafenib is associated with only marginal benefits among patients with PVTT. First-line lenvatinib, which was shown to be noninferior to sorafenib, excluded patients with main portal trunk invasion. Regorafenib and nivolumab, an immune-based therapy, were recently approved in the United States for second-line therapy after sorafenib. Preliminary results for cabozantinib suggest a benefit in the second-/third-line after sorafenib failure. In addition, rapid advances in many fields (surgery, interventional radiology, nuclear medicine, and immunotherapy) have increased the potential treatment options for the management of this complex disease entity. A large portion of the emerging evidence focuses on the broader category of advanced HCC of which PVTT is a subgroup. While many of these studies show promising results, the efficacy among PVTT patients requires validation in prospective studies. Real-world data may help fill the evidence gap for patients not eligible for clinical trials due to common hepatic function requirements. The variety of new treatment advances for the heterogeneous and complex disease entity of HCC with PVTT means that personalized, multidisciplinary management may be necessary to achieve optimal outcomes. In this narrative review, we summarize the evolving management strategies for patients with HCC and PVTT.

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Lenvatinib for Hepatocellular Carcinoma: A Literature Review

Pharmaceuticals ◽

10.3390/ph14010036 ◽

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.

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

Future Oncology ◽

10.2217/fon-2019-0658 ◽

2020 ◽

Vol 16 (1) ◽

pp. 4315-4325 ◽

Cited By ~ 5

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.

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The APAC Score: A Novel and Highly Performant Serological Tool for Early Diagnosis of Hepatocellular Carcinoma in Patients with Liver Cirrhosis

Journal of Clinical Medicine ◽

10.3390/jcm10153392 ◽

2021 ◽

Vol 10 (15) ◽

pp. 3392

Author(s):

Joeri Lambrecht ◽

Mustafa Porsch-Özçürümez ◽

Jan Best ◽

Fabian Jost-Brinkmann ◽

Christoph Roderburg ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

At Risk ◽

Liver Cirrhosis ◽

Early Stage ◽

Treatment Options ◽

Growth Factor Receptor ◽

Serum Samples ◽

Disease Etiology ◽

Risk Patients ◽

Scoring Tool

(1) Background: Surveillance of at-risk patients for hepatocellular carcinoma (HCC) is highly necessary, as curative treatment options are only feasible in early disease stages. However, to date, screening of patients with liver cirrhosis for HCC mostly relies on suboptimal ultrasound-mediated evaluation and α-fetoprotein (AFP) measurement. Therefore, we sought to develop a novel and blood-based scoring tool for the identification of early-stage HCC. (2) Methods: Serum samples from 267 patients with liver cirrhosis, including 122 patients with HCC and 145 without, were collected. Expression levels of soluble platelet-derived growth factor receptor beta (sPDGFRβ) and routine clinical parameters were evaluated, and then utilized in logistic regression analysis. (3) Results: We developed a novel serological scoring tool, the APAC score, consisting of the parameters age, sPDGFRβ, AFP, and creatinine, which identified patients with HCC in a cirrhotic population with an AUC of 0.9503, which was significantly better than the GALAD score (AUC: 0.9000, p = 0.0031). Moreover, the diagnostic accuracy of the APAC score was independent of disease etiology, including alcohol (AUC: 0.9317), viral infection (AUC: 0.9561), and NAFLD (AUC: 0.9545). For the detection of patients with (very) early (BCLC 0/A) HCC stage or within Milan criteria, the APAC score achieved an AUC of 0.9317 (sensitivity: 85.2%, specificity: 89.2%) and 0.9488 (sensitivity: 91.1%, specificity 85.3%), respectively. (4) Conclusions: The APAC score is a novel and highly accurate serological tool for the identification of HCC, especially for early stages. It is superior to the currently proposed blood-based algorithms, and has the potential to improve surveillance of the at-risk population.

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The Emerging Factors and Treatment Options for NAFLD-Related Hepatocellular Carcinoma

Cancers ◽

10.3390/cancers13153740 ◽

2021 ◽

Vol 13 (15) ◽

pp. 3740

Author(s):

Chunye Zhang ◽

Ming Yang

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Cancer ◽

Fatty Liver ◽

Early Stage ◽

Primary Liver Cancer ◽

Treatment Options ◽

Underlying Mechanism ◽

Diagnostic Methods ◽

T Cell Therapy ◽

Nonalcoholic Fatty Liver

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, followed by cholangiocarcinoma (CCA). HCC is the third most common cause of cancer death worldwide, and its incidence is rising, associated with an increased prevalence of obesity and nonalcoholic fatty liver disease (NAFLD). However, current treatment options are limited. Genetic factors and epigenetic factors, influenced by age and environment, significantly impact the initiation and progression of NAFLD-related HCC. In addition, both transcriptional factors and post-transcriptional modification are critically important for the development of HCC in the fatty liver under inflammatory and fibrotic conditions. The early diagnosis of liver cancer predicts curative treatment and longer survival. However, clinical HCC cases are commonly found in a very late stage due to the asymptomatic nature of the early stage of NAFLD-related HCC. The development of diagnostic methods and novel biomarkers, as well as the combined evaluation algorithm and artificial intelligence, support the early and precise diagnosis of NAFLD-related HCC, and timely monitoring during its progression. Treatment options for HCC and NAFLD-related HCC include immunotherapy, CAR T cell therapy, peptide treatment, bariatric surgery, anti-fibrotic treatment, and so on. Overall, the incidence of NAFLD-related HCC is increasing, and a better understanding of the underlying mechanism implicated in the progression of NAFLD-related HCC is essential for improving treatment and prognosis.

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Prognostic factors of disease-free and overall survival in patients with hepatocellular carcinoma undergoing partial hepatectomy in curative intent

Langenbeck s Archives of Surgery ◽

10.1007/s00423-018-1715-9 ◽

2018 ◽

Vol 403 (7) ◽

pp. 851-861 ◽

Cited By ~ 8

Author(s):

Georg Lurje ◽

Jan Bednarsch ◽

Zoltan Czigany ◽

Iakovos Amygdalos ◽

Franziska Meister ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

Prognostic Factors ◽

Partial Hepatectomy ◽

Curative Intent ◽

Disease Free

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Treatments for the early stage Hepatocellular Carcinoma: Laparoscopic Liver Resection or Percutaneous Radiofrequency, How to make the decision?

Liver Cancer ◽

10.1159/000521136 ◽

2021 ◽

Author(s):

Jinli Zheng ◽

Wei Xie ◽

Yunfeng Zhu ◽

Li Jiang

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

Survival Rate ◽

Liver Resection ◽

Complication Rate ◽

Early Stage ◽

Line Treatment ◽

Overall Survival Rate ◽

First Line ◽

First Line Treatment

Hepatectomy is still as the first-line treatment for the early stage HCC, but the complication rate is higher than p-RFA and the overall survival rate is comparable in these two treatments. Therefore, the patients with small single nodular HCCs could get more benefit from p-RFA, and we need to do further research about p-RFA.

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Decreased Expression of KPNA2 in Hepatocellular Carcinoma Infers Favorable Prognosis and High Immune Infiltrating Level

10.21203/rs.3.rs-691618/v1 ◽

2021 ◽

Author(s):

kangming zhu ◽

yvndi zhang ◽

hui yvan ◽

jing li

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

Logistic Regression ◽

Survival Rate ◽

Western Blotting ◽

Good Prognosis ◽

Overall Survival Rate ◽

Pathological Stage ◽

Down Regulation ◽

Immune Infiltration

Abstract BackgroundLiver hepatocellular carcinoma (LIHC) is an important pathological type of liver cancer. The immune infiltration of the tumor microenvironment is negatively correlated with the overall survival rate of LIHC. At present , the role and molecular mechanism of KPNA2 in LIHC have not been elucidated, and the prognostic correlation between the two and the immune infiltration of LIHC are still unclear. Our study evaluated the role of KPNA2 in LIHC through TCGA data.MethodGene expression profiling interactive analysis (GEPIA) is used to analyze the expression of KPNA2 in LIHC. We evaluated the impact of KPNA2 on the survival of LIHC patients through the survival module. Then, We downloaded the LIHC data set from TCGA. Logistic regression was used to analyze the correlation between clinical information and KPNA2 expression. Cox regression analysis was used to analyze the clinicopathological characteristics related to the overall survival rate of TCGA patients. In addition, we used the "correlation" modules of CIBERSORT and GEPIA to explore the correlation between KPNA2 and cancer immune infiltrate. Western blotting was used to detect the expression of KPNA2.ResultUsing logistic regression for univariate analysis, increased KPNA2 expression was significantly correlated with pathological stage, tumor status, and lymph node status. In addition, multivariate analysis showed that down-regulation of KPNA2 expression, negative pathological stage and distant metastasis are independent prognostic factors for good prognosis. Specifically, CIBERSORT analysis was used to establish a negative correlation between the up-regulated expression of KPNA2 and the level of immune infiltration of B cells, NK cells, mast cells, and T cells. In addition, we confirmed this in the "Association" module of GEPIA. The expression of KPNA2 in LIHC tissues was significantly lower than that in adjacent normal tissues by western blotting.ConclusionThe down-regulation of KPNA2 expression is associated with a good prognosis and an increase in the proportion of immune cells in LIHC. These conclusions indicate that KPNA2 is related to the level of immune infiltration of LIHC and can be used as a potential prognostic biomarker of LIHC and a potential target for clinical tumor treatment.

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Sorafenib for the Treatment of Unresectable Hepatocellular Carcinoma: Preliminary Toxicity and Activity Data in Dogs

Cancers ◽

10.3390/cancers12051272 ◽

2020 ◽

Vol 12 (5) ◽

pp. 1272 ◽

Cited By ~ 1

Author(s):

Laura Marconato ◽

Silvia Sabattini ◽

Giorgia Marisi ◽

Federica Rossi ◽

Vito Ferdinando Leone ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

Safety Profile ◽

Median Overall Survival ◽

Response Rate ◽

Treatment Options ◽

Objective Response ◽

Metronomic Chemotherapy ◽

Time To Progression ◽

Activity Data

Unresectable nodular and diffuse hepatocellular carcinoma (HCC) have a poor prognosis with limited treatment options. Systemic traditional chemotherapy has been only rarely reported, with unsatisfactory results. The aim of this prospective, non-randomized, non-blinded, single center clinical trial was to investigate safety profile, objective response rate, time to progression and overall survival of sorafenib in comparison with metronomic chemotherapy (MC) consisting of thalidomide, piroxicam and cyclophosphamide in dogs with advanced, unresectable HCC. Between December 2011 and June 2017, 13 dogs were enrolled: seven received sorafenib, and six were treated with MC. Median time to progression was 363 days (95% CI, 191–535) in dogs treated with sorafenib versus 27 days (95% CI, 0–68) in dogs treated with MC (p = 0.044). Median overall survival was 361 days (95% CI, 0–909) in dogs receiving sorafenib, while 32 days (95% CI, 0–235) in those receiving MC (p = 0.079). Sorafenib seems to be a good candidate for the treatment of dogs with advanced HCC, due to a benefit in disease control and an acceptable safety profile, offering a good basis on which new randomized prospective clinical trials should be undertaken to compare the efficacy and drawback of sorafenib versus MC or traditional chemotherapy.

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Baseline and Early Predictors of Good Patient Candidates for Second-Line after Sorafenib Treatment in Unresectable Hepatocellular Carcinoma

Cancers ◽

10.3390/cancers11091256 ◽

2019 ◽

Vol 11 (9) ◽

pp. 1256 ◽

Cited By ~ 5

Author(s):

Hitomi Takada ◽

Masayuki Kurosaki ◽

Kaoru Tsuchiya ◽

Yasuyuki Komiyama ◽

Jun Itakura ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Function ◽

Disease Progression ◽

Kinase Inhibitors ◽

Tumor Burden ◽

Second Line ◽

Inclusion Criteria ◽

Sorafenib Treatment ◽

Unresectable Hepatocellular Carcinoma ◽

Early Predictors

Background: Recent advances in the development of tyrosine kinase inhibitors (TKIs) have enabled patients with unresectable hepatocellular carcinoma (HCC) to receive multiple TKIs in sequence. The aim of this study was to identify predictors of good candidates for second-line treatment after disease progression during sorafenib treatment. Methods: This is a retrospective cohort study of 190 consecutive HCC patients who were treated with sorafenib in our hospital. Three criteria of good candidates for second-line TKI at the time of disease progression during sorafenib treatment were defined as follows: criterion 1 was the same as the inclusion criteria of the regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE) study, criterion 2 was the inclusion criteria of the RESORCE study plus Child–Pugh score 5, and criterion 3 was the inclusion criteria of the RESORCE study plus albumin–bilirubin (ALBI) grade 1. Factors at baseline and at week 4 during sorafenib treatment were used to predict patients fulfilling each of these three criteria. Results: The distribution of patients was 29%, 13%, and 6% in criteria 1, 2, and 3, respectively. Significant factors for meeting criterion 1 was the combination of baseline albumin >3.7 g/dL (odds ratio (OR) 2.7) plus degree of decrease in albumin (Δalbumin) at week 4 <0.2 g/dL (OR 2.6), or the combination of baseline ALBI score <−2.33 (OR 2.5) and ΔALBI at week 4 <0.255 (OR 4.9). For criterion 2, the value of baseline albumin and ALBI score was identical to criterion 1; however, Δalbumin (<0.1 g/dL) and ΔALBI score (<0.19) became stricter. For criterion 3, the value of baseline albumin (>3.8 g/dL) and ALBI (<−2.55) became stricter, as did Δalbumin (<0.1 g/dL) and ΔALBI (<0.085). Furthermore, tumor burden (>11) was selected as an additional predictor (OR 5.4). Conclusion: Predictors to satisfy the RESORCE study inclusion criteria were as follows: preserved liver function at baseline, as reflected by albumin or ALBI score, and small deterioration of liver function early during sorafenib therapy, as reflected by Δalbumin or ΔALBI at week 4. Liver function at baseline and degree of change in liver function during sorafenib treatment need to be stricter for better outcomes of liver function with disease progression.

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