Current State of Liver-Directed Therapies and Combinatory Approaches with Systemic Therapy in Hepatocellular Carcinoma (HCC)

Abstract

The increasing set of liver-directed therapies (LDT) have become an integral part of hepatocellular carcinoma (HCC) treatment. These range from percutaneous ablative techniques to arterial embolization, and varied radiotherapy strategies. They are now used for local disease control, symptom palliation, and bold curative strategies. The big challenge in the face of these innovative and sometimes overlapping technologies is to identify the best opportunity of use. In real practice, many patients may take benefit from LDT used as a bridge to curative treatment such as resection and liver transplantation. Varying trans-arterial embolization strategies are used, and comparison between established and developing technologies is scarce. Also, radioembolization utilizing yttrium-90 (Y-90) for locally advanced or intermediate-stage HCC needs further evidence of clinical efficacy. There is increasing interest on LDT-led changes in tumor biology that could have implications in systemic therapy efficacy. Foremost, additional to its apoptotic and necrotic properties, LDT could warrant changes in vascular endothelial growth factor (VEGF) expression and release. However, trans-arterial chemoembolization (TACE) used alongside tyrosine-kinase inhibitor (TKI) sorafenib has had its efficacy contested. Most recently, interest in associating Y-90 and TKI has emerged. Furthermore, LDT-led differences in tumor immune microenvironment and immune cell infiltration could be an opportunity to enhance immunotherapy efficacy for HCC patients. Early attempts to coordinate LDT and immunotherapy are being made. We here review LDT techniques exposing current evidence to understand its extant reach and future applications alongside systemic therapy development for HCC.

Efficacy and Safety of TACE Combined With Sorafenib Plus Immune Checkpoint Inhibitors for the Treatment of Intermediate and Advanced TACE-Refractory Hepatocellular Carcinoma: A Retrospective Study

“…Studies have demonstrated that TACE activates a hypoxic response, promoting the release of vascular endothelial growth factor (VEGF) and other proangiogenic cytokines (Sergio et al, 2008 ; Viveiros et al, 2019 ). Additionally, cell necrosis induced by TACE is predicted to be associated with antigen release and the exposure of damage-associated molecular patterns.…”

Liver lesions: types, risk factors, investigations and treatment

“…7 Local modalities for treating HCC include ablative therapies, such as radiofrequency ablation, and locoregional therapy such as transarterial chemoembolisation (TACE), transarterial radio embolisation (TARE) and stereotactic ablative radiotherapy (SABR). 8 For patients with advanced multifocal disease, the kinase inhibitor sorafenib has been shown to be effective in Childs Pugh Class A cirrhosis with unresectable hepatocellular carcinoma.…”

Liver-Targeting Class I Selective Histone Deacetylase Inhibitors Potently Suppress Hepatocellular Tumor Growth as Standalone Agents

“…Liver transplant has proven successful in treating cases of early stage HCC, but only an even smaller proportion of patients are eligible due to the late diagnosis of the disease and limited organ availability [5,6]. Other local strategies, such as transarterial chemo-embolization, radioembolization, and radiofrequency ablation, are largely palliative [7].…”