Local and Regional Therapies for Hepatocellular Carcinoma and Future Combinations

Abstract

Background: Hepatocellular carcinoma (HCC) can be treated by local and regional methods of percutaneous interventional radiological techniques. Indications depend on tumor size, type and stage, as well as patient’s condition, liver function and co-morbidities. According to international classification systems such as Barcelona Clinic Liver Cancer (BCLC) classification, very early, early or intermediate staged tumors can be treated either with ablative methods or with transarterial chemoembolization (TACE), depending on tumor characteristics. The combination of both allows for individualized forms of treatment with the ultimate goal of improving response and survival. In recent years, a lot of research has been carried out in combining locoregional approaches with immune therapy. Although recent developments in systemic treatment, especially immunotherapy, seem quite promising and have expanded possible combined treatment options, there is still not enough evidence in their favor. The aim of this review is to provide a comprehensive up-to-date overview of all these techniques, explaining indications, contraindications, technical problems, outcomes, results and complications. Moreover, combinations of percutaneous treatment with each other or with immunotherapy and future options will be discussed. Use of all those methods as down-staging or bridging solutions until surgery or transplantation are taken into consideration will also be reviewed. Conclusion: Local and regional therapies remain a mainstay of curative and palliative treatment of patients with HCC. Currently, evidence on potential combination of the local and regional treatment options with each other as well as with other treatment modalities is growing and has the potential to further individualize HCC therapy. To identify the most suitable treatment option out of these new various options, a repeated interdisciplinary discussion of each case by the tumor board is of utmost importance.

Transarterial chemoembolization for advanced hepatocellular carcinoma without macrovascular invasion or extrahepatic metastasis: analysis of factors prognostic of clinical outcomes

“…Second, we examined patients underwent only TACE as first-line treatment. Nowadays a lot of research has been made in adjuvant immuno therapy after TACE in advanced-stage HCC patients ( 47 – 52 ). Combining TACE with immunotherapeutic agents hypothesized that prolonged survival could be achieved because adjuvant immunotherapy can control TACE-induced neo-angiogenesis and reduce the risk of tumor recurrence and metastatic growth.…”

A Combination of Sorafenib, an Immune Checkpoint Inhibitor, TACE and Stereotactic Body Radiation Therapy versus Sorafenib and TACE in Advanced Hepatocellular Carcinoma Accompanied by Portal Vein Tumor Thrombus

“…Radiation therapy may upregulate the expression of both antigen-presenting cells as well as effector T cells and increase overall T-cell infiltration into tumors, and thus enhancing the effects of immunotherapies [ 25 ]. Furthermore, locoregional treatments might enhance local hypoxia and vascular permeability, induce immunogenicity via the release of tumor antigens following cancer cell death, and elicit damage-associated molecular patterns, which might be rescued by TKIs and ICIs [ 26 ]. It has also been reported that SBRT is particularly effective in tumor areas with high oxygenation, namely the tumor periphery, where TACE itself is less effective [ 27 ].…”

Surgical therapy and survival in young patients with stage I–II hepatocellular carcinoma: a retrospective cohort study

“…Therapy information included surgeries, radiotherapy, and chemotherapy. Patients were divided into five surgery groups: non-surgery, LTD, WSR, LR, and LT ( 6 , 18 ). LTD comprised RFA, cryosurgery, alcohol [percutaneous ethanol injection (PEI)], and photodynamic therapy (PDT).…”