Liver cancers are the second most frequent cause of global cancer-related mortality of which 90% are attributable to hepatocellular carcinoma (HCC). Despite the advent of screening programmes for patients with known risk factors, a substantial number of patients are ineligible for curative surgery at presentation with limited outcomes achievable with systemic chemotherapy/external radiotherapy. This has led to the advent of numerous minimally invasive options including but not limited to trans-arterial chemoembolization, radiofrequency/microwave ablation and more recently selective internal radiation therapy many of which are often the first-line treatment for select stages of HCC or serve as a conduit to liver transplant. The authors aim to provide a comprehensive overview of these various image guided minimally invasive therapies with a brief focus on the technical aspects accompanied by a critical analysis of the literature to assess the most up-to-date evidence from comparative systematic reviews and meta-analyses finishing with an assessment of novel combination regimens and future directions of travel.

In recent years, a combination of intervention therapies has been widely applied in the treatment of hepatocellular carcinoma (HCC). One such combined strategy is based on the combination of the percutaneous approach, such as radiofrequency ablation (RFA), and the intra-arterial locoregional approach, such as trans-arterial chemoembolization (TACE). Several types of evidence have supported the feasibility and benefit of combined therapy, despite some studies reporting conflicting results and outcomes. The aim of this review was to explain the technical aspects of different combined treatments and to comprehensively analyze and compare the clinical efficacy and safety of this combined treatment option and monotherapy, either as TACE or RFA alone, in order to provide clinicians with an unbiased opinion and valuable information. Based on a literature review and our experience, combined treatment seems to be a safe and effective option in the treatment of patients with early/intermediate HCC when surgical resection is not feasible; furthermore, this approach provides better results than RFA and TACE alone for the treatment of large HCC, defined as those exceeding 3 cm in size. It can also expand the indication for RFA to previously contraindicated "complex cases", with increased risk of thermal ablation related complications due to tumor location, or to "complex patients" with high bleeding risk.

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• DSM-TACE is safe and effective as second-line treatment in HCC patients dismissing or ineligible for sorafenib • DSM-TACE allows the temporary occlusion of the smaller arterial vessels, improving overall therapeutic effectiveness by reducing the immediate wash-out of the cytostatic agent • DSM-TACE also decreases the risk of systemic toxicity and post-embolic syndrome.