Transarterial chemoembolisation and combined therapy

Abstract

In Hepatocellular carcinoma (HCC), transarterial chemoembolisation (TACE) is the most widely used loco-regional treatment not only in the intermediate stage, but often also in early or advanced disease (“treatment stage migration”), but is the least standardised, both in terms of indications and techniques. The rationale for the efficacy of transarterial therapies is that the vascularisation of HCC is, for the most part, dependent on the hepatic artery. Conventional TACE (cTACE) consists of the intra-arterial administration of a chemotherapeutic drug emulsified with Lipiodol followed by embolisation of the tumour-feeding vessels with an embolic agent (most commonly gel foam particles). Drug-eluting bead-TACE (DEB-TACE) is progressively challenging cTACE; DEB-TACE is supposed to maximise the concentration of a cytotoxic drug at the tumour level, with a slower release of the drug into the tumour and minimal systemic exposure. Beads, along with their embolic properties, segregate the chemotherapeutic agent and release it over a one-week period. At present, data from the literature do not confirm the superiority of DEB-TACE over cTACE in terms of patient survival, tumour response and safety, and the choice is therefore left to the operator. Several cytotoxic drugs are administered in both conventional and DEB-TACE. The most widely used is doxorubicin, with no evidence of its superiority over other chemotherapeutics. Transarterial embolisation (TAE) consists of the embolisation of tumour-feeding arteries with embolic agents without adding any chemotherapeutic drugs. To date, the relative effectiveness of TACE over TAE has not been established in randomised trials. Combined treatment (radiofrequency ablation (RFA) plus TACE) is safe and effective for the treatment of unresectable patients with early/intermediate HCC exceeding 3 cm in size. Hepatic arterial infusion chemotherapy (HAIC) is frequently adopted for the treatment of locally advanced HCC in Japan, based on reports of high response rates and favourable long-term outcomes. Firm evidence of the superiority of one over the other has not yet been established. In the future, a demonstration of the survival advantage of HAIC over systemic therapies and the recognition of HAIC as one of the standard treatments for patients with advanced HCC are expected. In intrahepatic cholangiocarcinoma (ICC), hepatic arterial therapy (HAT) seems to be a promising strategy for improving outcomes in patients with unresectable ICC. The best outcomes in terms of response and OS are reported by HAIC even it is associated with increased toxicity. Targeted treatment strategy based on patient-disease characteristics is a goal for future research. In liver metastases, liver-directed therapies have become common due to the increased complexity of hepatic surgery. Intra-arterial treatment options include TACE, TAE, HAIC and ablative techniques, such as microwave irradiation (MWI) or RF ablation. The evidence supports their use to provide salvage options when first-line treatment has failed. Although these treatments have been applied without high-level clinical evidence, they have allowed tailoring the clinical approach to the individual based on disease status and clinical condition. In patients with well-differentiated unresectable hypervascular neuroendocrine tumour (NET) liver metastases, TAE, TACE and selective transarterial radioembolisation (TARE) are the preferred choices among other treatment modalities. Transarterial embolisation and TACE generally achieve average symptomatic, biological and radiological responses of 75%, 56% and 50%, respectively with a progression-free survival of 12–18 months, with acceptable tolerance.