Hepatocellular carcinoma (HCC) is the sixth most common type of cancer and the fourth leading cause of cancer-related deaths worldwide. Only approximately 30-40% of patients can be treated with any hope of recovery. The remaining patients undergo locoregional or systemic therapies of which transarterial chemoembolization (TACE) is the most frequent approach. However, the efficacy of TACE is poor in the treatment of large (>5 cm) and multinodular tumours. Furthermore, the presence of macroscopic neoplastic vascular invasion (MaVI) is generally considered a contraindication to this intra-arterial treatment.
Which HCC patient should be treated with radioembolization?
In the presence of large HCCs with or without MaVI, transarterial radioembolization (TARE) represents an intra-arterial therapy alternative to TACE or to systemic therapies and has been shown to be effective in inducing tumour necrosis and delaying its progression, ultimately leading to a survival benefit. TARE has recently entered at the left of the BCLC algorithm (i.e., BCLC 0-A), mainly because of negative phase III trials in BCLC C stage. TARE has shown a steady increase in nationwide studies over the past 20 years and has even been adopted in some tertiary centres as the primary HCC treatment across all BCLC stages. So, the crucial point is patient selection.
TARE is more potent than TACE in terms of damage to the healthy liver as well as tumour control. Therefore, the most favoured candidates for TARE are patients with an unresectable HCC who have Child-Pugh class A. The biggest advantage of TARE over TACE is that it induces minimal post-embolization syndrome irrespective of the tumour size, whereas post-embolization syndrome after TACE is commonly proportional to the tumour burden. Thus, TARE is commonly considered for patients with a large (>6 cm) unresectable HCC who can benefit more from TARE than for those with a small HCC. Moreover, TARE can be a good treatment option for patients with portal vein tumour invasion due to its minimal embolic effect. However, the extent of portal thrombosis is an important selection criterion; patients with segmental or bisegmental portal thrombosis are good candidates for TARE, while involvement of the lobar or common portal trunk is associated with worse progression.
What is the role of technical aspects in radioembolization, such as dosimetry ?
TARE is a sophisticated technical procedure requiring high skills and expertise together with multidisciplinary management, involving various medical and non-medical personnel, having a significant learning curve. Lack of experience may have influenced the selection of patients in the past, which was not entirely appropriate as well as having negatively influenced the significant impact of dosimetry. In this regard, the experience seems to be associated with the evolution of the role of dosimetry. In fact, it is now widely demonstrated that dosimetry is crucial for the effectiveness of TARE. In fact, personalized dosimetry has been found to be associated with improved overall survival and progression-free survival.
What are the possible future combinations?
Recent and preliminary results have led to enthusiasm for combining checkpoint inhibitors and TARE, in the setting of HCC. The immunomodulatory abilities of TARE remain largely unknown.
Prospective trials are needed to determine the optimal immunotherapy and optimal timing of sequential therapies administered in combination with TARE.
