Transarterial chemoembolisation and radioembolisation for the treatment of primary liver cancer and secondary liver cancer: A review of the literature

Liver‐directed therapies are continuing to evolve in the field of interventional oncology and are gaining increasing use in the treatment of unresectable primary and secondary liver cancers. In this article, we review two liver‐directed therapies that are currently used for the palliative treatment of primary and secondary hepatic tumours: transcatheter arterial chemoembolisation (TACE), including a new type of TACE with drug‐eluting beads (DEB‐TACE), and radioembolisation. The concept of these transcatheter intraarterial therapies is to selectively deliver high doses of anticancer treatment to the tumour. While TACE delivers one or more chemotherapeutic drugs into the hepatic arteries supplying the tumour, radioembolisation uses non‐embolic microspheres incorporating the radioactive isotope ⁹⁰Y. In this article, we discuss some technical aspects, patient selection, current clinical evidence, and future directions of TACE, TACE with drug‐eluting beads (DEB‐TACE) and radioembolisation for primary and secondary liver cancer.     

Contrasting Some Differences in Managing Advanced Unresectable Hepatocellular Carcinoma Between the East and the West

Hepatocellular carcinoma (HCC) is a common malignancy worldwide, although its aetiologies vary significantly between the East and the West. About a half of HCC cases present with advanced unresectable HCC at the time of diagnosis, leading to a worse prognosis. Over the past 20 years, the treatment paradigm for advanced unresectable HCC has shifted from an entirely palliative approach to a multidisciplinary treatment, with continuous reassessment and possible repeat treatment attributed to the advent of novel and improved local, regional and systemic therapeutic options, contributed by both the East and the West. An individualised treatment plan should be determined for each patient, as there can be substantial differences in the decision-making and treatment response to the same treatment for different patients and different patient populations. This review provides a summary of the recent advances in management and compares Eastern and Western strategies for HCC.     

Trans-arterial hepatic radioembolisation of yttrium-90 microspheres

The liver represents a frequent site for metastatic disease, in addition to being a site for primary cancer. Hepatic metastases from certain neoplasms, such as colon, neuroendocrine, melanoma and gastrointestinal stromal tumour have a distinct predilection to metastasize the liver, which in many cases may represent the only or the dominant site of disease. In these circumstances, cytoreduction via surgery or in situ ablative techniques aims to influence the natural history of the disease progression and improve clinical outcomes.Liver directed therapy utilising yttrium-90 microspheres represents a recently introduced in situ multidisciplinary cancer therapy that has caught the attention of many physicians faced with the challenges of treating these complex patients. Although similar to other forms of trans-arterial liver directed therapy, there are discrete differences and potentially fatal treatment consequences unique to this therapy. This objective of this review article is to provide the reader a basis for understanding the therapeutic principles, patient exclusion criteria, pre and post therapy investigations and salient clinical results in the two most commonly treated disease types; metastatic colorectal cancer and hepatocellular cancer.     

Current Status and Future Direction of Hepatic Radioembolisation

Radioembolisation is a locoregional treatment modality for hepatic malignancies. It consists of several stages that are vital to its success, which include a pre-treatment angiographic simulation followed by nuclear medicine imaging, treatment activity choice, treatment procedure and post-treatment imaging. All these stages have seen much advancement over the past decade. Here we aim to provide an overview of the practice of radioembolisation, discuss the limitations of currently applied methods and explore promising developments.     

Multi-centre phase II clinical trial of yttrium-90 resin microspheres alone in unresectable, chemotherapy refractory colorectal liver metastases

Background:

This multi-centre phase II clinical trial is the first prospective evaluation of radioembolisation of patients with colorectal liver metastases (mCRC) who failed previous oxaliplatin- and irinotecan-based systemic chemotherapy regimens.

Methods:

Eligible patients had adequate hepatic, haemopoietic and renal function, and an absence of major hepatic vascular anomalies and hepato-pulmonary shunting. Gastroduodenal and right gastric arteries were embolised before hepatic arterial administration of yttrium-90 resin microspheres (median activity, 1.7 GBq; range, 0.9–2.2).

Results:

Of 50 eligible patients, 38 (76%) had received ⩾4 lines of chemotherapy. Most presented with synchronous disease (72%), >4 hepatic metastases (58%), 25–50% replacement of total liver volume (60%) and bilateral spread (70%). Early and intermediate (>48 h) WHO G1–2 adverse events (mostly fever and pain) were observed in 16 and 22% of patients respectively. Two died due to renal failure at 40 days or liver failure at 60 days respectively. By intention-to-treat analysis using Response Evaluation Criteria in Solid Tumours, 1 patient (2%) had a complete response, 11 (22%) partial response, 12 (24%) stable disease, 22 (44%) progressive disease; 4 (8%) were non-evaluable. Median overall survival was 12.6 months (95% CI, 7.0–18.3); 2-year survival was 19.6%.

Conclusion:

Radioembolisation produced meaningful response and disease stabilisation in patients with advanced, unresectable and chemorefractory mCRC.     

Treatment options for unresectable HCC with a focus on SIRT with Yttrium‐90 resin microspheres

Hepatocellular carcinoma (HCC), the predominant form of primary liver cancer, is the second leading cause of cancer‐related deaths across the globe. Only a small percentage of HCC patients (~20%‐30%) are diagnosed at an early stage when first‐line treatment options may be effective. The majority of HCC patients (>70%) are diagnosed with unresectable disease and given a poor overall prognosis. Current treatment guidelines recommend locoregional therapy with transarterial chemoembolisation (TACE) and systemic therapy with sorafenib as first‐line treatment for patients with intermediate and advanced stage HCC. However, multiple factors including contraindications, technical considerations and treatment‐related toxicities pose significant challenges in achieving favourable treatment outcomes, underscoring the need for a paradigm shift in managing these patients. In 2002, yttrium‐90 (Y‐90) resin microspheres was approved by the U.S. Food and Drug Administration (FDA) for the treatment of unresectable metastatic colorectal cancer to the liver with adjuvant floxuridine chemotherapy. However, thousands of patients with unresectable HCC have also been treated with resin Y‐90. For over two decades, several small‐scale prospective trials and retrospective studies have investigated and reported on the efficacy of locoregional selective internal radiation therapy (SIRT) with Y‐90 microspheres in treating unresectable HCC. Although it is currently a treatment option for intermediate‐stage HCC patients, mainstream clinical application of resin Y‐90 has been largely limited because of the lack of sufficient clinical data from a randomised controlled trial. This could change with the imminent announcement of results from the phase 3 Sorafenib vs Radioembolization in Advanced Hepatocellular carcinoma (SARAH) trial. To provide the foundation and context for interpreting results from the SARAH trial, this article provides an overview of treatment modalities and current challenges in managing unresectable HCC. There is also a review of key prospective and retrospective studies evaluating the use of Y‐90 SIRT, specifically Y‐90 resin microspheres in unresectable HCC, which led to the development of the SARAH trial. Methods: To identify relevant publications, the PubMed database was queried using one or more of the following search terms alone or in combination with Boolean operators: epidemiology, hepatocellular, hepatocellular cancer, hepatocellular carcinoma, unresectable, radioembolisation, selective internal radiation therapy, SIR‐Spheres, yttrium 90, TACE, and sorafenib. The results were sorted or filtered by “Author”, “Publication dates” or “Article types” to identify articles relevant to each section of the review. To ensure that information on ongoing clinical trials involving Y‐90 resin was included, we conducted a search on “ClinicalTrials.gov”, by combining the search terms “HCC” OR “hepatocellular carcinoma” with “Y 90” OR “yttrium 90” OR “radioembo”, and screened for studies that involved treatment with Y‐90 resin microspheres.