Transarterial radioembolization for liver tumors as neoadjuvant therapy: three case reports / Radioembolização transarterial hepática como terapia neoadjuvante: relato de três casos

ABSTRACT Transarterial radioembolization (TARE) with yttrium-90 microspheres is a palliative locoregional treatment, minimally invasive for liver tumors. The neoadjuvant aim of this treatment is still controversial, however, selected cases with lesions initially considered unresectable have been enframed as candidates for curative therapy after hepatic transarterial radioembolization. We report three cases in which the hepatic transarterial radioembolization was used as neoadjuvant therapy in an effective way, allowing posterior potentially curative therapies.

RESUMO A radioembolização transarterial hepática com microesferas de ítrio-90 é uma modalidade paliativa de tratamento locorregional minimamente invasiva. O objetivo neoadjuvante deste tratamento ainda é controverso, mas casos selecionados de lesões consideradas inicialmente irressecáveis reenquadram-se como candidatos à terapia curativa após a radioembolização transarterial hepática. Relatamos três casos em que a radioembolização transarterial hepática foi utilizada como terapia neoadjuvante de forma efetiva possibilitando aplicação posterior de terapias potencialmente curativas.

Comparison of Radioembolization and Sorafenib for the Treatment of Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis: A Systematic Review and Meta-Analysis of Safety and Efficacy

OBJECTIVE: To compare the safety and efficacy of radioembolization with that of sorafenib for the treatment of hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). MATERIALS AND METHODS: MEDLINE, EMBASE, and Cochrane databases were searched for studies reporting outcomes in patients with HCC and PVTT treated with radioembolization or sorafenib. Meta-analyses of cumulative overall survival (OS) and Kaplan-Meier survival rates according to the time to progression (TTP) and incidence of adverse events (AEs) were performed. Subgroup analyses were conducted on 1-year OS data. RESULTS: Seventeen studies were identified (four involving radioembolization, 10 involving sorafenib, and three comparing both). Pooled OS rates were higher in the radioembolization group, notably at 6 months {76% (95% confidence interval [CI], 64–85%) vs. 54% (95% CI, 45–62%)} and 1 year (47% [95% CI, 38–57%] vs. 24% [95% CI, 18–30%]); TTP was also longer with radioembolization. In patients undergoing radioembolization, the proportion of patients with Eastern Cooperative Oncology Group status 0 (p < 0.0001), Child-Pugh A (p < 0.0001), extrahepatic metastasis (p = 0.0012), and a history of cancer treatment (p = 0.0048) was identified as a significant source of heterogeneity for the 1-year OS. Radioembolization was associated with a lower incidence of grade 3/4 AEs than sorafenib (9% [95% CI, 3–27%] vs. 28% [95% CI, 17–43%]). CONCLUSION: Compared with sorafenib, radioembolization is a safer and more effective treatment for HCC with PVTT and is associated with prolonged survival, delayed tumor progression, and fewer grade 3/4 AEs.

Radioembolization for the Treatment of Primary and Metastatic Liver Cancers / 대한핵의학회잡지

Radioembolization using ⁹⁰Y microspheres (glass or resin) has been introduced as an effective intraarterial therapy for unresectable primary and metastatic liver cancers. Although the basic therapeutic effect of chemoembolization results from ischemia, the therapeutic efficacy of radioembolization comes from radiation. Furthermore, compared with surgical resection and local ablation therapy, radioembolization is available with less limitation on the sites or number of liver cancers. The radioisotope ⁹⁰Y is a β-radiation emitter without γ-radiation, with the emission of secondary bremsstrahlung photons and small numbers of positrons. Administration of ⁹⁰Y microspheres into the hepatic artery can deliver a high dose of radiation selectively to the target tumor with limited radiation exposure to the surrounding normal parenchyma, and has low systemic toxicity. In general, radioembolization has been considered for patients with unresectable primary or metastatic liver-only or liver-dominant cancers with no ascites or other clinical signs of liver failure, life expectancy of > 12 weeks, and good performance status. Here, we review the current radioactive compounds, pretreatment assessment, and indications for radioembolization in patients with hepatocellular carcinoma, intrahepatic cholangiocarcinoma, and liver metastases from colorectal cancer.

Nuclear Theranostics in Taiwan / 대한핵의학회잡지

Boron neutron capture therapy and Y-90 radioembolization are emerging therapeutic methods for uncontrolled brain cancers and hepatic cancers, respectively. These advanced radiation therapies are heavily relied on theranostic nuclear medicine imaging before the therapy for the eligibility of patients and the prescribed-dose simulation, as well as the post-therapy scanning for assessing the treatment efficacy. In Taiwan, the Taipei Veterans General Hospital is the only institute performing the BNCT and also the leading institute performing Y-90 radioembolization. In this article, we present our single institute experiences and associated theranostic nuclear medicine approaches for these therapies.

Side effects and complications of yttrium-90 radioembolization therapy for hepatic malignancies. A series review of radioembolizat(i)on with 90Y microspheres(part V) / 介入放射学杂志

Radioembolization with yttrium-90(90Y) microspheres is an alternative treatment choice for hepatic malignancies and has become incorporated into guidelines by many international oncology and other professional organizations. The tumoricidal effects of radioembolization are predominantly derived from its radioactivity rather than ischemia. Therefore, the overall side effects that have been associated with this therapy, such as fatigue, nausea and vomiting, which are mild but common. Occasionally, severe complications may occur due to incidental embolization of non-target tissue by the microspheres. This review describes in detail the manifestation of side effects and various complications that may be associated with radioembolization using 90Y microspheres. Management and treatment options of these potential adverse events will also be discussed briefly.

Imaging Evaluation Following ⁹⁰Y Radioembolization of Liver Tumors: What Radiologists Should Know

Radioembolization using beta-emitting yttrium-90 microspheres is being increasingly used for the treatment of primary and metastatic liver cancers. It is a form of intra-arterial brachytherapy which delivers intense radiation to liver tumors with little embolic effect; this mode of action results in unique post-treatment imaging findings. It is important to understand these imaging findings to avoid misinterpretation of tumor response and to determine further management of the disease. Herein, we discuss the current concepts for assessing tumor response, common post-treatment imaging features, and associated complications following radioembolization.

Pretherapeutic aassessment of the hepatic arterial vasculature for hepatic malignancy with yttrium-90 radioembolization.A series review of radioembolization with 90Y microspheres (part Ⅲ) / 介入放射学杂志

Potential complications arising from yttrium-90 (90Y) radioembolization are often related to inadvertent embolization of non-target vasculature during particle administration.Therefore,careful pretherapeutic planning with arterial mapping is especially important to help identify potential high-risk arteries and vascular communications.A complete pre-therapeutic evaluation of hepatic arterial vasculature includes selective arteriography,precautionary embolization of potential risk arteries and identification of occurrences of hepatopulmonary shunting secondary to tumor-related pathologic arteriovenous channels.The aim of this review is to discuss the pertinent arterial anatomy during 90Y radioembolization therapy and strategies on how to evaluate the risk and prevent the occurrence of non-target embolization through those vascular structures.

Recent advances in transarterial embolotherapies in the treatment of hepatocellular carcinoma

Management of hepatocellular carcinoma (HCC) can be maximized with the utilization of multiple treatment modalities including transplant, surgical resection and locoregional therapies including ablative therapies and transarterial embolotherapies. Although transplant and surgical resection offer the best clinical outcomes, a limited number of patients are amenable to these surgical treatment options due to the advanced disease at presentation. Transarterial embolotherapies including conventional transarterial chemoembolization (cTACE), bland transarterial embolization (TAE), drug-eluting beads transarterial chemoembolization (DEB-TACE) and selective internal radiation therapy (SIRT) with Yttrium 90 (⁹⁰Y) have played an increasingly important role for these patients with unresectable HCC. With a better understanding of different transarterial embolotherapies, more personalized and precise treatment should be implemented for these patients with unresectable HCC. In this review, the updated evidence on the current role of each embolotherapy in the treatment of HCC is summarized.

Radioembolization for the treatment of hepatocellular carcinoma

Transarterial radioembolization (TARE) with yttrium 90 (⁹⁰Y), an intra-arterial procedure performed by interventional radiologists, has begun being utilized in managing hepatocellular carcinoma (HCC) in Korea. There are two available TARE products: glass and resin microspheres with different physical characteristics. All patients undergoing TARE must be assessed with clinical examination and laboratory tests as well as a thorough angiographic evaluation. TARE is safe and effective in the treatment of unresectable HCC, as it has longer time-to-progression, greater ability to downsize tumors for liver transplantation, less post-embolization syndrome, and shorter hospitalization compared with chemoembolization. TARE can also serve as an alternative to ablation, surgical resection, portal vein embolization, and sorafenib. The utility of TARE continues to expand with new insights in interventional oncology.

Preliminary evaluation of indigenous 90Y-labelled microspheres for therapy of hepatocellular carcinoma.

Background & objectives: Yttrium-90 (90Y)-based radioembolization has been employed to treat hepatocellular carcinoma (HCC) as commercial radioactive glass and polymeric resin microspheres. However, in India and other Asian countries, these preparations must be imported and are expensive, validating the need for development of indigenous alternatives. This work was aimed to develop an economically and logistically favourable indigenous alternative to imported radioembolizing agents for HCC therapy. Methods: The preparation of 90Y-labelled Biorex 70 microspheres was optimized and in vitro stability was assessed. Hepatic tumour model was generated in Sprague-Dawley rats by orthotopic implantation of N1S1 rat HCC cell line. In vivo localization and retention of the 90Y-labelled Biorex 70 microspheres was assessed for seven days, and impact on N1S1 tumour growth was studied by histological examination and biochemical assays. Results: Under optimal conditions, >95% 90Y-labelling yield of Biorex70 resin microspheres was obtained, and these showed excellent in vitro stability of labelling (>95%) at seven days. In animal studies, 90Y-labelled Biorex 70 microspheres were retained (87.72±1.56% retained in liver at 7 days). Rats administered with 90Y-labelled Biorex 70 microspheres exhibited lower tumour to liver weight ratio, reduced serum alpha-foetoprotein level and greater damage to tumour tissue as compared to controls. Interpretation & conclusions: 90Y-labelled Biorex 70 microspheres showed stable retention in the liver and therapeutic effect on tumour tissue, indicating the potential for further study towards clinical use.

Yttrium-90 radioembolization for unresectable neuroendocrine tumor liver metastases / 中华肝胆外科杂志

Neuroendocrine tumor liver metastases (NETLM) is a uncommon advanced tumor disease.Patients with unresectable NETLM have a poor outcome.The management of unresectable NETLM is a clinical dilemma.However,Yttrium-90 radioembolization is a safe and effective treatment for NETLM patients.The median disease control rate is 87.1％ (64.7％ ～ 100％);the median overall survival time is 34.4 months;and the median overall survival rate of 1,2,and 3 years are 79.8％ (63％～100％),62％ (57％ ～62.5％),45.5％ (45％ ～ 46％),respectively.Although there is good result of Yttrium-90 radioembolization in treatment of unresectable NETLM,the safety and effectiveness should be further verified.

Yttrium-90 Selective Internal Radiation Therapy with Glass Microspheres for Hepatocellular Carcinoma: Current and Updated Literature Review

Hepatocellular carcinoma is the most common primary liver cancer and it represents the majority of cancer-related deaths in the world. More than 70% of patients present at an advanced stage, beyond potentially curative options. Ytrrium-90 selective internal radiation therapy (Y90-SIRT) with glass microspheres is rapidly gaining acceptance as a potential therapy for intermediate and advanced stage primary hepatocellular carcinoma and liver metastases. The technique involves delivery of Y90 infused glass microspheres via the hepatic arterial blood flow to the appropriate tumor. The liver tumor receives a highly concentrated radiation dose while sparing the healthy liver parenchyma due to its preferential blood supply from portal venous blood. There are two commercially available devices: TheraSphere® and SIR-Spheres®. Although, Y90-SIRT with glass microspheres improves median survival in patients with intermediate and advanced hepatocellular carcinoma and has the potential to downstage hepatocellular carcinoma so that the selected candidates meet the transplantable criteria, it has not gained widespread acceptance due to the lack of large randomized controlled trials. Currently, there are various clinical trials investigating the use of Y90-SIRT with glass microspheres for treatment of hepatocellular carcinoma and the outcomes of these trials may result in the incorporation of Y90-SIRT with glass microspheres into the treatment guidelines as a standard therapy option for patients with intermediate and advanced stage hepatocellular carcinoma.

Treatments Other than Sorafenib for Patients with Advanced Hepatocellular Carcinoma

Sorafenib is the standard treatment for advanced hepatocellular carcinoma according to the Barcelona Clinic Liver Cancer staging system. However, because of its unsatisfactory efficacy, adverse effects, and high cost, the use of sorafenib is limited, and other treatment modalities are required. Recent studies reported that treatment modalities other than sorafenib, such as hepatic arterial infusion chemotherapy and transarterial radioembolization, showed comparable or better response rates and survival rates than sorafenib. In this review, treatment modalities that could be used as alternatives to sorafenib will be discussed.

Role of Yttrium-90 Radioembolization in the Management of Hepatocellular Carcinoma

Yttrium-90 radioembolization has emerged as a novel therapy for hepatocellular carcinoma (HCC) of intermediate or advanced stage. Yttrium-90 has characteristics of short half-life and tissue penetration depth. Potent anti-cancer effect by this isotope enables to kill the tumor for 6 months after administration. Although transarterial chemoembolization (TACE) is the standard modality for multinodular HCC without vascular invasion, big size or numerous nod-ules does not allow enough treatment effect of TACE. Post-embolization syndrome resulting poor quality of life, liver dysfunction and hepatic arterial damage are other pitfalls of TACE. In several studies, radioembolization showed survival comparable to TACE, shorter hospital stay and less treatment sessions. In advanced HCC with portal vein invasion, radioemboliza-tion demonstrated similar or better survival compared with sorafenib. The atrophy of lobe treated by radioembolization and hypertrophy in the contralateral lobe can be called radia-tion lobectomy, which makes it possible to perform a following curative therapy. The role of radioembolization in unresectable HCC in terms of downstaging or bridge to transplantation needs to be further studied. Radioembolization is contraindicated in HCC patients with main portal vein occlusion and with poor liver function. The International guidelines for HCC have some limitations and thus rooms for radioembolization to be incorporated.

Gastrectomy for the treatment of refractory gastric ulceration after radioembolization with 90Y microspheres

Transcatheter arterial radioembolization (TARE) with Yttrium-90 (90Y)-labeled microspheres has an emerging role in treatment of patients with unresectable hepatocellular carcinoma. Although complication of TARE can be minimized by aggressive pre-evaluation angiography and preventive coiling of aberrant vessels, radioembolization-induced gastroduodenal ulcer can be irreversible and can be life-threatening. Treatment of radioembolization-induced gastric ulcer is challenging because there is a few reported cases and no consensus for management. We report a case of severe gastric ulceration with bleeding that eventually required surgery due to aberrant deposition of microspheres after TARE.

Recent advance in international management of hepatocellular carcinoma

During the most recent decade, remarkable progress has taken place in intra-arterial therapy for hepatocellular carcinoma. Advances in knowledge of hepatic vascular anatomy and tumor blood supply have contributed to the safety and efficacy of intra-arterial therapies. Technological advances in C-arm computed tomography and microcatheter systems have improved the technical success rates for superselective or ultraselective catheterization of tumor-feeding arteries. Drug-eluting bead technology has provided the option of performing chemoembolization with less systemic exposure to anticancer drugs and a more standardized delivery. Radio-embolization with yttrium-90 microspheres has emerged as a promising option offering increased quality of life. In addition, chemoembolization plays a central role in recently developed combination therapy strategies. In this era of advanced technologies and new treatment options, efforts should be made to understand the advantages and disadvantages of new technologies and treatment strategies and to apply them properly, which may lead to better local control of tumors, better quality of life, and longer patient survival.