Chinese expert consensus on selective internal radiation therapy with yttrium-90 for primary and metastatic hepatocellular carcinoma / 中华肝脏病杂志

Liver malignant tumors are one of the most common causes of cancer-related deaths in China. Selective internal yttrium-90 radioembolization therapy ((90)Y-SIRT) is a kind of promising local minimally invasive method, and its effectiveness and safety has been confirmed in clinical application over the past two decades. Moreover, it has been approved by the U.S. National Comprehensive Cancer Network and other international guidelines for the topical treatment of patients with liver malignancies. Taking into account the complexity of the (90)Y-SIRT and the need for multidisciplinary collaboration to improve the safety and success rate of treatment, the Nuclear Medicine Expert Committee of the Chinese society of Clinical Oncology, along with Beijing Nuclear Medicine Quality Control and Improvement Center invited experts from surgical oncology, interventional medicine, nuclear medicine, and other related fields to discuss and form a consensus on the clinical diagnosis, treatment and management, which mainly included definition, indications and contraindications, treatment procedures, postoperative follow-up, adverse reactions and complications, radiation safety management, etc. Herein, we provide the reference guidance to establish (90)Y-SIRT standardized management and treatment system various units for relevant practitioners.

25 años de CENTIS. Pandemia y Radiofármacos / 25 years of CENTIS. Pandemic and Radiopharmaceuticals

Resumen Próximo a su 25 aniversario CENTIS reflexiona sobre su quehacer en el contexto de los trastornos que causa la COVID-19. Con ese propósito se examinan el estado de la medicina nuclear y la radiofarmacia antes y durante la epidemia y sus perspectivas de desarrollo. La producción global de radiofármacos continúa siendo una industria consolidada y aunque la pandemia afecta a esta esfera, la presencia de otras enfermedades no cesa, por lo que los servicios de medicina nuclear esenciales y críticos siguen siendo necesarios. Se espera su paulatina reapertura y que se retome con más fuerza la investigación, dado que la COVID-19 es tan compleja y se asocia a tantos factores que constituye, en perspectiva, terreno virgen para las técnicas diagnósticas en medicina nuclear. Ha de permanecer asimismo el papel de los radiofármacos terapéuticos en un grupo importante de enfermedades, en cáncer sobre todo. El Centro de Isótopos pone por ello énfasis tanto en la consolidación, bajo buenas prácticas, de la producción y el suministro de radiofármacos, como en el desarrollo de nuevos productos. Ambos aspectos se basan principalmente en dos radionúclidos: Tc-99m e Y-90.

Abstract Close to its 25th anniversary, CENTIS evaluates its work in the context of the disorders triggered by COVID-19. For this purpose, the situation of nuclear medicine and radiopharmacy, before and during the epidemic and their current development prospects is examined. The production of radiopharmaceuticals continues to be a consolidated global industry and although the pandemic affects this area, the presence of other diseases does not cease, so essential and critical nuclear medicine services are still needed, therefore its gradual reopening is expected. In addition, research will be taken with more strength, given that COVID-19 is so complex and associated with so many factors that it constitutes virgin terrain in perspective for diagnostic techniques in nuclear medicine. The role of therapeutic radiopharmaceuticals in an important set of diseases, especially cancer, will also remain. As a result, the Isotope Center focus its attention under good management practices, on the consolidation of the production and distribution of radiopharmaceuticals and in the development of new products. Both aspects are mainly based on two radionuclides: Tc-99m and Y-90.

Hepatocellular Carcinoma with Segmental Portal Vein Invasion Exhibiting a Complete Response after Transarterial Radioembolization

The treatment options available for patients with hepatocellular carcinoma (HCC) with portal vein invasion (PVI) include sorafenib, transarterial radioembolization (TARE), radiation therapy (RT), transarterial chemoembolization with RT, and proton beam irradiation. Herein, we present a case of HCC with segmental PVI that was managed via TARE. The patient had a 4 cm HCC that invaded the segment VIII portal vein branch without extrahepatic spread. Liver function was Child-Pugh grade A, and performance status was good. TARE was performed without any adverse events, and a radiological complete response (CR) was achieved. Thereafter, the patient was followed-up every 3–6 months without any further treatment, and the CR was maintained for >3 years. Therefore, TARE may be a useful alternative therapeutic option for patients with HCC exhibiting segmental PVI.

Efficacy and safety of yttrium-90 radioembolization for unresectable hepatocellular carcinoma: A systematic review and meta analysis / 解放军医学杂志

Objective To compare the efficacy and safety of yttrium-90 (Y-90 or 90Y) radioembolization for unresectable HCC using randomized clinical trials. Methods We reviewed data from the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase to collect randomized controlled trials about Y-90 radioembolization for unresectable HCC. We also checked reference lists of primary original studies and review manually-searched articles for further related articles up to September 30, 2018. Summarized odds ratio (OR) or hazard ratio (HR) with 95% confidence intervals (CI) were used to assess the differences in outcomes. Results A total of 6 randomized controlled trials containing 956 patients with unresectable HCC were included in this analysis. Y-90 microsphere radioembolisation was associated with a higher response rate (OR=1.76, 95% CI 1.07- 2.90, P=0.03), and showed a significantly larger decrease in haemorrhage (OR=0.26, 95% CI 0.11-0.61, P=0.02), hypertension (OR=0.17, 95% CI 0.08-0.38, P0.05). Conclusions Y-90 microsphere radioembolisation seems to be a safe and effective treatment for patients with unresectable hepatocellular carcinoma due to its higher response rate and reduced the adverse event rates as haemorrhage, hypertension and infection. However, further randomized clinical trials are mandatory to better assess the potential beneficial and harmful outcomes of Y-90 microsphere by arterial radioembolisation in the patients with unresectable hepatocellular carcinoma.

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.

Effect of ME Collimator Characteristic, Energy Window Width, and Reconstruction Algorithm Selection on Imaging Performance of Yttrium-90: Simulation Study / 대한핵의학회잡지

PURPOSE: The treatment efficiency of ⁹⁰Y and providing reliable estimates of activity are evaluated by SPECT imaging of bremsstrahlung radiation released during beta therapy. In this technique, the resulting spectrum from ⁹⁰Y is very complex and continuous, which creates difficulties on the imaging protocol. Moreover, collimator geometry has an impressive effect on the spatial resolution, system sensitivity, image contrast, and the signal-to-noise ratio (SNR), which should be optimized.METHODS: We evaluated the effect of energy window width, reconstruction algorithms, and different geometries of a medium-energy (ME) parallel-hole collimator on the image contrast and SNR of ⁹⁰Y SPECT images. The Siemens E.Cam gamma camera equipped with a ME collimator and a digital Jaszczak phantom were simulated by SIMIND Monte Carlo program to generate the ⁹⁰Y bremsstrahlung SPECT images.RESULTS: Our results showed that optimal image quality can be acquired by the reconstruction algorithm of OS-EM in the energy window width of 60 to 400 keV for ⁹⁰Y bremsstrahlung SPECT imaging. Furthermore, the optimal values of the hole diameter and hole length of a ME collimator were obtained 0.235 and 4.4 cm, respectively.CONCLUSIONS: The acquired optimal ME collimator and energy window along with using a suitable reconstruction algorithm lead to improved contrast and SNR of ⁹⁰Y bremsstrahlung images of hot spheres of the digital Jaszczak phantom. This can improve the accuracy and precision of the ⁹⁰Y activity distribution estimation after radioembolization in targeted radionuclide therapy.

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.

Series review of radioembolization with yttrium-90 microspheres (Part Ⅳ): dose calculation of yttrium-90 microspheres / 介入放射学杂志

Accurate doses of yttrium-90 (90Y) microspheres are critical for the treatment of liver malignancies,because it is closely related to the clinical efficacy and adverse reactions.The dose calculationis primarily based on the type of ~Y delivery medium,whether it is glass microsphere (TheraSpheres) or resin microsphere (SIR-Spheres).The dose calculation of glass microspheres is based on the assumption that the expected radiation dose of the liver and the microspheres can be evenly distributed throughout the liver,while the dose calculation of resin microspheres is based on the assumption that the microspheres are not uniformly distributed throughout the liver,and the degree of this inhomogeneous distribution depends on the extent to which the normal liver is replaced by the tumor tissue.Many other factors may also potentially affect the therapeutic dose of 90Y microspheres.This review will introduce the calculation methods of 90Y microsphere dose,and describe the factors that need to be considered in order to achieve maximum efficacy and avoid adverse effects.

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.

Criterios de calidad de dispersiones radiactivas en radiosinovectomía / Quality criteria of the radiopharmaceutical suspensions used in radiosynoviorthesis

En el trabajo se examinan los criterios de calidad de dispersiones radiactivas utilizadas en radiosinovectomía a partir de los requisitos recogidos en la farmacopea para el Fosfato Crómico- de la firma Mallinkrodt, las recomendaciones de uso de radiofármacos registrados de la Asociación Europea de Medicina Nuclear y datos aportados por las firmas comercializadoras. Tomando como base el estudio de dos formulaciones propias de Fosfato Crómico, una marcada con y la otra, con , en las que se estudia la consistencia (reproducibilidad) tanto de la pureza radioquímica como de la distribución de tamaños de partículas, se prueba que el tenor de 5 % de fosfato libre admitido en la formulación de la firma Mallinkrodt y que se extendiera a formas iónicas de otros radiofármacos de matrices diferentes, se debe probablemente al efecto inevitable de la esterilización a vapor sobre la suspensión y de que tanto al momento de decidir sobre el empleo de un lote, como en los requisitos de las farmacopeas, debiera prestarse más atención a la distribución de tamaños por estar más vinculada a la eficacia y seguridad de los radiofármacos

The quality criteria of radioactive dispersions used in radiosynovectomy are examined, taking into account the requirements of the Pharmacopoeia for the Chromic Phosphate P-32 of Mallinckrodt, recommendations for the use of approved radiopharmaceuticals of the European Association of Nuclear Medicine and data provided by others marketing firms. The behavior of two formulations of chromic phosphate, one -labeled and the second -labeled, from the point of view of the consistency (reproducibility) of both the radiochemical purity and the particle size distribution was assayed. It is proven that the presence of 5% of free phosphate admitted in the Mallinckrodt formulation, and extended to the presence of ionic forms of other radiopharmaceuticals of different matrices, is probably due to the inevitable effect of steam sterilization on the suspension. Based on these results and the accumulated clinical experience, it is considered that to establish the quality requirements of the radioactive suspensions for radiosynovectomy, more attention should be paid to the particle size distribution than to the percentage of free ionic forms. The first one is more related to the efficacy and safety of this kind of radiopharmaceuticals

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.

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.

Series review of radioembolization with yttrium-90 microspheres (Part Ⅱ) : pre-treatment evaluation and post-treatment follow-up for patients with hepatic malignancy receiving yttrium-90 microspheres embolization / 介入放射学杂志

Yttrium-90 (90Y) radioembolization therapy can directly deliver a high dose of radiation to the tumor being targeted,which has been demonstrated to be effective in treating patients with hepatic malignancy.Compared with transarterial chemoembolization,90Yradioembolization is less frequently associated with toxicities such as abdominal pain,fever,nausea,and vomiting.However,the efficacy and safety of 90Y radioembolization therapy are largely reliant on careful preprocedural evaluation and diligent follow-up.This review discusses the details of essential preprocedural work-up and postprocedural follow-up for patients treated with 90Y radioembolization.

Better late than never: discussion on the localization of yttrium-90 microspheres / 介入放射学杂志

In Europe and America,especially in the United States,transcatheter arterial radiotherapy embolization(TARE) with yttrium-90(90Y)microspheres has become one of the major treatment for primary and secondary liver malignancy that cannot be resected or ablated.Its safety and efficacy were verified with large amounts of studies.It is imperative for TARE with 90Y microspheres in China mainland,though there are no 90Y microspheres available at present.But it is hard to popularize TARE only with 90Y microspheres imported for the unique characters based on techniques.Since we had experience in making 90Y glass microspheres in early 1990s,we must work hard with many joints to remake home made 90Y microspheres to benefit patients in China.

Characteristics of yttrium-90 microsphere, techniques and radiation safety of radioembolization procedure.A series review of radioembolization with yttrium-90 microspheres (part Ⅰ) / 介入放射学杂志

Radioembolization with yttrium-90 (90Y) microspheres is a locoregional procedure during which either resin or glass microspheres loaded with β-emitting 90Y are selectively injected into a hepatic artery.The microspheres are trapped in downstream vasculatures,at which point they deliver a cytotoxic dose of radiation to the target tumor.The safety and efficacy of this method have been demonstrated in studies of survival outcomes in patients with nonresectable hepatic malignancies.In this first part of a series of reviews on radioembolization with 90Y microspheres,we cover the basic characteristics of 90Y and 90Y microspheres,techniques for the radioembolization procedure,and methods for ensuring radiation safety and protection.

Fósforo-32 e itrio-90 como opciones en el tratamiento del dolor óseo metastásico / Phosphorous-32 and Yttrium-90 as options in the treatment of metastatic bone pain

En el trabajo se estima la prevalencia del dolor óseo metastásico en nuestro país en no menos de 3 750 pacientes. Se examina, asimismo, el papel del Fosfato de sodio-[], de eficacia comparable y menor costo que el de otros radiofármacos, lo que hace posible el renacer de su uso. Aunque más radiotóxico, ello no lo invalida como opción, lo que se evidencia también en la experiencia cubana. El Centro de Isótopos (Centis) puso en marcha una línea de producción con posibilidad de obtener hasta 37 GBq (1 Ci) de de alta calidad cada semana. El hecho de que se produzca por separación electroquímica mediante un generador de radionúclidos, a partir del 90Sr, hace que no se requiera importación de materia prima radiactiva, prácticamente, por tiempo indefinido, es decir, que el radionúclido estaría disponible de manera sostenible. Al tener el una energía de emisión β- mayor, pudiera pensarse que debiera ser más radiotóxico que el . Sin embargo, se dan evidencias de que el en forma de fosfato es más radiotóxico que el 90Y en forma de citrato. En Europa un radiofármaco basado en un liofilizado de EDTMP y Cloruro de itrio-[] ha tenido buen efecto para el alivio del dolor en 191 pacientes. (Centis) tiene registrado el Cloruro de itrio-[] para marcaje y se trata de introducir en el mercado un radiofármaco con este precursor radioactivo y el liofilizado importado, a los efectos de dar adecuada atención al importante número de pacientes que se beneficiarían

In this paper the prevalence of metastatic bone pain is estimated in our country in no less than 3 750 patients. Moreover, the role of -phosphate, which effectiveness is comparable to other radiopharmaceuticals, and the possible return to its previous general use, as it is cheaper, is examined. The fact that is considered more radiotoxic doesn’t invalidate it as a treatment option, which is also evidenced by the Cuban experience. The Center of Isotopes (Centis) has established a production line of up to 37 GBq (1 Ci) per week of high quality . The fact of its being obtained through a radionuclide generator by electrochemical separation from makes the import of radioactive raw material practically not required for indefinite time. This implies that the radionuclide could be available in a sustainable way. By having the greater β- emission energy, it might be more radiotoxic than . Nevertheless, some evidences show that in the form of orthophosphate is more radiotoxic than 90Y citrate. In Europe, a radiopharmaceutical consisting of a lyophilized kit of EDTMP and Chloride solution was able to relief pain in 191 patients. Centis has registered the chloride solution for labeling. Then the task is to introduce in the market a radiopharmaceutical with this radioactive precursor and the imported lyophilized kit in order to increase the treatment to an important number of patients that, as a result, could be benefitted

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.

Long-Term Palliative Effect of Stenting in Gastric Outlet Obstruction Due to Transarterial Chemoembolization with Yttrium-90 in a Patient with Metastatic Neuroendocrine Tumor

Internal radioembolization with yttrium-90 is a promising treatment method, predominantly for liver tumors. However, the shifting of yttrium-90-loaded spherules into the arteries and veins that supply the duodenum and stomach, leading to ulceration, hemorrhage, perforation, and outlet obstruction of these organs, is one of the major undesirable consequences of this technique. We report a case of gastric outlet obstruction (GOO) due to antropyloric stenosis with ulceration, edema, and inflammation following transarterial yttrium-90 treatment for a metastatic neuroendocrine tumor in a 58-year-old man. Stenting was used for palliation in this case. GOO improved after stenting and recovery of oral intake was permanent after stent removal.

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.