Yttrium-90(Y-90)microsphere therapy,known as radioembolization,has emerged as a pivotal treatment modality for hepatocellular carcinoma(HCC),delivering targeted radiation with minimal collateral damage to healthy live...Yttrium-90(Y-90)microsphere therapy,known as radioembolization,has emerged as a pivotal treatment modality for hepatocellular carcinoma(HCC),delivering targeted radiation with minimal collateral damage to healthy liver tissues.This review meticulously synthesizes current evidence regarding the clinical efficacy,underlying therapeutic mechanisms,patient selection criteria,and comparative advantages of Y-90 therapy.Clinical studies consistently demonstrate significant improvements in overall survival and progression-free survival,coupled with robust tumor response rates and manageable adverse events.The therapy’s efficacy is substantially enhanced by advanced dosimetric techniques,enabling precise radiation delivery tailored to individual tumor profiles.Comparative analyses reveal that Y-90 therapy provides superior local tumor control and a preferable safety profile compared to conventional treatments such as transarterial chemoembolization and external beam radiation therapy.Additionally,its clinical outcomes are comparable to those achieved with contemporary systemic therapies.Ongoing research into combination treatments incorporating Y-90 with systemic therapies,including targeted agents and immune checkpoint inhibitors,suggests promising advancements in comprehensive HCC management.Future directions highlight the necessity for continued refinement of dosimetry and patient stratification approaches,aiming to further optimize therapeutic outcomes.展开更多
Hepatocellular carcinoma （HCC） recurs with a reported frequency of 12%-18% after liver transplantation. Recurrence is associated with a mortality rate exceeding 75%. Approximately one-third of recurrences develop in...Hepatocellular carcinoma （HCC） recurs with a reported frequency of 12%-18% after liver transplantation. Recurrence is associated with a mortality rate exceeding 75%. Approximately one-third of recurrences develop in the transplanted liver and are therefore amenable to local therapy. A variety of treatment modalities have been reported including resection, transarterial chemoembolization （TACE）, radiofrequency ablation （RFA）, ethanol ablation, cryoablation, and external beam irradiation. Goals of treatment are tumor control and the minimization of toxic effect to functional parenchyma. Efficacy of treatment is mitigated by the need for ongoing immunosuppression. Yttrium-90 microspheres have been used as a treatment modality both for primary HCC and for pre-transplant management of HCC with promising results. Twenty-two months after liver transplantation for hepatitis C cirrhosis complicated by HCC, a 42-year old man developed recurrence of HCC in his transplant allograft. Treatment of multiple right lobe lesions with anatomic resection and adjuvant chemotherapy was unsuccessful. Multifocal recurrence in the remaining liver allograft was treated with hepatic intra-arterial infusion of yttrium-90 microspheres （SIR-Spheres, Sirtex Medical Inc., Lake Forest, IL, USA）. Efficacy was demonstrated by tumor necrosis on imaging and a decrease in alpha-fetoprotein （AFP） level. There were no adverse consequences of initial treatment.展开更多
Liver malignancy,including primary liver cancer and metastatic liver cancer has become one of the most common causes of cancer-related death worldwide due to the high malignant degree and limited systematic treatment ...Liver malignancy,including primary liver cancer and metastatic liver cancer has become one of the most common causes of cancer-related death worldwide due to the high malignant degree and limited systematic treatment strategy.Radioembolization with yttrium-90(^(90)Y)-loaded microspheres is a relatively novel technology that has made significant progress in the local treatment of liver malignancy.The different steps in the extensive work-up of radioembolization for patients with an indication for treatment with^(90)Y microspheres,from patient selection to follow up,both technically and clinically,are discussed in this paper.It describes the application and development of^(90)Y microspheres in the treatment of liver cancer.展开更多
Transarterial radioembolization(TARE) is a form of brachytherapy in which intra-arterially injected yttrium-90-loaded microspheres serve as a source for internal radiation purposes.On the average,it produces disease c...Transarterial radioembolization(TARE) is a form of brachytherapy in which intra-arterially injected yttrium-90-loaded microspheres serve as a source for internal radiation purposes.On the average,it produces disease control rates exceeding 80% and it is a consolidated therapy for hepatocellular carcinoma(HCC);however,current data are all based on retrospective series or non-controlled prospective studies since randomized controlled trials comparing it with the other liver-directed therapies for intermediate and locally advanced stage HCC are still underway.The data available show that TARE provides similar or even better survival rates when compared to transarterial chemoembolization(TACE).First-line TARE is best indicated for both intermediatestage patients(staged according to the barcelona clinic liver cancer staging classification) who have lesions which respond poorly to TACE due to multiple tumors or a large tumor burden,and for locally advanced-stage patients with solitary tumors,and segmental or lobar portal vein tumor thrombosis.In addition,emerging data have suggested the use of TARE in patients who are classified slightly beyond the Milan criteria regarding radical treatment for downstaging purposes.As a secondline treatment,TARE can also be applied in patients progressing to TACE or sorafenib;a large number of phase Ⅱ/Ⅲ trials are ongoing with the purpose of evaluating the best association with systemic therapies.Transarterial radioembolization is very well tolerated and has a low rate of complications which are mainly related to unintended non-target tissue irradiation,including the surrounding liver parenchyma.The complications can be additionally reduced by accurate patient selection and a strict pre-treatment evaluation including dosimetry and assessment of the vascular anatomy.Since a correct treatment algorithm for potential TARE candidates is not clear and standardized,this comprehensive review analyzes the best selection criteria for patients who really benefit from TARE and also the new advances of this therapy,which can be a very important weapon against HCC.展开更多
Radiation segmentectomy(RS) is a new approach to90 Y radioembolization that has been designed to increase the safety and efficacy of radioembolization in patients with unresectable hepatic malignancies. With this tech...Radiation segmentectomy(RS) is a new approach to90 Y radioembolization that has been designed to increase the safety and efficacy of radioembolization in patients with unresectable hepatic malignancies. With this technique,high doses(>190 Gy) of radiation are delivered to the tumor through radioembolization performed in a segmental fashion, potentially increasing the radiation dose to the tumor while minimizing injury to the liver parenchyma. The aim of this review is to provide a summary of the indications, device choice, dosimetry, procedure, clinical outcomes, and toxicity of RS based on the clinical series currently available.展开更多
Adrenocortical carcinoma(ACC)is a rare malignancy with generally poor outcomes and limited treatment options.While surgical resection can be curative for early local disease,most patients present with advanced ACC owi...Adrenocortical carcinoma(ACC)is a rare malignancy with generally poor outcomes and limited treatment options.While surgical resection can be curative for early local disease,most patients present with advanced ACC owing to nonspecific symptoms.For those patients,treatment options include systemic chemotherapy and locoregional therapies including radiofrequency ablation and transarterial chemoembolization.We present the first reported case of utilizing yttrium-90 microsphere selective internal radiation therapy(SIRT)in combination with first line EDP-M(Etoposide,Doxorubicin,Cisplatin,Mitotane)chemotherapy and debulking surgical primary tumor resection for treatment of metastatic ACC.Stable complete radiologic response has been maintained after twelve months with resolution of clinical symptoms.These findings prompt the need for further consideration and studies to elucidate the role of SIRT in combination with systemic and surgical treatment for metastatic ACC.展开更多
AIM: To further define variables associated with increased incidences of severe toxicities following administration of yttrium-90 (<sup>90</sup>Y) microspheres.METHODS: Fifty-eight patients undergoing 79 t...AIM: To further define variables associated with increased incidences of severe toxicities following administration of yttrium-90 (<sup>90</sup>Y) microspheres.METHODS: Fifty-eight patients undergoing 79 treatments were retrospectively assessed for development of clinical and laboratory toxicity incidence following <sup>90</sup>Y administration. Severe toxicity events were defined using Common Terminology Criteria for Adverse Events version 4.03 and defined as grade ≥ 3. Univariate logistic regression analyses were used to evaluate the effect of different factors on the incidence of severe toxicity events. Multicollinearity was assessed for all factors with P < 0.1 using Pearson correlation matrices. All factors not excluded due to multicollinearity were included in a multivariate logistic regression model for each measurement of severe toxicity.RESULTS: Severe (grade ≥ 3) toxicities occurred following 21.5% of the 79 treatments included in our analysis. The most common severe laboratory toxicities were severe alkaline phosphatase (17.7%), albumin (12.7%), and total bilirubin (10.1%) toxicities. Decreased pre-treatment albumin (OR = 26.2, P = 0.010) and increased pre-treatment international normalized ratio (INR) (OR = 17.7, P = 0.048) were associated with development of severe hepatic toxicity. Increased pre-treatment aspartate aminotransferase (AST; OR = 7.4, P = 0.025) and decreased pre-treatment hemoglobin (OR = 12.5, P = 0.025) were associated with severe albumin toxicity. Increasing pre-treatment model for end-stage liver disease (MELD) score (OR = 1.8, P = 0.033) was associated with severe total bilirubin toxicity. Colorectal adenocarcinoma histology was associated with severe alkaline phosphatase toxicity (OR = 5.4, P = 0.043).CONCLUSION: Clinicians should carefully consider pre-treatment albumin, INR, AST, hemoglobin, MELD, and colorectal histology when choosing appropriate candidates for <sup>90</sup>Y microsphere therapy.展开更多
Radioactive microspheres have demonstrated excellent therapeutic effects and good tolerance in the treatment of unresectable primary and secondary liver malignancies.This is attributed to precise embolization and pote...Radioactive microspheres have demonstrated excellent therapeutic effects and good tolerance in the treatment of unresectable primary and secondary liver malignancies.This is attributed to precise embolization and potent anti-tumor effect.However,certain limitations such as unstable loading,perfusion stasis,heterogeneous distribution,ectopic distribution,and insufficient dosage,restrict their clinical application.Herein,a novel personalized Y-90 carbon microsphere with high uniformity,high specific activity and high availability(^(90)Y-HUACM)is presented.It is synthesized through planar molecular complex adsorption and chemical deposition solidification.^(90)Y-HUACM exhibited controllable size,excellent biocompatibility,outstanding in vitro and in vivo stability.The radiolabeling efficiency of Y-90 exceeded 99%and the leaching rate of Y-90 is far below 0.1%.Furthermore,the excellent anti-tumor effect,nuclide loading stability,anti-reflux characteristics,precise embolization,and biosafety of^(90)Y-HUACM were validated in a rabbit VX2liver tumor model.In summary,this new,high-performance,and customizable radioactive microsphere provides a superior choice for selective internal radiation treatment of advanced liver cancer is expected to be rapidly applied in clinical practice.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)with advanced features such as Budd-Chiari syndrome,chronic liver failure and multiple intrahepatic metastases poses significant therapeutic challenges.Yttrium-90(90Y)radioembol...BACKGROUND Hepatocellular carcinoma(HCC)with advanced features such as Budd-Chiari syndrome,chronic liver failure and multiple intrahepatic metastases poses significant therapeutic challenges.Yttrium-90(90Y)radioembolization is a locoregional treatment option with potential benefits in such complex cases.This case report explores the application of 90Y radioembolization in combination with systemic therapies,highlighting its potential role in managing advanced HCC.CASE SUMMARY A 51-year-old male presented with HCC characterized by massive intrahepatic lesions,multiple metastases,and chronic liver failure secondary to Budd-Chiari syndrome.The patient underwent 90Y radioembolization following hepatic arterial infusion chemotherapy and was subsequently combined with lenvatinib.Posttreatment follow-up revealed a significant reduction in tumor size,with the maximum diameter decreasing from 142.45 mm to 73.16 mm over six months.Liver function improved from Child-Pugh class B to A.However,new intrahepatic lesions emerged at ten months,and liver function deteriorated to Child-Pugh class C.The patient survived for 18 months after initial diagnosis.CONCLUSION Yttrium-90 radioembolization combined with systemic therapies demonstrated significant tumor regression and temporary liver function improvement in a patient with advanced HCC,suggesting its potential as a treatment option in complex cases.展开更多
Hepatocellular carcinoma(HCC)is a leading cause of cancer-related mortality,with a majority of patients presenting at intermediate or advanced stages,precluding curative interventions.Radioembolization,also known as s...Hepatocellular carcinoma(HCC)is a leading cause of cancer-related mortality,with a majority of patients presenting at intermediate or advanced stages,precluding curative interventions.Radioembolization,also known as selective internal radiation therapy,has emerged as a promising locoregional therapy that delivers high-dose yttrium-90 microspheres directly to hepatic tumors while sparing healthy parenchyma.This technique is especially beneficial for patients with portal vein tumor thrombosis or impaired liver function.This editorial provides a comprehensive overview of the mechanism,technical considerations,and clinical efficacy of radioembolization in advanced HCC.Landmark trials such as SARAH,SIRveNIB,and DOSISPHERE-01 demonstrate comparable or superior outcomes to systemic therapies like sorafenib,particularly when personalized dosimetry is applied.Radioembolization contributes to tumor downstaging,transplant bridging,and improved disease control rates.The integration of radioembolization with systemic therapies,including immune checkpoint inhibitors and tyrosine kinase inhibitors,represents a key area of ongoing research.Despite current challenges such as microsphere heterogeneity,dosimetry standardization,and limited accessibility,emerging innovations in imaging,isotopes,and personalized treatment strategies are expected to refine its application.Overall,radioembolization is poised to play an increasingly central role in the multidisciplinary management of advanced HCC.展开更多
Yttrium-90 (Y-90) radioembolization,also known as selective internal radiation therapy (SIRT),is a regional hepatic therapy used in the treatment of unresectable colorectal cancer (CRC) liver metastases. In SIRT,Y-90 ...Yttrium-90 (Y-90) radioembolization,also known as selective internal radiation therapy (SIRT),is a regional hepatic therapy used in the treatment of unresectable colorectal cancer (CRC) liver metastases. In SIRT,Y-90 impregnated microspheres are injected into the VASCULAR SUPPLY of hepatic tumor,leading to selective irradiation and necrosis of tumor TISSUE. While several studies demonstrate improved local control and survival with SIRT,the specific indications for this therapy have yet to be defined. Typically,SIRT is given in combination with chemotherapy as multimodal treatment for unresectable hepatic CRC. However,it HAS ALSO FOUND INCREASING USE as a salvage therapy in chemo-refractory patients. Herein,the authors describe their experience with SIRT as "stand alone" therapy in a surgically-prohibitive,chemotherapy naive patient with hepatic CRC metastasis. The results suggest that Y-90 SIRT may have potential applications beyond its usual role as a palliative or salvage therapy for unresectable hepatic CRC.展开更多
Objective: To compare the effects and safety of conventional transarterial chemoembolization(c TACE) and yttrium-90 transarterial radioembolization [TARE(90 Y)] for hepatocellular carcinoma(HCC)Methods: Nine high-qual...Objective: To compare the effects and safety of conventional transarterial chemoembolization(c TACE) and yttrium-90 transarterial radioembolization [TARE(90 Y)] for hepatocellular carcinoma(HCC)Methods: Nine high-quality observational studies, one low bias-risk randomized controlled trial(RCT), and one moderate biasrisk RCT included 1,652 patients [c TACE, 1,124; TARE(90 Y), 528], from whom data were extracted for this systematic review and meta-analysis.Results: The extracted study outcomes included 1-year and 2-year overall survival(OS) rates, objective responses(ORs), and serious adverse events(AEs). 1-year OS rates: OR = 0.939, 95 % CI: 0.705-1.251, P = 0.66. 2-year OS rates: overall pooled OR =0.641, 95% CI: 0.382-1.075, P = 0.092; observational study subgroup OR = 0.575, 95% CI: 0.336-0.984, P = 0.043; RCT subgroup OR* = 0.641, 95% CI: 0.382-1.075, P = 0.346. OR: overall pooled OR = 0.781, 95% CI: 0.454-1.343, P = 0.371; m RECIST subgroup OR = 0.584, 95 % CI: 0.349-0.976, P = 0.040; WHO subgroup OR = 1.065; 95% CI: 0.500-2.268, P = 0.870. Serious AEs: overall pooled RR = 1.477, 95% CI: 0.864-2.526, P = 0.154; RCT subgroup RR = 0.680, 95% CI: 0.325-1.423, P = 0.306; observational study subgroup RR = 1.925; 95 % CI: 0.978-3.788, P = 0.058.Conclusions: TARE(90 Y) increased 2-year OS rates in the observational subgroup and resulted in better OR rates, according to m RECIST criteria, in comparison with c TACE. Furthermore, a lower risk of AEs was observed for TARE(90 Y) than for c TACE.展开更多
The liver is a common site of metastasis, with essentially all metastatic malignancies having been known to spread to the liver. Nearly half of all patients with extrahepatic primary cancer have hepatic metastases. Th...The liver is a common site of metastasis, with essentially all metastatic malignancies having been known to spread to the liver. Nearly half of all patients with extrahepatic primary cancer have hepatic metastases. The severe prognostic implications of hepatic metastases have made surgical resection an important first line treatment in management. However, limitations such as the presence of extrahepatic spread or poor functional hepatic reserve exclude the majority of patients as surgical candidates, leaving chemotherapy and locoregional therapies as next best options. Selective internal radiation therapy(SIRT) is a form of catheter-based locoregional cancer treatment modality for unresectable tumors, involving trans-arterial injection of microspheres embedded with a radioisotope Yttrium-90. The therapeutic radiation dose is selectively delivered as the microspheres permanently embed themselves within the tumor vascular bed. Use of SIRT has been conventionally aimed at treating primary hepatic tumors(hepatocellular carcinoma) or colorectal and neuroendocrine metastases. Numerous reviews are available for these tumor types. However, little is known or reviewed on non-colorectal or nonneuroendocrine primaries. Therefore, the aim of this paper is to systematically review the current literature to evaluate the effects of Yttrium-90 radioembolization on non-conventional liver tumors including those secondary to breast cancer, cholangiocarcinoma, ocular and percutaneous melanoma, pancreatic cancer, renal cell carcinoma, and lung cancer.展开更多
BACKGROUND Liver metastases secondary to breast cancer are associated with unfavourable prognosis.Radioembolization with ytrrium-90 is an emerging option for management of liver metastases of breast cancer when other ...BACKGROUND Liver metastases secondary to breast cancer are associated with unfavourable prognosis.Radioembolization with ytrrium-90 is an emerging option for management of liver metastases of breast cancer when other systemic therapies have failed to achieve disease control.However,unlike the case of other liver tumours(colorectal/melanoma metastases/cholangiocarcinoma),its role in the management of breast liver metastases is yet to be elucidated.AIM The aims of this systematic review were to(1)assess the effect of radioembolization with yttrium-90 on tumour response;and(2)to estimate patient survival post radioembolization.METHODS The review was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses.A systematic literature search was performed using the PubMed and EMBASE databases from January 2007 to December 2018.The initial search yielded 265 reports which were potentially suitable for inclusion in this review.Studies published in English reporting at least one outcome of interest were considered to be suitable for inclusion.Conference abstracts;case reports,animal studies and reports not published in English were excluded from this review.Data was retrieved from each individual report on the name of primary author,year of publication,patient demographics,type of microspheres used,radiation dose delivered to tumour,duration of follow-up,disease control rate(%),tumour response,and overall patient survival.RESULTS The final number of studies which met the inclusion criteria was 12 involving 452 patients.There were no randomized controlled trials identified after the literature search.The age of the patients included in this review ranged from 52 to 61 years.The duration of the follow up period post-radioembolization ranged from 6 to 15.7 mo.The total number of patients with breast metastases not confined to the liver was 236(52.2%).Cumulative analysis revealed that radioembolization with yttrium-90 conferred tumour control rate in 81%of patients.Overall survival post-radioembolization ranged from 3.6 to 20.9 mo with an estimated mean survival of 11.3 mo.CONCLUSION Radioembolization with ytrrium-90 appears to confer control of tumour growth rate in most patients,however its effect on patient survival need to be elucidated further.Furthermore,quality evidence in the form of randomized trials is needed in order to assess the effect of radioembolization in more depth.展开更多
As the third leading cause of cancer-related deaths worldwide,hepatocellular carcinoma(HCC)represents a significant global health challenge.This paper provides an introduction and comprehensive review of transarterial...As the third leading cause of cancer-related deaths worldwide,hepatocellular carcinoma(HCC)represents a significant global health challenge.This paper provides an introduction and comprehensive review of transarterial radioembolization(TARE)with Yttrium-90(Y90),a widely performed transcatheter procedure for HCC patients who are not suitable candidates for surgery.TARE involves the targeted delivery of radioactive microspheres to liver tumors,offering a promising treatment option for managing HCC across various stages of the disease.By evaluating Y90 TARE outcomes across early,intermediate,and advanced stages of HCC,the review aims to present a thorough understanding of its efficacy and safety.Additionally,this paper highlights future research directions focusing on the potential of combination therapies with systemic and immunotherapies,as well as personalized treatments.The exploration of these innovative approaches aims to improve treatment outcomes,reduce adverse events,and provide new therapeutic opportunities for HCC patients.The review underscores the importance of ongoing research and clinical trials to optimize TARE further and integrate it into comprehensive HCC treatment paradigms.展开更多
BACKGROUND The coronavirus disease 2019(COVID-19)pandemic has made it more challenging for patients to undergo yttrium-90(Y-90)radioembolization(RE).Same day Y-90 RE provides an opportunity to minimize logistical chal...BACKGROUND The coronavirus disease 2019(COVID-19)pandemic has made it more challenging for patients to undergo yttrium-90(Y-90)radioembolization(RE).Same day Y-90 RE provides an opportunity to minimize logistical challenges and infection risk associated with COVID-19,thus improving patient access.AIM To describe the use of same day Y-90 RE with routine single photon emission computed tomography/computed tomography(SPECT/CT)in order to optimize therapy.METHODS All patients were selected for Y-90 RE through a multidisciplinary tumor board,and were screened and tested for COVID-19 infection per institutional protocol.A same day procedure was developed,consisting of angiography,imaging,and Y-90 resin particle delivery.Routine SPECT/CT after technetium-99m macroaggregated albumin(Tc-99m MAA)administration was performed for assessment of arterial supply,personalized dosimetry,and extrahepatic activity.Post-treatment Y-90 bremsstrahlung SPECT/CT was performed for confirmation of particle delivery,by utilization of energy windowing to limit signal from previously administered Tc-99m MAA particles.RESULTS A total of 14 patients underwent same day Y-90 RE between March and June 2020.Mean lung shunt fraction was 6.13%(range 3.5%-13.1%).Y-90 RE was performed for a single lesion in 7 patients,while the remaining 7 patients had treatment of multifocal lesions.The largest lesion measured 8.3 cm.All patients tolerated the procedure well and were discharged the same day.CONCLUSION Same day Y-90 RE with resin-based microspheres is feasible,and provides an opportunity to mitigate infection risk and logistical challenges associated with the COVID-19 pandemic and beyond.We recommend consideration of SPECT/CT,especially among patients with complex malignancies,for the potential to improve outcomes and eligibility of patients to undergo same day Y-90 RE.展开更多
BACKGROUND Liver cancer is the 6 th most common cancer in the world and the 4 th most common death from cancer worldwide.Hepatic radioembolization is a minimally invasive treatment involving intraarterial administrati...BACKGROUND Liver cancer is the 6 th most common cancer in the world and the 4 th most common death from cancer worldwide.Hepatic radioembolization is a minimally invasive treatment involving intraarterial administration of radioembolic microspheres.AIM To develop a neutron-activated,biodegradable and theranostics samarium-153 acetylacetonate(153SmAcAc)-poly-L-lactic acid(PLLA)microsphere for intraarterial radioembolization of hepatic tumors.METHODS Microspheres with different concentrations of 152SmAcAc(i.e.,100%,150%,175%and 200%w/w)were prepared by solvent evaporation method.The microspheres were then activated using a nuclear reactor in a neutron flux of 2×10^12n/cm^2/s^1,converting 152Sm to Samarium-153(153)Sm)via 152Sm(n,γ) 153Sm reaction.The SmAcAc-PLLA microspheres before and after neutron activation were characterized using scanning electron microscope,energy dispersive X-ray spectroscopy,particle size analysis,Fourier transform infrared spectroscopy,thermo-gravimetric analysis and gamma spectroscopy.The in-vitro radiolabeling efficiency was also tested in both 0.9% sodium chloride solution and human blood plasma over a duration of 550 h.RESULTS The SmAcAc-PLLA microspheres with different SmAcAc contents remained spherical before and after neutron activation.The mean diameter of the microspheres was about 35μm.Specific activity achieved for 153SmAcAc-PLLA microspheres with 100%,150%,175%and 200%(w/w)SmAcAc after 3 h neutron activation were 1.7±0.05,2.5±0.05,2.7±0.07,and 2.8±0.09 GBq/g,respectively.The activity of per microspheres were determined as 48.36±1.33,74.10±1.65,97.87±2.48,and 109.83±3.71 Bq for 153SmAcAc-PLLA microspheres with 100%,150%,175%and 200%(w/w)SmAcAc.The energy dispersive X-ray and gamma spectrometry showed that no elemental and radioactive impurities present in the microspheres after neutron activation.Retention efficiency of 153Sm in the SmAcAc-PLLA microspheres was excellent(approximately 99%)in both 0.9%sodium chloride solution and human blood plasma over a duration of 550 h.CONCLUSION The 153SmAcAc-PLLA microsphere is potentially useful for hepatic radioembolization due to their biodegradability,favorable physicochemical characteristics and excellent radiolabeling efficiency.The synthesis of the formulation does not involve ionizing radiation and hence reducing the complication and cost of production.展开更多
文摘Yttrium-90(Y-90)microsphere therapy,known as radioembolization,has emerged as a pivotal treatment modality for hepatocellular carcinoma(HCC),delivering targeted radiation with minimal collateral damage to healthy liver tissues.This review meticulously synthesizes current evidence regarding the clinical efficacy,underlying therapeutic mechanisms,patient selection criteria,and comparative advantages of Y-90 therapy.Clinical studies consistently demonstrate significant improvements in overall survival and progression-free survival,coupled with robust tumor response rates and manageable adverse events.The therapy’s efficacy is substantially enhanced by advanced dosimetric techniques,enabling precise radiation delivery tailored to individual tumor profiles.Comparative analyses reveal that Y-90 therapy provides superior local tumor control and a preferable safety profile compared to conventional treatments such as transarterial chemoembolization and external beam radiation therapy.Additionally,its clinical outcomes are comparable to those achieved with contemporary systemic therapies.Ongoing research into combination treatments incorporating Y-90 with systemic therapies,including targeted agents and immune checkpoint inhibitors,suggests promising advancements in comprehensive HCC management.Future directions highlight the necessity for continued refinement of dosimetry and patient stratification approaches,aiming to further optimize therapeutic outcomes.
文摘Hepatocellular carcinoma （HCC） recurs with a reported frequency of 12%-18% after liver transplantation. Recurrence is associated with a mortality rate exceeding 75%. Approximately one-third of recurrences develop in the transplanted liver and are therefore amenable to local therapy. A variety of treatment modalities have been reported including resection, transarterial chemoembolization （TACE）, radiofrequency ablation （RFA）, ethanol ablation, cryoablation, and external beam irradiation. Goals of treatment are tumor control and the minimization of toxic effect to functional parenchyma. Efficacy of treatment is mitigated by the need for ongoing immunosuppression. Yttrium-90 microspheres have been used as a treatment modality both for primary HCC and for pre-transplant management of HCC with promising results. Twenty-two months after liver transplantation for hepatitis C cirrhosis complicated by HCC, a 42-year old man developed recurrence of HCC in his transplant allograft. Treatment of multiple right lobe lesions with anatomic resection and adjuvant chemotherapy was unsuccessful. Multifocal recurrence in the remaining liver allograft was treated with hepatic intra-arterial infusion of yttrium-90 microspheres （SIR-Spheres, Sirtex Medical Inc., Lake Forest, IL, USA）. Efficacy was demonstrated by tumor necrosis on imaging and a decrease in alpha-fetoprotein （AFP） level. There were no adverse consequences of initial treatment.
文摘Liver malignancy,including primary liver cancer and metastatic liver cancer has become one of the most common causes of cancer-related death worldwide due to the high malignant degree and limited systematic treatment strategy.Radioembolization with yttrium-90(^(90)Y)-loaded microspheres is a relatively novel technology that has made significant progress in the local treatment of liver malignancy.The different steps in the extensive work-up of radioembolization for patients with an indication for treatment with^(90)Y microspheres,from patient selection to follow up,both technically and clinically,are discussed in this paper.It describes the application and development of^(90)Y microspheres in the treatment of liver cancer.
文摘Transarterial radioembolization(TARE) is a form of brachytherapy in which intra-arterially injected yttrium-90-loaded microspheres serve as a source for internal radiation purposes.On the average,it produces disease control rates exceeding 80% and it is a consolidated therapy for hepatocellular carcinoma(HCC);however,current data are all based on retrospective series or non-controlled prospective studies since randomized controlled trials comparing it with the other liver-directed therapies for intermediate and locally advanced stage HCC are still underway.The data available show that TARE provides similar or even better survival rates when compared to transarterial chemoembolization(TACE).First-line TARE is best indicated for both intermediatestage patients(staged according to the barcelona clinic liver cancer staging classification) who have lesions which respond poorly to TACE due to multiple tumors or a large tumor burden,and for locally advanced-stage patients with solitary tumors,and segmental or lobar portal vein tumor thrombosis.In addition,emerging data have suggested the use of TARE in patients who are classified slightly beyond the Milan criteria regarding radical treatment for downstaging purposes.As a secondline treatment,TARE can also be applied in patients progressing to TACE or sorafenib;a large number of phase Ⅱ/Ⅲ trials are ongoing with the purpose of evaluating the best association with systemic therapies.Transarterial radioembolization is very well tolerated and has a low rate of complications which are mainly related to unintended non-target tissue irradiation,including the surrounding liver parenchyma.The complications can be additionally reduced by accurate patient selection and a strict pre-treatment evaluation including dosimetry and assessment of the vascular anatomy.Since a correct treatment algorithm for potential TARE candidates is not clear and standardized,this comprehensive review analyzes the best selection criteria for patients who really benefit from TARE and also the new advances of this therapy,which can be a very important weapon against HCC.
文摘Radiation segmentectomy(RS) is a new approach to90 Y radioembolization that has been designed to increase the safety and efficacy of radioembolization in patients with unresectable hepatic malignancies. With this technique,high doses(>190 Gy) of radiation are delivered to the tumor through radioembolization performed in a segmental fashion, potentially increasing the radiation dose to the tumor while minimizing injury to the liver parenchyma. The aim of this review is to provide a summary of the indications, device choice, dosimetry, procedure, clinical outcomes, and toxicity of RS based on the clinical series currently available.
文摘Adrenocortical carcinoma(ACC)is a rare malignancy with generally poor outcomes and limited treatment options.While surgical resection can be curative for early local disease,most patients present with advanced ACC owing to nonspecific symptoms.For those patients,treatment options include systemic chemotherapy and locoregional therapies including radiofrequency ablation and transarterial chemoembolization.We present the first reported case of utilizing yttrium-90 microsphere selective internal radiation therapy(SIRT)in combination with first line EDP-M(Etoposide,Doxorubicin,Cisplatin,Mitotane)chemotherapy and debulking surgical primary tumor resection for treatment of metastatic ACC.Stable complete radiologic response has been maintained after twelve months with resolution of clinical symptoms.These findings prompt the need for further consideration and studies to elucidate the role of SIRT in combination with systemic and surgical treatment for metastatic ACC.
基金Supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under award number UL1TR00165 through our institution’s Center for Clinical and Translational Science(in part)
文摘AIM: To further define variables associated with increased incidences of severe toxicities following administration of yttrium-90 (<sup>90</sup>Y) microspheres.METHODS: Fifty-eight patients undergoing 79 treatments were retrospectively assessed for development of clinical and laboratory toxicity incidence following <sup>90</sup>Y administration. Severe toxicity events were defined using Common Terminology Criteria for Adverse Events version 4.03 and defined as grade ≥ 3. Univariate logistic regression analyses were used to evaluate the effect of different factors on the incidence of severe toxicity events. Multicollinearity was assessed for all factors with P < 0.1 using Pearson correlation matrices. All factors not excluded due to multicollinearity were included in a multivariate logistic regression model for each measurement of severe toxicity.RESULTS: Severe (grade ≥ 3) toxicities occurred following 21.5% of the 79 treatments included in our analysis. The most common severe laboratory toxicities were severe alkaline phosphatase (17.7%), albumin (12.7%), and total bilirubin (10.1%) toxicities. Decreased pre-treatment albumin (OR = 26.2, P = 0.010) and increased pre-treatment international normalized ratio (INR) (OR = 17.7, P = 0.048) were associated with development of severe hepatic toxicity. Increased pre-treatment aspartate aminotransferase (AST; OR = 7.4, P = 0.025) and decreased pre-treatment hemoglobin (OR = 12.5, P = 0.025) were associated with severe albumin toxicity. Increasing pre-treatment model for end-stage liver disease (MELD) score (OR = 1.8, P = 0.033) was associated with severe total bilirubin toxicity. Colorectal adenocarcinoma histology was associated with severe alkaline phosphatase toxicity (OR = 5.4, P = 0.043).CONCLUSION: Clinicians should carefully consider pre-treatment albumin, INR, AST, hemoglobin, MELD, and colorectal histology when choosing appropriate candidates for <sup>90</sup>Y microsphere therapy.
基金supported by the National Major Scientific and Technological Special Project for“Significant New Drugs Development”(No.2018ZX09201018–028)the nuclear energy development projects of China during the 13thFive Year Plan periodthe key research and development project of the Sichuan Provincial Department of Science and Technology(No.18ZDYF1466)。
文摘Radioactive microspheres have demonstrated excellent therapeutic effects and good tolerance in the treatment of unresectable primary and secondary liver malignancies.This is attributed to precise embolization and potent anti-tumor effect.However,certain limitations such as unstable loading,perfusion stasis,heterogeneous distribution,ectopic distribution,and insufficient dosage,restrict their clinical application.Herein,a novel personalized Y-90 carbon microsphere with high uniformity,high specific activity and high availability(^(90)Y-HUACM)is presented.It is synthesized through planar molecular complex adsorption and chemical deposition solidification.^(90)Y-HUACM exhibited controllable size,excellent biocompatibility,outstanding in vitro and in vivo stability.The radiolabeling efficiency of Y-90 exceeded 99%and the leaching rate of Y-90 is far below 0.1%.Furthermore,the excellent anti-tumor effect,nuclide loading stability,anti-reflux characteristics,precise embolization,and biosafety of^(90)Y-HUACM were validated in a rabbit VX2liver tumor model.In summary,this new,high-performance,and customizable radioactive microsphere provides a superior choice for selective internal radiation treatment of advanced liver cancer is expected to be rapidly applied in clinical practice.
文摘BACKGROUND Hepatocellular carcinoma(HCC)with advanced features such as Budd-Chiari syndrome,chronic liver failure and multiple intrahepatic metastases poses significant therapeutic challenges.Yttrium-90(90Y)radioembolization is a locoregional treatment option with potential benefits in such complex cases.This case report explores the application of 90Y radioembolization in combination with systemic therapies,highlighting its potential role in managing advanced HCC.CASE SUMMARY A 51-year-old male presented with HCC characterized by massive intrahepatic lesions,multiple metastases,and chronic liver failure secondary to Budd-Chiari syndrome.The patient underwent 90Y radioembolization following hepatic arterial infusion chemotherapy and was subsequently combined with lenvatinib.Posttreatment follow-up revealed a significant reduction in tumor size,with the maximum diameter decreasing from 142.45 mm to 73.16 mm over six months.Liver function improved from Child-Pugh class B to A.However,new intrahepatic lesions emerged at ten months,and liver function deteriorated to Child-Pugh class C.The patient survived for 18 months after initial diagnosis.CONCLUSION Yttrium-90 radioembolization combined with systemic therapies demonstrated significant tumor regression and temporary liver function improvement in a patient with advanced HCC,suggesting its potential as a treatment option in complex cases.
文摘Hepatocellular carcinoma(HCC)is a leading cause of cancer-related mortality,with a majority of patients presenting at intermediate or advanced stages,precluding curative interventions.Radioembolization,also known as selective internal radiation therapy,has emerged as a promising locoregional therapy that delivers high-dose yttrium-90 microspheres directly to hepatic tumors while sparing healthy parenchyma.This technique is especially beneficial for patients with portal vein tumor thrombosis or impaired liver function.This editorial provides a comprehensive overview of the mechanism,technical considerations,and clinical efficacy of radioembolization in advanced HCC.Landmark trials such as SARAH,SIRveNIB,and DOSISPHERE-01 demonstrate comparable or superior outcomes to systemic therapies like sorafenib,particularly when personalized dosimetry is applied.Radioembolization contributes to tumor downstaging,transplant bridging,and improved disease control rates.The integration of radioembolization with systemic therapies,including immune checkpoint inhibitors and tyrosine kinase inhibitors,represents a key area of ongoing research.Despite current challenges such as microsphere heterogeneity,dosimetry standardization,and limited accessibility,emerging innovations in imaging,isotopes,and personalized treatment strategies are expected to refine its application.Overall,radioembolization is poised to play an increasingly central role in the multidisciplinary management of advanced HCC.
文摘Yttrium-90 (Y-90) radioembolization,also known as selective internal radiation therapy (SIRT),is a regional hepatic therapy used in the treatment of unresectable colorectal cancer (CRC) liver metastases. In SIRT,Y-90 impregnated microspheres are injected into the VASCULAR SUPPLY of hepatic tumor,leading to selective irradiation and necrosis of tumor TISSUE. While several studies demonstrate improved local control and survival with SIRT,the specific indications for this therapy have yet to be defined. Typically,SIRT is given in combination with chemotherapy as multimodal treatment for unresectable hepatic CRC. However,it HAS ALSO FOUND INCREASING USE as a salvage therapy in chemo-refractory patients. Herein,the authors describe their experience with SIRT as "stand alone" therapy in a surgically-prohibitive,chemotherapy naive patient with hepatic CRC metastasis. The results suggest that Y-90 SIRT may have potential applications beyond its usual role as a palliative or salvage therapy for unresectable hepatic CRC.
文摘Objective: To compare the effects and safety of conventional transarterial chemoembolization(c TACE) and yttrium-90 transarterial radioembolization [TARE(90 Y)] for hepatocellular carcinoma(HCC)Methods: Nine high-quality observational studies, one low bias-risk randomized controlled trial(RCT), and one moderate biasrisk RCT included 1,652 patients [c TACE, 1,124; TARE(90 Y), 528], from whom data were extracted for this systematic review and meta-analysis.Results: The extracted study outcomes included 1-year and 2-year overall survival(OS) rates, objective responses(ORs), and serious adverse events(AEs). 1-year OS rates: OR = 0.939, 95 % CI: 0.705-1.251, P = 0.66. 2-year OS rates: overall pooled OR =0.641, 95% CI: 0.382-1.075, P = 0.092; observational study subgroup OR = 0.575, 95% CI: 0.336-0.984, P = 0.043; RCT subgroup OR* = 0.641, 95% CI: 0.382-1.075, P = 0.346. OR: overall pooled OR = 0.781, 95% CI: 0.454-1.343, P = 0.371; m RECIST subgroup OR = 0.584, 95 % CI: 0.349-0.976, P = 0.040; WHO subgroup OR = 1.065; 95% CI: 0.500-2.268, P = 0.870. Serious AEs: overall pooled RR = 1.477, 95% CI: 0.864-2.526, P = 0.154; RCT subgroup RR = 0.680, 95% CI: 0.325-1.423, P = 0.306; observational study subgroup RR = 1.925; 95 % CI: 0.978-3.788, P = 0.058.Conclusions: TARE(90 Y) increased 2-year OS rates in the observational subgroup and resulted in better OR rates, according to m RECIST criteria, in comparison with c TACE. Furthermore, a lower risk of AEs was observed for TARE(90 Y) than for c TACE.
文摘The liver is a common site of metastasis, with essentially all metastatic malignancies having been known to spread to the liver. Nearly half of all patients with extrahepatic primary cancer have hepatic metastases. The severe prognostic implications of hepatic metastases have made surgical resection an important first line treatment in management. However, limitations such as the presence of extrahepatic spread or poor functional hepatic reserve exclude the majority of patients as surgical candidates, leaving chemotherapy and locoregional therapies as next best options. Selective internal radiation therapy(SIRT) is a form of catheter-based locoregional cancer treatment modality for unresectable tumors, involving trans-arterial injection of microspheres embedded with a radioisotope Yttrium-90. The therapeutic radiation dose is selectively delivered as the microspheres permanently embed themselves within the tumor vascular bed. Use of SIRT has been conventionally aimed at treating primary hepatic tumors(hepatocellular carcinoma) or colorectal and neuroendocrine metastases. Numerous reviews are available for these tumor types. However, little is known or reviewed on non-colorectal or nonneuroendocrine primaries. Therefore, the aim of this paper is to systematically review the current literature to evaluate the effects of Yttrium-90 radioembolization on non-conventional liver tumors including those secondary to breast cancer, cholangiocarcinoma, ocular and percutaneous melanoma, pancreatic cancer, renal cell carcinoma, and lung cancer.
文摘BACKGROUND Liver metastases secondary to breast cancer are associated with unfavourable prognosis.Radioembolization with ytrrium-90 is an emerging option for management of liver metastases of breast cancer when other systemic therapies have failed to achieve disease control.However,unlike the case of other liver tumours(colorectal/melanoma metastases/cholangiocarcinoma),its role in the management of breast liver metastases is yet to be elucidated.AIM The aims of this systematic review were to(1)assess the effect of radioembolization with yttrium-90 on tumour response;and(2)to estimate patient survival post radioembolization.METHODS The review was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses.A systematic literature search was performed using the PubMed and EMBASE databases from January 2007 to December 2018.The initial search yielded 265 reports which were potentially suitable for inclusion in this review.Studies published in English reporting at least one outcome of interest were considered to be suitable for inclusion.Conference abstracts;case reports,animal studies and reports not published in English were excluded from this review.Data was retrieved from each individual report on the name of primary author,year of publication,patient demographics,type of microspheres used,radiation dose delivered to tumour,duration of follow-up,disease control rate(%),tumour response,and overall patient survival.RESULTS The final number of studies which met the inclusion criteria was 12 involving 452 patients.There were no randomized controlled trials identified after the literature search.The age of the patients included in this review ranged from 52 to 61 years.The duration of the follow up period post-radioembolization ranged from 6 to 15.7 mo.The total number of patients with breast metastases not confined to the liver was 236(52.2%).Cumulative analysis revealed that radioembolization with yttrium-90 conferred tumour control rate in 81%of patients.Overall survival post-radioembolization ranged from 3.6 to 20.9 mo with an estimated mean survival of 11.3 mo.CONCLUSION Radioembolization with ytrrium-90 appears to confer control of tumour growth rate in most patients,however its effect on patient survival need to be elucidated further.Furthermore,quality evidence in the form of randomized trials is needed in order to assess the effect of radioembolization in more depth.
文摘As the third leading cause of cancer-related deaths worldwide,hepatocellular carcinoma(HCC)represents a significant global health challenge.This paper provides an introduction and comprehensive review of transarterial radioembolization(TARE)with Yttrium-90(Y90),a widely performed transcatheter procedure for HCC patients who are not suitable candidates for surgery.TARE involves the targeted delivery of radioactive microspheres to liver tumors,offering a promising treatment option for managing HCC across various stages of the disease.By evaluating Y90 TARE outcomes across early,intermediate,and advanced stages of HCC,the review aims to present a thorough understanding of its efficacy and safety.Additionally,this paper highlights future research directions focusing on the potential of combination therapies with systemic and immunotherapies,as well as personalized treatments.The exploration of these innovative approaches aims to improve treatment outcomes,reduce adverse events,and provide new therapeutic opportunities for HCC patients.The review underscores the importance of ongoing research and clinical trials to optimize TARE further and integrate it into comprehensive HCC treatment paradigms.
文摘BACKGROUND The coronavirus disease 2019(COVID-19)pandemic has made it more challenging for patients to undergo yttrium-90(Y-90)radioembolization(RE).Same day Y-90 RE provides an opportunity to minimize logistical challenges and infection risk associated with COVID-19,thus improving patient access.AIM To describe the use of same day Y-90 RE with routine single photon emission computed tomography/computed tomography(SPECT/CT)in order to optimize therapy.METHODS All patients were selected for Y-90 RE through a multidisciplinary tumor board,and were screened and tested for COVID-19 infection per institutional protocol.A same day procedure was developed,consisting of angiography,imaging,and Y-90 resin particle delivery.Routine SPECT/CT after technetium-99m macroaggregated albumin(Tc-99m MAA)administration was performed for assessment of arterial supply,personalized dosimetry,and extrahepatic activity.Post-treatment Y-90 bremsstrahlung SPECT/CT was performed for confirmation of particle delivery,by utilization of energy windowing to limit signal from previously administered Tc-99m MAA particles.RESULTS A total of 14 patients underwent same day Y-90 RE between March and June 2020.Mean lung shunt fraction was 6.13%(range 3.5%-13.1%).Y-90 RE was performed for a single lesion in 7 patients,while the remaining 7 patients had treatment of multifocal lesions.The largest lesion measured 8.3 cm.All patients tolerated the procedure well and were discharged the same day.CONCLUSION Same day Y-90 RE with resin-based microspheres is feasible,and provides an opportunity to mitigate infection risk and logistical challenges associated with the COVID-19 pandemic and beyond.We recommend consideration of SPECT/CT,especially among patients with complex malignancies,for the potential to improve outcomes and eligibility of patients to undergo same day Y-90 RE.
基金Supported by Fundamental Research Grant Scheme sanctioned by the Ministry of Education,Malaysia,No.FRGS/1/2019/SKK06/TAYLOR/02/3。
文摘BACKGROUND Liver cancer is the 6 th most common cancer in the world and the 4 th most common death from cancer worldwide.Hepatic radioembolization is a minimally invasive treatment involving intraarterial administration of radioembolic microspheres.AIM To develop a neutron-activated,biodegradable and theranostics samarium-153 acetylacetonate(153SmAcAc)-poly-L-lactic acid(PLLA)microsphere for intraarterial radioembolization of hepatic tumors.METHODS Microspheres with different concentrations of 152SmAcAc(i.e.,100%,150%,175%and 200%w/w)were prepared by solvent evaporation method.The microspheres were then activated using a nuclear reactor in a neutron flux of 2×10^12n/cm^2/s^1,converting 152Sm to Samarium-153(153)Sm)via 152Sm(n,γ) 153Sm reaction.The SmAcAc-PLLA microspheres before and after neutron activation were characterized using scanning electron microscope,energy dispersive X-ray spectroscopy,particle size analysis,Fourier transform infrared spectroscopy,thermo-gravimetric analysis and gamma spectroscopy.The in-vitro radiolabeling efficiency was also tested in both 0.9% sodium chloride solution and human blood plasma over a duration of 550 h.RESULTS The SmAcAc-PLLA microspheres with different SmAcAc contents remained spherical before and after neutron activation.The mean diameter of the microspheres was about 35μm.Specific activity achieved for 153SmAcAc-PLLA microspheres with 100%,150%,175%and 200%(w/w)SmAcAc after 3 h neutron activation were 1.7±0.05,2.5±0.05,2.7±0.07,and 2.8±0.09 GBq/g,respectively.The activity of per microspheres were determined as 48.36±1.33,74.10±1.65,97.87±2.48,and 109.83±3.71 Bq for 153SmAcAc-PLLA microspheres with 100%,150%,175%and 200%(w/w)SmAcAc.The energy dispersive X-ray and gamma spectrometry showed that no elemental and radioactive impurities present in the microspheres after neutron activation.Retention efficiency of 153Sm in the SmAcAc-PLLA microspheres was excellent(approximately 99%)in both 0.9%sodium chloride solution and human blood plasma over a duration of 550 h.CONCLUSION The 153SmAcAc-PLLA microsphere is potentially useful for hepatic radioembolization due to their biodegradability,favorable physicochemical characteristics and excellent radiolabeling efficiency.The synthesis of the formulation does not involve ionizing radiation and hence reducing the complication and cost of production.
