Yttrium-90 radioembolization treatment strategies for management of hepatocellular carcinoma

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.

Radioembolization with Yttrium-90 microspheres in hepatocellular carcinoma:Role and perspectives

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.

Hepatic intra-arterial infusion of yttrium-90 microspheres in the treatment of recurrent hepatocellular carcinoma after liver transplantation: A case report

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.

Effects of Yttrium-90 selective internal radiation therapy on non-conventional liver tumors

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.

Complete eradication of hepatic metastasis from colorectal cancer by Yttrium-90 SIRT

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.

Radiation segmentectomy for hepatic malignancies: Indications, devices,dosimetry, procedure, clinical outcomes, and toxicity of yttrium-90 microspheres

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.

Yttrium-90 transarterial radioembolization versus conventional transarterial chemoembolization for patients with hepatocellular carcinoma：a systematic review and meta-analysis

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.

Yttrium-90 microsphere selective internal radiation therapy for liver metastases following systemic chemotherapy and surgical resection for metastatic adrenocortical carcinoma

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.

Same day yttrium-90 radioembolization with single photon emission computed tomography/computed tomography: An opportunity to improve care during the COVID-19 pandemic and beyond

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.

Yttrium-90 radioembolization for unresectable hepatic metastases of breast cancer: A systematic review

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.

Factors associated with increased incidence of severe toxicities following yttrium-90 resin microspheres in the treatment of hepatic malignancies

AIM: To further define variables associated with increased incidences of severe toxicities following administration of yttrium-90 (90Y) microspheres.METHODS: Fifty-eight patients undergoing 79 treatments were retrospectively assessed for development of clinical and laboratory toxicity incidence following 90Y 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 90Y microsphere therapy.

Current status of yttrium-90 microspheres radioembolization in primary and metastatic liver cancer

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.

Poly(Vinyl Alcohol)/Collagen/Hydroxyapatite Nanoparticles Hybrid System Containing Yttrium-90 as a Potential Agent to Treat Osteosarcoma

Osteosarcoma is the most common primary malignant bone tumors, affecting mostly children, adolescents and young adults. This is an aggressive tumor that results in a high mortality rate and poor prognosis. Due to the low sensitivity of osteosarcoma to ionizing radiation, such treatment is not used very often and it can be recommended only to postsurgical therapy. As an alternative therapy, functionalized nanomaterials allow their accumulation in tumor tissues due to their unique properties, making them good agents to act as stable carriers for radionuclides. In this work, mesoporous hydroxyapatite nanoparticles were synthesized and the functionalization process with poly(vinyl alcohol) and collagen was investigated. The samples were characterized by X-ray diffraction (XRD), N2 adsorption, elemental analysis (CHN), Fourier Transform Infrared Spectroscopy (FTIR), Nitrogen Adsorption, Transmission Electron Microscopy (TEM), and Thermal Analysis. Also, the yttrium incorporation potential and its release kinetics in the hydroxyapatite matrix were evaluated to study the capacity of this system to treat osteosarcomas. The results indicate that this material has a promisor potential to treat this kind of tumor.

Clinical outcome of Yttrium-90 selective internal radiation therapy (Y-90 SIRT) in unresectable hepatocellular carcinoma: Experience from a tertiary care center

Background and aim:Whereas Yttrium-90 selective internal radiation therapy(Y-90 SIRT)was shown to improve local tumor control in non-Asian population,the efficacy of this therapy for Asian population in real-world setting remains poorly detailed.We aimed to determine outcomes and identify predictors of response in hepatocellular carcinoma(HCC)patients treated by Y-90 SIRT.Methods:We retrospectively enrolled 52 HCC patients receiving Y-90 SIRT at our tertiary center between 2014 and 2019.Overall survival(OS),progression free survival(PFS),and predictive factors were determined by KaplaneMeier method and Cox-proportional hazard analysis.Results:Of the 52 patients(81% male,mean age 64.9 years),71%and 29% were classified as Barcelona Clinic Liver Cancer stage C and B HCC,respectively;63% had portal vein thrombosis,and 35% had objective tumor response defined by the modified Response Evaluation Criteria in Solid Tumors(mRE-CIST)criteria.OS and PFS were 11.0 and 2.4 months,respectively.Two patients were successfully down-staged and further underwent surgical resection.Multifocal lesion,alpha-fetoprotein(AFP)≥200 ng/mL,and Eastern Cooperative Oncology Group(ECOG)score≥1 were significantly associated with poor sur-vival,with adjusted hazard ratio(95% confidence interval)of 7.7(2.0e29.8),5.4(2.0e14.7),and 3.1(1.0 e9.6),respectively(all in P<0.05).Conclusions:Y-90 SIRT is an effective treatment for the local tumor control of HCC without serious adverse events.Single lesion,AFP level and ECOG status were predictors of response.

Severe bile duct complication after yttrium-90 radioembolization therapy in a patient with recurrent hepatocellular carcinoma after liver transplantation: A case report

Patients with recurrent hepatocellular carcinoma(HCC)following liver transplantation(LT)have a poor prognosis owing to rapid tumor progression.Yttrium-90 radioembolization(^(90)Y-RE)has been shown to be a safe and efficacious transarterial radioembolization treatment for patients with advanced HCC.However,to our knowledge,no data are available for patients with recurrent HCC following LT.Here we report a case of severe bile duct complication after transarterial radioembolization with yttrium-90 in a patient who experienced HCC recurrence following LT.The present case suggests that ^(90)Y-RE should be cautiously performed in patients with recurrent HCC following LT.

“90后”员工离职倾向影响因素研究

在竞争激烈的商业环境中,90后员工离职成为大多数企业面临的挑战。通过问卷调查,从员工需求与激励、工作与生活平衡、工作前景与预期这3个维度运用SPSS探究90后员工离职倾向的影响因素。研究发现:本科学历的90后员工对工作的前景与预期更高;需求与激励因素对90后员工离职倾向影响最大。因此,企业应该采取措施如建立并完善激励机制、为90后布置个性化任务和采取弹性工作制等减少员工离职现象发生。

基于MSISE-90研究高海拔宇宙线观测站处的大气深度廓线模型

高海拔宇宙线观测站(LHAASO)位于四川省稻城县海子山,它的广角切伦科夫望远镜阵(WFCTA)主要是通过观测广延大气簇射过程中产生的切伦科夫光信号对宇宙线进行研究.WFCTA的标定、模拟和重建都和大气深度有关,目前使用的大气深度模型是美国标准大气深度廓线模型.本研究中将美国标准大气深度廓线模型与卫星TIMED搭载的红外辐射计SABER记录到的LHAASO处14-50 km处的大气深度廓线进行比较,同时也与LHAASO处地面气象站记录的大气深度进行比较,美国标准大气模型的大气深度均偏小.MSISE-90大气模型描述了地球大气中从地面到热层的中性温度和密度,进一步研究发现MSISE-90大气模型与TIMED/SABER和LHAASO处地面标准气象站记录的大气深度的一致性较好.根据MSISE-90大气模型计算得到LHAASO处的大气深度均值廓线在1月最低,其次是2月、3月、4月、11月和12月,这也是WFCTA运行的最佳观测月份.4月份的大气边界层最高,其大气深度存在约2%的日变化.利用美国标准大气模型的函数形式,拟合每月的4.4-100 km处的大气深度廓线,得到了LHAASO处的每月的大气深度廓线模型,并比较了30°天顶角入射的100 TeV的宇宙线质子在MSISE-90大气模型和美国标准大气模型中产生的切伦科夫光的横分布的差异,二者最大差异约可以达到20%.

基于自我决定理论的高职院校“90后”辅导员个性特征与激励对策研究

在阐释自我决定理论内涵的基础上,根据其核心观点将高职院校“90后”辅导员群体的个性特征归纳为自主导向类、胜任导向类和归属导向类三大类别,进而深入把握“90后”辅导员队伍的心理需求。基于这一理论分析,高职院校应制定更具针对性的激励策略,从建立参与式管理的工作情境、探索复合型能力提升机制、营造协作互助式的工作氛围等方面入手,满足“90后”辅导员的三种基本心理需求,提升他们的工作投入感和幸福感。

90°转角微流道内导流板应用特性数值研究

改善转角微流道内流体的二次流特性对提高微流体传输的可靠性具有重要意义。针对90°转角矩形截面微流道,本文提出在微流道转角处增加导流板来实现该区域二次流的主动调节和控制。本文设计了圆弧型和弧—直组合型两种导流板结构,建立了五种不同结构微流道模型,开展了流场对称性和Dean涡分析,流体相对横向动能ksec和流道局部阻力系数ζ90°计算。结果表明,导流板结构能有效改善微流道转角区的流场对称性,加速Dean涡的消失,降低二次流强度,同时也会引起流体流动局部阻力系数有所增加。

结肠癌中Hsp90α的表达及临床意义

目的探讨热休克蛋白90α(heat shock protein 90α,Hsp90α)在结肠癌中的表达及潜在的临床价值。方法采用生物信息学和免疫组化法分析结肠癌中Hsp90α的表达水平,及其与临床病理学特征、预后和免疫细胞浸润水平的关系;采用CCK-8细胞增殖实验和平板克隆实验检测敲除Hsp90AA1前后结肠癌细胞的增殖能力。结果生物信息学分析结果显示,Hsp90AA1在结肠癌组织中异常高表达,其表达水平越高,患者预后越差;Hsp90AA1表达与CD4^(+)T细胞(Th2)、CD8^(+)T细胞、髓样抑制细胞、Tregs细胞、中性粒细胞、巨噬细胞、M1巨噬细胞、M2巨噬细胞的浸润水平呈正相关;免疫组化结果显示结肠癌组织中Hsp90α表达明显高于癌旁正常组织,Hsp90α表达与患者性别、肿瘤大小、位置、分化程度、TNM分期、淋巴结转移、脉管癌栓、神经侵犯、远处转移等无关(P>0.05),与结肠癌患者年龄具有相关性(P<0.05)。Hsp90α高表达是影响结肠癌患者预后的独立危险因素。细胞实验结果显示,敲除Hsp90AA1可抑制结肠癌细胞的生长及增殖能力。结论Hsp90α在结肠癌中高表达,可能是结肠癌预后不良的潜在分子学标志物。