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.

Combination of transarterial radioembolization with atezolizumab and bevacizumab for intermediate and advanced staged hepatocellular carcinoma:A preliminary report of safety and feasibility

Purpose:The IMbrave150 PhaseⅢtrial demonstrated superiority of atezolizumab and bevacizumab(Atezo/Bev)over sorafenib for unresectable hepatocellular carcinoma(HCC).The present study aims to evaluate the feasibility of TARE in combination with Atezo/Bev for treatment of intermediate and advanced staged HCC.Methods:Retrospective review at a single institution was performed between May 2021 and December 2022.Patients who received TARE using yttrium-90(Y90)with concomitant or sequential Atezo/Bev systemic treatment were included.The following outcomes were retrieved:overall survival(OS),radiologic tumor response,progression-free survival,technical adverse events related to TARE,and toxicity based on the National Cancer Institute–Common Terminology Criteria for Adverse Events version 5.0.Results:Ten consecutive patients with intermediate(n=4)and advanced stage HCC(n=6)were treated with TARE and sequential/concomitant Atezo/Bev.Tumor control was achieved in all TARE-treated target lesions(100%).Overall disease progression occurred in 4 patients with PFS of 78.8%and 66.7%at 6-and 12-months,respectively.Two patients died at follow-up,with 6-month and 12-month OS rates of 90.0%and 77.1%,respectively.Three(75%)patients with intermediate stage disease were downstaged into Milan criteria.One patient developed grade 3 transaminitis and hypoglobulinemia,while Atezo/Bev was switched to Lenvatinib in another patient due to immunotherapy related myositis.Conclusion:This study demonstrates initial safety and feasibility of combined TARE with Atezo/Bev for intermediate/advanced stage HCC.Further prospective studies with larger sample size are warranted.

Any role for transarterial radioembolization in unresectable intrahepatic cholangiocarcinoma in the era of advanced systemic therapies?

Intrahepatic cholangiocarcinoma(iCCA)is recognized as the second most frequently diagnosed liver malignancy,following closely after hepatocellular carcinoma.Its incidence has seen a global upsurge in the past several years.Unfortunately,due to the lack of well-defined risk factors and limited diagnostic tools,iCCA is often diagnosed at an advanced stage,resulting in a poor prognosis.While surgery is the only potentially curative option,it is rarely feasible.Currently,there are ongoing investigations into various treatment approaches for unresectable iCCA,including conventional chemotherapies,targeted therapies,immunotherapies,and locoregional treatments.This study aims to explore the role of transarterial radioembolization(TARE)in the treatment of unresectable iCCA and provide a comprehensive review.The findings suggest that TARE is a safe and effective treatment option for unresectable iCCA,with a median overall survival(OS)of 14.9 months in the study cohort.Studies on TARE for unresectable iCCA,both as a first-line treatment(as a neo-adjuvant down-staging strategy)and as adjuvant therapy,have reported varying median response rates(ranging from 34%to 86%)and median OS(12-16 mo).These differences can be attributed to the heterogeneity of the patient population and the limited number of participants in the studies.Most studies have identified tumor burden,portal vein involvement,and the patient’s performance status as key prognostic factors.Furthermore,a phase 2 trial evaluated the combination of TARE and chemotherapy(cisplatin-gemcitabine)as a first-line therapy for locally advanced unresectable iCCA.The results showed promising outcomes,including a median OS of 22 mo and a 22%achievement in down-staging the tumor.In conclusion,TARE represents a viable treatment option for unresectable iCCA,and its combination with systemic chemotherapy has shown promising results.However,it is important to consider treatment-independent factors that can influence prognosis.Further research is necessary to identify optimal treatment combinations and predictive factors for a favorable response in iCCA patients.

Portal vein embolization for closure of marked arterioportal shunt of hepatocellular carcinoma to enable radioembolization:A case report

BACKGROUND Marked arterioportal shunt(APS)can be a contraindication for transarterial radioembolization(TARE)because of the risk of radiation-induced liver toxicity or pneumonitis.To date,the best method to close marked APS to reduce intrahepatic shunt(IHS)and hepatopulmonary shunt(HPS)before TARE has not been elucidated.CASE SUMMARY This case report describes a novel strategy of embolization of the portal venous outlet to reduce IHS and HPS caused by marked APS before TARE in a patient with advanced hepatocellular carcinoma(HCC).The patient had a significant intratumoral shunt from the tumor artery to the portal vein and had already been suspected based on pre-interventional magnetic resonance angiography,and digital subtraction angiography(DSA)confirmed the shunt.Selective right portal vein embolization(PVE)was performed to close the APS outlet and DSA confirmed complete closure.Technetium-99m macroaggregated albumin was administered and single photon emission computed tomography revealed a low HPS with 8.4%.Successful TARE was subsequently performed.No major procedurerelated complication occurred.CONCLUSION Closure of APS with PVE during mapping angiography of advanced-stage HCC to enable reduction of HPS and subsequent TARE is feasible.

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.

Transarterial radioembolization for hepatocellular carcinoma:An update and perspectives

In the last decade trans-arterial radioembolization has given promising results in the treatment of patients with intermediate or advanced stage hepatocellular carcinoma(HCC),both in terms of disease control and tolerability profile.This technique consists of the selective intra-arterial administration of microspheres loaded with a radioactive compound(usually Yttrium90),and exerts its therapeutic effect through the radiation carried by these microspheres.A careful and meticulous selection of patients is crucial before performing the radioembolization to correctly perform the procedure and reduce the incidence of complications.Radioembolization is a technically complex and expensive technique,which has only recently entered clinical practice and is supported by scant results from phase Ⅲ clinical trials.Nevertheless,it may represent a valid alternative to transarterial chemoembolization(TACE) in the treatment of intermediate-stage HCC patients,as shown by a comparative retrospective assessment that reported a longer time to progression,but not of overall survival,and a more favorable safety profile for radioembolization.In addition,this treatment has reported a higher percentage of tumor shrinkage,if compared to TACE,for pre-transplant downsizing and it represents a promising therapeutic option in patients with large extent of disease and insufficient residual liver volume who are not immediately eligible for surgery.Radioembolization might also be a suitable companion to sorafenib in advanced HCC or it can be used as a potential alternative to this treatment in patients who are not responding or do not tolerate sorafenib.

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.

Transarterial radioembolization vs chemoembolization for hepatocarcinoma patients:A systematic review and metaanalysis

AIM: To compare the efficacy and safety of yttrium-90 radioembolization(Y90RE) and transarterial chemoembolization(TACE) in hepatocellular carcinoma patients. METHODS: Bibliographic research was conducted on main scientific databases. When there was no statistically significant heterogeneity, pooled effects were calculated using a fixed-effects model by means of Mantel-Haenszel test, otherwise, a random-effects model was used with Der Simonian and Laird test. Summary estimates were expressed in terms of odds ratios(ORs) and 95%CI. The probability of publication bias was assessed using funnel plots and with Begg and Mazumdar's test. Sensitivity analysis was finally conducted using the method of excluding extreme data.RESULTS: A total of 10 studies were analyzed, of which 2 randomized controlled trials. Survival rate(SR) assessed at 1 year showed an absolute similarity between the two treatment groups(OR = 1.01, 95%CI: 0.78-1.31, P = 0.93). As long as time elapsed since the treatment, ORs for survival rate tended to significantly increase, thus meaning better long-term outcomes in patients who underwent Y90RE(2-year SR: OR = 1.43, 1.08-1.89, P = 0.01; 3-year SR: OR = 1.48, 1.03-2.13, P = 0.04). Meta-analysis of plotted hazard ratios(HRs) determined a non-significant overall estimate in favor of Y90RE(HR = 0.91, 0.80-1.04, P = 0.16). Y90 RE showed a statistically significant benefit as compared to TACE in terms of higher progression-free survival rateassessed at 1 year(OR = 1.67; 95%CI: 1.10-2.55; P = 0.02). Pooled analyses do not revealed a statistically significant increase in OR for tumor objective responses after Y90 RE with respect to TACE(OR = 1.22, 95%CI: 0.69-2.16, P = 0.50). A non-significant trend in favor of Y90 RE was observed according to adverse event rate(OR = 0.70, 0.38-1.30, P = 0.26).CONCLUSION: Our meta-analysis reveals that Y90 RE and TACE show similar effects in terms of survival, response rate and safety profile, although tumor progression is delayed after radioembolization.

Prognostic value of pre-treatment F-18-FDG PET-CT in patients with hepatocellular carcinoma undergoing radioembolization

AIM To evaluate the value of pre-treatment 18F-FDG PET/CT in patients with HCC following liver radioembolization.METHODS We identified 34 patients with HCC who underwent an FDG PET/CT scan prior to hepatic radioembolization at our institution between 2009 and 2013. Patients wereseen in clinic one month after radioembolization and then at 2-3 mo intervals. We assessed the influence of FDG tumor uptake on outcomes including local liver control(LLC), distant liver control(DLC), time to distant metastases(DM), progression free survival(PFS) and overall survival(OS).RESULTS The majority of patients were males(n = 25, 74%), and had Child Pugh Class A(n = 31, 91%), with a median age of 68 years(46-84 years). FDG-avid disease was found in 19(56%) patients with SUVmax ranging from 3 to 20. Female patients were more likely to have an FDG-avid HCC(P = 0.02). Median follow up of patients following radioembolization was 12 months(1.2-62.8 mo). FDG-avid disease was associated with a decreased 1 year LLC, DLC, DM and PFS(P < 0.05). Using multivariate analysis, FDG avidity predicted for LLC, DLC, and PFS(all P < 0.05).CONCLUSION In this retrospective study, pre-treatment HCC FDGavidity was found to be associated with worse LLC, DLC, and PFS following radioembolization. Larger studies are needed to validate our initial findings to assess the role of F-18-FDG PET/CT scans as biomarker for patients with HCC following radioembolization.

Long-term follow-up study of gastroduodenal lesions after radioembolization of hepatic tumors

AIM:To evaluate the long-term natural history of the gastroduodenal lesions secondary to extrahepatic embolization with Ytrium 90(90 Y) spheres.METHODS:From September 2003 to January 2012,379 procedures of liver radioembolization(RE) using resin microspheres loaded with 90 Y were performed in our center.We have retrospectively compiled the data from 379 RE procedures performed in our center.We report a comprehensive clinical,analytical,endoscopic and histologic long-term follow-up of a series of patients who developed gastroduodenal lesions after the treatment.RESULTS:Six patients(1.5%) developed gastrointestinal symptoms and had gastrointestinal lesions as shown by upper endoscopy in the next 12 wk after RE.The mean time between RE and the appearance of symptoms was 5 wk.Only one patient required endoscopic and surgical treatment.The incidence of gastrointestinal ulcerations was 3.75%(3/80) when only planar images were used for the pre-treatment evaluation.It was reduced to 1%(3/299) when singlephoton emission computed tomography(SPECT) images were also performed.The symptoms that lasted for a longer time were nausea and vomiting,until 25 mo after the treatment.CONCLUSION:All patients were free from severe symptoms at the end of follow-up.The routine use of SPECT has decreased the incidence of gastrointestinal lesions due to unintended deployment of 90 Y particles.

Contra-lateral liver lobe hypertrophy after unilobar Y90 radioembolization:An alternative to portal vein embolization?

Liver resection(LR) with negative margins confers survival advantage in many patients with hepatic malignancies.However,an adequate future liver remnant(FLR) is imperative for safe LR.Presently,in patients with an inadequate FLR; the 2 most established clinical techniques performed to induce liver hypertrophy are portal vein embolization(PVE) and portal vein ligation.More recently,it has been observed that patients who undergo treatment via Y90 radioembolization experience hypertrophy of the contra-lateral untreated liver lobe.Based on these observations,several investigators have proposed the potential use of this modality as an alternative technique for increasing the FLR prior to liver resection.Y90 radioembolization induces hypertrophy at a slower rate than PVE but has the added advantage of concomitant local disease control and tumour downstaging.

Current status of transarterial radioembolization

Unresectable primary and secondary liver malignancies present a major problem in the treatment of solid tumors. Transarterial radioembolization(TARE) is an increasingly used technique for treating various types of malignant liver tumors. This approach is appealing, as the mechanism of action is independent from other loco-regional treatments and potentially complementary to systemic therapies. There are two commercially available products in use for TARE: 90Y-resin and 90Y-glass microspheres. Currently available data indicates TARE so be safe and effective in hepatocellular carcinoma(HCC) and metastatic liver disease. In HCC the results compare well with chemoembolization, while the role of TARE in combination with kinase inhibitors has yet to be established. Current data on TARE in metastatic liver disease is promising, but there is a strong need for prospective randomized trials comparing TARE and modern chemotherapeutic regimen to support the growing role of TARE in metastatic liver disease.

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.

Disease control and failure patterns of unresectable hepatocellular carcinoma following transarterial radioembolization with yttrium-90 microspheres and with/without sorafenib

BACKGROUND Impressive survival outcome of our previous study in unresectable hepatocellular carcinoma(HCC)patients undergoing yttrium-90 glass microspheres transarterial radioembolization(TARE)with/without sorafenib according to individuals’disease burden,i.e.,intrahepatic tumor load(IHT)and adverse disease features(ADFs)might partly be confounded by other treatments and underlying hepatic function.Therefore,a dedicated study focusing on treatment response and assessment of failure patterns might be a way to improve treatment outcome in addition to patient selection based on the disease burden.AIM To assess the tumor response,disease control and patterns of disease progression following TARE with/without sorafenib in unresectable HCC patients.METHODS This retrospective study was conducted in successful TARE procedures with available pre-and post-treatment imaging studies(n=169).Three treatment subgroups were(1)TARE only(TARE_alone)for IHT≤50%without ADFs,i.e.,macrovascular invasion,extrahepatic disease(EHD)and infiltrative/ill-defined HCC(n=63);(2)TARE with sorafenib(TARE_sorafenib)for IHT>50%and/or presence of ADFs(n=81);and(3)TARE only for patients who could not receive sorafenib due to contraindication or intolerance(TARE_no_sorafenib)(n=25).Objective response rate(ORR;consisted of complete response(CR)and partial response(PR)),disease control rate(DCR;consisted of CR,PR and stable disease)and failure patterns of treated,intrahepatic and extrahepatic sites were assessed using the modified response evaluation criteria in solid tumors.Time to progression(TTP)was calculated from TARE to the first radiologic progression at any site using Kaplan-Meier method.Identification of prognostic factors for TTP using the univariate Kaplan-Meier method and multivariate Cox proportional hazard model were performed in major population subgroups,TARE_alone and TARE_sorafenib.RESULTS The median radiologic follow-up time was 4.4 mo(range 0.5-48.8).In treated area,ORR was highest in TARE_sorafenib(53.1%),followed by TARE_alone(41.3%)and TARE_no_sorafenib(16%).In intrahepatic area,DCR remained highest in TARE_sorafenib(84%),followed by TARE_alone(79.4%)and TARE_no_sorafenib(44%).The overall DCR was highest in TARE_alone(79.4%),followed by TARE_sorafenib(71.6%)and TARE_no_sorafenib(40%).Dominant failure patterns were intrahepatic for both TARE_alone(44.5%)and TARE_sorafenib(38.4%).Extrahepatic progression was more common in TARE_sorafenib(32%)and TARE_no_sorafenib(40%)than in TARE_alone(12.7%).TTP was longest in TARE_alone(8.6 mo;95%CI:3.4-13.8),followed by TARE_sorafenib(5.1 mo;95%CI:4.0-6.2)and TARE_no_sorafenib(2.7 mo;95%CI:2.2-3.1).Pre-existing EHD(HR:0.37,95%CI:0.24-0.56,P<0.001)was a sole prognostic factor for TTP in TARE_sorafenib with no prognostic factor for TTP in TARE_alone.CONCLUSION TARE with/without sorafenib according to individuals’disease burden provided DCR approximately 70%with intrahepatic progression as dominant failure pattern.Extrahepatic progression was more common in procedures with initially high disease burden.

Sequential tumor-directed and lobar radioembolization before major hepatectomy for hepatocellular carcinoma

Preoperative radioembolization may improve the resectability of liver tumor by inducing tumor shrinkage, atrophy of the embolized liver and compensatory hypertrophy of non-embolized liver. We describe the case of a cirrhotic Child-Pugh A patient with a segment Ⅳ hepatocellular carcinoma requiring a left hepatectomy. Preoperative angiography demonstrated 2 separated left hepatic arteries, for segment Ⅳ and segments Ⅱ-Ⅲ. This anatomic variant allowed sequential radioembolizations, delivering high-dose ^(90)Yttrium(160 Gy) to the tumor, followed 28 d later by lower dose(120 Gy) to segments Ⅱ-Ⅲ. After 3 mo, significant tumor response and atrophy of the future resected liver were obtained, allowing uneventful left hepatectomy. This case illustrates that, when anatomic disposition permits it, sequential radioembolizations, delivering different ^(90)Yttrium doses to the tumor and the future resected liver, could represent a new strategy to prepare major hepatectomy in cirrhotic patients, allowing optimal tumoricidal effect while reducing the toxicity of the global procedure.

Y90-radioembolization via variant hepatic arteries: Is there a relevant risk for non-target embolization?

BACKGROUND The hepatic arterial anatomy is highly variable, with the two most common variants being a replaced right hepatic artery(RHA) originating from the superior mesenteric artery(SMA) and a left hepatic artery(LHA) originating from the left gastric artery(LGA). These anatomical variants could potentially increase the risk for non-target embolization during Y90-Radioembolization due to the close proximity between hepatic and enteric vessel branches.AIM To evaluate the safety of Yttrium-90radioembolization(90Y-RE) with resin microspheres in patients with a variant hepatic arterial anatomy.METHODS In this retrospective single-center observational study, 11 patients who underwent RE with 90Y-resin microspheres via a LHA originating from the LGA,and 13 patients via a RHA originating from the SMA were included. Patient and treatment data were reviewed regarding clinical and imaging evidence of nontarget embolization of 90Y-resin microspheres to the GI tract. Positioning of the tip of the microcatheter in relationship to the last hepatoenteric side branch was retrospectively analyzed using angiographic images, cone-beam CT and preinterventional CT-angiograms.RESULTS None of the 24 patients developed clinical symptoms indicating a potential nontarget embolization to the GI tract within the first month after 90Y-RE. On thepostinterventional 90Y-bremsstrahlung images and/or 90Y-positron emission tomographies, no evidence of extrahepatic 90Y-activity in the GI tract was noted in any of the patients. The mean distance between the tip of the microcatheter and the last enteric side branch during delivery of the 90Y microspheres was 3.2 cm(range: 1.9-5 cm) in patients with an aberrant LHA originating from a LGA. This was substantially shorter than the mean distance of 5.2 cm(range: 2.9-7.7 cm) in patients with an aberrant right hepatic originating from the SMA.CONCLUSION90Y-RE via aberrant hepatic arteries appears to be safe;at least with positioning of the microcatheter tip no less than 1.9 cm distal to the last hepatoenteric side branch vessel.

Metastatic appendiceal cancer treated with Yttrium 90 radioembolization and systemic chemotherapy:A case report

BACKGROUND Primary appendiceal cancers are rare,and they generally present with liver and/or peritoneal metastases.Currently there are no guidelines to treat metastatic appendiceal cancer,and hence they are treated as metastatic colorectal cancer.Combining Yttrium 90(Y-90)radioembolization(RE)with systemic chemotherapy early in the treatment of right sided colon cancers has been shown to improve survival.Based on this data,a combination of systemic chemotherapy and Y-90 RE was used to treat a case of metastatic appendiceal cancer.CASE SUMMARY A 76-year-old male presented to the emergency room with progressive right lower quadrant pain.A Computed Tomography of the abdomen and pelvis was performed which showed acute appendicitis and contained perforation.Urgent laparoscopic appendectomy was then followed by histological analysis,which was significant for appendiceal adenocarcinoma.After complete workup he underwent right hemicolectomy and lymph node dissection.He received adjuvant chemotherapy as the local lymph nodes were positive.Follow-up imaging was significant for liver metastasis.Due to rapid growth of the liver lesions and new peritoneal nodules,the patient was treated with a combination of Y-90 RE and folinic acid,fluorouracil,and irinotecan with bevacizumab and not microwave ablation as previously planned.Follow up imaging demonstrated complete response of the liver lesions.At 12-mo follow-up,the patient continued to enjoy good quality of life with no recurrent disease.CONCLUSION Utilization of Y-90 RE concomitantly with systemic chemotherapy early in the treatment of appendiceal cancer may provide improved control of this otherwise aggressive cancer.

One case of intrahepatic cholangiocarcinoma amenable to resection after radioembolization

We report the case of a 57-year-old man who was diagnosed with a large unresectable cholangiocarcinoma associated with 2 satellite nodules and without clear margins with the right hepatic vein.Despite 4 cycles of GEMOX(stopped due to a hypertransaminasemia believed to be due to gemcitabine)and 4 cycles of FOLFIRINOX,the tumor remained stable and continued to be considered unresectable.Radioembolization(resin microspheres,SIRS-spheres)targeting the left liver(474 MBq)and segment IV(440 MBq)was performed.This injection was very well tolerated,and 4 more cycles of FOLFIRINOX were given while waiting for radioembolization efficacy.On computed tomography scan,a partial response was observed;the tumor was far less hypervascularized,and a margin was observed between the tumor and the right hepatic vein.A left hepatectomy enlarged to segmentⅧwas performed.On pathological exam,most of the tumor was acellular,with dense fibrosis around visible microspheres.Viable cells were observed only at a distance from beads.Radioembolization can be useful in the treatment of cholangiocarcinoma,allowing in some cases a secondary resection.

Two-stage hepatectomy with radioembolization for bilateral colorectal liver metastases:A case report

BACKGROUND Two-stage hepatectomy(TSH)is a well-established surgical technique,used to treat bilateral colorectal liver metastases(CRLM)with a small future liver remnant(FLR).However,in classical TSH,drop-out is reported to be around 25%-40%,due to insufficient FLR increase or progression of disease.Trans-arterial radioembolization(TARE)has been described to control locally tumor growth of liver malignancies such as hepatocellular carcinoma,but it has been also reported to induce a certain degree of contralateral liver hypertrophy,even if at a lower rate compared to portal vein embolization or ligation.CASE SUMMARY Herein we report the case of a 75-year-old female patient,where TSH and TARE were combined to treat bilateral CRLM.According to computed tomography(CT)-scan,the patient had a hepatic lesion in segment VI-VII and two other confluent lesions in segment II-III.Therefore,one-stage posterior right sectionectomy plus left lateral sectionectomy(LLS)was planned.The liver volumetry estimated a FLR of 38%(segments I-IV-V-VIII).However,due to a more than initially planned,extended right resection,simultaneous LLS was not performed and the patient underwent selective TARE to segments II-III after the first surgery.The CT-scan performed after TARE showed a reduction of the treated lesion and a FLR increase of 55%.Carcinoembryonic antigen and CA 19.9 decreased significantly.Nearly three months later after the first surgery,LLS was performed and the patient was discharged without any postoperative complications.CONCLUSION According to this specific experience,TARE was used to induce liver hypertrophy and simultaneously control cancer progression in TSH settings for bilateral CRLM.

Neutron-activated biodegradable samarium-153 acetylacetonate-poly-L-lactic acid microspheres for intraarterial radioembolization of hepatic tumors

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.