Repeat Evaluation of Lung Shunt Fraction is Unnecessary: A Retrospective Observational Study of Successive Lung Shunt Fractions from Variable Arterial Distributions in Patients Undergoing Radioembolization of Primary and Secondary Liver Tumors

PurposeTo evaluate whether the recalculation of lung shunt fraction (LSF) is necessary prior to next-stage or same lobe repeat radioembolization.Materials and MethodsRetrospective chart review was performed for patients who underwent radioembolization between February 2008 and December 2018. Eighty of 312 patients had repeat mapping angiograms and LSF calculations. A total of 160 LSF calculations were made using planar imaging (155, [97%]) and single-photon emission computed tomography (5 [3%]) technetium-99m macroaggregated albumin hepatic arterial injection imaging. The mean patient age was 61.8 years ± 12.7; 69 (86%) patients had metastatic disease and 11 (14%) had hepatocellular carcinoma.ResultsPatients had a median LSF of 5% (interquartile range [IQR] 3%–9%) with a median absolute difference of 1.25 (IQR 0.65–3.4) and a median of 76 days (IQR 42.5–120 days) between repeat LSF calculations. There was a median change in LSF of 0.2% between mapping studies (P = .11). There was no statistical significance between the repeat LSFs regardless of the arterial distribution (P = .79) or between tumor types (P = .75). No patients exceeded lung dose limits using actual or predicted prescribed dose amounts. The actual median lung dose was 2.6 Gy (IQR 1.8–4.4 Gy, maximum = 20.5) for the first radioembolization and 2.0 Gy (IQR 1.3–3.7 Gy, maximum = 10.1) for the second radioembolization.ConclusionsNo significant difference in LSF was identified between different time points and arterial distributions within the same patient undergoing repeat radioembolization. In patients who receive well under 30-Gy lung dose for the initial treatment and a 50-Gy cumulative lung dose, repeat radioembolization treatments in the same patient may not require a repeat LSF calculation.     

Outpatient Single-Session Yttrium-90 Glass Microsphere Radioembolization

PurposeTo investigate the feasibility of yttrium-90 (⁹⁰Y) glass microsphere radioembolization (including angiography, lung shunt assessment, and treatment) as a single-session, outpatient procedure.Materials and MethodsBetween January 2008 and June 2013, 14 patients underwent outpatient, single-session radioembolization with ⁹⁰Y glass microspheres. As part of the routine diagnostic work-up, all patients underwent either computed tomography (CT) or magnetic resonance imaging of the liver with three-dimensional analysis and had laboratory results forwarded to our center for confirmation of candidacy before treatment. On treatment day, all patients underwent planning mesenteric angiography with flat panel cone-beam CT imaging. Patients were administered 33–85 MBq of technetium-99m macroaggregated albumin (^99mTc-MAA) via a microcatheter positioned in a hepatic artery supplying the tumor of interest. Planar scintigraphy was initiated within 2 hours after the administration of ^99mTc-MAA and lung shunt fraction was determined. Final dosimetry calculations were performed while the patient was being transferred back from nuclear medicine to interventional radiology.ResultsAll patients successfully underwent planning angiography with administration of ^99mTc-MAA and ⁹⁰Y radioembolization as a single-session treatment. There were no reportable or recordable medical events; treatment was carried out to the desired dose in all cases. The mean total procedure time was 2.70 hours ± 0.72 (range, 1.63–3.97 h).ConclusionsThis study reports a novel proof of concept for performing radioembolization in a single-session setting. By using the described method, time between initial clinical assessments and radioembolization treatment is decreased, and costs are minimized.     

A Simple Method for Estimating Dose Delivered to Hepatocellular Carcinoma after Yttrium-90 Glass-Based Radioembolization Therapy: Preliminary Results of a Proof of Concept Study

PurposeTo investigate a simple semiquantitative method to estimate yttrium-90 (⁹⁰Y) dose delivered with radioembolization to infiltrative hepatocellular carcinoma (HCC).Materials and MethodsIn a prospective study, patients with infiltrative HCC and portal vein thrombosis (PVT) underwent glass-based ⁹⁰Y radioembolization including technetium-99m macroaggregated albumin (^99mTc-MAA) hepatopulmonary shunt study before therapy and bremsstrahlung single photon emission computed tomography (SPECT)/computed tomography (CT) after ⁹⁰Y radioembolization. Baseline magnetic resonance imaging was coregistered with ^99mTc-MAA and bremsstrahlung SPECT/CT imaging separately. Unit tumor activity (⁹⁰Y radioactivity delivered to each cubic centimeter of tumor) was estimated based on a lobar infusion approach. Correlation between proportions of ^99mTc-MAA and ⁹⁰Y delivered to the tumor was investigated. Survival analysis was performed using Kaplan-Meier estimations.Results⁹⁰Y therapy was administered in 18 consecutive patients (median age, 55.3 y; mean tumor volume, 588 cm³). Higher intratumoral ⁹⁰Y dose predicted prolonged survival, with 13.2-month median survival in patients with HCC and mean ⁹⁰Y dose of ≥ 100 Gy versus 4.6-month median survival for other patients (P < .001). Of administered ⁹⁰Y dose, 51.9% was delivered to the targeted tumors compared with 74.1% of ^99mTc-MAA with linear correlation between biodistribution of ^99mTc-MAA and ⁹⁰Y observed (Pearson r = 0.774, P < .001).ConclusionsThe findings in this study suggest that approximately 50% of administered ⁹⁰Y dose is taken up by targeted infiltrative HCC with PVT. Intratumoral ⁹⁰Y dose ≥ 100 Gy in unresectable infiltrative HCC via a lobar intraarterial approach is a positive prognostic factor for survival.     

Is prophylactic embolization of the hepatic falciform artery needed before radioembolization in patients with <Superscript>99m</Superscript>Tc-MAA accumulation in the anterior abdominal wall?

Purpose  

While influx of chemoembolic agents into the hepatic falciform artery (HFA) from the hepatic artery can cause supraumbilical skin rash, epigastric pain and even skin necrosis, the significance of a patent HFA in patients undergoing radioembolization is not completely clear. Furthermore, the presence of tracer in the anterior abdominal wall seen in ^99mTc-macroaggregated albumin (^99mTc-MAA) images, which is generally performed prior to radioembolization, has been described as a sign of a patent HFA. The aim of this retrospective study was to evaluate the incidence and consequences of ^99mTc-MAA accumulation in the anterior abdominal wall, indicating a patent HFA, in patients undergoing radioembolization of liver tumours.     

<Superscript>99m</Superscript>Tc-MAA/<Superscript>90</Superscript>Y-Bremsstrahlung SPECT/CT after simultaneous Tc-MAA/<Superscript>90</Superscript>Y-microsphere injection for immediate treatment monitoring and further therapy planning for radioembolization

Purpose  

An angiographic evaluation combined with ^99mTc-macroaggregated albumin (Tc-MAA) scanning should precede the treatment of any selected candidates for radioembolization (RE) of the liver. If the tumours in one liver lobe have not been targeted in the test angiogram, it should be repeated. However, in a few cases treatment of one liver lobe or at least some segments is safe and feasible and performing a repeated test angiogram with Tc-MAA (Re-MAA) in a separate session leads to more radiation exposure and could be time consuming. Our aim was to evaluate the feasibility of concurrent RE of a part of the liver and therapy planning for another region by simultaneous injection of the Tc-MAA and ⁹⁰Y-microspheres in two different locations in the therapy session. Tc-MAA and bremsstrahlung (BS) single photon emission computed tomography (SPECT)/CT were performed separately in an effort to distinguish between the distributions of these two different radiopharmaceuticals.     

Correlation of Technetium-99m Macroaggregated Albumin and Yttrium-90 Glass Microsphere Biodistribution in Hepatocellular Carcinoma: A Retrospective Review of Pretreatment Single Photon Emission CT and Posttreatment Positron Emission Tomography/CT

Purpose

To evaluate whether technetium-99 (^99mTc)-labeled macroaggregated albumin (MAA) can predict subsequent yttrium-90 (⁹⁰Y) distribution and imaging response in patients with hepatocellular carcinoma (HCC).

Benign Biliary Stricture after Yttrium-90 Radioembolization for Hepatocellular Carcinoma

PurposeTo determine the frequency and possible causative factors of benign biliary stricture after radioembolization in patients with hepatocellular carcinoma (HCC).Materials and MethodsThis retrospective study comprised 232 patients with HCC who underwent yttrium-90 radioembolization between October 2015 and September 2019. Benign biliary stricture was defined as biliary ductal dilatation of segmental or lobar biliary ducts on follow-up images. Clinical and radiologic characteristics were compared using χ² test or independent t test.ResultsMean target perfused tissue dose was 224.6 Gy ± 106.8 (median, 205.7 Gy; range, 47.0–694.7 Gy). Of 232 patients, 15 (6.5%) had benign biliary stricture, which was detected from 3 weeks to 10.3 months (mean, 3.9 months; median, 3.2 months). Whereas 5 patients did not have any symptoms or signs associated with benign biliary stricture, 10 patients had cholangitis and/or laboratory abnormality requiring biliary drainage procedures and intravenous antibiotic therapy. Selective radioembolization through a caudate artery was performed in 55 (23.7%) patients. The incidence of benign biliary stricture was 16.4% (9/55) and 3.4% (6/177) in patients with and without selective radioembolization through a caudate artery, respectively (P = .002).ConclusionsBenign biliary stricture following yttrium-90 radioembolization may be common among patients receiving selective treatment via a caudate artery.     

Feasibility of temporary protective embolization of normal liver tissue using degradable starch microspheres during radioembolization of liver tumours

Purpose

To describe a new approach to protect nontarget healthy liver tissue using degradable starch microspheres (DSM) as a short-term embolizate during radioembolization of liver tumours with ⁹⁰Y microspheres.

Methods

Between December 2011 and July 2012 radioembolization was performed in 54 patients. Five of these patients (three women, two men; mean age 67 years) underwent protective temporary embolization using DSM (EmboCept® S) of normal liver tissue that could not be excluded from the area treated by radioembolization through catheter repositioning. Clinical symptoms, laboratory findings, preinterventional imaging, and ^99mTc-MAA and bremsstrahlung SPECT/CT, as well as baseline and follow-up imaging with ¹⁸F-FDG PET/CT and MRI, were evaluated in relation to the technical and clinical success of the protective embolization.

Results

Temporary embolization of arteries supplying normal liver tissue using DSM was technically successful in all five patients. ^99mTc-MAA SPECT/CT performed in the first two patients after DSM injection showed no increased pulmonary shunting compared to the MAA test injection without DSM. Bremsstrahlung SPECT/CT after radioembolization demonstrated satisfactory irradiation of the tumour and successful protection of normal liver tissue. There were only mild hepatotoxic effects (grade 1) on laboratory follow-up examinations, and no adverse events associated with DSM embolization or radioembolization were recorded.

Conclusion

Temporary embolization with DSM before radioembolization is feasible and can effectively protect areas of normal liver tissue from irradiation and avoid permanent embolization if other methods such as catheter repositioning are not possible due to the location of the metastases.     

Predictors of Survival after Yttrium-90 Radioembolization of Chemotherapy-Refractory Hepatic Metastases from Breast Cancer

PurposeTo determine predictors of survival after transarterial radioembolization of hepatic metastases from breast cancer.Materials and MethodsTwenty-four patients with chemotherapy-refractory hepatic metastases from breast cancer who underwent radioembolization from 2013 to 2018 were evaluated based on various demographic and clinical factors before and after treatment. Overall survival (OS) was estimated by Kaplan–Meier method. Log-rank analysis was performed to determine predictors of prolonged OS from the time of first radioembolization and first hepatic metastasis diagnosis.ResultsMedian OS times were 35.4 and 48.6 months from first radioembolization and time of hepatic metastasis diagnosis, respectively. Radioembolization within 6 months of hepatic metastasis diagnosis was a positive predictor of survival from first radioembolization, with median OS of 38.9 months vs 22.1 months for others (P = .033). Estrogen receptor (ER)–positive status predicted prolonged survival (38.6 months for ER⁺ vs 5.4 months for ER⁻; P = .005). The presence of abdominal pain predicted poor median OS: 12.8 months vs 38.6 months for others (P < .001). The presence of ascites was also a negative predictor of OS (1.7 months vs 35.4 months for others; P = .037), as was treatment-related grade ≥ 2 toxicity at 3 months (5.4 months vs 38.6 months for others; P = .017).ConclusionsIn patients with metastatic breast cancer, radioembolization within 6 months of hepatic metastasis diagnosis and ER⁺ status appear to be positive predictors of prolonged survival. Conversely, baseline abdominal pain, baseline ascites, and treatment-related grade ≥ 2 toxicity at 3 months after treatment appear to be negative predictors of OS.     

Accuracy and Safety of Scout Dose Resin Yttrium-90 Microspheres for Radioembolization Therapy Treatment Planning: A Prospective Single-Arm Clinical Trial

PurposeTo compare the accuracy and safety of 0.56 GBq resin yttrium-90 (⁹⁰Y) (scout⁹⁰Y) microspheres with those of technetium-99m macroaggregated albumin (MAA) in predicting the therapeutic ⁹⁰Y (Rx⁹⁰Y) dose for patients with hepatocellular carcinoma (HCC).Materials and MethodsThis prospective single-arm clinical trial (Clinicaltrials.gov: NCT04172714) recruited patients with HCC. Patients underwent same-day mapping with MAA and scout⁹⁰Y. Rx⁹⁰Y activity was administered 3 days after mapping. Using paired t test and Pearson correlation, the tumor-to-normal ratio (TNR), lung shunt fraction (LSF), predicted mean tumor dose (TD), and nontumoral liver dose (NTLD) by MAA and scout⁹⁰Y were compared with those by Rx⁹⁰Y. Bland-Altman plots compared the level of agreement between the TNR and LSF of scout⁹⁰Y and MAA with that of Rx⁹⁰Y. The safety of scout⁹⁰Y was evaluated by examining the discrepancy in extrahepatic activity between MAA and scout⁹⁰Y.ResultsThirty patients were treated using 19 segmental and 14 nonsegmental (ie, 2 contiguous segments or nonsegmental) therapies. MAA had weak LSF, moderate TNR, and moderate TD linear correlation with Rx⁹⁰Y. Scout⁹⁰Y had a moderate LSF, strong TNR, strong TD, and very strong NTLD in correlation with those of Rx⁹⁰Y. Furthermore, the TNR and LSF of scout⁹⁰Y had a stronger agreement with those of Rx⁹⁰Y than with those of MAA. In the nonsegmental subgroup, MAA had no significant correlation with the TD and NTLD of Rx⁹⁰Y, whereas scout⁹⁰Y had a very strong correlation with both of these factors. In the segmental subgroup, both MAA and scout⁹⁰Y had a strong linear correlation with the TD and NTLD of Rx⁹⁰Y.ConclusionsCompared with MAA, scout⁹⁰Y is a more accurate surrogate for Rx⁹⁰Y biodistribution for nonsegmental therapies.     

Yttrium-90 Radioembolization in Intrahepatic Cholangiocarcinoma: A Multicenter Retrospective Analysis

PurposeTo report outcomes of yttrium-90 (⁹⁰Y) radioembolization in patients with unresectable intrahepatic cholangiocarcinoma (ICC).Materials and MethodsRetrospective review was performed of 115 patients at 6 tertiary care centers; 92 were treated with resin microspheres (80%), 22 were treated with glass microspheres (19%), and 1 was treated with both. Postintervention outcomes were compared between groups with χ² tests. Survival after diagnosis and after treatment was assessed by Kaplan–Meier method.ResultsGrade 3 laboratory toxicity was observed in 4 patients (4%); no difference in toxicity profile between resin and glass microspheres was observed (P = .350). Clinical toxicity per Society of Interventional Radiology criteria was noted in 29 patients (25%). Partial response per Response Evaluation Criteria In Solid Tumors 1.1 was noted in 25% of patients who underwent embolization with glass microspheres and 3% of patients who were treated with resin microspheres (P = .008). Median overall survival (OS) from first diagnosis was 29 months (95% confidence interval [CI], 21–37 mo) for all patients, and 1-, 3-, and 5-year OS rates were 85%, 31%, and 8%, respectively. Median OS after treatment was 11 months (95% CI, 8–13 mo), and 1- and 3-year OS rates were 44% and 4%, respectively. These estimates were not significantly different between resin and glass microspheres (P = .730 and P = .475, respectively). Five patients were able to undergo curative-intent resection after ⁹⁰Y radioembolization (4%).ConclusionsThis study provides observational data of treatment outcomes after ⁹⁰Y radioembolization in patients with unresectable ICC.     

Ex Vivo Evaluation of Residual Activity and Infusion Dynamics in a Commercially Available Yttrium-90 Resin Microsphere Administration System

PurposeTo evaluate the infusion dynamics and residual yttrium-90 activity during and after resin microsphere radioembolization with different injection techniques and initial activities. To assess the distribution of residual activity in the administration systems to allow optimization of the procedure and the equipment.Materials and MethodsIn a setup similar to that in standard clinical practice, radioembolization procedures were performed ex vivo. The influence of different injection techniques was assessed by comparing pulsatile and continuous injections. The influence of the absolute amount of activity to the residual activity was assessed by comparing pulsatile 0.5-GBq- with 1.0-GBq-procedures. Continuous dose rate measurements were performed. Activity distribution was determined by positron-emission tomography (PET)/CT.ResultsFifteen procedures were performed: 5 pulsatile 0.5-GBq-, 5 continuous 0.5-GBq-, and 5 pulsatile 1.0-GBq-procedures. Mean residual activity was 4.0% ± 1.7% (range 1.2%–6.6%), without statistically significant differences between injection techniques (P = .841) or between prescribed activities (P = .222). Dose-rate measurements revealed an exponential decrease of the activities in the vials with high variability. Activity fell rapidly to 32% ± 7.9% (range 23%–55%) after injection of 4 of 20 mL 5% dextrose solution. Residual activity accumulations were identified at the 3-way stopcock (100% of procedures), in the C-line (80%), at the microcatheter connector (20%), and in the A-line (6.7%), but not in the vials.ConclusionsResidual activity in a commercial administration system for resin microsphere radioembolization is variable and does not systematically depend on initial yttrium-90 activity or on injection technique. Predilection sites for residual activity were identified, which should receive special attention when performing resin transarterial radioembolization procedures, and for further administration system developments.     

Yttrium-90 Radioembolization in the VX2 Rabbit Model: Radiation Safety and Factors Influencing Delivery Efficiency

The purpose of this study was to define the optimal infusion parameters and operator radiation exposure for yttrium-90 (⁹⁰Y) radioembolization in the VX2 rabbit model of liver cancer. Forty-one rabbits with VX2 were treated with glass microspheres with vial sizes of 1, 3, and 5 GBq. The mean administered activity was 51.5 MBq (95% CI, 39.1–63.9). Delivery efficiency improved with 1 GBq versus with 3 GBq (residual 11.0% vs 46.4%, respectively; P = .0013) and improved with 1 GBq versus with 5 GBq (residual 11.0% vs 33.8%, respectively; P = .0060). The mean operator extremity exposure was 41.7 μSv/infusion. The optimal minimum infusion volume and rate was 49 mL and 21 mL/min, respectively. Fecal elimination occurred with microsphere uptake in the gallbladder at 1 and 2 weeks. ⁹⁰Y radioembolization can be safely and efficiently performed in the VX2 rabbit model. Methodological considerations as a “how-to” for the setup of a preclinical ⁹⁰Y laboratory are included to support future translational research.     

Outcomes of Yttrium-90 Radioembolization for Unresectable Combined Biphenotypic Hepatocellular-Cholangiocarcinoma

PurposeTo evaluate outcomes of yttrium-90 radioembolization in patients with combined biphenotypic hepatocellular-cholangiocarcinoma (cHCC-CC).Materials and MethodsA retrospective review of patients with biopsy-confirmed cHCC-CC treated with yttrium-90 radioembolization between 2012 and 2018 was performed. Twenty-two patients with cHCC-CC (mean age 65.6 y, 17 men, 5 women) underwent 29 radioembolization treatments (5 resin, 24 glass microspheres). Survival data were available in 21 patients, and hepatic imaging response data were available in 20 patients. Hepatic imaging response to radioembolization was assessed on follow-up CT or MR imaging using modified Response Evaluation Criteria In Solid Tumours criteria. Univariate stepwise Cox regression analysis was used to evaluate the association between demographic and clinical factors and survival. Logistic regression evaluated associations between clinical factors and response to treatment, overall response, and disease control.ResultsHepatic imaging response was as follows: 15% complete response, 40% partial response, 10% stable disease, and 35% progressive disease (55% response rate, 65% disease control rate). Two patients were downstaged or bridged to transplant, and 1 patient was downstaged to resection. Median overall survival was 9.3 mo (range, 2.5–31.0 mo) from time of radioembolization. Nonreponse to treatment, bilobar disease, presence of multiple tumors, and elevated carbohydrate antigen 19-9 before treatment were associated with reduced survival after radioembolization.ConclusionsRadioembolization is a viable option for locoregional control of cHCC-CC with good response and disease control rates.     

Increasing Yttrium-90 Dose Conformality Using Proximal Radioembolization Enabled by Distal Angiosomal Truncation for the Treatment of Hepatic Malignancy

PurposeTo evaluate safety and feasibility of improving radiation dose conformality via proximal radioembolization enabled by distal angiosomal truncation where selective administration was not practical.Materials and MethodsHepatic malignancies treated via angiosomal truncation between January 2017 and March 2019 were retrospectively evaluated. Thirty-three patients (8 women, 25 men; mean age, 62.2 y; range, 36–78 y) underwent 39 treatments. Of treatments, 74.3% (n = 29) were for hepatocellular carcinomas, 10.2% (n = 4) were for cholangiocarcinomas, and 15.4% (n = 6) were for metastatic tumors (1 colorectal adenocarcinoma, 1 pancreatic adenocarcinoma, 3 melanomas, and 1 endometroid carcinoma). Truncation was achieved using temporary embolic devices including a microvascular plug, detachable coil, gelatin slurry, and balloon microcatheter, after which proximal radioembolization was performed. Range of treatment activity was 0.47–5.75 GBq. Technetium-99m macroaggregated albumin and bremsstrahlung single photon emission computed tomography (CT)/CT threshold analysis was conducted to delineate and compare distribution of activity within the treatment angiosome before and after radioembolization.ResultsDosimetric analysis of 14 patients demonstrated a significant reduction in nontarget liver radiation exposure at 5, 20, and 40% thresholds (P = .002, P = .001, and P = .008, respectively). There were no grade 3 or higher adverse events. There was no significant change in Albumin-Bilirubin grade and Eastern Cooperative Oncology Group Performance Status (P = .09 and P = .74) before and 3 months after the procedure. Truncated arteries were patent on subsequent angiography in 11 cases and on MR angiography or CT angiography in 38 of 39 cases.ConclusionsProximal radioembolization enabled by distal angiosomal truncation is safe and decreases nontarget parenchymal radioembolization dose in cases not amenable to selective administration.     

Transarterial Radioembolization with Yttrium-90 Glass Microspheres: Distribution of Residual Activity and Flow Dynamics during Administration

PurposeTo evaluate the microsphere flow dynamics and residual yttrium-90 (⁹⁰Y) activity during and after transarterial radioembolization with glass microspheres and to assess the distribution and predilection sites of residual activity in the administration devices.Materials and MethodsIn this laboratory investigation, after 18 consecutive clinical transarterial radioembolization and 4 ex vivo experimental procedures with ⁹⁰Y glass microspheres, the distribution of residual activity in the administration devices was assessed by activimeter and positron emission tomography (PET)/CT measurements. During ex vivo procedures, microsphere outflow from the administration device was assessed by dynamic scintigraphic measurements.ResultsMean residual activity was 3.4% ± 1.7 (range, 0.9%–8.8%). Calculations showed a negative correlation between relative residual activity and prescribed activity (r = −0.4258, P = .0486) and a positive correlation between absolute residual activity and prescribed activity (r = 0.5345, P = .0104). The main predilection site was the Luer-Lok microcatheter connector. Lower activities were detected in the dose vial. Flow measurements showed that more than 98% of the final injected activity was transferred to the patient with the first 20 mL of saline solution.ConclusionsResidual activity in the standard administration device for glass microsphere radioembolization is considered to be low compared with similar procedures, but is variable. The microsphere flow profile shows an initial peak, resulting in a rapid activity transfer at the beginning of the injection process. The findings may have implications for safe handling of the administration device and for dose calculation of ⁹⁰Y glass microspheres.     

Transarterial Yttrium-90 Radioembolization of Hepatocellular Carcinoma Perfused by the Cystic Artery: Multi-institutional Feasibility Study

PurposeTo assess the safety and efficacy of transarterial yttrium-90 radioembolization via the cystic artery for patients with hepatocellular carcinoma (HCC) adjacent to the gallbladder with cystic artery supply.Materials and MethodsThis retrospective study included 17 patients treated at 4 institutions. Patients with HCC perfused by the cystic artery who received ablative-dose radioembolization were included. Median tumor size was 3.8 cm (range, 2.0–8.8 cm). Fourteen patients (82%) had Child–Pugh class A cirrhosis and 3 (18%) had class B cirrhosis. Adverse events, tumor response, and time to progression were analyzed.ResultsMedian dose to the tissue perfused by the cystic artery was 340 Gy (range, 200–720 Gy). There were no occurrences of acute cholecystitis warranting invasive intervention. Four patients (24%) experienced transient right upper quadrant pain, with symptom resolution within 3 mo. Six patients (35%) exhibited gallbladder wall edema on follow-up imaging. Two (12%) and 0 grade 3/4 increases in alkaline phosphatase and bilirubin were observed, respectively. Follow-up imaging demonstrated complete response in 13 target tumors (76%) and partial response in 4 (24%). There were no cases of target tumor progression during a median follow-up of 9 mo (range, 3–72 mo).ConclusionsDirect infusion of ⁹⁰Y microspheres via the cystic artery appears to have an acceptable safety profile, without resulting in acute cholecystitis warranting invasive intervention. In selected patients with HCC in whom other treatments may be contraindicated and the tumor is supplied via the cystic artery, treatment with selective ablative radioembolization can be considered.     

Prospective Study of Systemic Yttrium-90 Elution during Radioembolization of Hepatic Metastases

PurposeTo evaluate total blood radioactivity (BR) after SIR-Spheres yttrium-90 (⁹⁰Y) radioembolization and differences in BR based on delivery method.Materials and MethodsTwenty participants with hepatic metastases undergoing first radioembolization were prospectively enrolled from December 2017 to June 2018. Blood samples were drawn at baseline and 0, 10, 20, 60, and 120 minutes after ⁹⁰Y administration. BR was measured with a γ-counter and scaled by estimated blood volume. Percentage of instilled radioactivity in the bloodstream was calculated as area under the fitted curve, and differences between delivery methods were examined with nonparametric statistical tests.ResultsIn 10 participants, resin microspheres were instilled with 50% Isovue 300 diluted in saline solution in the D line, and 10 others were treated with dextrose 5% in water (D5W) in the D line. Median administered activities were 944 MBq (range, 746–1,993 MBq) and 1,213 MBq (range, 519–2,066 MBq), respectively. Fraction of ⁹⁰Y in blood was significantly higher with dilute contrast agent than with D5W (median, 0.5% of injected activity vs 0.2%; P = .001). Among all participants, the maximum activity delivered was 2,066 MBq, and a maximum of 1% of administered radioactivity was measured as free ⁹⁰Y in blood. Assuming these highest-case values and complete decay of all free ⁹⁰Y in bone, a dose to red marrow of 132.3 mGy was calculated by Organ Level INternal Dose Assessment/EXponential Modeling.ConclusionsBlood sampling after radioembolization allowed for estimation of the time–activity curve and BR. Delivery with 50% contrast agent in saline solution resulted in a significant increase in BR vs D5W, even though the total BR for both groups was nominal.     

Radioembolization with Yttrium-90 Glass Microspheres as a First-Line Treatment for Unresectable Intrahepatic Cholangiocarcinoma—A Prospective Feasibility Study

PurposeTo evaluate the safety and effectiveness of yttrium-90 (⁹⁰Y) radioembolization as first-line treatment for unresectable intrahepatic cholangiocarcinoma (ICC).Materials and MethodsThis prospective study enrolled patients who had never received chemotherapy, liver embolization, and radiation therapy. The tumors were solitary in 16 patients, multiple in 8 patients, unilobar in 14 patients, and bilobar in 10 patients. Patients underwent transarterial radioembolization with ⁹⁰Y-labeled glass microspheres. The primary end point was hepatic progression-free survival (HPFS). Secondary end points were overall survival (OS), tumor response, and toxicity.ResultsTwenty-four patients (age, 72.3 years ± 9.3; 12 women) were included in the study. The median delivered radiation dose was 135.5 Gy (interquartile range, 77.6 Gy). The median HPFS was 5.5 months (95% CI, 3.9–7.0 months). Analysis failed to identify any prognostic factor associated with HPFS. Imaging response at 3 months showed 56% disease control, and the best radiographic response was 71% disease control. The median OS from the radioembolization treatment was 19.4 months (95% CI, 5.0–33.7). Patients with solitary ICC had significantly longer median OS than patients with multifocal ICC: 25.9 months (95% CI, 20.8–31.0 months) versus 10.7 months (95% CI, 8.0–13.4 months) (P = .02). Patients with progression on the 3-month imaging follow-up had significantly shorter median OS than patients who had stable disease at 3 months: 10.7 months (95% CI, 0.7–20.7 months) versus 37.3 months (95% CI, 16.5–58.1 months) (P = .003). Two (8%) Grade 3 toxicities were reported.ConclusionsFirst-line treatment of ICC with radioembolization showed promising OS and minimal toxicity, especially in patients with solitary tumor. Radioembolization may be considered as a first-line treatment option for unresectable ICC.     

Transarterial Yttrium-90 Radioembolization for Unresectable Intrahepatic Cholangiocarcinoma: A Systematic Review and Meta-Analysis

PurposeTo investigate the overall efficacy and survival profile of yttrium-90 (⁹⁰Y) radioembolization for unresectable intrahepatic cholangiocarcinoma (ICC).Materials and MethodsA systematic literature review and meta-analysis was completed using a random-effects model. Studies describing the use of ⁹⁰Y for unresectable ICC were included. The disease control rate (DCR), downstaged-to-resectable rate, cancer antigen 19-9 (CA19-9) response rate, pooled median overall survival (OS), pooled median progression-free survival (PFS), and mean reported survival rates ranging from 3 to 36 months were evaluated.ResultsTwenty-one studies detailing a total of 921 patients were included. The overall DCR was 82.3% (95% confidence interval [CI], 76.7%–87.8%; I² = 81%). In 11% of the cases, patients were downstaged to being surgically resectable (95% CI, 6.1%–15.9%; I² = 78%). The CA19-9 response rate was 67.2% (95% CI, 54.5%–79.8%; I² = 60%). From the time of radioembolization, PFS was 7.8 months (95% CI, 4.2–11.3 months; I² = 94%) and median OS was 12.7 months (95% CI, 10.6–14.8 months; I² = 62%). Lastly, the mean overall reported survival proportions were 84% at 3 months (standard deviation [SD], 10%), 69% at 6 months (SD, 16%), 47% at 12 months (SD, 19%), 31% at 18 months (SD, 21%), 30% at 24 months (SD, 19%), 21% at 30 months (SD, 27%), and 5% at 36 months (SD, 7%).ConclusionsRadioembolization with ⁹⁰Y for unresectable ICC results in substantial downstaging, disease control, and survival.