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.     

Chronic Hepatotoxicity in Patients with Metastatic Neuroendocrine Tumor: Transarterial Chemoembolization versus Transarterial Radioembolization

PurposeTo compare the manifestations of chronic liver injury following transarterial chemoembolization with those of transarterial radioembolization (TARE) in patients with neuroendocrine tumor (NET).Materials and MethodsThis study consisted of an Institutional Review Board-approved single-institution retrospective analysis of NET patients who received transarterial chemoembolization from 2006 to 2016 and TARE from 2005 to 2014 and survived at least 1 year from the initial treatment. Patients receiving only transarterial chemoembolization (n = 63) or TARE (n = 28) were evaluated for the presence or absence of durable hepatic toxicities occurring at least 6 months after initial treatment. The definitions and grades of liver injury were adapted from Common Terminology Criteria for Adverse Events version 4.0 and were characterized by the presence of laboratory or clinical toxicities of Grade 3 or above.ResultsChronic hepatic toxicity occurred in 14 of 63 transarterial chemoembolization patients (22%) with a total of 26 Grade 3-4 events, in whom elevation of bilirubin was the most common toxicity, compared to 8 of 28 TARE patients (29%) with a total of 16 Grade 3-4 and 2 Grade 5 events, in whom ascites were the most frequent toxicity. There were more laboratory toxicities in the transarterial chemoembolization group (65% vs 38%, P = .11) and fewer Grade 4–5 injuries (6% vs 27% of patients, P = .06). There was also a significantly higher number of patients who experienced intrahepatic progression of disease in the transarterial chemoembolization cohort than in the TARE patients (75% vs 43%, respectively; P = .005).ConclusionsDelayed hepatotoxicity from transarterial chemoembolization and TARE occurred in 22% and 29% of patients, respectively, from 6 months to several years following treatment. Transarterial chemoembolization-related toxicities on average were less severe and manifested primarily as laboratory derangements, compared to TARE toxicities which consisted of clinical hepatic decompensation.     

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.     

Transarterial Radioembolization Treatment of Pancreatic Cancer Patients with Liver-Dominant Metastatic Disease Using Yttrium-90 Glass Microspheres: A Single-Institution Retrospective Study

PurposeTo retrospectively evaluate the safety and efficacy of transarterial radioembolization (TARE) with yttrium-90 (⁹⁰Y)-labeled glass microspheres in pancreatic adenocarcinoma patients with liver-dominant metastatic disease.Materials and MethodsThis retrospective, single-center study evaluated 26 patients (12 men and 14 women; mean age, 65.5 ± 11.2 years) with liver-dominant metastatic pancreatic cancer who were treated with TARE from April 2010 to September 2017. All patients received systemic chemotherapy before TARE, and 19 received systemic therapy after embolization. Nineteen patients had extrahepatic disease at the time of TARE. Response to treatment was determined by Response Evaluation Criteria in Solid Tumors at 3 months.ResultsMedian overall survival (OS) from pancreatic cancer diagnosis was 33.0 months (range, 8.5–87.5 months); median OS from diagnosis of liver metastasis was 21.8 months (range, 2.0–86.2 months); and median OS from TARE treatment was 7.0 months (range, 1.0–84.1 months). Grade 1–2 clinical toxicities were noted in 21 patients (80.8%), and 24 patients (92.3%) had grade 1–2 biochemical toxicities. Four patients (15.4%) had grade 3 clinical toxicities, and 6 patients (23.1%) had grade 3 biochemical toxicities. Imaging was available in 22 patients (84.6%) and demonstrated partial response in 1 patient, stable disease in 9 patients, and progressive disease in 12 patients. Improved hepatic progression-free survival was associated in patients younger than 65 years and in those whose carbohydrate antigen 19-9 level decreased or remained stable after treatment.ConclusionsTARE with ⁹⁰Y-labeled glass microspheres is safe and led to promising OS in liver-dominant metastatic pancreatic cancer.     

Safety and Effectiveness of Yttrium-90 Radioembolization around the Time of Immune Checkpoint Inhibitors for Unresectable Hepatic Metastases

PurposeTo assess the safety and effectiveness of yttrium-90 radioembolization and checkpoint inhibitor immunotherapy within a short interval for the treatment of unresectable hepatic metastases.Materials and MethodsThis single-institution retrospective study included 22 patients (12 men; median age, 65 y ± 11) with unresectable hepatic metastases and preserved functional status (Eastern Cooperative Oncology Group performance status 0/1) who received immunotherapy and radioembolization within a 15-month period (median, 63.5 d; interquartile range, 19.7–178.2 d) from February 2013 to March 2018. Primary malignancies were uveal melanoma (12 of 22; 54.5%), soft tissue sarcoma (3; 13.6%), cutaneous melanoma (3; 14%), and others (4; 18.2%). Studies were reviewed to March 2019 to assess Common Terminology Criteria for Adverse Events grade 3/4 toxicities, disease progression, and death.ResultsThere were no grade 4 toxicities within 6 mo of radioembolization. Grade 3 hepatobiliary toxicities occurred in 3 patients (13.6%) within 6 months, 2 from rapid disease progression and 1 from a biliary stricture. Two patients (9.1%) experienced clinical toxicities, including grade 4 colitis at 6 months and hepatic abscess at 3 months. Median overall survival (OS) from first radioembolization was 20 mo (95% confidence interval [CI], 12.5–27.5 mo), and median OS from first immunotherapy was 23 months (95% CI, 15.9–30.1 mo). Within the uveal melanoma subgroup, the median OS from first radioembolization was 17.0 months (95% CI, 14.2–19.8 mo). Median time to progression was 7.8 months (95% CI, 3.3–12.2 mo), and median progression-free survival was 7.8 mo (95% CI, 3.1–12.4 mo).ConclusionsCheckpoint immunotherapy around the time of radioembolization is safe, with a low incidence of toxicity independent of primary malignancy.     

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.     

Radiation Dose during Transarterial Radioembolization: A Dosimetric Comparison of Cone-Beam CT and Angio-CT Technologies

PurposeTo evaluate the radiation dose differences for intraprocedural computed tomography (CT) imaging between cone-beam CT and angio-CT acquired during transarterial radioembolization (TARE) therapies for hepatocellular carcinoma.Materials and MethodsA retrospective cohort of 22 patients who underwent 23 TARE procedures were selected. Patients were imaged in both cone-beam CT and angio-CT rooms as a part of their conventional treatment plan. Effective dose contributions from individual CT acquisitions as well as the cumulative dose contributions from procedural 3D imaging were evaluated. Angiography dose contributions were omitted. Cone-beam CT images were acquired on a C-arm Philips Allura system. Effective doses were evaluated by coupling previously published conversion factors (effective dose per dose-area product) to patient’s dose-area product meter readings after the procedure. Angio-CT images were acquired on a hybrid Canon Infinix-i Aquilion PRIME system. Effective doses from angio-CT scans were estimated using Radimetrics. Comparisons of a single patient’s dose differential between the 2 technologies were made.ResultsThe mean effective dose from a single CT scan was 6.42 mSv and 5.99 mSv in the cone-beam CT room and the angio-CT room, respectively (P = .3224), despite the greater field of view and average craniocaudal scan coverage in angio-CT. The mean effective dose summed across all CTs in a procedure was 12.89 mSv and 34.35 mSv in the cone-beam CT room and the angio-CT room, respectively (P = .0018).ConclusionsThe mean effective dose per CT scan is comparable between cone-beam CT and angio-CT when considered in direct comparison for a single patient.     

Yttrium-90 Activity Quantification in PET/CT–Guided Biopsy Specimens from Colorectal Hepatic Metastases Immediately after Transarterial Radioembolization Using Micro–CT and Autoradiography

PurposeTo evaluate the yttrium-90 (⁹⁰Y) activity distribution in biopsy tissue samples of the treated liver to quantify the dose with higher spatial resolution than positron emission tomography (PET) for accurate investigation of correlations with microscopic biological effects and to evaluate the radiation safety of this procedure.Materials and MethodsEighty-six core biopsy specimens were obtained from 18 colorectal liver metastases (CLMs) immediately after ⁹⁰Y transarterial radioembolization (TARE) with either resin or glass microspheres using real-time ⁹⁰Y PET/CT guidance in 17 patients. A high-resolution micro–computed tomography (micro-CT) scanner was used to image the microspheres in part of the specimens and allow quantification of ⁹⁰Y activity directly or by calibrating autoradiography (ARG) images. The mean doses to the specimens were derived from the measured specimens’ activity concentrations and from the PET/CT scan at the location of the biopsy needle tip for all cases. Staff exposures were monitored.ResultsThe mean measured ⁹⁰Y activity concentration in the CLM specimens at time of infusion was 2.4 ± 4.0 MBq/mL. The biopsies revealed higher activity heterogeneity than PET. Radiation exposure to the interventional radiologists during post-TARE biopsy procedures was minimal.ConclusionsCounting the microspheres and measuring the activity in biopsy specimens obtained after TARE are safe and feasible and can be used to determine the administered activity and its distribution in the treated and biopsied liver tissue with high spatial resolution. Complementing ⁹⁰Y PET/CT imaging with this approach promises to yield more accurate direct correlation of histopathological changes and absorbed dose in the examined specimens.     

Transarterial Radioembolization versus Transarterial Chemoembolization Plus Percutaneous Ablation for Unresectable,Solitary Hepatocellular Carcinoma of ≥3 cm: A Propensity Score–Matched Study

PurposeTo compare the safety and effectiveness of transarterial radioembolization (TARE) and transarterial chemoembolization with drug-eluting embolic agents combined with percutaneous ablation (transarterial chemoembolization [TACE] + ablation) in the treatment of treatment-naïve, unresectable, solitary hepatocellular carcinoma (HCC) of ≥3 cm.Materials and MethodsTwenty-nine patients with treatment-naïve, unresectable, solitary HCC of ≥3 cm received combined TACE + ablation, and 40 patients received TARE at a single institution. Local tumor response, tumor progression-free survival (PFS), overall survival, need for reintervention, bridge to transplant, and major complications were compared. Clinical variables and outcomes were compared before and after propensity score matching (PSM).ResultsBefore PSM, patients who underwent TARE had a larger tumor size (3.7 vs 5.5 cm; P = .0005) and were older (61.5 vs 69.3 years; P = .0014). After PSM, there was no difference in baseline characteristics between the 2 groups, with the mean tumor sizes measuring 3.9 and 4.1 cm in the TACE + ablation and TARE cohorts, respectively. After PSM (n = 19 in each group), no statistically significant difference was observed in local radiological response (disease control rates, 100% vs 94.7%; P = .31), survival (subdistribution hazard ratio [SHR], 0.71; 95% confidence interval [CI], 0.28–1.80; P = .469), PFS (SHR, 0.61; 95% CI, 0.21–1.71; P = .342), bridge to transplant (21.1% vs 31.6%, P = .46), and major adverse event rates (15.8% vs 10.5%, P = .63) between the 2 groups. The mean total number of locoregional interventions was higher in the TACE + ablation cohort (1.9 vs 1.3 sessions, P = .02), with an earlier median reintervention trend (SHR, 0.61; 95% CI, 0.20–1.32; P = .167).ConclusionsThe present study showed that TARE and the combination of TACE and ablation are comparable in safety and effectiveness for treating treatment-naïve, unresectable, solitary HCC of ≥3 cm.     

Induction of Contralateral Hepatic Hypertrophy by Unilobar Yttrium-90 Transarterial Radioembolization versus Portal Vein Embolization: An Animal Study

PurposeTo compare hepatic hypertrophy in the contralateral lobe achieved by unilobar transarterial radioembolization (TARE) versus portal vein embolization (PVE) in a swine model.MethodsAfter an escalation study to determine the optimum dose to achieve hypertrophy after unilobar TARE in 4 animals, 16 pigs were treated by TARE (yttrium-90 resin microspheres) or PVE (lipiodol/n-butyl cyanoacrylate). Liver volume was calculated based on CT before treatment and during 6 months of follow-up. Independent t-test (P < .05) was used to compare hypertrophy. The relationship between hypertrophy after TARE and absorbed dose was calculated using the Pearson correlation.ResultsAt 2 and 4 weeks after treatment, a significantly higher degree of future liver remnant hypertrophy was observed in the PVE group versus the TARE group, with a median volume gain of 31% (interquartile range [IQR]: 16%–66%) for PVE versus 23% (IQR: 6%–36%) for TARE after 2 weeks and 51% (IQR: 47%–69%) for PVE versus 29% (IQR: 20%–50%) for TARE after 4 weeks. After 3 and 6 months, hypertrophy converged without a statistically significant difference, with a volume gain of 103% (IQR: 86%–119%) for PVE versus 82% (IQR: 70%–96%) for TARE after 3 months and 115% (IQR: 70%–46%) for PVE versus 86% (IQR: 58%–111%) for TARE after 6 months. A strong correlation was observed between radiation dose (median 162 Gy, IQR: 139–175) and hypertrophy.ConclusionsPVE resulted in rapid hypertrophy within 1 month of the procedure, followed by a plateau, whereas TARE resulted in comparable hypertrophy by 3–6 months. TARE-induced hypertrophy correlated with radiation absorbed dose.     

Survival and Toxicities after Yttrium-90 Transarterial Radioembolization of Cholangiocarcinoma in the RESiN Registry

PurposeTo report outcomes in patients with intrahepatic cholangiocarcinoma treated with yttrium-90 resin microspheres (transarterial radioembolization [TARE]) from a multicenter, prospective observational registry.Materials and MethodsNinety-five patients (median age, 67 years [interquartile range {IQR}, 59–74]; 50 men) were treated in 27 centers between July 2015 and August 2020. Baseline demographic characteristics included imaging findings, performance status, and previous systemic or locoregional treatments. Dosimetry method was tracked. Overall survival (OS) and progression-free survival were calculated using the Kaplan-Meier method. The best imaging response was calculated using the Response Evaluation Criteria in Solid Tumors v1.1. Grade ≥3 toxicities were assessed using Common Terminology Criteria for Adverse Events v5. Cox regression analysis was performed.ResultsFifty-two of 86 (60%) patients had multifocal tumors, and 24/89 (27%) had extrahepatic tumors. The median index tumor diameter was 7.0 cm (IQR, 4.9–10 cm). The activity calculation method was reported in 59/95 (62%) patients, with body surface area being the most frequently used method (45/59, 76%). Median OS for the cohort was 14 months (95% confidence interval, 12–22). OS at 3, 6, 12, and 24 months was 94%, 80%, 63%, and 34%, respectively. Median OS was longer in patients without cirrhosis (19.1 vs 12.2 months, P = .05). Cirrhosis, previous chemotherapy (OS, 19.1 vs 10.6 months for treatment-naïve; P = .07), and imaging response at 6 months (OS, 16.4 vs 9.5 months for no response; P = .06) underwent regression analysis. Imaging response predicted OS at regression (hazard ratio, 0.39; P = .008). Grade 3–4 bilirubin toxicities were noted in 5 of 72 (7%) patients. Grade 3 albumin toxicity was noted in 1 of 72 (1.4%) patients.ConclusionsObjective response at 6 months predicted longer OS after TARE for intrahepatic cholangiocarcinoma. The incidence of liver function toxicity was <10%.     

Systematic Review and Meta-Analysis of Prophylactic Transarterial Embolization for High-Risk Bleeding Peptic Ulcer Disease

The present systematic review determined the role of transarterial embolization (TAE) as a prophylactic treatment in bleeding peptic ulcers after initial successful endoscopic hemostasis. PubMed and Ovid Medline databases were searched from inception until July 2019 for studies that included patients deemed high-risk based on Forrest Classification, Rockall score ≥ 5, or endoscopic evaluation in addition to those who underwent prophylactic TAE after initial successful endoscopic hemostasis. Meta-analysis was performed to compare patients who underwent endoscopic therapy (ET) and TAE with those who underwent ET alone. The primary outcomes measured included rates of rebleeding, reintervention, and 30-day mortality. Secondary outcome measures evaluated length of hospitalization, technical success rates, and complications associated with TAE. Of 916 publications, 5 were eligible for inclusion; 310 patients with high-risk peptic ulcer bleeding underwent prophylactic TAE, and 255 were compared against a control group of 580 patients that underwent standard treatment with ET alone. Patients who underwent ET with TAE had lower 30-day rebleeding rates (odds ratio [OR], 0.35; 95% confidence interval [CI] 0.15–0.85; P = .02; I² = 50%). The ET with TAE group had a lower 30-day mortality rate (OR, 0.28; 95% CI, 0.10–0.83; P = .02; I² = 58%). There was no difference in pooled reintervention rates (OR, 0.68; 95% CI, 0.43–1.08; P = .10; I² = 0%) and length of hospitalization (mean difference, ?0.32; 95% CI, ?1.88 to 1.24; P = .69; I² = 0%). Technical success rate of prophylactic TAE was 90.5% (95% CI, 83.09–97.98; I² = 75.9%). Pooled proportion of overall complication rate was 0.18% (95% CI, 0.00–1.28; I² = 0%). Prophylactic TAE has lower rebleeding and mortality with a good success rate and low complications. Prophylactic TAE after primary ET may be recommended for selected patients with high-risk bleeding ulcers; however, further studies should be performed to establish this as a routine tool in patients with bleeding peptic ulcer disease.     

Cryoablation of Venous Malformations: A Systematic Review

This study aimed to review systematically the efficacy, safety, and technical aspects of cryoablation in the treatment of venous malformations (VMs) and to provide the groundwork for future studies. A literature search for clinical studies utilizing percutaneous cryoablation of VMs was performed. All clinical studies related to primary or secondary treatment of VMs with percutaneous cryoablation were included in this review. These selected studies were evaluated for patient characteristics, cryoablation technique, technical success, lesion size and pain scores before and after cryoablation, and adverse outcomes. Random effects analysis of postprocedural changes in lesion volume and pain scores was performed. There were 54 patients with 55 cases of cryoablation of VMs. Of these cases, 27 recorded changes in lesion volume and 31 recorded changes in pain scores. The weighted mean postprocedural decrease in lesion size was 92.0% (raw average, 71.7%). The weighted mean reduction in pain score was 77% (raw average, 78.2%). Considering all treated cases (55), complete resolution of symptoms was seen in 35 cases (63.6%) and overall (complete or partial) improvement in 52 cases (94.5%). Common postprocedural symptoms included pain, bruising, swelling and numbness lasting less than 2 weeks. There were two major adverse events (3.7%), with both cases due to persistent dysesthesia. Patients with a history of prior sclerotherapy demonstrated lower preprocedural and postprocedural pain scores (4.7 and 1.3) than patients without prior treatments (5.8 and 2.8). Cryoablation of VMs appears to be potentially safe and effective on limited short-interval follow-up.     

Transarterial Radioembolization for Hepatocellular Carcinoma with Major Vascular Invasion: A Nationwide Propensity Score–Matched Analysis with Target Trial Emulation

PurposeTo examine National Cancer Database (NCDB) data to comparatively evaluate overall survival (OS) between patients undergoing transarterial radioembolization (TARE) and those undergoing systemic therapy for hepatocellular carcinoma with major vascular invasion (HCC-MVI).MethodsOne thousand five hundred fourteen patients with HCC-MVI undergoing first-line TARE or systemic therapy were identified from the NCDB. OS was compared using propensity score–matched Cox regression and landmark analysis. Efficacy was also compared within a target trial framework.ResultsTARE usage doubled between 2010 and 2015. Intervals before treatment were longer for TARE than for systemic therapy (mean [median], 66.5 [60] days vs 46.8 (35) days, respectively, P < .0001). In propensity-score–matched and landmark-time–adjusted analyses, TARE was found to be associated with a hazard ratio of 0.74 (95 % CI, 0.60–0.91; P = .005) and median OS of 7.1 months (95 % CI, 5.0–10.5) versus 4.9 months (95 % CI, 3.9–6.5) for systemically treated patients. In an emulated target trial involving 236 patients with unilobular HCC-MVI, a low number of comorbidities, creatinine levels <2.0 mg/dL, bilirubin levels <2.0 mg/dL, and international normalized ratio <1.7, TARE was found to be associated with a hazard ratio of 0.57 (95 % CI, 0.39–0.83; P = .004) and a median OS of 12.9 months (95 % CI, 7.6–19.2) versus 6.5 months (95 % CI, 3.6–11.1) for the systemic therapy arm.ConclusionsIn propensity-score–matched analyses involving pragmatic and target trial HCC-MVI cohorts, TARE was found to be associated with significant survival benefits compared with systemic therapy. Although not a substitute for prospective trials, these findings suggest that the increasing use of TARE for HCC-MVI is accompanied by improved OS. Further trials of TARE in patients with HCC-MVI are needed, especially to compare with newer systemic therapies.     

Transarterial Chemoembolization for the Palliation of Painful Bone Metastases Refractory to First-Line Radiotherapy

PurposeTo compare the efficacy and safety of transarterial chemoembolization for the palliation of radiotherapy (RT)-failure bone metastases (BMs) with those of re-radiotherapy (Re-RT) in achieving pain relief.Materials and MethodsFifty consecutive patients with RT-failure BMs who had undergone Re-RT (23 patients) and transarterial chemoembolization (27 patients) were retrospectively analyzed. The primary endpoint was clinical response, and the secondary endpoints were objective response and adverse events. Pain assessment was performed using the numerical rating scale, and tumor response was evaluated using the modified Response Evaluation Criteria in Solid Tumors. Pain relief was defined as lack of pain with no analgesic usage (complete pain response) or a decrease in pain score by ≥3 points with analgesic usage (partial pain response).ResultsThe pain relief rates in the Re-RT and transarterial chemoembolization groups were 57% and 92%, respectively (P = .006). The median pain relief duration was 2 and 3 months in the Re-RT and transarterial chemoembolization groups, respectively (P = .002). The 6-month pain-free survival rates were 30% and 51% in the Re-RT and transarterial chemoembolization groups, respectively (P = .08). The median tumor reduction rates were –4% and 9% in the Re-RT and transarterial chemoembolization groups, respectively (P < .001). The objective response rates were 0% and 11% in the Re-RT and transarterial chemoembolization groups, respectively (P = .29). No serious adverse events or complications were observed.ConclusionsTransarterial chemoembolization achieved a superior response rate and longer duration of palliation in symptomatic RT-failure BMs.     

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.     

Alpha-Fetoprotein,Des-Gamma-Carboxy Prothrombin,and Modified RECIST Response as Predictors of Survival after Transarterial Radioembolization for Hepatocellular Carcinoma

PurposeTo evaluate the prognostic role of alpha-fetoprotein (AFP), des-gamma-carboxy protein (DCP), and modified Response Evaluation Criteria in Solid Tumors (mRECIST) in patients with hepatocellular carcinoma after transarterial radioembolization (TARE).Materials and MethodsDuring 2009–2016, 63 patients with AFP >20 ng/mL, DCP >20 mAU/mL, and Child-Pugh class A who were treated with TARE were evaluated using landmark and risk-of-death method after TARE. Both resin microspheres (n = 46) and glass microspheres (n = 17) were used. AFP or DCP response was defined as more than 50% decrease from baseline. mRECIST response was defined as complete or partial response. Median age was 60 years, and the proportion of male sex was 77.8% (n = 49). The proportions of patients with Barcelona Clinic Liver Cancer stages A, B, and C were 7.9% (n = 5), 46.0% (n = 29), and 46.0% (n = 29), respectively.ResultsAt the 3-month landmark, AFP, DCP, and mRECIST responders lived longer than nonresponders (median overall survival, 75.8 vs 7.6 months for AFP; 75.8 vs 7.1 months for DCP; and 75.8 vs 10.0 months for mRECIST; all P < .05). The 6-month risk of death at the 3-month landmark was statistically different only between DCP responders and nonresponders (P = .002). In multivariate analysis, age less than 70 years (P = .024), absence of distant metastasis (P = .049), DCP response (P = .003), and mRECIST response (P = .003) were independent predictors for overall survival at the 3-month landmark after TARE.ConclusionsAFP, DCP, and mRECIST responders showed better prognosis than nonresponders after TARE, and DCP response was a more potent predictor than AFP response. Tumor marker response, as well as radiologic response, may be useful to predict post-TARE survival.     

Neoadjuvant Yttrium-90 Transarterial Radioembolization with Resin Microspheres Prescribed Using the Medical Internal Radiation Dose Model for Intrahepatic Cholangiocarcinoma

PurposeTo evaluate outcomes of patients with intrahepatic cholangiocarcinoma (iCCA) undergoing neoadjuvant yttrium-90 (⁹⁰Y) transarterial radioembolization (TARE) with resin microspheres prescribed using the Medical Internal Radiation Dose (MIRD) model.Materials and MethodsThis retrospective institutional review board–approved study included 37 patients with iCCA treated with ⁹⁰Y-TARE from October 2015 to September 2020. The primary outcome was overall survival (OS) from ⁹⁰Y-TARE. The secondary outcomes were progression-free survival (PFS), Response Evaluation Criteria In Solid Tumors 1.1 imaging response, and downstaging to resection. Patients with tumor proximity to the middle hepatic vein (<1 cm) and/or insufficient future liver remnant were treated with neoadjuvant intent (n = 21). Patients were censored at the time of surgery or at the last follow-up for the Kaplan-Meier survival analysis.ResultsFor 31 patients (69 years; interquartile range, 64–74 years; 20 men [65%]) included in the study, the first-line therapy was ⁹⁰Y-TARE for 23 (74%) patients. Imaging assessment at 6 months showed a disease control rate of 86%. The median PFS was 5.4 months (95% confidence interval [CI], 3–not reached). The PFS was higher after first-line ⁹⁰Y-TARE (7.4 months [95% CI, 5.3–not reached]) than that after subsequent ⁹⁰Y-TARE (2.7 months [95% CI, 2–not reached]) (P = .007). The median OS was 22 months (95% CI, 7.3–not reached). The 1- and 2-year OS rates were 60% (95% CI, 41%–86%) and 40% (95% CI, 19.5%–81%). In patients treated with neoadjuvant intent, 11 of 21 patients (52%) underwent resections. The resection margins were R0 and R1 in 8 (73%) and 3 (27%) of 11 patients, respectively. On histological review in 10 patients, necrosis of ≥90% tumor was achieved in 7 of 10 patients (70%).ConclusionsFirst-line ⁹⁰Y-TARE prescribed using the MIRD model as neoadjuvant therapy for iCCA results in good survival outcome and R0 resection for unresectable patients.     

Intra-Arterial Therapy for Unresectable Colorectal Liver Metastases: A Meta-Analysis

PurposeTo evaluate the efficacy of hepatic arterial infusion (HAI), conventional transarterial chemoembolization, drug-eluting embolic transarterial chemoembolization (DEE-TACE), transarterial radioembolization, and their combinations with systemic chemotherapy (SCT) for unresectable colorectal liver metastases.MethodsA search was conducted on Embase, Scopus, PubMed, and Web of Science for prospective nonrandomized studies and randomized controlled trials (RCTs) from inception to June 20, 2020. Survival data of patients were recovered from original Kaplan-Meier curves by exploiting a graphical reconstructive algorithm. One-stage meta-analyses were conducted for the median overall survival (OS), survival rates (SRs), and restricted mean survival time (RMST), whereas two-stage meta-analyses of proportions were conducted to determine response rates (RRs) and conversion to resection rates (CRRs).ResultsA total of 71 prospective nonrandomized studies and 21 RCTs were identified, comprising 6,695 patients. Among patients treated beyond the first-line, DEE-TACE + SCT (n = 152) had the best survival outcomes of median OS of 26.5 (95% confidence interval [CI], 22.5–29.1) months and a 3-year RMST of 23.6 (95% CI, 21.8–25.5) months. Upon further stratification by publication year, DEE-TACE + SCT appeared to consistently have the highest pooled SRs at 1 year (81.9%) and 2 years (66.1%) in recent publications (2015–2020). DEE-TACE + SCT and HAI + SCT had the highest pooled RRs of 56.7% (I² = 0.90) and 62.6% (I² = 0.87) and pooled CRRs of 35.5% (I² = 0.00) and 30.3% (I² = 0.80), respectively.ConclusionsAlbeit significant heterogeneity, the paucity of high-quality evidence, and the noncomparative nature of all analyses, the overall evidence suggests that patients treated with DEE-TACE + SCT have the best oncological outcomes and greatest potential to be converted for resection.     

MR Imaging Volumetric Response after Yttrium-90 Radioembolization for Colorectal Liver Metastases: Predictability at Baseline and Correlation with Survival

PurposeTo prove the utility of magnetic resonance (MR) imaging response as a surrogate end point of treatment efficacy and survival after yttrium-90 transarterial radioembolization (TARE) for colorectal liver metastases (CRLMs), and to investigate whether outcomes can be predicted at baseline using MR imaging or clinical variables.Materials and MethodsA total of 50 (135) patients with TARE for CRLMs between August 2008 and January 2020 and peri-interventional MR imaging within defined timeframes were included for tumor segmentation. Pretreatment and posttreatment target tumor volumes were measured according to the volumetric Response Evaluation Criteria In Solid Tumors (vRECIST) and the quantitative European Association for the Study of the Liver (qEASL) criteria. Cox regression models were used to analyze the impact of MR morphologic response, vascularity at baseline, and clinical variables on patient survival. Logistic regression analyses were used to evaluate the predictors of MR morphologic response at baseline.ResultsThe median survival was 337 days (95% confidence interval [CI], 243–431). As opposed to the vRECIST, the application of the qEASL criteria 3 months after the treatment allowed for a significant (P < .05) separation of the survival curves for partial response, stable disease, and progressive disease with a median survival of 412 days (95% CI, 57–767) in responders. High tumor burden and technetium-99m lung shunt significantly decreased the probability of survival. MR morphologic response was not predictable at baseline using imaging or clinical data.ConclusionsMR response according to the qEASL criteria outperformed the vRECIST in measuring the biologic impact of TARE and predicting patient survival. Baseline contrast enhancement did not predict MR response to treatment, which may reflect elevated dose requirements in tumors with a high proportion of viable tumor volume.