Clinical, dosimetric, and reporting considerations for Y-90 glass microspheres in hepatocellular carcinoma: updated 2022 recommendations from an international multidisciplinary working group.

PURPOSE: In light of recently published clinical reports and trials, the TheraSphere Global Dosimetry Steering Committee (DSC) reconvened to review new data and to update previously published clinical and dosimetric recommendations for the treatment of hepatocellular carcinoma (HCC). METHODS: The TheraSphere Global DSC is comprised of health care providers across multiple disciplines involved in the treatment of HCC with yttrium-90 (Y-90) glass microsphere-based transarterial radioembolization (TARE). Literature published between January 2019 and September 2021 was reviewed, discussed, and adjudicated by the Delphi method. Recommendations included in this updated document incorporate both the results of the literature review and the expert opinion and experience of members of the committee. RESULTS: Committee discussion and consensus led to the expansion of recommendations to apply to five common clinical scenarios in patients with HCC to support more individualized efficacious treatment with Y-90 glass microspheres. Existing clinical scenarios were updated to reflect recent developments in dosimetry approaches and broader treatment paradigms evolving for patients presenting with HCC. CONCLUSION: Updated consensus recommendations are provided to guide clinical and dosimetric approaches for the use of Y-90 glass microsphere TARE in HCC, accounting for disease presentation, tumor biology, and treatment intent.

Balloon-occluded middle adrenal artery embolization and percutaneous microwave ablation of a metastatic adrenal tumor from renal cell carcinoma.

Renal cell carcinomas present with locally advanced or metastatic disease in 25% of patients. Thermal ablation may be considered in selected patients with single-site or oligometastatic disease in selected patients. We describe single-session transarterial particle embolization with the assistance of a balloon-occlusion catheter and microwave ablation of a large hypervascular adrenal metastasis using cone beam CT and fluoroscopic XperGuide needle guidance.

Role of Radioembolization in Metastatic Neuroendocrine Tumors.

The liver is the most common site of metastasis for neuroendocrine tumors originating from the gastrointestinal tract. Neuroendocrine liver metastases (NELMs) portend a worsening clinical course, making local management important. Local treatment options include surgery, thermal ablation, and trans-catheter intra-arterial therapies, such as radioembolization. Radioembolization is generally preferred over other embolotherapies in patients with colonized biliary systems. Current best practice involves personalized treatment planning, optimizing tumor radiation absorbed dose and minimizing radiation to the normal hepatic parenchyma. As part of a multidisciplinary approach, radioembolization is a versatile embolotherapy offering neoadjuvant, palliative, and ablative treatment options for patients with NELMs.

Radioembolization With Chemotherapy for Colorectal Liver Metastases: A Randomized, Open-Label, International, Multicenter, Phase III Trial.

PURPOSE: To study the impact of transarterial Yttrium-90 radioembolization (TARE) in combination with second-line systemic chemotherapy for colorectal liver metastases (CLM). METHODS: In this international, multicenter, open-label phase III trial, patients with CLM who progressed on oxaliplatin- or irinotecan-based first-line therapy were randomly assigned 1:1 to receive second-line chemotherapy with or without TARE. The two primary end points were progression-free survival (PFS) and hepatic PFS (hPFS), assessed by blinded independent central review. Random assignment was performed using a web- or voice-based system stratified by unilobar or bilobar disease, oxaliplatin- or irinotecan-based first-line chemotherapy, and KRAS mutation status. RESULTS: Four hundred twenty-eight patients from 95 centers in North America, Europe, and Asia were randomly assigned to chemotherapy with or without TARE; this represents the intention-to-treat population and included 215 patients in the TARE plus chemotherapy group and 213 patients in the chemotherapy alone group. The hazard ratio (HR) for PFS was 0.69 (95% CI, 0.54 to 0.88; 1-sided P = .0013), with a median PFS of 8.0 (95% CI, 7.2 to 9.2) and 7.2 (95% CI, 5.7 to 7.6) months, respectively. The HR for hPFS was 0.59 (95% CI, 0.46 to 0.77; 1-sided P < .0001), with a median hPFS of 9.1 (95% CI, 7.8 to 9.7) and 7.2 (95% CI, 5.7 to 7.6) months, respectively. Objective response rates were 34.0% (95% CI, 28.0 to 40.5) and 21.1% (95% CI, 16.2 to 27.1; 1-sided P = .0019) for the TARE and chemotherapy groups, respectively. Median overall survival was 14.0 (95% CI, 11.8 to 15.5) and 14.4 months (95% CI, 12.8 to 16.4; 1-sided P = .7229) with a HR of 1.07 (95% CI, 0.86 to 1.32) for TARE and chemotherapy groups, respectively. Grade 3 adverse events were reported more frequently with TARE (68.4% v 49.3%). Both groups received full chemotherapy dose intensity. CONCLUSION: The addition of TARE to systemic therapy for second-line CLM led to longer PFS and hPFS. Further subset analyses are needed to better define the ideal patient population that would benefit from TARE.

Survival Advantage of Yttrium-90 Radioembolization to Systemic Therapy in Patients with Hepatic Metastases from Colorectal Cancer in the Salvage Setting: Results of a Matched Pair Study.

RATIONALE AND OBJECTIVES: Patients with hepatic metastases from colorectal cancer have a poor prognosis in the salvage setting. This study assessed the survival benefit of adding transarterial 90Y radioembolization in the salvage setting to systemic therapy. MATERIALS AND METHODS: In this retrospective, matched-pair study, 21 patients who underwent radioembolization plus systemic therapy were matched with a cohort of 173 patients who received systemic chemotherapy alone in the salvage setting, defined as progression on at least two different regimens of systemic chemotherapy. Patients were matched one-to-one on Eastern Cooperative Oncology Group Performance Status, presence of extrahepatic disease, and presence of tumor KRAS mutation. Radioembolization patients underwent treatment using standard dosimetry to either a hepatic lobe or the whole liver. Survival data was analyzed using Kaplan-Meier analysis. RESULTS: Patients who underwent radioembolization plus systemic therapy vs. those who had systemic therapy alone had similar demographics and exposure to prior systemic chemotherapies. Median survival from the date of primary diagnosis was 38 (95% CI 26 to 50) v 25 (95% CI 15 to 35) months in radioembolization with systemic therapy vs. systemic therapy alone (p = 0.17). Median survival from the date of hepatic metastases was 31 (95% CI 23.8 to 38.2) v 20 months (95% CI 10.2 to 29.8) in radioembolization with systemic therapy vs. systemic therapy alone (p = 0.03). CONCLUSION: The addition of radioembolization to systemic therapy in patients with metastatic colorectal cancer to the liver may improve survival in the salvage setting.

Accuracy and Safety of 1,055 Transjugular Liver Biopsies in Postliver Transplant Patients.

INTRODUCTION: The purpose of this study was to investigate the rates of complications and diagnostic yield of transjugular liver biopsy (TJLB) in deceased donor liver transplant (DDLT) recipients. METHODS: From January 2009 to December 2019, 1,055 TJLBs were performed in 603 adult DDLT recipients with a mean age of 54 (±12 years). Data were retrospectively reviewed to determine the diagnostic efficacy and incidence of major and minor complications in the 3-day and 1-month period after TJLB. In addition, data were stratified according to platelet count and international normalized ratio to determine the safety of TJLB in patients with varying degrees of coagulopathy. RESULTS: TJLB yielded diagnostic rate of 98.1% (1,035/1,055), with an overall complication rate of 8.3% (88/1,055). Major complications accounted for 0.85% (9/1,055), and minor complications occurred in 7.48% (79/1,055). When patients were stratified by platelet count (0-50, 51-100, 101-200, 201-300, and >300 × 103 platelets/µL), no significant difference was noted in complication rates (9.5%, 8.6%, 7.6%, 8.5%, and 10.7%, respectively). When grouped by international normalized ratio (0-1, 1.1-2.0, 2.1-3.0, and >3.0), there was no statistical difference in complication rates (8.3%, 8.5%, 7.7%, and 0%, respectively). DISCUSSION: TJLB is a safe, adequate, and effective method to investigate hepatic disorders in DDLT recipients with severe coagulopathy.

ACR-ABS-ACNM-ASTRO-SIR-SNMMI practice parameter for selective internal radiation therapy or radioembolization for treatment of liver malignancies.

PURPOSE: The American College of Radiology (ACR), American Brachytherapy Society (ABS), American College of Nuclear Medicine (ACNM), American Society for Radiation Oncology (ASTRO), Society of Interventional Radiology (SIR), and Society of Nuclear Medicine and Molecular Imaging (SNMMI) have jointly developed a practice parameter on selective internal radiation therapy (SIRT) or radioembolization for treatment of liver malignancies. Radioembolization is the embolization of the hepatic arterial supply of hepatic primary tumors or metastases with a microsphere yttrium-90 brachytherapy device. MATERIALS AND METHODS: The ACR -ABS -ACNM -ASTRO -SIR -SNMMI practice parameter for SIRT or radioembolization for treatment of liver malignancies was revised in accordance with the process described on the ACR website (https://www.acr.org/ClinicalResources/Practice-Parameters-and-Technical-Standards) by the Committee on Practice Parameters-Interventional and Cardiovascular Radiology of the ACR Commission on Interventional and Cardiovascular, Committee on Practice Parameters and Technical Standards-Nuclear Medicine and Molecular Imaging of the ACR Commission on Nuclear Medicine and Molecular Imaging and the Committee on Practice Parameters-Radiation Oncology of the ACR Commission on Radiation Oncology in collaboration with ABS, ACNM, ASTRO, SIR, and SNMMI. RESULTS: This practice parameter is developed to serve as a tool in the appropriate application of radioembolization in the care of patients with conditions where indicated. It addresses clinical implementation of radioembolization including personnel qualifications, quality assurance standards, indications, and suggested documentation. CONCLUSIONS: This practice parameter is a tool to guide clinical use of radioembolization. It focuses on the best practices and principles to consider when using radioemboliozation effectively. The clinical benefit and medical necessity of the treatment should be tailored to each individual patient.

Yttrium-90 Radioembolization for the Treatment of Solitary, Unresectable HCC: The LEGACY Study.

BACKGROUND AND AIMS: Locoregional therapies, including yttrium-90 radioembolization, play an important role in the treatment of unresectable HCC. The aim of the LEGACY (Local radioEmbolization using Glass Microspheres for the Assessment of Tumor Control with Y-90) study was to evaluate objective response rate (ORR) and duration of response (DoR) in patients with solitary unresectable HCC treated with yttrium-90 glass microspheres. APPROACH AND RESULTS: LEGACY is a multicenter, single-arm, retrospective study conducted at three sites that included all eligible, consecutive patients with HCC treated with radioembolization between 2014 and 2017. Eligibility criteria included solitary HCC ≤ 8 cm, Child-Pugh A cirrhosis, and Eastern Cooperative Oncology Group performance status 0-1. Primary endpoints were ORR and DoR based on modified Response Evaluation Criteria in Solid Tumors in the treated area (localized), as evaluated by blinded, independent, central review. Radioembolization was performed with intent of ablative-level dosimetry in a selective fashion when possible. Overall survival was evaluated using Kaplan-Meier and multivariate Cox proportional hazards. Among the 162 patients included, 60.5% were Eastern Cooperative Oncology Group 0, and the median tumor size was 2.7 cm (range: 1-8) according to blinded, independent, central review. Radioembolization served as neoadjuvant therapy for transplantation or resection in 21.0% (34 of 162) and 6.8% (11 of 162) of patients, respectively, and as primary treatment for all others. Median follow-up time was 29.9 months by reverse Kaplan-Meier. ORR (best response) was 88.3% (CI: 82.4-92.4), with 62.2% (CI: 54.1-69.8) exhibiting a DoR ≥ 6 months. Three-year overall survival was 86.6% for all patients and 92.8% for those neoadjuvant patients with resected or transplanted liver. CONCLUSIONS: In this multicenter study of radioembolization, clinical meaningful response rates and prolonged DoR were observed in the treatment of unresectable, solitary HCC ≤ 8 cm.

Yttrium-90 radiation segmentectomy for hepatic metastases: A multi-institutional study of safety and efficacy.

BACKGROUND AND OBJECTIVES: This study assessed the outcomes of Yttrium-90 (90 Y) radiation segmentectomy for hepatic metastases unamenable to resection or ablation. MATERIALS AND METHODS: Over 6 years, 36 patients with 53 tumors underwent segmental radioembolization. Patients were not candidates for surgical resection or thermal ablation. Malignancies included metastases from colorectal cancer (31%), neuroendocrine tumors (28%), sarcoma (19%), and others (22%). Eighty-one percent of patients had undergone prior treatment with systemic chemotherapy. Ongoing systemic chemotherapy was continued. Toxicity, tumor response, tumor progression, and survival were assessed. RESULTS: The median tumor size was 3.6 cm (range 1.2-6.1 cm). Adverse event rates were low, with no hepatic-related Common Terminology Criteria for Adverse Events Grade 3 or 4 toxicity. Target tumor Response Evaluation Criteria in Solid Tumors disease control rate was 92% (28% partial response, 64% stable disease). For patients with enhancing tumors (n = 14), modified Response Evaluation Criteria in Solid Tumors target tumor objective response rate was 100%. During a median follow-up of 12 months, target tumor progression occurred in 28% of treated tumors. Overall survival was 96% and 83% at 6 and 12 months, respectively. CONCLUSIONS: 90 Y radiation segmentectomy for hepatic metastases demonstrates high rates of tumor control and minimal toxicity. Radiation segmentectomy should be considered for patients with metastatic hepatic malignancy who are not candidates for surgical resection.

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

PURPOSE: To 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 METHODS: This 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. RESULTS: Median 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). CONCLUSIONS: Direct 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.

Irreversible Electroporation for Hepatic Tumors: Protocol Standardization Using the Modified Delphi Technique.

PURPOSE: A consensus study of panelists was performed to provide a uniform protocol regarding (contra) indications, procedural parameters, perioperative care, and follow-up of irreversible electroporation (IRE) for the treatment of hepatic malignancies. MATERIALS AND METHODS: Interventional radiologists who had 2 or more publications on IRE, reporting at least 1 patient cohort in the field of hepatobiliary IRE, were recruited. The 8 panelists were asked to anonymously complete 3 iterative rounds of IRE-focused questionnaires to collect data according to a modified Delphi technique. Consensus was defined as having reached 80% or greater agreement. RESULTS: Panel members' response rates were 88%, 75%, and 88% in rounds 1, 2, and 3, respectively; consensus was reached on 124 of 136 items (91%). Percutaneous or intraoperative hepatic IRE should be considered for unresectable primary and secondary malignancies that are truly unsuitable for thermal ablation because of proximity to critical structures. Absolute contraindications are ventricular arrhythmias, cardiac stimulation devices, and congestive heart failure of New York Heart Association class 3 or higher. A metal stent outside the ablation zone should not be considered a contraindication. For the only commercially available IRE device, the recommended settings are an inter-electrode distance of 10-20 mm and an exposure length of 20 mm. After 10 test pulses, 90 treatment pulses of 1500 V/cm should be delivered continuously, with a pulse length of 70-90 µs. The first post-procedural follow-up should take place 1 month after IRE and thereafter every 3 months, using cross-sectional imaging plus tumor marker assessment. CONCLUSIONS: This article provides recommendations, created by a modified Delphi consensus study, regarding patient selection, workup, procedure, and follow-up of IRE treatment for hepatic malignancies.

Interventional Radiology Image-Guided Suprapubic Cystostomy Using Trocar versus Seldinger Technique: A Comparative Analysis of Outcomes and Complications.

OBJECTIVE: To compare two techniques-trocar and Seldinger-for performing percutaneous suprapubic cystostomy. MATERIALS AND METHODS: 125 patients, mean age 71.8 ± 16.5 years (range, 15-102 years), underwent primary suprapubic cystostomy from January 2013 to December 2018. Trocar access (N = 60) was performed as a single step using a puncture cannula without guidewire access. Seldinger access (N = 65) involved needle puncture, guidewire placement, and serial dilation. A retrospective review of patient records was conducted. RESULTS: All procedures were technically successful. Mean catheter size was 13.1 ± 2.0 and 13.9 ± 2.0 French for trocar and Seldinger, respectively (P = .044). Mean procedure time was significantly reduced using trocar technique, 12.4 ± 7.7 versus 25.7 ± 12.1 minutes (P <.001), and was associated with lower anxiolytic dose, 1.2 ± 0.8 versus 1.9 ± 1.1 mg midazolam (P = .003), and less radiation exposure, 20.2 ± 59.5 versus 100.7 ± 98.5 mGy (P <.001). Catheter occlusion was the most common complication (28.8%), followed by UTI (13.6%) and bladder spasm (8.0%). All but 2 complications were classified as Clavien-Dindo grade I or II. Catheter occlusion was more frequent in the trocar group (41.7% vs 16.9%, P = .003), while bladder spasms were more frequent in the Seldinger group (13.8% vs 1.7%, P = .018). CONCLUSION: Suprapubic cystostomy via trocar is associated with faster procedure time, lower anxiolytic dose, and less radiation. While major complications are rare, catheter occlusion is a common occurrence that may be overlooked. Although we detected more occlusions with trocar technique, this may be confounded by a catheter-tract size discrepancy.

Clinical and dosimetric considerations for Y90: recommendations from an international multidisciplinary working group.

The TheraSphere Global Dosimetry Steering Committee was formed in 2017 by BTG International to review existing data and address gaps in knowledge related to dosimetry. This committee is comprised of health care providers with diverse areas of expertise and perspectives on radiation dosimetry. The goal of these recommendations is to optimize glass microspheres radiation therapy for hepatocellular carcinoma while accounting for variables including disease presentation, tumour vascularity, liver function, and curative/palliative intent. The recommendations aim to unify glass microsphere users behind standardized dosimetry methodology that is simple, reproducible and supported by clinical data, with the overarching goal of improving clinical outcomes and advancing the knowledge of dosimetry.

Y90 Clinical Data Update: Cholangiocarcinoma, Neuroendocrine Tumor, Melanoma, and Breast Cancer Metastatic Disease.

While the most compelling levels of evidence for the use of Yttrium-90 (90Y) radioembolization are in patients with hepatocellular carcinoma and hepatic metastases from colorectal cancer, a growing body of literature supports its use in other primary and secondary hepatic malignancies. This includes intrahepatic cholangiocarcinoma, as well as hepatic metastases from neuroendocrine cancer, ocular melanoma, and breast cancer. While is it not feasible to conduct prospective, randomized trials for radioembolization in the setting of these malignancies due to the low overall prevalence of liver-only disease, numerous single-arm studies in the last several years make a compelling argument for its use in select situations. This clinical update summarizes those findings.

Dosimetry of Y-90 Microspheres Utilizing Tc-99m SPECT and Y-90 PET.

Dosimetry for yttrium-90 radioembolization continues to generate interest and controversy, as multiple approaches have been used effectively. Traditionally, simple formulas primarily based on patients' body weight or perfused liver volume were used. Over the past several years, dosimetry refinements have led to marked improvements in this therapy from both a safety and efficacy standpoint. Technetium-99m macroaggregated albumin single photon emission computed tomography (SPECT) optimizes pretreatment dosimetry to ensure delivery of a therapeutic radiation dose to the tumor while minimizing nontarget radiation to healthy hepatic tissue. Post-treatment yttrium-90 PET utilizing the inherent internal pair production of yttrium-90 accurately calculates the absorbed dose to tumors and to the normal hepatic parenchyma, which correlates with patient outcomes. As dosimetric calculations become more complex, quantitative imaging with Tc-99m SPECT and Y-90 PET may set the new standard for radioembolization dosimetry.