Multidisciplinary Delphi Consensus on Safety of Combining Transarterial Radioembolization with Yttrium-90 Microspheres with Systemic Anticancer Agents for the Treatment of Liver Malignancy.

PURPOSE: To provide guidance, via multidisciplinary consensus statements, on the safety interactions between systemic anticancer agents (such as radiosensitizing chemotherapy, immunotherapy, targeted therapy, and peptide receptor radionuclide therapy) and transarterial radioembolization (TARE) with yttrium-90 (90Y)-labeled microspheres in the treatment of primary and metastatic liver malignancies. MATERIALS AND METHODS: A literature search identified 59 references that informed 26 statements on the safety of 90Y TARE combined with systemic therapies. Modified Delphi method was used to develop consensus on statements through online anonymous surveys of the 12 panel members representing the fields of interventional radiology, medical oncology, surgical oncology, hepatology, and pharmacy, focusing on hepatocellular carcinoma (HCC), metastatic colorectal cancer (mCRC), neuroendocrine tumors, metastatic breast cancer, and intrahepatic cholangiocarcinoma. RESULTS: High-level evidence was limited. Level 1 data in patients with mCRC suggest that some radiosensitizing chemotherapies (eg, oxaliplatin) require temporary dose reduction when used concomitantly with 90Y TARE, and some targeted therapies (eg, vascular endothelial growth factor inhibitors and antiangiogenic tyrosine kinase inhibitors) should be avoided for at least 4 weeks before 90Y TARE. In patients with HCC, the feasibility of 90Y TARE and immunotherapy has been demonstrated with Level 4 evidence. Data are more limited for other primary and secondary liver malignancies, and consensus statements were driven by expert opinion (Level 5). CONCLUSIONS: Given the absence of evidence-based guidelines on the safety of 90Y TARE in combination with systemic anticancer therapy, these consensus statements provide expert guidance on the potential risks when considering specific combinations.

Effect of Previous Transarterial Chemoembolization on Survival and Toxicity after Yttrium-90 Transarterial Radioembolization of Hepatocellular Carcinoma in the Radiation-Emitting SIR-Spheres in Nonresectable Liver Tumor Registry.

PURPOSE: To determine overall survival (OS), best response, and toxicities in patients with hepatocellular carcinoma (HCC) previously treated with chemoembolization (TACE+) or yttrium-90 resin transarterial radioembolization (TARE) compared with those of TACE-naïve (T-N) participants. MATERIALS AND METHODS: In this prospective, observational study, 262 adult participants with HCC were divided into TACE+ (n = 93, 35%) or T-N (n = 169, 65%) groups, included from 36 centers in the United States. Overall survival (OS) was assessed using Kaplan-Meier analysis from the date of TARE. Best response at 6 months was evaluated using modified Response Evaluation Criteria in Solid Tumors. Six-month toxicities were reported using Common Terminology Criteria for Adverse Events, version 5. RESULTS: Median OS for patients in the TACE+ and T-N groups was 22.3 months (95% CI: 17.2 to not reachable) and 21.5 months (95% confidence interval [CI]: 14.9-29.9), respectively (P = .6). Imaging at 6 months ± 2 weeks was available in 156 of 262 (60%) participants. Partial or complete response was seen in 27 of 55 patients (49%) in the TACE+ group and 65 of 101 patients (64%) in the T-N group (P = .2). Six-month toxicities were available in 69 of 93 patients (74%) in the TACE+ group and 135 of 167 patients (81%) in the T-N group. Attributable Grade 3 or greater liver function toxicities were similar between the study groups (all P > .05). CONCLUSIONS: OS and imaging response at 6 months in the TACE+ group was similar to that in the T-N group with similar toxicities. Radioembolization is an acceptable treatment option for patients with HCC previously treated with TACE.

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

PURPOSE: To report outcomes in patients with intrahepatic cholangiocarcinoma treated with yttrium-90 resin microspheres (transarterial radioembolization [TARE]) from a multicenter, prospective observational registry. MATERIALS AND METHODS: Ninety-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. RESULTS: Fifty-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. CONCLUSIONS: Objective response at 6 months predicted longer OS after TARE for intrahepatic cholangiocarcinoma. The incidence of liver function toxicity was <10%.

Survival and Toxicities after 90Y Transarterial Radioembolization of Metastatic Colorectal Cancer in the RESIN Registry.

Background Patients with unresectable, chemorefractory hepatic metastases from colorectal cancer have considerable mortality. The role of transarterial radioembolization (TARE) with yttrium 90 (90Y) microspheres is not defined because most reports are from a single center with limited patient numbers. Purpose To report outcomes in participants with colorectal cancer metastases treated with resin 90Y microspheres from a prospective multicenter observational registry. Materials and Methods This study treated enrolled adult participants with TARE using resin microspheres for liver-dominant metastatic colorectal cancer at 42 centers, with enrollment from July 2015 through August 2020. TARE was used as the first-, second-, or third-line therapy or beyond. Overall survival (OS), progression-free survival (PFS), and toxicity outcomes were assessed by line of therapy by using Kaplan-Meier analysis for OS and PFS and Common Terminology Criteria for Adverse Events, version 5, for toxicities. Results A total of 498 participants (median age, 60 years [IQR, 52-69 years]; 298 men [60%]) were treated. TARE was used in first-line therapy in 74 of 442 participants (17%), second-line therapy in 180 participants (41%), and third-line therapy or beyond in 188 participants (43%). The median OS of the entire cohort was 15.0 months (95% CI: 13.3, 16.9). The median OS by line of therapy was 13.9 months for first-line therapy, 17.4 months for second-line therapy, and 12.5 months for third-line therapy (χ2 = 9.7; P = .002). Whole-group PFS was 7.4 months (95% CI: 6.4, 9.5). The median PFS by line of therapy was 7.9 months for first-line therapy, 10.0 months for second-line therapy, and 5.9 months for third-line therapy (χ2 = 8.3; P = .004). TARE-attributable grade 3 or 4 hepatic toxicities were 8.4% for bilirubin (29 of 347 participants) and 3.7% for albumin (13 of 347). Grade 3 and higher toxicities were greater with third-line therapy for bilirubin (P = .01) and albumin (P = .008). Conclusion Median overall survival (OS) after transarterial radioembolization (TARE) with yttrium 90 microspheres for liver-dominant metastatic colorectal cancer was 15.0 months. The longest OS was achieved when TARE was part of second-line therapy. Grade 3 or greater hepatic function toxicity rates were less than 10%. Clinical trial registration no. NCT02685631 Published under a CC BY 4.0 license. Online supplemental material is available for this article. See also the editorial by Liddell in this issue.

Long-term outcomes following 90Y Radioembolization of neuroendocrine liver metastases: evaluation of the radiation-emitting SIR-spheres in non-resectable liver tumor (RESiN) registry.

BACKGROUND: The goal of this study was to evaluate efficacy and safety of 90Y radioembolization for neuroendocrine liver metastases (NELM) in a multicenter registry. METHODS: One hundred-seventy patients with NELM were enrolled in the registry (NCT02685631). Prior treatments included hepatic resection (n = 23, 14%), arterial therapy (n = 62, 36%), octreotide (n = 119, 83%), cytotoxic chemotherapy (n = 58, 41%), biologic therapy (n = 49, 33%) and immunotherapy (n = 10, 6%). Seventy-seven (45%) patients had extrahepatic disease. Seventy-eight (48%), 61 (37%), and 25 (15%) patients were Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or ≥ 2. Tumor grade was known in 81 (48%) patients: 57 (70%) were well-, 12 (15%) moderate-, and 12 (15%) poorly-differentiated. Kaplan-Meier analysis and log rank tests were performed to compare overall and progression-free survival (OS/PFS) by tumor location and grade. Toxicities were reported using Common Terminology Criteria for Adverse Events v.5. Cox Proportional Hazards were calculated for pancreatic primary, performance status, extrahepatic disease at treatment, unilobar treatment, baseline ascites, and > 25% tumor burden. RESULTS: One, 2, and 3-year OS rates were 75, 62 and 46%, respectively. Median OS was 33 months [(95% CI: 25-not reached (NR)]. The longest median OS was in patients with pancreatic (42 months, 95% CI: 33-NR) and hindgut 41 months, 95% CI: 12-NR) primaries. The shortest OS was in foregut primaries (26 months; 95% CI: 23-NR; X2 = 7, p = 0.1). Median OS of well-differentiated tumors was 36 months (95% CI: 10-NR), compared to 44 (95% CI: 7-NR) and 25 (95% CI: 3-NR) months for moderate and poorly differentiated tumors. Median progression-free survival (PFS) was 25 months with 1, 2, and 3-year PFS rates of 70, 54, and 35%, respectively. Thirteen patients (7.6%) developed grade 3 hepatic toxicity, most commonly new ascites (n = 8, 5%) at a median of 5.5 months. Performance status of ≥2 (HR 2.7, p = 0.01) and baseline ascites (HR 2.8, P = 0.049) predicted shorter OS. DISCUSSION: In a population with a high incidence of extrahepatic disease, 90Y was effective and safe in treatment of NELM, with median OS of 41 months for well differentiated tumors. Grade 3 or greater hepatic toxicity was developed in 7.6% of patients. TRIAL REGISTRATION: NCT02685631 .

Overall survival and toxicity of Y90 radioembolization for hepatocellular carcinoma patients in Barcelona Clinic Liver Cancer stage C (BCLC-C).

INTRODUCTION: National Comprehensive Cancer Network HCC guidelines recommend Y90 to treat BCLC-C patients only in select cases given the development of systemic regimens. We sought to identify ideal candidates for Y90 by assessing survival and toxicities in this patient group. MATERIALS AND METHODS: The Radiation-Emitting Selective Internal radiation spheres in Non-resectable tumor registry is a prospective observational study (NCT: 02,685,631). Patients with advanced HCC were stratified into 3 groups based on tumor location, Eastern Cooperative Oncology Group (ECOG) performance status, and liver function. Group 1: liver isolated HCC, ECOG 0 and Child Pugh (CP) A (n = 12, 16%), Group 2: liver isolated HCC, ECOG ≥ 1 or CP B/C (n = 37, 49%), and Group 3: extrahepatic HCC with any ECOG or CP score (n = 26, 35%). Patients in any group could have macrovascular invasion. Overall survival (OS) and progression-free survival (PFS) with 95% confidence intervals (95% CI) were calculated. Grade 3 + toxicities were tracked using Common Terminology Criteria for Adverse Events v5. Cox proportional hazard model was performed to determine factors affecting OS. RESULTS: Seventy-five BCLC-C patients treated between 2015 and 2019 were reviewed. The groups were similar in age, sex, race, and ethnicity (all p > 0.05). Bilobar disease was least common in Group 1 (p < 0.001). Median OS of the entire cohort was 13.6 (95% CI 7.5-16.1) months. Median OS of Groups 1-3 were 21.8, 13.1 and 11.5 months respectively (p = 0.6). Median PFS for the cohort was 6.3 (4.8-14.7) months. Median PFS for group 1 was not reached. Mean PFS for Group 1 was 17.3 ± 4.8 months. Median PFS for Groups 2 and 3 was 6.8 and 5.9 months (X2 = 1.5, p = 0.5). Twenty-four Grade 3 or greater toxicities developed, most commonly hyperbilirubinemia (8/75, 11%) and thrombocytopenia (2/75, 3%). The incidence of toxicities between groups was similar (all p > 0.05). Cox Proportional Hazard analysis predicted shorter OS with CP class B/C (X2 = 6.7, p = 0.01), while macrovascular invasion (X2 = 0.5, p = 0.5) and ECOG score of ≥ 1 (X2 = 2.1, p = 0.3) was not associated with OS. CONCLUSIONS: OS of CPA patients with advanced HCC and performance status of 0 was 21.8 months following Y90. CP A cirrhosis is the best predictor of prolonged OS in advanced (BCLC-C) HCC.

Multicenter Evaluation of Survival and Toxicities of Hepatocellular Carcinoma following Radioembolization: Analysis of the RESiN Registry.

PURPOSE: To determine overall survival (OS), progression-free survival (PFS), and toxicity in patients with hepatocellular carcinoma (HCC) in a multicenter, real-world data registry using transarterial radioembolization (TARE) with resin microspheres. MATERIALS AND METHODS: A total of 448 patients with HCC were treated at 36 centers between 2015 and 2019. Treatment history, baseline laboratory and imaging, and treatment goal were assessed. OS and PFS were stratified using Barcelona Clinic Liver Cancer (BCLC) and Child-Pugh (CP) classifications. Kaplan-Meier analyses compared OS and PFS with 95% confidence intervals. Transplants were tracked. Toxicities were assessed using Common Terminology Criteria for Adverse Events v5. Cox proportional hazard of baseline demographics assessed factors affecting survival. RESULTS: Prior chemoembolization and systemic therapy were used in 107 (26%) and 68 (16%) patients, respectively. Using the BCLC staging system, 66 patients (19%) were BCLC A and 202, 51, and 26 were BCLC B, C, and D, respectively. Median OS for patients with BCLC A disease was not achieved at 30 months. Median OS for patients with BCLC B, C, and D disease were 19.5, 13.6, and 11.5 months, respectively (P = .0006). Median PFS for patients with BCLC A, B, C, and D were 19.8, 10.0, 6.3, and 5.9 months, respectively (P = .003). Twenty patients underwent transplantation, representing 14 of 43 (33%) and 6 of 28 (21%) patients who underwent bridging and downstaging therapy, respectively. Common Grade 3 toxicities were encephalopathy (11/448, 2.5%), hyperbilirubinemia (10/448, 2.2%), and ascites (9/448, 2.0%). Factors predicting longer survival included CP A (χ2 = 4.2, P = .04) and BCLC A (χ2 = 5.2, P = .02). CONCLUSIONS: In a frequently pretreated patient cohort with disease burden in 81% beyond the Milan criteria, TARE with resin microspheres provided OS comparable to other studies in this multicenter registry.

Hepatopulmonary Shunting: A Prognostic Indicator of Survival in Patients with Metastatic Colorectal Adenocarcinoma Treated with 90Y Radioembolization.

Purpose To determine if high lung shunt fraction (LSF) is an independent prognostic indicator of poor survival in patients who undergo yttrium 90 radioembolization for unresectable liver-dominant metastatic colorectal cancer. Materials and Methods Retrospective data were analyzed from 606 patients (62% men; mean age, 62 years) who underwent radioembolization to treat liver metastases from colorectal adenocarcinoma between July 2002 and December 2011 at 11 U.S. centers. Institutional review board exemptions were granted prior to the collection of data at each site. Overall survival was estimated by using Kaplan-Meier survival and univariate Cox proportional hazards models to examine the effect of LSF on survival and to compare this to other potential prognostic indicators. Multivariate analysis was also performed to determine whether LSF is an independent risk factor for poor survival. Results LSF higher than 10% was predictive of significantly decreased survival (median, 6.9 months vs 10.0 months; hazard ratio, 1.60; P < .001) and demonstrated a mild but significant correlation to serum carcinoembryonic antigen levels and tumor-to-liver volume ratio (Pearson correlation coefficients, 0.105 and 0.113, respectively; P < .05). A progressive decrease in survival was observed as LSF increased from less than 5% to more than 20% (P < .05). LSF did not correlate with the presence of extrahepatic metastases or prior administration of bevacizumab. Conclusion Increased LSF is an independent prognostic indicator of worse survival in patients undergoing radioembolization for liver-dominant metastatic colorectal adenocarcinoma. High LSF correlates poorly to other potential markers of tumor size, such as tumor-to-liver volume ratio or serum carcinoembryonic antigen level, and does not correlate to the presence of extrahepatic metastases. © RSNA, 2016 Online supplemental material is available for this article.

A review of conventional and drug-eluting chemoembolization in the treatment of colorectal liver metastases: principles and proof.

The management of colorectal liver metastasis has undergone a significant change since the development of novel ablation and embolization. Drug-eluting microsphere platforms, designed to deliver targeted concentrations of systemic therapy directly into the tumor via its arterial vasculature, have garnered interest and gained in popularity in recent years. Based on in vitro and in vivo data, multiple factors contribute to locoregional exposure including carrier base, smaller particle size (larger surface area), chemotherapeutic and chemotherapeutic intensity. Based on the current published clinical data, therapy appears well tolerated but the questions remain as to the ideal technique, patient population and overall efficacy. The purpose of this article is to provide a perspective on the scientific basis, and clinical review of the current data supporting the use of this platform in the setting of metastatic colorectal carcinoma.

Nonsurgical treatment for localized hepatocellular carcinoma.

The most common non-surgical approaches for the treatment of localized hepatocellular carcinoma remain hepatic artery-delivered particles laden with chemotherapy (TACE), or radioactive microparticles (TARE). External beam radiotherapy has been an effective option in many parts of the world for selected HCC patients, but now has an expanded role with stereotactic and proton beam technologies. This review focuses on existing evidence and current guidance for utilizing these modalities for localized, but unresectable, non-transplantable HCC patients.x.

Acetyl-CoA carboxylase obstructs CD8+ T cell lipid utilization in the tumor microenvironment.

The solid tumor microenvironment (TME) imprints a compromised metabolic state in tumor-infiltrating T cells (TILs), hallmarked by the inability to maintain effective energy synthesis for antitumor function and survival. T cells in the TME must catabolize lipids via mitochondrial fatty acid oxidation (FAO) to supply energy in nutrient stress, and it is established that T cells enriched in FAO are adept at cancer control. However, endogenous TILs and unmodified cellular therapy products fail to sustain bioenergetics in tumors. We reveal that the solid TME imposes perpetual acetyl-coenzyme A (CoA) carboxylase (ACC) activity, invoking lipid biogenesis and storage in TILs that opposes FAO. Using metabolic, lipidomic, and confocal imaging strategies, we find that restricting ACC rewires T cell metabolism, enabling energy maintenance in TME stress. Limiting ACC activity potentiates a gene and phenotypic program indicative of T cell longevity, engendering T cells with increased survival and polyfunctionality, which sustains cancer control.

Overall survival and toxicity of hepatocellular carcinoma Barcelona Clinic Liver Cancer B patients receiving Y90 radioembolization: analysis of the radiation-emitting SIR-spheres in non-resectable liver tumor (RESiN) registry.

Background: To evaluate overall survival (OS), progression-free survival (PFS) and toxicity after resin Yttrium-90 (Y-90) radioembolization in Barcelona Clinic Liver Cancer B (BCLC B) hepatocellular carcinoma (HCC) patients using the Bolondi subgroup classification. Methods: A total of 144 BCLC B patients were treated between 2015-2020. Patients were broken into 4 subgroups by tumor burden/liver function tests with 54, 59, 8 and 23 in subgroups 1, 2, 3 and 4. OS and PFS were calculated with Kaplan-Meier analysis with 95% confidence intervals. Toxicities were assessed using Common Terminology Criteria for Adverse Events (CTCAE) v5. Results: Prior resection and chemoembolization were performed in 19 (13%) and 34 (24%) of patients. There were no deaths within 30 days. Median OS and PFS for the cohort were 21.5 and 12.4 months. Median OS was not reached for subgroup 1 at a mean 28.8 months, and was 24.9, 11.0 and 14.6 months for subgroups 2-4 (χ2=19.8, P=0.0002). PFS by BCLC B subgroup was 13.8, 12.4, 4.5, and 6.6 months (χ2=16.8, P=0.0008). The most common Grade 3 or 4 toxicities were elevated bilirubin (n=16, 13.3%) and decreased albumin (n=15, 12.5%). Grade 3 or greater bilirubin (32% vs. 10%, P=0.03) and albumin (26% vs. 10%, P=0.03) toxicity were more common in the subgroup 4 patients. Conclusions: The Bolondi subgroup classification stratifies OS, PFS and development of toxicity in patients treated with resin Y-90 microspheres. OS in subgroup 1 approaches 2.5 years and Grade 3 or greater hepatic toxicity profile in subgroups 1-3 is low.

Recommendations of the American Association of Physicists in Medicine on dosimetry, imaging, and quality assurance procedures for 90Y microsphere brachytherapy in the treatment of hepatic malignancies.

Yttrium-90 microsphere brachytherapy of the liver exploits the distinctive features of the liver anatomy to treat liver malignancies with beta radiation and is gaining more wide spread clinical use. This report provides a general overview of microsphere liver brachytherapy and assists the treatment team in creating local treatment practices to provide safe and efficient patient treatment. Suggestions for future improvements are incorporated with the basic rationale for the therapy and currently used procedures. Imaging modalities utilized and their respective quality assurance are discussed. General as well as vendor specific delivery procedures are reviewed. The current dosimetry models are reviewed and suggestions for dosimetry advancement are made. Beta activity standards are reviewed and vendor implementation strategies are discussed. Radioactive material licensing and radiation safety are discussed given the unique requirements of microsphere brachytherapy. A general, team-based quality assurance program is reviewed to provide guidance for the creation of the local procedures. Finally, recommendations are given on how to deliver the current state of the art treatments and directions for future improvements in the therapy.

DNAJB12 and Hsp70 triage arrested intermediates of N1303K-CFTR for endoplasmic reticulum-associated autophagy.

The transmembrane Hsp40 DNAJB12 and cytosolic Hsp70 cooperate on the endoplasmic reticulum's (ER) cytoplasmic face to facilitate the triage of nascent polytopic membrane proteins for folding versus degradation. N1303K is a common mutation that causes misfolding of the ion channel CFTR, but unlike F508del-CFTR, biogenic and functional defects in N1303K-CFTR are resistant to correction by folding modulators. N1303K is reported to arrest CFTR folding at a late stage after partial assembly of its N-terminal domains. N1303K-CFTR intermediates are clients of JB12-Hsp70 complexes, maintained in a detergent-soluble state, and have a relatively long 3-h half-life. ER-associated degradation (ERAD)-resistant pools of N1303K-CFTR are concentrated in ER tubules that associate with autophagy initiation sites containing WIPI1, FlP200, and LC3. Destabilization of N1303K-CFTR or depletion of JB12 prevents entry of N1303K-CFTR into the membranes of ER-connected phagophores and traffic to autolysosomes. In contrast, the stabilization of intermediates with the modulator VX-809 promotes the association of N1303K-CFTR with autophagy initiation machinery. N1303K-CFTR is excluded from the ER-exit sites, and its passage from the ER to autolysosomes does not require ER-phagy receptors. DNAJB12 operates in biosynthetically active ER microdomains to triage membrane protein intermediates in a conformation-specific manner for secretion versus degradation via ERAD or selective-ER-associated autophagy.

Modernizing Clinical Trial Eligibility Criteria: Recommendations of the ASCO-Friends of Cancer Research Washout Period and Concomitant Medication Work Group.

PURPOSE: Washout periods and concomitant medication exclusions are common in cancer clinical trial protocols. These exclusion criteria are often applied inconsistently and without evidence to justify their use. The authors sought to determine how washout period and concomitant medication allowances can be broadened to speed trial enrollment and improve the generalizability of trial data to a larger oncology practice population without compromising the safety of trial participants. EXPERIMENTAL DESIGN: A multistakeholder working group was convened to define problems associated with excessively long washout periods and exclusion of patients due to concomitant medications. The group performed a literature search and evaluated study data from the Pancreatic Cancer Action Network (PanCAN), Emory University School of Medicine (Atlanta, GA), and the FDA to understand recent approaches to these eligibility criteria. The group convened to develop consensus recommendations for broadened eligibility criteria. RESULTS: The data analysis found that exclusion criteria based on washout periods and concomitant medications are frequently inconsistent and lack scientific rationale. Scientific rationale for appropriate eligibility criteria are presented in the article; for washout periods, rationale is presented by treatment type. CONCLUSIONS: Arbitrary or blanket washout and concomitant medication exclusions should be eliminated. Where there is evidence to support them, clinically relevant washout periods and concomitant medication-related eligibility criteria may be included.See related commentary by Giantonio, p. 2369.

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.

Use of yttrium-90 microspheres in patients with advanced hepatocellular carcinoma and portal vein thrombosis.

PURPOSE: Patients with portal vein thrombosis (PVT) and hepatocellular carcinoma (HCC) have limited treatment options because of increased disease burden and diminished hepatic perfusion. Yttrium-90 ((90)Y) microspheres may be better tolerated than chemoembolization in these patients. The present study reviews the safety and efficacy of (90)Y microspheres in HCC with major PVT. MATERIALS AND METHODS: A retrospective review of HCC with main (n = 10) or first-branch (n = 12) PVT treated with (90)Y microspheres (N = 22) was conducted. Cancer of the Liver Italian Program (CLIP) scores ranged from 2 to 5, with 18% of patients having a score of 4 or greater. Imaging response at 8-12 was based on Response Evaluation Criteria In Solid Tumors. Overall survival (OS) was estimated by the Kaplan-Meier method. RESULTS: A total of 32 microsphere treatments (26 glass, six resin) were administered to 22 patients. Common grade 1/2 toxicities included abdominal pain (38%), nausea (28%), and fatigue (22%). Four posttreatment hospitalizations occurred, all less than 48 hours in duration. One death occurred 10 days after therapy. The partial response rate was 8% and progressive disease was seen in 42% of patients. Stable disease was achieved in 50% of treatments. Median OS was 7 months from initial treatment. Patients with Child-Pugh class A disease had a median OS of 7.7 months; those with class B/C disease had an OS of 2.7 months (P = .01). Median OS for patients with CLIP scores of 2/3 was 7 months, versus 1.3 months for those with scores of 4/5 (P = .04). CONCLUSIONS: Yttrium-90 microspheres are tolerated in patients with HCC and major PVT. Compared with chemoembolization, rates of severe adverse events appear low. Radiographic response rates are low. The median OS of 7 months is promising and warrants further study versus systemic therapy.

A first report of radioembolization for hepatic metastases from ocular melanoma.

BACKGROUND: Ocular melanoma (OM) metastasizes to the liver and is rapidly fatal despite aggressive therapy. Yttrium-90 microspheres (radioembolization) delivered via the hepatic artery is an established and effective approach for primary and metastatic hepatic tumors, although (90)Y use in OM has not been reported previously. METHODS: A retrospective review was performed for all patients with OM who received radioembolization at 5 centers. RESULTS: 11 patients received 12 treatments with a median activity of 1.55 GBq delivered per treatment. Toxicity was minimal, with PET/CT at 3 months posttreatment showing a response in all patients; 1 patient had a complete response. CONCLUSIONS: Radioembolization can control hepatic metastases of OM with very few side effects.