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.

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%.

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.

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 .

Erratum to updated survival outcomes and analysis of long-term survivors from the MORE study on safety and efficacy of radioembolization in patients with unresectable colorectal cancer liver metastases.

[This corrects the article DOI: 10.21037/jgo.2017.03.10.].

Restoration of Blood Flow to the Proximal Femoral Epiphysis in Unstable Slipped Capital Femoral Epiphysis by Modified Dunn Procedure: A Preliminary Angiographic and Intracranial Pressure Monitoring Study.

BACKGROUND: The major complication of unstable slipped capital femoral epiphysis (SCFE) is avascular necrosis (AVN) of the femoral head. The purpose of this study was to document by angiography the preoperative and postoperative perfusion to the proximal femoral epiphysis following an unstable SCFE. A specific aim was to determine whether blood flow could be restored. A secondary aim was to determine the efficacy of an intracranial pressure (ICP) monitor to assess blood flow within the femoral head intraoperatively. METHODS: Nine patients with an unstable SCFE underwent superselective angiogram of the medial circumflex femoral artery preoperatively, followed by operative fixation with an open reduction using a modified Dunn approach. Femoral head blood flow was evaluated with an ICP monitor. Angiography was repeated postoperatively. Patients were followed radiographically to assess for AVN. RESULTS: Follow-up averaged 22 months. Six patients did not have arterial flow to the femoral head on the preoperative angiogram. Flow was restored postoperatively on angiogram in 4 of the 6 patients. Two patients developed AVN. One had no flow to the femoral head preoperatively or postoperatively on angiogram and complete tearing of the periosteum was noted. In 1 patient, there was no ICP waveform after the initial reduction. After removing more callous and repeating reduction, the waveform returned. Of the 2 patients with AVN, 1 had an ICP waveform after reduction. CONCLUSIONS: This study documents that some patients with unstable SCFE present with reduced femoral head blood supply due to SCFE. It also demonstrates blood flow restoration in 4 patients by angiogram and 5 by ICP monitor after surgical treatment. No patient immediately lost blood flow due to surgery. ICP monitor is a safe intraoperative tool for real-time assessment of femoral head blood flow during open reduction of unstable SCFE. Presence of flow by ICP is not a guarantee that AVN will not develop, but absence of flow was predictive of AVN. LEVEL OF EVIDENCE: Therapeutic level I-prognostic. See Instructions for Authors for a complete description of levels of evidence.

Updated survival outcomes and analysis of long-term survivors from the MORE study on safety and efficacy of radioembolization in patients with unresectable colorectal cancer liver metastases.

BACKGROUND: The Metastatic colorectal cancer liver metastases Outcomes after RadioEmbolization (MORE) study was a retrospective analysis of 606 patients with unresectable colorectal liver metastases treated with radioembolization (RE) using 90Y-labeled resin microspheres. The first analysis of this study was completed with a last patient follow-up of 77.7 months. We now provide an updated survival analysis through September 15, 2016, with a last patient follow-up of 125 months. METHODS: 90Y-RE was considered for patients with advanced liver-only or liver-dominant metastatic colorectal cancer which was deemed not suitable for surgery, ablation, or systemic therapy, and which had progressed or become refractory to at least one line of systemic therapy. All patients with a diagnosis of metastatic colorectal cancer who had received at least 1 RE treatment and 1 follow-up visit were included in the analysis. Patients were treated between July 2002 and December 2011 at one of 11 U.S. tertiary care centers. Data were collected at baseline, on the day of the first 90Y-RE treatment (day 0), and at all subsequent visits or until death. Patient medical charts and/or public records were accessed to obtain dates of death. RESULTS: Dates of death were obtained for 574 out of a total of 606 patients, and overall survival (OS) data analyzed. Updated median OS was 10.0 months (95% CI: 9.2-11.8 months) at a median follow-up of 9.5 months versus the originally reported median OS of 9.6 months (95% CI: 9.0-11.1 months) at a follow-up of 8.6 months in the first MORE analysis. Patients received a median (range) of 2 (0 to 6) lines of chemotherapy. Baseline characteristics and factors significantly associated with patient survival (P<0.01) are consistent with those reported in the first safety analysis of the MORE study. These factors include poor ECOG performance status, markers of advanced disease such as increased extent of tumor-to-target liver involvement, poor baseline liver function, pre-treatment anemia, lung shunt fraction, and number of lines of prior chemotherapy. Patient age did not significantly affect survival outcomes. CONCLUSIONS: Long-term follow-up confirms that 90Y-RE treatment offers favorable survival benefits for patients with unresectable metastatic colorectal cancer, even among patients who received 3 or more prior lines of chemotherapy. Our analysis also supports earlier reported prognostic factors for survival after 90Y-RE. Overall, our updated analysis confirms that 90Y-RE treatment provided a meaningful response and survival advantage for MORE patients across all ages and across diverse community and academic centers in the U.S.

Treatment options for unresectable HCC with a focus on SIRT with Yttrium-90 resin microspheres.

Hepatocellular carcinoma (HCC), the predominant form of primary liver cancer, is the second leading cause of cancer-related deaths across the globe. Only a small percentage of HCC patients (~20%-30%) are diagnosed at an early stage when first-line treatment options may be effective. The majority of HCC patients (>70%) are diagnosed with unresectable disease and given a poor overall prognosis. Current treatment guidelines recommend locoregional therapy with transarterial chemoembolisation (TACE) and systemic therapy with sorafenib as first-line treatment for patients with intermediate and advanced stage HCC. However, multiple factors including contraindications, technical considerations and treatment-related toxicities pose significant challenges in achieving favourable treatment outcomes, underscoring the need for a paradigm shift in managing these patients. In 2002, yttrium-90 (Y-90) resin microspheres was approved by the U.S. Food and Drug Administration (FDA) for the treatment of unresectable metastatic colorectal cancer to the liver with adjuvant floxuridine chemotherapy. However, thousands of patients with unresectable HCC have also been treated with resin Y-90. For over two decades, several small-scale prospective trials and retrospective studies have investigated and reported on the efficacy of locoregional selective internal radiation therapy (SIRT) with Y-90 microspheres in treating unresectable HCC. Although it is currently a treatment option for intermediate-stage HCC patients, mainstream clinical application of resin Y-90 has been largely limited because of the lack of sufficient clinical data from a randomised controlled trial. This could change with the imminent announcement of results from the phase 3 Sorafenib vs Radioembolization in Advanced Hepatocellular carcinoma (SARAH) trial. To provide the foundation and context for interpreting results from the SARAH trial, this article provides an overview of treatment modalities and current challenges in managing unresectable HCC. There is also a review of key prospective and retrospective studies evaluating the use of Y-90 SIRT, specifically Y-90 resin microspheres in unresectable HCC, which led to the development of the SARAH trial. METHODS: To identify relevant publications, the PubMed database was queried using one or more of the following search terms alone or in combination with Boolean operators: epidemiology, hepatocellular, hepatocellular cancer, hepatocellular carcinoma, unresectable, radioembolisation, selective internal radiation therapy, SIR-Spheres, yttrium 90, TACE, and sorafenib. The results were sorted or filtered by "Author", "Publication dates" or "Article types" to identify articles relevant to each section of the review. To ensure that information on ongoing clinical trials involving Y-90 resin was included, we conducted a search on "ClinicalTrials.gov", by combining the search terms "HCC" OR "hepatocellular carcinoma" with "Y 90" OR "yttrium 90" OR "radioembo", and screened for studies that involved treatment with Y-90 resin microspheres.

Selective internal radiation therapy with SIR-Spheres in hepatocellular carcinoma and cholangiocarcinoma.

Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) often present at stages where patients have limited treatment options. Use of selective internal radiation therapy (SIRT) with yttrium-90 (Y-90) resin microspheres has progressed as data increasingly speak to its utility in patients with both intermediate and late stage disease in these cancers. In anticipation of the pending completion of several prospective randomized controlled multicenter studies exploring the use of Y-90 resin microspheres in primary liver cancers, this article outlines mechanisms involved in SIRT administration and reviews key efficacy and safety data that are currently available in the literature involving use of this therapy in both HCC and ICC.

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.

Safety and Efficacy of Radioembolization in Elderly (≥ 70 Years) and Younger Patients With Unresectable Liver-Dominant Colorectal Cancer.

BACKGROUND: The effects of advancing age on clinical outcomes after radioembolization (RE) in patients with unresectable liver-dominant metastatic colorectal cancer (mCRC) are largely unknown. PATIENTS AND METHODS: This study was a retrospective analysis of 160 elderly (≥ 70 years) and 446 younger (< 70 years) consecutive patients from 11 US centers who received RE using ytrrium-90 ((90)Y) resin microspheres ((90)Y radioembolization [(90)Y-RE]) between July 2002 and December 2011. A further analysis was conducted in 98 very elderly patients (≥ 75 years). Statistical analyses of safety, tolerability, and overall survival were conducted. RESULTS: Mean ages (± standard deviation) in the younger (< 70 years), elderly (≥ 70 years), and very elderly (≥ 75 years) cohorts were 55.9 ± 9.4 years, 77.2 ± 4.8 years, and 80.2 ± 3.8 years, respectively. Overall survival was similar between elderly and younger patients: 9.3 months (95% confidence interval [CI], 8.0-12.1) and 9.7 months (95% CI, 9.0-11.4) (P = .335). There were no differences between cohorts for any grade adverse events (P = .433) or grade 3+ events (P = .482). Analysis of patients ≥ 75 years and < 75 years confirmed similar overall survival (median, 9.3 months vs. 9.6 months, respectively; P = .987) and grade 3+ events (P = .398) or any adverse event (P = .158) within 90 days of RE. CONCLUSION: For patients with unresectable liver-dominant mCRC who meet eligibility criteria for RE, (90)Y-RE microspheres appear to be effective and well-tolerated, regardless of age. Criteria for selecting patients for RE should not include age for exclusion from this potentially beneficial intervention.

Hepatic imaging response to radioembolization with yttrium-90-labeled resin microspheres for tumor progression during systemic chemotherapy in patients with colorectal liver metastases.

BACKGROUND: To assess response and the impact of imaging artifacts following radioembolization with yttrium-90-labeled resin microspheres ((90)Y-RE) based on the findings from a central independent review of patients with liver-dominant metastatic colorectal cancer (mCRC). METHODS: Patients with mCRC who received (90)Y-RE (SIR-Spheres(®); Sirtex Medical, Sydney, Australia) at nine US institutions between July 2002 and December 2011 were included in the analysis. Tumor response was assessed at baseline and 3 months using either the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 or 1.1. For each lesion, known artifacts affecting the interpretation of response (peri-tumoral edema and necrosis) were documented. Survivals (Kaplan-Meier analyses) were compared in responders [partial response (PR)] and non-responders [stable (SD) or progressive disease (PD)]. RESULTS: Overall, 195 patients (mean age 62 years) received (90)Y-RE after a median of 2 (range, 1-6) lines of prior chemotherapy. Using RECIST 1.0 and RECIST 1.1, 7.6% and 6.9% of patients were partial responders, 47.3% and 48.1% had SD, and 55.0% and 55.0% PD, respectively. RECIST 1.0 and RECIST 1.1 showed excellent agreement {Kappa =0.915 [95% confidence interval (CI): 0.856-0.975]}. Peri-tumoral edema was documented in 32.8%, necrosis in 48.1% and both in 57.3% of cases (using RECIST 1.0). Although baseline characteristics were similar in responders and non-responders (P>0.05), responders survived significantly longer in an analysis according to RECIST 1.0: PR median (95% CI) 25.2 (range, 9.2-49.4) months vs. SD 15.8 (range, 9.3-21.1) months vs. PD 7.1 (range, 6.0-9.5) months (P<0.0001). CONCLUSIONS: RECIST 1.0 and RECIST 1.1 imaging responses provide equivalent interpretations in the assessment of hepatic tumors following (90)Y-RE. Radiologic lesion responses at 3 months must be interpreted with caution due to the significant proportion of patients with peri-tumoral edema and necrosis, which may lead to an under-estimation of PR/SD. Nevertheless, 3-month radiologic responses were predictive of prolonged survival.

Multicenter evaluation of the safety and efficacy of radioembolization in patients with unresectable colorectal liver metastases selected as candidates for (90)Y resin microspheres.

BACKGROUND: Metastatic colorectal cancer liver metastases Outcomes after RadioEmbolization (MORE) was an investigator-initiated case-control study to assess the experience of 11 US centers who treated liver-dominant metastases from colorectal cancer (mCRC) using radioembolization [selective internal radiation therapy (SIRT)] with yttrium-90-((90)Y)-labeled resin microspheres. METHODS: Data from 606 consecutive patients who received radioembolization between July 2002 and December 2011 were collected by an independent research organization. Adverse events (AEs) and survival were compared across lines of treatment using Fisher's exact test and Kaplan-Meier estimates, respectively. RESULTS: Patients received a median of 2 (range, 0-6) lines of prior chemotherapy; 35.1% had limited extrahepatic metastases. Median tumor-to-liver ratio and -activity administered at first procedure were 15% and 1.17 GBq, respectively. Hospital stay was <24 hours in 97.8% cases. Common grade ≥3 AEs over 184 days follow-up were: abdominal pain (6.1%), fatigue (5.5%), hyperbilirubinemia (5.4%), ascites (3.6%) and gastrointestinal ulceration (1.7%). There was no statistical difference in AEs across treatment lines (P>0.05). Median survivals [95% confidence interval (CI)] following radioembolization as a 2(nd)-line, 3(rd)-line, or 4(th)-plus line were 13.0 (range, 10.5-14.6), 9.0 (range, 7.8-11.0), and 8.1 (range, 6.4-9.3) months, respectively; and significantly prolonged in patients with ECOG 0 vs. ≥1 (P=0.009). Statistically significant independent variables for survival at radioembolization were: disease stage [extrahepatic metastases, extent of liver involvement (tumor-to-treated-liver ratio)], liver function (uncontrolled ascites, albumin, alkaline phosphatase, aspartate transaminase), leukocytes, and prior chemotherapy. CONCLUSIONS: Radioembolization appears to have a favorable risk/benefit profile, even among mCRC patients who had received ≥3 prior lines of chemotherapy.