Liver-dominant Metastatic Colorectal Cancer Research Articles

Abstract CT190: Oncolytic virus TG6002 safety and activity after intrahepatic artery administration in patients with liver-dominant metastatic colorectal cancer

Abstract The TG6002.03 trial is a dose-escalation phase 1 clinical trial of TG6002 infusion via the hepatic artery in patients with liver-dominant colorectal cancer metastases. TG6002 is an engineered Copenhagen strain oncolytic Vaccinia virus, deleted of thymidine kinase and ribonucleotide reductase to enhance tumor selective viral replication and expressing FCU1, an enzyme converting the non-cytotoxic prodrug 5-fluorocytosine (5-FC) into the chemotherapeutic compound 5-fluorouracil (5-FU). In this trial, patients with advanced unresectable liver-dominant metastatic colorectal cancer who had failed previous oxaliplatin and irinotecan-based chemotherapy were treated with up to 2 cycles of TG6002 infusion 6 weeks apart via the hepatic artery on day 1 combined with oral 5-FC on days 5 to 14 (where day 1 = TG6002 infusion). TG6002 infusion was performed over 30 minutes via selective catheterization of the hepatic artery proper. 5-FC oral dosing was 50mg/kg x4 daily. Blood was sampled for TG6002 pharmacokinetics and 5-FC and 5-FU measurements. Sampling of liver metastases was performed at screening and on day 4 or day 8 for virus detection and 5-FC and 5-FU quantification. In total, 15 patients (median age 61 years, range 37-78) were treated in 1 UK centre and 2 centres in France and received a dose of TG6002 of 1 × 106 (n=3), 1 × 107 (n=3), 1 × 108 (n=3), or 1 × 109 pfu (n=6). Fourteen of the 15 patients received a single cycle of treatment, including one patient who did not received 5-FC, and one patient received two cycles. TG6002 was transiently detected in plasma following administration, suggesting a strong tissue selectivity for viral replication. In the highest dose cohort, a virus rebound was observed on day 8, concordant with replication time of the virus. In serum samples, 5-FU was present on day 8 in all patients with a high variability ranging from 0.8 to 1072 ng/mL and was measurable over several days after initiation of therapy. Seven of the 9 patients evaluable showed the biodistribution of the virus in liver lesions by PCR testing on day 4 or day 8. Translational blood samples showed evidence for T-cell activation and immune checkpoint receptor-ligand expression. At 1 × 109 pfu, there was evidence for T-cell proliferation and activation against tumour-associated antigens by ELISpot and for immunogenic cell death. In terms of safety, a total of 34 TG6002-related adverse events were reported, of which 32 were grade 1-2 and 2 were grade 3. The maximum tolerated dose was not reached, and a single dose-limiting toxicity was observed consisting of a myocardial infarction in a context of recent Covid-19 infection in a 78-year-old patient. These results indicate that TG6002 infused via the hepatic artery in combination with oral 5-FC was well tolerated, effectively localized and replicated in the tumor tissues, expressed its therapeutic payload and showed anti-tumoral immunological activity. Citation Format: Adel Samson, Cristina Smolenschi, Philippe Cassier, Jai V. Patel, Chris Hammond, Marta Kurzawa, Sophie Sainte-Croix, Emma West, Alain Sadoun, Kaidre Bendjama. Oncolytic virus TG6002 safety and activity after intrahepatic artery administration in patients with liver-dominant metastatic colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT190.

Abstract No. 75 Carcinoembryonic Antigen, Tumor Response and Quality of Life with Glass Transarterial Radioembolization (TARE) in Liver-Dominant Metastatic Colorectal Cancer Patients: Results from the EPOCH Trial

Abstract No. 75 Carcinoembryonic Antigen, Tumor Response and Quality of Life with Glass Transarterial Radioembolization (TARE) in Liver-Dominant Metastatic Colorectal Cancer Patients: Results from the EPOCH Trial

The EPOCH trial: Identifying key patient subgroups to optimize treatment planning.

130 Background: The primary objective of the original EPOCH trial was to evaluate the potential benefit of adding transarterial radioembolization (TARE) with yttrium-90 glass microspheres to second-line chemotherapy (chemo) versus chemo alone in patients with liver-dominant metastatic colorectal cancer (mCRC). Randomization was stratified by key prognostic factors, including KRAS status; however, it did not account for ECOG status and baseline CEA levels. We present post-hoc analyses investigating the impact of prognostic factors on primary and secondary endpoints to help optimize patient selection. Methods: EPOCH was a 1:1 randomized, open-label, global, multicenter Phase 3 trial. Primary endpoints were progression-free survival (PFS) and hepatic PFS (hPFS). Overall survival (OS) and time to deterioration of quality of life (TTDQOL) were secondary. Post-hoc analyses of the following subgroups were performed: Subgroup A (excluding patients with both ECOG=1 and CEA≥35ng/mL) and Subgroup B (patients with KRAS wild-type and either ECOG=0 or CEA<35ng/mL). Kaplan-Meier analyses, hazard ratios (HRs) and log-rank tests were used to compare outcomes between TARE plus chemo and chemo only groups. Results: In Subgroup A, 160 (75.1%) patients were randomized to chemo only, versus 143 (66.5%) to the TARE arm. In Subgroup B, 91 (42.7%) patients were randomized to chemo only, versus 77 (35.8%) to the TARE arm. Results are shown for PFS, hPFS, OS, and TTDQOL in the intent-to-treat population. In both subgroups A and B, PFS, hPFS, and TTDQOL were significantly improved for the TARE plus chemo arm as compared to the chemo only arm; no OS difference was found. Conclusions: Careful patient selection using multiple prognostic factors is necessary to identify those who will benefit most from TARE with second-line chemo. Prognostic factors were important in identifying the level of benefit seen in patients treated with TARE and chemo versus chemo alone. Clinical trial information: NCT01483027 . [Table: see text]

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.

Abstract No. 243 Treatment Timing and Overall Survival of Liver-Dominant Metastatic Colorectal Cancer Patients Treated with Glass Transarterial Radioembolization: Analyses from the EPOCH Trial

The EPOCH trial investigated the potential benefit of adding transarterial radioembolization (TARE) with yttrium-90 glass microspheres to second-line chemotherapy in patients with liver-dominant metastatic colorectal cancer (mCRC). Post-hoc analyses evaluated the effect of TARE treatment day post calibration on clinical and safety outcomes.

Role of yttrium-90 selective internal radiation therapy in the treatment of liver-dominant metastatic colorectal cancer: an evidence-based expert consensus algorithm.

Surgical resection of colorectal liver metastases is associated with greater survival compared with non-surgical treatment, and a meaningful possibility of cure. However, the majority of patients are not eligible for resection and may require other non-surgical interventions, such as liver-directed therapies, to be converted to surgical eligibility. Given the number of available therapies, a general framework is needed that outlines the specific roles of chemotherapy, surgery, and locoregional treatments [including selective internal radiation therapy (SIRT) with Y-90 microspheres]. Using a data-driven, modified Delphi process, an expert panel of surgical oncologists, transplant surgeons, and hepatopancreatobiliary (HPB) surgeons convened to create a comprehensive, evidence-based treatment algorithm that includes appropriate treatment options for patients stratified by their eligibility for surgical treatment. The group coined a novel, more inclusive phrase for targeted locoregional tumor treatment (a blanket term for resection, ablation, and other emerging locoregional treatments): local parenchymal tumor destruction therapy. The expert panel proposed new nomenclature for 3 distinct disease categories of liver-dominant metastatic colorectal cancer that is consistent with other tumor types: (I) surgically treatable (resectable); (II) surgically untreatable (borderline resectable); (III) advanced surgically untreatable (unresectable) disease. Patients may present at any point in the algorithm and move between categories depending on their response to therapy. The broad intent of therapy is to transition patients toward individualized treatments where possible, given the survival advantage that resection offers in the context of a comprehensive treatment plan. This article reviews what is known about the role of SIRT with Y-90 as neoadjuvant, definitive, or palliative therapy in these different clinical situations and provides insight into when treatment with SIRT with Y-90 may be appropriate and useful, organized into distinct treatment algorithm steps.

Hepatic Resection Following Selective Internal Radiation Therapy for Colorectal Cancer Metastases in the FOXFIRE Clinical Trial: Clinical Outcomes and Distribution of Microspheres.

The FOXFIRE (5-Fluorouracil, OXaliplatin and Folinic acid ± Interventional Radio-Embolisation) clinical trial combined systemic chemotherapy (OxMdG: Oxaliplatin, 5-fluorouracil and folic acid) with Selective Internal Radiation Therapy (SIRT or radio-embolisation) using yttrium-90 resin microspheres in the first-line management for liver-dominant metastatic colorectal cancer (CRC). We report clinical outcomes for patients having hepatic resection after this novel combination therapy and an exploratory analysis of histopathology. Multi-Disciplinary Teams deemed all patients inoperable before trial registration and reassessed them during protocol therapy. Proportions were compared using Chi-squared tests and survival using Cox models. FOXFIRE randomised 182 participants to chemotherapy alone and 182 to chemotherapy with SIRT. There was no statistically significant difference in the resection rate between groups: Chemotherapy alone was 18%, (n = 33); SIRT combination was 21% (n = 38) (p = 0.508). There was no statistically significant difference between groups in the rate of liver surgery, nor in survival from time of resection (hazard ratio (HR) = 1.55; 95% confidence interval (CI) = 0.83–2.89). In the subgroup studied for histopathology, microsphere density was highest at the tumour periphery. Patients treated with SIRT plus chemotherapy displayed lower values of viable tumour in comparison to those treated with chemotherapy alone (p < 0.05). This study promotes the feasibility of hepatic resection following SIRT. Resin microspheres appear to preferentially distribute at the tumour periphery and may enhance tumour regression.

SIR-Spheres® Y-90 resin microspheres in chemotherapy refractory or intolerant patients with metastatic colorectal cancer

Selective internal radiation therapy is a form of intra-arterial brachytherapy used to treat primary liver cancer and liver metastases. This article aims to provide an overview of the clinical, economic, organizational legal, social and ethical impact of selective internal radiation therapy using SIR-Spheres Y-90 resin microspheres in the treatment of patients with unresectable, liver-dominant metastatic colorectal cancer who are refractory to or intolerant of chemotherapy. A systematic literature review was performed by querying PubMed, Scopus, EBSCO, CRD and GIN. Two reviewers blindly screened the records retrieved against predefined inclusion/exclusion criteria. The selected studies where summarized following a simplified version of the EuNetHTA Core Model® 2.1. The studies included evaluated selective internal radiation therapy in first-line or further-line treatment and showed a good safety and tolerability profile and significant improvement in efficacy expressed as time to liver progression, progression-free survival and overall survival. Selective internal radiation therapy should be provided in specialized centres and administered by a multidisciplinary team. A hub-and-spoke network could be a viable option to guarantee access to this technology across jurisdictions. The lack of a specific diagnosis-related group tariff accounting for the cost of the device could be seen as the major obstacle to a fair diffusion of this technology. The economic evaluations currently available show the cost-effectiveness of this technology in the population under study. Selective internal radiation therapy using SIR-Spheres Y-90 resin microspheres appears to be a clinically effective and cost-effective option in the treatment of metastatic colorectal cancer patients who are chemotherapy refractory or chemotherapy intolerant.

Radioembolization in Colorectal Metastases: A Review

AbstractRadioembolization has gained wide acceptance as a safe and efficient treatment for unresectable liver-dominant metastatic colorectal cancer. In this comprehensive article, we focus on clinical outcomes and dosimetry models in the era of personalized medicine.

First-line selective internal radiotherapy plus chemotherapy versus chemotherapy alone in patients with liver metastases from colorectal cancer (FOXFIRE, SIRFLOX, and FOXFIRE-Global): a combined analysis of three multicentre, randomised, phase 3 trials

SummaryBackgroundData suggest selective internal radiotherapy (SIRT) in third-line or subsequent therapy for metastatic colorectal cancer has clinical benefit in patients with colorectal liver metastases with liver-dominant disease after chemotherapy. The FOXFIRE, SIRFLOX, and FOXFIRE-Global randomised studies evaluated the efficacy of combining first-line chemotherapy with SIRT using yttrium-90 resin microspheres in patients with metastatic colorectal cancer with liver metastases. The studies were designed for combined analysis of overall survival.MethodsFOXFIRE, SIRFLOX, and FOXFIRE-Global were randomised, phase 3 trials done in hospitals and specialist liver centres in 14 countries worldwide (Australia, Belgium, France, Germany, Israel, Italy, New Zealand, Portugal, South Korea, Singapore, Spain, Taiwan, the UK, and the USA). Chemotherapy-naive patients with metastatic colorectal cancer (WHO performance status 0 or 1) with liver metastases not suitable for curative resection or ablation were randomly assigned (1:1) to either oxaliplatin-based chemotherapy (FOLFOX: leucovorin, fluorouracil, and oxaliplatin) or FOLFOX plus single treatment SIRT concurrent with cycle 1 or 2 of chemotherapy. In FOXFIRE, FOLFOX chemotherapy was OxMdG (oxaliplatin modified de Gramont chemotherapy; 85 mg/m2 oxaliplatin infusion over 2 h, L-leucovorin 175 mg or D,L-leucovorin 350 mg infusion over 2 h, and 400 mg/m2 bolus fluorouracil followed by a 2400 mg/m2 continuous fluorouracil infusion over 46 h). In SIRFLOX and FOXFIRE-Global, FOLFOX chemotherapy was modified FOLFOX6 (85 mg/m2 oxaliplatin infusion over 2 h, 200 mg leucovorin, and 400 mg/m2 bolus fluorouracil followed by a 2400 mg/m2 continuous fluorouracil infusion over 46 h). Randomisation was done by central minimisation with four factors: presence of extrahepatic metastases, tumour involvement of the liver, planned use of a biological agent, and investigational centre. Participants and investigators were not masked to treatment. The primary endpoint was overall survival, analysed in the intention-to-treat population, using a two-stage meta-analysis of pooled individual patient data. All three trials have completed 2 years of follow-up. FOXFIRE is registered with the ISRCTN registry, number ISRCTN83867919. SIRFLOX and FOXFIRE-Global are registered with ClinicalTrials.gov, numbers NCT00724503 (SIRFLOX) and NCT01721954 (FOXFIRE-Global).FindingsBetween Oct 11, 2006, and Dec 23, 2014, 549 patients were randomly assigned to FOLFOX alone and 554 patients were assigned FOLFOX plus SIRT. Median follow-up was 43·3 months (IQR 31·6–58·4). There were 411 (75%) deaths in 549 patients in the FOLFOX alone group and 433 (78%) deaths in 554 patients in the FOLFOX plus SIRT group. There was no difference in overall survival (hazard ratio [HR] 1·04, 95% CI 0·90–1·19; p=0·61). The median survival time in the FOLFOX plus SIRT group was 22·6 months (95% CI 21·0–24·5) compared with 23·3 months (21·8–24·7) in the FOLFOX alone group. In the safety population containing patients who received at least one dose of study treatment, as treated, the most common grade 3–4 adverse event was neutropenia (137 [24%] of 571 patients receiving FOLFOX alone vs 186 (37%) of 507 patients receiving FOLFOX plus SIRT). Serious adverse events of any grade occurred in 244 (43%) of 571 patients receiving FOLFOX alone and 274 (54%) of 507 patients receiving FOLFOX plus SIRT. 10 patients in the FOLFOX plus SIRT group and 11 patients in the FOLFOX alone group died due to an adverse event; eight treatment-related deaths occurred in the FOLFOX plus SIRT group and three treatment-related deaths occurred in the FOLFOX alone group.InterpretationAddition of SIRT to first-line FOLFOX chemotherapy for patients with liver-only and liver-dominant metastatic colorectal cancer did not improve overall survival compared with that for FOLFOX alone. Therefore, early use of SIRT in combination with chemotherapy in unselected patients with metastatic colorectal cancer cannot be recommended. To further define the role of SIRT in metastatic colorectal cancer, careful patient selection and studies investigating the role of SIRT as consolidation therapy after chemotherapy are needed.FundingBobby Moore Fund of Cancer Research UK, Sirtex Medical.

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.

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. 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. 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. 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.

Mapping EORTC-QLQ-C30 to EQ-5D-3L in patients with colorectal cancer

Aims: The primary aim of this study was to perform a mapping of the EORTC-QLQ-C30 scores to EQ-5D-3L for the SIRFLOX study; a large dataset of patients with previously untreated liver-only or liver-dominant metastatic colorectal cancer (mCRC). A secondary aim was to compare the predictive validity of existing mappings from EORTC-QLQ-C30 to EQ-5D-3L conducted in other cancers.Methods and materials: Questionnaires (completed within 529 patients) were used in a linear mixed regression to model EQ-5D-3L utility values (scored using the UK tariff) as a function of the five function scores, nine symptom scores, and the global score from the EORTC-QLQ-C30 questionnaire. A Tobit regression was also performed. The mean EQ-5D-3L values for the SIRFLOX trial were calculated and compared with predicted EQ-5D-3L values derived using published mapping algorithms.Results: The linear mixed regression model provided a satisfactory mapping between the EORTC-QLQ-C30 and the EQ-5D-3L, whilst the Tobit model did not perform as well. When utilities from the SIRFLOX data were calculated with previously published mapping studies, three out of five studies performed well (< 10% mean difference).Limitations: The main limitation of the study was the lack of meaningful observations post-progression (67 paired observations). For this reason, this study was unable to test whether the mapping holds by disease stage. Additionally, although the study adds to the literature of mappings to the EQ-5D-3L, it is not known how results would differ using the EQ-5D-5L.Conclusion: This study is the first of its kind in liver-only or liver-dominant mCRC, and mCRC in general. The mapping constructed showed a good fit to the data and provides practitioners with an additional mapping between EORTC-QLQ-C30 to EQ-5D-3L using a large dataset (529 patients, 707 paired observations). The study also confirmed the generalizability of mappings published by Proskorovsky, Kontodimopoulos, and Longworth to liver-only or liver-dominant mCRC.

494P - DC-beads loaded with irinotecan combined with systemic chemotherapy for pretreated liver dominant metastatic colorectal cancer: Procedure and outcomes of 49 patients

494P - DC-beads loaded with irinotecan combined with systemic chemotherapy for pretreated liver dominant metastatic colorectal cancer: Procedure and outcomes of 49 patients

Administered activity and outcomes of glass versus resin (90)Y microsphere radioembolization in patients with colorectal liver metastases.

Given the differences in size, specific activity, and dosing methods for glass yttrium-90 microspheres ((90)Y-glass) and resin (90)Y microspheres ((90)Y-resin), these therapies may expose the liver to different amounts of radiation, thereby affecting their efficacy and tolerability. We aimed to compare the prescribed activity of (90)Y-glass and (90)Y-resin for real-world patients undergoing selective internal radiation therapy (SIRT) for liver-dominant metastatic colorectal cancer (mCRC) and to assess efficacy and safety outcomes in these patients. We examined the records of 28 consecutive patients with unresectable colorectal liver metastases treated with SIRT between June 2008 and May 2011 at our institution. Using baseline CT and MR images, we calculated a projected activity as if we had used the other product and compared it to the actual prescribed activity of (90)Y-glass and (90)Y-resin for each SIRT treatment per manufacturer guidelines. Progression and adverse events were evaluated at follow up visits. Survival was analyzed by the Kaplan-Meier method. For (90)Y-glass treatments with a mean prescribed (90)Y activity of 1.77 GBq, the mean projected (90)Y-resin activity was 0.84 GBq. For (90)Y-resin treatments with a mean prescribed (90)Y activity of 1.05 GBq, the mean projected (90)Y-glass activity was 2.48 GBq. The median survival was 9.3 months versus 18.2 months for (90)Y-glass and (90)Y-resin, respectively (P=0.292). During the second year after SIRT, the hazard ratio of death for patients treated with (90)Y-glass versus (90)Y-resin was 4.0 (95% CI: 1.3, 12.3; P=0.017). No significant difference in progression, adverse events or liver toxicity was observed. Using manufacturer recommended guidelines, (90)Y-resin delivers significantly less activity than (90)Y-glass to patients with liver-dominant mCRC undergoing SIRT with no significant difference in adverse events and a trend toward improved survival.

Y90 Radioembolization in chemo-refractory metastastic, liver dominant colorectal cancer patients: outcome assessment applying a predictive scoring system.

BackgroundIn treatment-refractory liver dominant metastatic colorectal cancer, the role of liver directed therapies still is unclear. We sought to determine a prognostic score for Y90 radioembolization in these patients.MethodsWe analyzed 106 patients with refractory liver dominant mCRC who had undergone a total of 178 Y90 radioembolizations with resin microspheres was collected. Potential factors influencing survival were analyzed using a Cox regression. The Log rank test served to establish prognostic factors and to form a clinical score for outcome prediction after Y90 radioembolization.ResultsMedian survival of all patients was 6.7 months. Neither age nor prior surgical or systemic therapy nor metastatic spread had an effect on survival. In contrast, hepatic tumor load, Karnofsky index as well as CEA and CA19-9 serums level had a significant influence (p < 0.001, p = 0.037, p = 0.023 and p < 0.001, respectively). These three factors formed a score with 1 point each for tumor load >20 %, CEA >130 ng/ml or CA19-9 > 200U/ml and Karnofsky index <80 %. Patients with a score of 0 and 1 displayed a median OS of 10.4 months. Patients with a score of 2 and 3 demonstrated a median OS of 5.1 months only (p < 0.001).ConclusionOveraggressive patient selection for Y90 radioembolization of liver dominant chemorefractory mCRC is of questionable benefit. A scoring system comprising hepatic tumor load, CEA and CA19-9 serum levels and Karnofsky index (TuCK-score) may support an improved patient selection. In our cohort of liver only versus liver dominant disease, extrahepatic lung or lymphatic metastases did not significantly alter the prognosis.

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.

P-150 Locoregional therapy in liver dominant metastatic colorectal cancer having failed standard drug therapy: Outcome and prognostic parameters in 133 consecutive patients

P-150 Locoregional therapy in liver dominant metastatic colorectal cancer having failed standard drug therapy: Outcome and prognostic parameters in 133 consecutive patients

Current role of selective internal radiation with yttrium-90 in liver tumors.

An expert panel met to review the evidence for selective internal radiation therapy (SIRT) using yttrium-90 microspheres in hepatocellular carcinoma and metastases from colorectal cancer and neuroendocrine tumors. There is now convincing evidence for the safety and efficacy of SIRT in these situations albeit mostly from retrospective cohort studies. There are a number of ongoing prospective randomized controlled clinical trials investigating the role of SIRT in liver tumors; however, data from these trials are still several years away (although the SIRFLOX study has been recently published). In this evolving environment, published evidence and the authors' experience were used to summarize the current and potential role of SIRT in the management of hepatocellular carcinoma of intermediate or advanced stage and in liver-dominant metastatic colorectal cancer and metastatic neuroendocrine tumors.

3:27 PMAbstract No. 72 - DC-Beads M1™ loaded with Irinotecan combined with systemic chemotherapy for pretreated liver dominant metastatic colorectal cancer: procedure and patients outcomes

3:27 PMAbstract No. 72 - DC-Beads M1™ loaded with Irinotecan combined with systemic chemotherapy for pretreated liver dominant metastatic colorectal cancer: procedure and patients outcomes

Efficacy and Toxicity of Hepatic Intra-Arterial Drug-Eluting (Irinotecan) Bead (DEBIRI) Therapy in Irinotecan-Refractory Unresectable Colorectal Liver Metastases.

Response rates to systemic chemotherapy for patients who have failed irinotecan-based chemotherapy for liver-dominant metastatic colorectal cancer range between 10 and 18 % with overall survival between 7 and 9 months. The aim of this study was to assess the efficacy and safety of hepatic arterial irinotecan therapy in patients with hepatic-dominant metastatic colorectal cancer who had failed systemic irinotecan. This was a multi-institutional, multi-national, analysis of patients who received DEBIRI in the setting of unresectable liver-dominant metastatic colorectal cancer. Patients had received between 1 and 4 lines of prior chemotherapy, the majority of which included systemic irinotecan. Primary endpoints were toxicity profile and tumor response rate. 296 patients with unresectable liver metastases who had undergone 666 DEBIRI treatments were reviewed. 192 treatments were performed in patients who had received prior systemic irinotecan. 222 treatments were performed in irinotecan-naïve patients. The median number of DEBIRI treatments was 1 (range 1-8); median treatment dose was 100 mg (range 50-200 mg), with total hepatic treatment of approximately 100 mg (range 20/30-200/300 mg). All-grade adverse events occurred in 18 % of patients receiving prior systemic irinotecan compared with 15 % of patients receiving no prior systemic irinotecan (including chemo-naïve patients). Response rates in patients with prior systemic irinotecan were 44 % at 3 months, 43 % at 6 months, and 44 % at 12 months, compared with 45, 40, and 35 % during the same time point in patients without prior systemic irinotecan. All-grade adverse events occurred in 10, 20, 10, and 37 % of patients receiving 0, 1, 2, and 3+ lines of systemic chemotherapy, respectively. Overall survival was 90 %, 93 %, 90 %, 90 % at 6 months and 76 %, 71 %, 77 %, 87 % at 12 months in patients undergoing DEBIRI therapy after receiving 0, 1, 2, and 3+ lines of systemic chemotherapy, respectively. The safety and efficacy of hepatic arterial drug-eluting irinotecan bead (DEBIRI) therapy are not affected by non-response to prior systemic irinotecan. While DEBIRI complete response rates are greatest and overall adverse events are least in chemotherapy-naïve individuals, it retains its respectable efficacy and low rate of serious adverse events even in the setting of previous administration of systemic chemotherapy.