Yttrium-90 Radioembolization Therapy Research Articles

Implications of lung shunt fraction calculation discrepancy in Y-90 radioembolization treatment from 2D planar vs 3D SPECT imaging

Abstract The safety and efficacy of Yttrium-90 (Y-90) radio-embolization therapy is partly dependent on the lung shunt fraction (LSF). There may be a notable disparity between LSF when calculated using 2D planar imaging vs 3D SPECT; this can affect the total allowable Y-90 dose delivered and therefore change the effectiveness of the procedure. The case presented demonstrates an 81% decrease in LSF when calculated by SPECT as compared to 2D planar imaging. This case highlights the importance of considering the imaging technique and the potential discrepancies that can arise between planar and SPECT imaging in LSF assessment.

Chinese expert consensus on selective internal radiation therapy with yttrium-90 for primary and metastatic hepatocellular carcinoma

Liver malignant tumors are one of the most common causes of cancer-related deaths in China. Selective internal yttrium-90 radioembolization therapy ((90)Y-SIRT) is a kind of promising local minimally invasive method, and its effectiveness and safety has been confirmed in clinical application over the past two decades. Moreover, it has been approved by the U.S. National Comprehensive Cancer Network and other international guidelines for the topical treatment of patients with liver malignancies. Taking into account the complexity of the (90)Y-SIRT and the need for multidisciplinary collaboration to improve the safety and success rate of treatment, the Nuclear Medicine Expert Committee of the Chinese society of Clinical Oncology, along with Beijing Nuclear Medicine Quality Control and Improvement Center invited experts from surgical oncology, interventional medicine, nuclear medicine, and other related fields to discuss and form a consensus on the clinical diagnosis, treatment and management, which mainly included definition, indications and contraindications, treatment procedures, postoperative follow-up, adverse reactions and complications, radiation safety management, etc. Herein, we provide the reference guidance to establish (90)Y-SIRT standardized management and treatment system various units for relevant practitioners.

Therapy of Intermediate-Stage Hepatocellular Carcinoma: Current Evidence and Clinical Practice.

Intermediate-stage Hepatocellular Carcinoma (HCC) represents a wide range of disease burden. Patients with different levels of liver function, tumor size, and number of lesions may all have intermediate-stage disease according to the Barcelona Clinic Liver Cancer (BCLC) staging system. Several minimally invasive image-guided locoregional therapies are available for the treatment of intermediate-stage HCC, including conventional transarterial chemoembolization (cTACE), drug-eluting bead TACE (DEB-TACE), yttrium-90 radioembolization (Y-90 RE), thermal ablation, bland embolization, and combination therapy. Available clinical evidence points to cTACE as the current gold standard for the locoregional treatment of intermediate-stage HCC. DEB-TACE is at best non-inferior to cTACE in terms of survival benefit. Y-90 RE is a maturing therapy, and some institutions have adopted it as first-line therapy for intermediate-stage HCC. Thermal ablation combined with TACE may be used in select patients, while bland embolization has only limited evidence for its use. The combination of locoregional therapy with VEGF inhibitors or immune checkpoint inhibitors has also been explored. This article will examine in detail the clinical evidence supporting available locoregional treatment options for intermediate-stage HCC.

3:54 PM Abstract No. 28 Predictors of survival in patients with advanced (Barcelona Clinic Liver Cancer C) hepatocellular carcinoma undergoing Yttrium-90 radioembolization therapy

To identify key clinical and imaging predictors of survival in patients undergoing Yttrium-90 radioembolization (Y90-RE) for advanced, Barcelona Clinic Liver Cancer (BCLC) C, hepatocellular carcinoma (HCC). In an IRB-approved study, patients with BCLC C HCC who underwent Y90-RE were retrospectively identified. Reason for BCLC C Status (i.e., Eastern Cooperative Oncology Group performance status (ECOG-PS), macrovascular invasion, and/or extrahepatic metastasis) and additional pre and post Y90-RE prognostic factors were recorded and analyzed. Median overall survival (OS) from first Y90-RE was calculated using Kaplan-Meier estimation and potential prognostic factors were tested for significance (p ≤0.05) using log-rank analysis. Between 2013 and 2018, 97 BCLC C HCC patients (79% male; 65 years mean age) underwent Y90-RE with a median OS (95% CI) of 13.7 months (10.8-16.9). Median OS for the 40 (41%) ECOG-PS driven BCLC C patients versus the 57 (59%) macrovascular invasion and/or extrahepatic metastasis driven BCLC C patients was 14.5 (10.8-20.5) versus 13.2 (6.9-16.9) months, respectively (p = 0.9). Prognostic factors associated with a prolonged median OS were absence of hepatic vein invasion (14.9 vs. 5.3; p = 0.0002), single hepatic lobe burden (15.4 vs. 7.2; p = 0.04), absence of anorexia (14.6 vs. 6.1; p = 0.004), normal baseline alkaline phosphatase (19.1 vs. 9.0; P <0.0001), normal baseline serum sodium (14.9 vs. 5.2; p = 0.01), greater post Y90-RS tumor shrinkage (14.9 vs. 5.2; p = 0.01), attainment of Milan eligibility status (20.8 vs. 9.6; p = 0.001), and complete/partial tumor response per mRECIST (17.5 vs. 7.3; p = 0.01). Y90-RE is an effective therapy for the treatment of BCLC C hepatocellular carcinoma patients, resulting in an overall survival that is equivalent, if not favorable, to currently allocated therapies per BCLC guidelines. Certain pre Y90-RE clinical and imaging characteristics are associated with an improved overall survival.Tabled 1Prognostic Factors, in median OS (95% CI) monthsPresentAbsentPHepatic vein invasion5.314.90.0002Single hepatic lobe burden15.47.20.04Anorexia6.114.60.004Normal baseline alkaline phosphatase19.19.00.0001Normal baseline sodium blood levels18.07.10.014Greater tumor shrinkage14.95.20.01Attained Milan eligibility status20.89.60.001Attained complete or partial tumor response, per mRECIST17.57.30.01 Open table in a new tab

Abstract No. 567 Yttrium-90 radioembolization therapy for combined hepatocellular and cholangiocarcinoma

To report outcomes of transarterial radioembolization (TARE) using glass microspheres for the treatment of mixed hepatocellular-cholangiocarcinoma (HCC-CC). Between 2013 and 2019, 10 consecutive patients with histologically confirmed HCC-CC received 1 or 2 TARE treatments of a targeted territory using glass microspheres. Baseline demographics in addition to tumor distribution, Child Pugh score, and BCLC were recorded. Tumor response was assessed according to modified RECIST criteria. Six-month mortality and adverse events were monitored for each patient. Adverse events were graded by standardized criteria using the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Eight (80%) patients (4 males, 4 females) received a single TARE treatment and two (20%) patients underwent two. Tumor responses at 6 months were complete and partial in 80% and 20% patients respectively. No patients demonstrated tumor progression. No major toxicity was observed after 1st or 2nd treatment of RE. Two grade 2 adverse events were seen (Table 1). 6-month mortality was 10% (n = 1). While outcomes of combined HCC-CC are poor and optimal treatment remains undefined, TARE appears to represent a safe and promising locoregional treatment for disease control with an acceptable toxicity profile.Table 1Patient #Adverse Events after 1st Procedure (CTCAE Grade)Adverse Events after 2nd Procedure (CTCAE Grade)6 Month Mortality1 Year Mortality2 Year MortalityChild Pugh ScoreBCLCTumor LocationRECIST Rating1NoneNoneYYY6 (A)BRPartial2Abdominal Pain and Fatigue (2)NoneNNN5 (A)BLComplete3Fever (2)NoneNNN5 (A)ARComplete4NoneNoneNNN5 (A)ABiliary DuctComplete5NoneNoneNNN6 (A)ALComplete6NoneNoneNNN5 (A)ARComplete7NoneNoneNNN5 (A)ARPartial8NoneNoneNNN5 (A)ARComplete9NoneNoneNNN5 (A)ARComplete10NoneNoneNNN5 (A)ALComplete Open table in a new tab

Yttrium-90 Radioembolization Therapy for Combined Hepatocellular and Cholangiocarcinoma

Purpose: To report outcomes of transarterial radioembolization (TARE) using glass microspheres for the treatment of mixed hepatocellular-cholangiocarcinoma (HCC-CC) in a propensity-matched study. Material and Methods: Between 2013 and 2019, 10 consecutive patients with histologically confirmed HCC-CC received TARE of a targeted territory using glass microspheres as a primary initial treatment. Baseline demographics in addition to tumor distribution, Child Pugh score, and BCLC were recorded. Tumor response was assessed according to modified RECIST criteria. The HCC-CC cohort was matched to the HCC cohort, and objective response and survival analysis was performed. Results: In the HCC-CC cohort, patients had a 70% objective response rate (ORR), and in the HCC cohort, patients had a 90% ORR after matching (p = 0.54). The median overall survival (OS) for HCC patients was 12.3 months (95% CI: 6.0–17.4 months) in the matched population, and for HCC-CC patients, the median OS was 15.2 months (95% CI: 2.7–20.2 months) (p = 0.98). The median progression-free survival (PFS) for HCC patients was 11.6 months (95% CI: 2.53–19.3 months) in the matched population, and for HCC-CC patients, the median PFS was 15.2 months (95% CI: 2.7–20.2 months) (p = 0.94). The median transplant-free survival (TFS) for HCC patients was 12.3 months (95% CI: 6.0–17.4 months) in the matched population, and for HCC-CC patients, the median TFS was 15.2 months (95% CI: 2.7–20.2 months) (p = 0.98). Conclusions: While outcomes of combined HCC-CC are poor and optimal treatment remains undefined, TARE appears to represent an effective locoregional treatment with survival outcomes similar to that of HCC treated by TARE.

Prognostic Factors in Overall Survival of Patients with Unresectable Intrahepatic Cholangiocarcinoma Treated by Means of Yttrium-90 Radioembolization: Results in Therapy-Naïve Patients.

To investigate prognostic factors in unresectable intrahepatic cholangiocarcinoma (ICC) therapy-naïve patients after yttrium-90 (Y-90) radioembolization (RE) therapy. Between 2005 and 2016, 21 patients with ICC were treated with Y-90 RE only and their survival data were analyzed. Patients were stratified and response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. The overall median survival was 15months. Survival was significantly (p=0.009) prolonged in patients with tumor burden of≤25% (n=8, OS 37.5months) versus those with a tumor burden of 25-50% (n=13, OS 15months). The other variables: tumor morphology (infiltrative vs. peripheral), tumor distribution (solitary vs. multifocal), lobes involved (unilobar vs. bilobar), FDG PET status (FDG avid vs. non-avid), RE treatment sessions (1 session vs. 2 sessions), metastases (metastasis vs. no metastasis) and RECIST criteria, had no significant impact on survival. Tumor burden represents a key prognostic factor of survival in therapy-naïve patients with unresectable ICC treated with Y-90 RE therapy only.

Predictors and prognosticators for survival with Yttrium-90 radioembolization therapy for unresectable colorectal cancer liver metastasis.

This critical review aims to explore predictive and prognostic biomarkers of Yttrium-90 (Y90) radioembolization therapy of colorectal liver metastases. A brief overview of established predictive and prognostic molecular and genetic biomarkers in colorectal cancer therapies will be discussed. A review of the literature on imaging modalities, genetic, metabolic and other molecular markers and the subsequent outcomes in post-Y90 treatment will be presented. How these biomarkers and future biomarker research can inform locoregional treatment decisions in the clinical setting of metastatic colorectal cancer lesions of the liver will be explored. There are opportunities for personalized cancer treatment in the setting of Y90 radioembolization. The ability to predict tumor response after Ytrium-90 radioembolization therapy can greatly impact clinical decision making and enhance treatment outcomes, therefore further research into the field is needed.

Selective Internal Yttrium-90 Radioembolization Therapy (90Y-SIRT) Versus Best Supportive Care in Patients With Unresectable Metastatic Melanoma to the Liver Refractory to Systemic Therapy: Safety and Efficacy Cohort Study.

To investigate survival, efficacy, and safety of selective internal yttrium-90 radioembolization therapy (Y-SIRT) in patients with unresectable metastatic melanoma (MM) to liver refractory to systemic therapy. An IRB-approved retrospective review of 58 patients diagnosed with unresectable MM to the liver, refractory to systemic therapy, between February 2003 and March 2012 was conducted. Of these, 28 received resin-based Y-SIRT (group A), and 30 patients received best supportive care (group B). Survival was calculated using the Kaplan-Meier method and Cox proportional hazard models. Groups A and B were similar for the Child-Pugh class, ECOG scores, age, sex, and race. Median overall survival (OS) from diagnosis of primary melanoma in groups A and B were 119.9 and 26.1 months, respectively (P<0.001). Median OS from hepatic metastasis in groups A and B were 19.9 and 4.8 months, respectively (P<0.0001). In group A, median OS from hepatic metastasis in the Child-Pugh A, B, and C patients was 37.7, 4.2, and 3.6 months, respectively (P<0.001). In group B, median OS from hepatic metastasis in the Child-Pugh A, B, and C patients was 7.8, 4.2, and 1.9 months, respectively (P=0.04). Within group A, median OS from first Y-SIRT was 10.1 months; median OS of the Child-Pugh A, B, and C patients from first Y-SIRT was 10.3, 1.2, and 0.9 months, respectively (P=0.04). Median OS from first Y-SIRT was significantly greater in the absence of diffuse (>10) liver metastases (15.1 vs. 4.7 mo, P=0.02), and in the absence of extrahepatic metastases (21.3 vs. 8.6 mo, P<0.001). Common clinical toxicities following Y-SIRT included abdominal pain (17.9%), fatigue (14.3%), and self-limiting grade III bilirubin toxicity (10.7%). For patients with unresectable MM to the liver refractory to systemic therapy, resin-based Y was associated with longer survival from liver metastases than best supportive care. Child-Pugh A patients with <10 metastatic lesions and absence of extrahepatic metastases demonstrated greatest survival following Y-SIRT.

Internal dosimetry for radioembolization therapy with Yttrium-90 microspheres.

The absorbed doses in the liver and adjacent viscera in Yttrium‐90 radioembolization therapy for metastatic liver lesions are not well‐documented. We sought for a clinically practical way to determine the dosimetry of this advent treatment. Six different female XCAT BMIs and seven different male XCAT BMIs were generated. Using Monte Carlo GATE code simulation, the total of 100MBq 90Y was deposited uniformly in the source organ, liver. Self‐irradiation and absorbed doses in lung, kidney and bone marrow were calculated. The mean energy of Yittrium‐90 (i.e., 0.937 MeV) was used. The S‐values and equivalent doses in target organs were estimated. The dose absorbed in the liver was between 84 and 53 Gy and below the target of 80 to 150 Gy. The absorbed dose in the bone marrow, lungs, and kidneys are very low and below 0.1 , 0.4, and 0.5 Gy respectively. Our study indicates that larger activities than the conventional dose of 3 GBq may be both required and safe. Further confirmations in clinical settings are needed.

A Lesion-Based Response Prediction Model Using Pretherapy PET/CT Image Features for Y90 Radioembolization to Hepatic Malignancies

We present a probabilistic approach to identify patients with primary and secondary hepatic malignancies as responders or nonresponders to yttrium-90 radioembolization therapy. Recent advances in computer-aided detection have decreased false-negative and false-positive rates of perceived abnormalities; however, there is limited research in using similar concepts to predict treatment response. Our approach is driven by the goal of precision medicine to determine pretherapy fluorine-18-2-fluoro-2-deoxy-d-glucose positron emission tomography and computed tomography imaging parameters to facilitate the identification of patients who would benefit most from yttrium-90 radioembolization therapy, while avoiding complex and costly procedures for those who would not. Our algorithm seeks to predict a patient's response by discovering common co-occurring image patterns in the lesions of baseline fluorine-18-2-fluoro-2-deoxy-d-glucose positron emission tomography and computed tomography scans by extracting invariant shape and texture features. The extracted imaging features were represented as a distribution of each subject based on the bag-of-feature paradigm. The distribution was applied in a multinomial naive Bayes classifier to predict whether a patient would be a responder or nonresponder to yttrium-90 radioembolization therapy based on the imaging features of a pretherapy fluorine-18-2-fluoro-2-deoxy-d-glucose positron emission tomography and computed tomography scan. Comprehensive published criteria were used to determine lesion-based clinical treatment response based on fluorine-18-2-fluoro-2-deoxy-d-glucose positron emission tomography and computed tomography imaging findings. Our results show that the model is able to predict a patient with liver cancer as a responder or nonresponder to yttrium-90 radioembolization therapy with a sensitivity of 0.791 using extracted invariant imaging features from the pretherapy fluorine-18-2-fluoro-2-deoxy-d-glucose positron emission tomography and computed tomography test. The sensitivity increased to 0.821 when combining extracted invariant image features with variable features of tumor volume.

KRAS Status as an Independent Prognostic Factor for Survival after Yttrium-90 Radioembolization Therapy for Unresectable Colorectal Cancer Liver Metastases

PurposeTo evaluate Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation status as a prognostic factor for survival after yttrium-90 (90Y) radioembolization for colorectal cancer (CRC) liver metastases. Materials and MethodsConsecutive patients with unresectable CRC liver metastases and documented KRAS mutation status who were treated with 90Y radioembolization during the period 2007–2014 were investigated. Patient demographics, disease characteristics, therapy regimens, and overall survival (OS) from first 90Y radioembolization were compared between patients with KRAS wild-type (wt) and mutant status. Kaplan-Meier estimation and Cox regression were used for survival analysis and to assess independent prognostic factors for OS. ResultsOf 186 patients, 104 underwent KRAS mutation analysis before 90Y radioembolization, with 45 (43.3%) identified as mutant. The wt and mutant groups were similar in demographics, liver status, overall performance status, and tumor characteristics (all P > .05). Mean time from liver metastasis to 90Y radioembolization was greater in patients with KRAS wt status (P = .033). A greater percentage of wt patients received anti–epidermal growth factor receptor therapies before 90Y radioembolization (66.1% vs 8.9%; P < .001). Median OS from first 90Y radioembolization was significantly greater in KRAS wt patients (9.5 mo vs 4.8 mo; P = .041). Univariate analysis identified Child-Pugh class, carcinoembryonic antigen (CEA), chemotherapy after 90Y radioembolization, KRAS status, and treatment-induced toxicity as prognostic factors for OS. Multivariate Cox regression analysis demonstrated Child-Pugh class, CEA, and KRAS status to be independent prognostic factors for OS, even when correcting for the effect of chemotherapy after 90Y radioembolization. ConclusionsPatients with CRC and KRAS wt may derive greater survival benefit from 90Y radioembolization therapy than patients with KRAS mutant.

1:36 PM, Abstract No. 190 - KRAS status as an independent prognostic factor of survival for unresectable colorectal cancer after Yttrium-90 radioembolization therapy

1:36 PM, Abstract No. 190 - KRAS status as an independent prognostic factor of survival for unresectable colorectal cancer after Yttrium-90 radioembolization therapy

Gene expression in hepatocellular carcinoma (HCC): pilot study of potential transarterial chemoembolization (TACE) response biomarkers

Genetic analysis is an encouraging approach to improve the understanding of biochemical mechanisms that underlie tumor therapeutic outcome. While gene assays have been previously applied to liver tissues to identify genetic signatures associated with cytotoxic and ischemic tissue insults, investigation of the association between HCC gene expression and TACE treatment outcomes has not been performed. This study was undertaken to explore the relationship between HCC genetics and TACE response in order to identify potential biomarkers associated with enhanced treatment efficacy. In this single-institution study, pre-treatment HCC biopsy specimens for tumors treated with TACE between 2007-2013 were analyzed for a panel of 60 chemosensitivity, hypoxia response, mitosis, and inflammatory mediator genes using the QuantiGene® Plex 2.0 mRNA detection assay (Affymetrix). Medical record and imaging review was used to collect demographic, disease, and procedure data, as well as tumor response outcomes, assessed using necrosis (EASL) criteria. Quantitative mRNA levels were compared between tumors exhibiting complete (CR) versus partial (PR) radiographic response. The study sample included 19 biopsied index tumors (mean size 3.0 cm) from 19 patients (14 men, 5 women; mean age 59 years) who underwent mean 2 TACE sessions using 1:1 chemotherapy to ethiodized oil ± particle embolization. Thirteen and 6 tumors exhibited CR and PR, respectively, at mean 116 days post-treatment. CR tumors showed a statistical increase (P<0.05) in or trend (P<0.1) toward higher pre-treatment chemosensitivity and mitosis (ATF4, BAX, CCNE1, KIF11, NFX1, PPP3CA, SNX1, TOP2A, and TOP2B) gene mRNA expression compared to PR tumors, lower CXCL10 levels, and statistically higher (P<0.05) baseline VEGF-alpha levels. Genetic signatures may allow pre-TACE stratification of tumor response probability, and gene analysis may thus offer an opportunity to personalize locoregional therapy by enhancing treatment modality allocation (e.g. TACE vs. yttrium-90 radioembolization vs. ablative therapy). Further confirmation of identified markers and exploration of their respective predictive capacity thresholds is necessary.

KRAS mutations to predict survival of yttrium-90 radioembolization therapy in patients with unresectable colorectal liver metastases.

754 Background: The significance of KRAS mutations in predicting response to Yttrium-90 radioembolization (Y90) of colorectal cancer (CRC) liver metastases is unknown. The purpose of this study was to compare overall survival (OS) in patients receiving Y90 with wild-type (wt) and mutant KRAS. Methods: Consecutive patients with unresectable CRC liver metastases and KRAS mutation status who were treated with Y90 from 2002-2014 were studied. Patient demographics, lab and molecular markers, disease stages, therapy regimens, treatment parameters, OS from primary CRC diagnosis, from liver metastasis and from first Y90 were compared between patients with KRAS wt and mutant. Kaplan-Meier estimation and Cox proportional hazard models were used for survival analysis and to assess independent prognostic factors for OS. Results: A total of 107 patients with unresectable CRC liver metastases underwent KRAS mutation analysis prior to Y90; 43 (40.2%) were mutant and 64 (59.8%) were wt. At the time of analysis, 13 patients were censored due to loss to follow-up. Groups were similar in age, sex, race, Child class, mean pre-Y90 carcino-embryonic antigen (CEA) levels, and % receiving Y90 as third-line therapy (p&gt;0.05 for all). OS from primary diagnosis, liver metastasis, and from first Y90 was significantly greater in KRAS wt than in mutant (p=0.022, 0.002, and 0.022). Median OS from first Y90 for KRAS wt and mutant were 9.4 and 5.1 months, respectively. On multivariate analysis adjusting for age, sex, race, Child class, and pre-treatment CEA level, wt KRAS remained an independent predictor of greater survival (HR=0.64, p=0.049). Conclusions: Patients with unresectable mCRC to the liver with KRAS wt demonstrated significantly greater post-Y90 survival compared with KRAS mutant. [Table: see text]

Treatment of Hepatocellular Cancer Due to Hepatitis Delta with Yttrium-90 Radioembolization in a Patient with Cirrhosis: A Case Report

OZET Cirrhosis due to delta hepatitis is one of the most important etiologic factors in our country. Hepatocellular carcinoma (HCC) often develops on the base of cirrhosis. Recently, yttrium-90 radioembolization therapy has been increasingly used in the treatment of HCC. Transarterial infusion of yttrium-90 radioactive microspheres is a new promising method in treating unresectable liver tumors. Herein, we present a 55-year-old male HCC patient who developed HCC due cirrhosis associated with delta hepatitis and was successfully treated with yttrium-90 radioembolization therapy. (Viral Hepatitis Journal 2014; 20(3): 131-133)

8:09 AM; Abstract No. 222 - Prognostic indicators of overall survival after resin-based Yttrium-90 radioembolization (Y90) therapy in patients who failed chemotherapy for metastatic colorectal cancer to liver

8:09 AM; Abstract No. 222 - Prognostic indicators of overall survival after resin-based Yttrium-90 radioembolization (Y90) therapy in patients who failed chemotherapy for metastatic colorectal cancer to liver

Modified Response Evaluation Criteria in Solid Tumors and European Association for the Study of the Liver Criteria Using Delayed-Phase Imaging at an Early Time Point Predict Survival in Patients with Unresectable Intrahepatic Cholangiocarcinoma following Yttrium-90 Radioembolization

PurposeTo investigate early imaging prognostic factors in unresectable intrahepatic cholangiocarcinoma (ICC) refractory to standard chemotherapy after yttrium-90 (90Y) radioembolization therapy. Materials and MethodsIn an institutional review board–approved prospective correlative study, 21 consecutive patients with ICC refractory to standard chemotherapy underwent 90Y radioembolization therapy. Target and overall Response Evaluation Criteria In Solid Tumors (RECIST), modified RECIST (mRECIST), and European Association for the Study of the Liver (EASL) treatment responses were assessed. The mRECIST and EASL criteria were modified for application on delayed phases of dynamic contrast-enhanced cross-sectional imaging studies. Conventional definitions for complete and partial response were applied; these responses comprised objective response. Restaging imaging was obtained at 1- and 3-month intervals until patient death. Survival analyses by Kaplan–Meier and log-rank proportional models including application of the landmark method to avoid lead-time bias were performed from the day of treatment. Significance was set at P < .05. ResultsMedian overall survival (OS) from the time of 90Y therapy was 16.3 months (95% confidence interval, 7.2–25.4 mo). Significant differences between mRECIST and EASL versus RECIST were found when categorizing patients into responders and nonresponders (P < .001). Significantly prolonged OS was observed for patients with targeted objective response based on modified mRECIST and EASL criteria (P = .005 and P = .001, respectively) at 3 months. RECIST was not found to correlate with survival at 1- or 3-month follow-up. ConclusionsModified target mRECIST and EASL criteria that employ delayed-phase contrast enhancement at 3 months after 90Y radioembolization therapy for ICC predicted OS. RECIST did not correlate with survival.

PERCIST criteria to predict survival at 3 months following intra-arterial resin-based yttrium-90 (Y-90) radioembolization therapy of unresectable intrahepatic cholangiocarcinoma refractory to standard chemotherapy: A proof of concept study.

e15141 Background: To investigate the prognostic value of PET Response Criteria in Solid Tumors (PERCIST) on predicting survival in patients with unresectable intrahepatic cholangiocarcinoma (ICC) after resin-basedYttrium-90 (Y-90) radioembolization. Methods: IRB approved prospective correlative study in ICC patients refractory to standard chemotherapy who had 18F-FDG PET-CT before and after Y-90 therapy. Measurable tumor was defined as a lesion ≥ 1 cm in diameter and maximum standardized uptake ((max) SUV) ≥ 2.5. (Max) SUV was measured in targeted and non-targeted lesions after local therapy (overall response). PERCIST criteria defined complete response (CR) as no FDG uptake within target lesion, and partial response (PR) as reduction of 30% in FDG (max) SUV peak in measurable lesions. Objective response included PR/CR. PET imaging was acquired pre-treatment, 1-3-and-6 months following Y90. Survival analyses were carried out with Kaplan–Meier and Log-Rank proportional models using SPSS software v20 (IBM, Armonk, NY) with significance set at &lt;0.05. Results: 9 consecutive patients were enrolled (56% men, mean age 58). Median overall survival from Y90 was 21.7 months. Average max SUV pretreatment was 10.02 and after Y90, 6.03. At 1-month after Y90, target PERCIST criteria showed CR= 1 (11.1%), PR=1 (11.1%), SD=7 (33.3%) and PD=0 (0.0%). Following 3-month after Y90, target response was CR= 2 (22.2%), PR=3 (33.3%), SD=3 (33.3%) and PD=1 (11.1%). No correlation between survival and either target or overall PERCIST criteria response on 1-month follow-up scan was seen(p=0.260). Statistically significant prolonged overall survival was observed for patients with objective targeted response based on PERCIST criteria at 3-month scan (P=0.022). In addition, objective overall PERCIST response at 3-month showed significant correlation with overall survival (p= 0.011). Conclusions: In patients with unresectable ICC refractory to standard chemotherapy, PERCIST criteria at 3-months following Y-90 therapy predict overall survival.

8:40 AM Abstract No. 64 - Selective internal Yttrium-90 radioembolization therapy (90-Y SIRT) in patients with unresectable metastatic melanoma (MM) to liver, refractory to systemic therapy: analysis of imaging findings, survival and factors associated with prolonged survival

Purpose To investigate the correlation of imaging findings with survivals in patients (pts) with unresectable metastatic melanoma (MM) to liver, refractory to systemic therapy , treated with selective internal yttrium-90 radioembolization therapy (90-Y SIRT). Materials and Methods Consecutive pts with unresectable MM to liver, who failed with systemic therapy, treated with resin-based 90Y SIRT in last 9 years, and who had cross sectional imaging (PET in 75% and chest abdomen pelvis CT or MR in 25% of pts) before 90-Y SIRT were evaluated retrospectively. Imaging findings were correlated with progression free survival (PFS) and overall survival (OS). RECIST 1.1 criteria were used for liver disease. The OS times were calculated from diagnosis of primary melanoma (OS-dx), from first 90Y SIRT (OS–90-Y) and from MM to liver (OS-MM). Absence of progression of MM to liver was considered as PFS. Kaplan Meir method tested with log rank test and Cox proportional hazard model were used for survival analysis. Results 24 pts (mean age 48.8 years, SD 14.5) with MM to liver underwent 42 90-Y SIRTs. The median OS-dx, OS-MM and OS-90Y were 121.4, 27.9 and 13.4 months(m) respectively. The median PFS was 10.1 m. PFS in partially responded (n=3), stable disease (n=15) and progressive disease (n=6) according RECIST 1.1 criteria were 19.6, 10.3 and 1.3 m respectively (p=0.001). Before 90-Y SIRT, the pts had Child-Pugh class A (n=21), B (n=2) and C (n=1) with corresponding median OS-90Y of 15, 2.6 and 0.9 m (p=0.02) respectively. More than 8 MM lesions to liver were present in 29.2% pts and had median OS–90-Y of 5.5 m vs 17.7 m in pts with Conclusion RECIST 1.1 responses, less than 8 MM to liver lesions and absence of extrahepatic MM disease before 90Y SIRT were found predictor of prolonged survival.