A multicenter analysis was conducted to evaluate the main prognostic factors driving survival after radioembolization using yttrium‐90–labeled resin microspheres in patients with hepatocellular carcinoma at eight European centers. In total, 325 patients received a median activity of 1.6 GBq between September 2003 and December 2009, predominantly as whole‐liver (45.2%) or right‐lobe (38.5%) infusions. Typically, patients were Child‐Pugh class A (82.5%), had underlying cirrhosis (78.5%), and had good Eastern Cooperative Oncology Group (ECOG) performance status (ECOG 0‐1; 87.7%), but many had multinodular disease (75.9%) invading both lobes (53.1%) and/or portal vein occlusion (13.5% branch; 9.8% main). Over half had advanced Barcelona Clinic Liver Cancer (BCLC) staging (BCLC C, 56.3%) and one‐quarter had intermediate staging (BCLC B, 26.8%). The median overall survival was 12.8 months (95% confidence interval, 10.9‐15.7), which varied significantly by disease stage (BCLC A, 24.4 months [95% CI, 18.6‐38.1 months]; BCLC B, 16.9 months [95% CI, 12.8‐22.8 months]; BCLC C, 10.0 months [95% CI, 7.7‐10.9 months]). Consistent with this finding , survival varied significantly by ECOG status, hepatic function (Child‐Pugh class, ascites, and baseline total bilirubin), tumor burden (number of nodules, alpha‐fetoprotein), and presence of extrahepatic disease. When considered within the framework of BCLC staging, variables reflecting tumor burden and liver function provided additional prognostic information. The most significant independent prognostic factors for survival upon multivariate analysis were ECOG status, tumor burden (nodules >5), international normalized ratio >1.2, and extrahepatic disease. Common adverse events were: fatigue, nausea/vomiting, and abdominal pain. Grade 3 or higher increases in bilirubin were reported in 5.8% of patients. All‐cause mortality was 0.6% and 6.8% at 30 and 90 days, respectively. Conclusion: This analysis provides robust evidence of the survival achieved with radioembolization, including those with advanced disease and few treatment options. (HEPATOLOGY 2011;)

Purpose A multidisciplinary expert panel convened to formulate state-of-the-art recommendations for optimisation of selective internal radiation therapy (SIRT) with yttrium-90 (90Y)-resin microspheres. Methods A steering committee of 23 international experts representing all participating specialties formulated recommendations for SIRT with 90Y-resin microspheres activity prescription and post-treatment dosimetry, based on literature searches and the responses to a 61-question survey that was completed by 43 leading experts (including the steering committee members). The survey was validated by the steering committee and completed anonymously. In a face-to-face meeting, the results of the survey were presented and discussed. Recommendations were derived and level of agreement defined (strong agreement ≥ 80%, moderate agreement 50%–79%, no agreement ≤ 49%). Results Forty-seven recommendations were established, including guidance such as a multidisciplinary team should define treatment strategy and therapeutic intent (strong agreement); 3D imaging with CT and an angiography with cone-beam-CT, if available, and 99mTc-MAA SPECT/CT are recommended for extrahepatic/intrahepatic deposition assessment, treatment field definition and calculation of the 90Y-resin microspheres activity needed (moderate/strong agreement). A personalised approach, using dosimetry (partition model and/or voxel-based) is recommended for activity prescription, when either whole liver or selective, non-ablative or ablative SIRT is planned (strong agreement). A mean absorbed dose to non-tumoural liver of 40 Gy or less is considered safe (strong agreement). A minimum mean target-absorbed dose to tumour of 100–120 Gy is recommended for hepatocellular carcinoma, liver metastatic colorectal cancer and cholangiocarcinoma (moderate/strong agreement). Post-SIRT imaging for treatment verification with 90Y-PET/CT is recommended (strong agreement). Post-SIRT dosimetry is also recommended (strong agreement). Conclusion Practitioners are encouraged to work towards adoption of these recommendations.

Radioembolization is an effective and safe option for patients with unresectable ICC. Predictors for prolonged survival are performance status, tumor burden, and RECIST response.

90 Y radioembolization (selective internal radiation therapy [SIRT]) is a valuable therapeutic option for unresectable hepatic metastases arising from primary colorectal cancer. The present study evaluated the prognostic value of 18 F-FDG PET/CT metabolic parameters for predicting survival after SIRT. Methods: Eighty patients with hepatic metastases of colorectal cancer were treated with SIRT. 18 F-FDG PET/CT was performed at baseline and 3 mo after the treatment. Metabolic volume, total lesion glycolysis, and maximum and peak standardized uptake value (SUV max and SUV peak , respectively) according to PET Response Criteria in Solid Tumors (PER-CIST 1.0) were obtained from 3 liver lesions in each patient, and the corresponding percentage changes from baseline to follow-up were calculated. Tumor response was defined as more than a 30% decrease in these parameters. Furthermore, response was evaluated in accordance with Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Toxicity events and survival were recorded. Results: Overall median survival after SIRT was 60 wk. Responders who had a change in metabolic volume or total lesion glycolysis had significantly longer survival (92 vs. 49 wk [P 5 0.006] and 91 vs. 48 wk [P 5 0.025], respectively). However, neither RECIST 1.1 criteria nor changes in SUV peak or SUV max after treatment predicted outcome (P 5 0.086 for RECIST; P 5 0.310 for change in SUV peak ; P 5 0.155 for change in SUV max ). Conclusion: Changes in metabolic volume and total lesion glycolytic rate as measured by 18 F-FDG PET predicted survival in patients with hepatic metastases from colorectal cancer, whereas changes in SUV peak or SUV max and RECIST 1.1 criteria did not predict survival.

This study analyzed the predictive value of 99m Tc-labeled macroaggregated albumin ( 99m Tc-MAA) SPECT for 90 Y-labeled resin microsphere therapy (radioembolization) by comparing uptake on pretherapeutic 99m Tc-MAA SPECT with uptake on posttherapeutic 90 Y-bremsstrahlung SPECT. Methods: We included 502 patients (55% male; mean age ± SD, 62 ± 11 y) who underwent radioembolization between 2005 and 2013 because of primary or secondary liver malignancies (colorectal cancer [n 5 195, 38 Y-bremsstrahlung scans were used to quantify mean counts per pixel and evaluate the mean tumor-to-background ratio (TBR). Data were given as mean ± SD. Additionally, uptake in lesions on 99m Tc-MAA and 90 Y-bremsstrahlung scans was graded visually as homogeneously higher than (grade 1), heterogeneously higher than (grade 2), equal to (grade 3), or lower than (grade 4) uptake in normal liver tissue. The Mann-Whitney U test and Spearman correlation were used to evaluate statistically significant differences between 99m Tc-MAA and 90 Y-bremsstrahlung SPECT. Results: In total, 1,008 lesions were analyzed. Of the 23% (230/ 1,008) of lesions that had grade 1 uptake on 99m Tc-MAA SPECT, 81% (186/230) remained grade 1 after radioembolization whereas 16% (37/230) were grade 2. Of the lesions with grade 2 uptake on 99m Tc-MAA SPECT, 16% had grade 1 uptake and 82% grade 2 uptake after radioembolization. Of the lesions with grade 3 uptake, however, 27% had grade 1 uptake and 47% grade 2 uptake after radioembolization. Even among the lesions with grade 4 uptake on 99m Tc-MAA SPECT, 21% had grade 1 uptake and 46% grade 2 uptake after radioembolization. The mean TBR on 99m Tc-MAA and 90 Y-bremsstrahlung SPECT showed a significant, though low, correlation in the total population (r 5 0.26; P , 0.001) and in hepatocellular carcinoma (r 5 0.4; P , 0.001), cholangiocellular carcinoma (r 5 0.3; P , 0.05), breast cancer (r 5 0.3; P , 0.001), colorectal cancer (r 5 0.2; P , 0.001), and neuroendocrine tumors (r 5 0.2; P , 0.01). Conclusion: Although significant for most lesions, the correlation between 99m Tc-MAA and 90 Y-microsphere mean TBR was low. Classifying uptake into 4 grades revealed that lesions with high uptake on 99m Tc-MAA SPECT maintain high uptake within radioembolization. More than 60% of lesions with a pretherapeutically lower uptake than in healthy liver tissue, however, showed high uptake within radioembolization. Patients with low tumor uptake on pretherapeutic 99m Tc-MAA imaging should not be excluded from radioembolization.