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Background: This multi-centre phase II clinical trial is the first prospective evaluation of radioembolisation of patients with colorectal liver metastases (mCRC) who failed previous oxaliplatin- and irinotecan-based systemic chemotherapy regimens.Methods: Eligible patients had adequate hepatic, haemopoietic and renal function, and an absence of major hepatic vascular anomalies and hepato-pulmonary shunting. Gastroduodenal and right gastric arteries were embolised before hepatic arterial administration of yttrium-90 resin microspheres (median activity, 1.7 GBq; range, 0.9-2.2).Results: Of 50 eligible patients, 38 (76%) had received > or =4 lines of chemotherapy. Most presented with synchronous disease (72%), >4 hepatic metastases (58%), 25-50% replacement of total liver volume (60%) and bilateral spread (70%). Early and intermediate (>48 h) WHO G1-2 adverse events (mostly fever and pain) were observed in 16 and 22% of patients respectively. Two died due to renal failure at 40 days or liver failure at 60 days respectively. By intention-to-treat analysis using Response Evaluation Criteria in Solid Tumours, 1 patient (2%) had a complete response, 11 (22%) partial response, 12 (24%) stable disease, 22 (44%) progressive disease; 4 (8%) were non-evaluable. Median overall survival was 12.6 months (95% CI, 7.0-18.3); 2-year survival was 19.6%.Conclusion: Radioembolisation produced meaningful response and disease stabilisation in patients with advanced, unresectable and chemorefractory mCRC. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to evaluate the radiation dose in patients undergoing liver angiographic procedure and verify the usefulness of different dose measurements to prevent deterministic effects. Gafchromic film, MicroMOSFET data and DIAMENTOR device of the X-ray system were used to characterize the examined interventional radiology (IR) procedure., Materials and Methods: A liver embolization procedure, the SIRT (Selective Internal Radiation Therapy), was investigated. The exposure parameters from the DIAMENTOR as well as patient and geometrical data were registered. Entrance skin dose map obtained using Gafchromic film (ESDGAF) in a standard phantom as well as in 12 patients were used to calculate the maximum skin dose (MSDGAF). MicroMOSFETs were used to assess ESD in relevant points/areas. Moreover, the maximum value of five MicroMOSFETs array, due to the extension of treated area and to the relative distance of 2-3 cm of two adjacent MicroMOSFETs, was useful to predict the MSD without interfering with the clinical practice. PCXMC vers.1.5 was used to calculate effective dose (E) and equivalent dose (H)., Results: The mean dose-area product (DAPDIAMENTOR) for SIRT procedures was 166 Gycm2, although a wide range was observed. The mean MSDGAF for SIRT procedures was 1090 mGy, although a wide range was experienced. A correlation was found between the MSDGAF measured on a patient and the DAPDIAMENTOR value for liver embolizations. MOSFET and Gafchromic data were in agreement within 5% in homogeneous area and within 20% in high dose gradient regions. The mean equivalent dose in critical organs was 89.8 mSv for kidneys, 22.9 mSv for pancreas, 20.2 mSv for small intestine and 21.0 mSv for spleen. Whereas the mean E was 3.7 mSv (range: 0.5-13.7)., Conclusions: Gafchromic films result useful to study patient exposure and determine localization and amplitude of high dose skin areas to better predict the skin injuries. Then, DAPDIAMENTOR or MOSFET data could offer real-time methods, as on-line dose alert, to avoid any side effects during liver embolization with prolonged duration.

Background & Aims: The European Network on Radioembolization with Yttrium-90 resin microspheres study group (ENRY) conducted a retrospective study to evaluate the outcomes among elderly (≥ 70 years) and younger patients (<70 years) with unresectable hepatocellular carcinoma (HCC) who received radioembolization at 8 European centers., Methods: Patients with confirmed diagnosis of unresectable HCC who either progressed following resection or locoregional treatment and/or who were considered poor candidates for chemoembolization were evaluated by a multidisciplinary team for radioembolization with (90)Y-resin microspheres (SIR-Spheres; Sirtex Medical). The survival outcome and all adverse events were compared between the two age groups., Results: Between 2003 and 2009, 128 elderly and 197 younger patients received radioembolization. Patients in both groups had similar demographic characteristics. Many elderly and younger patients alike had multinodular, BCLC stage C disease, invading both lobes (p = 0.648). Elderly patients had a lower tumor burden, a smaller median target liver volume (p = 0.016) and appeared more likely to receive segmental treatment (p = 0.054). Radioembolization was equally well tolerated in both cohorts and common procedure-related adverse events were predominantly grade 1-2 and of short duration. No significant differences in survival between the groups were found (p = 0.942) with similar median survival in patients with early, intermediate or advanced BCLC stage disease., Conclusions: Radioembolization appears to be as well-tolerated and effective for the elderly as it is for younger patients with unresectable HCC. Age alone should not be a discriminating factor for the management of HCC patients., (Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

In a prospective multicenter phase II trial of radioembolization with yttrium-90 ((90)Y-RE) in chemorefractory liver-dominant metastatic colorectal cancer (mCRC), we showed that median survival was 12.6 months (95% CI 7.0-18.3) with 48% of 50 patients achieving disease control. In this extension retrospective study, we analyzed whether a panel of biomarkers, known to be associated to an adverse clinical outcome, underwent variations in CRC liver metastases pre and post (90)Y-RE.Of the 50 patients included in the study, 29 pre-(90)Y-RE therapy and 15 post-(90)Y-RE had liver biopsy specimens available. In these series we investigated survivin, p53, Bcl-2 and Ki-67 expression pre- and post-(90)Y-RE by immuhistochemistry (IHC). Our findings evidenced a decrease of survivin (77% vs 33%), p53 (93% vs 73%), Bcl-2 (37% vs 26%) expression as well as of Ki-67 proliferation index (62.5% vs 40%) on liver biopsies collected post-(90)Y-RE as compared to pre-(90)Y-RE. In the subset of 13 matched liver metastases we further confirmed the reduction of survivin (92.3% vs 53.8%; p = 0.06), p53 (100% vs 69.2%; p = 0.05) and Bcl-2 (69.2% vs 53.8%; p = 0.05) expression post-(90)Y-RE. This biomarker modulation was accompanied by morphological changes as steatohepatitis, hepatocyte necrosis, collagen deposition, proliferating and/or bile duct ectasia, focal sinusoidal dilatation and fibrosis.Although our analysis was conducted in a very limited number cases, these changes appear strictly related to the response to (90)Y-RE therapy and may deserve further investigation on a larger series of patients.

Introduction: Radioembolisation (selective internal radiation therapy; SIRT), as part of a continuous strategy contributed to the improvement in response rates and median survival for unresectable metastatic colorectal cancer. Therefore, the role of SIRT in the different stages of treatment plan was investigated in this review., Areas Covered: After a brief description of the principles of SIRT, the review focused on the clinical evidences of published trials on the current experience of radioembolisation and its role in both salvage setting and earlier lines of chemotherapy., Expert Opinion: Evidence from Phase I studies and small Phase II/III randomised controlled trials has provided an early signal of the safety and improved overall survival, which can be achieved with radioembolisation and chemotherapy compared with chemotherapy (alone), due to an improved liver control. In the salvage setting, interesting results were observed in term of response, toxicity and median overall survival. Until the results of these early-line randomised trials will be available, radioembolisation could be considered either alone or combined with an appropriate chemotherapy regimen following failure of first- or second-line therapy.

Unlabelled: 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., (Copyright © 2011 American Association for the Study of Liver Diseases.)