Yttrium-90 Radioembolization in Patients with Hepatocellular Carcinoma Who have Previously Received Sorafenib

Abstract

Purpose: Yttrium-90 radioembolization (RE) is a locoregional therapy option for hepatocellular carcinoma (HCC). Sorafenib is a multikinase inhibitor used in HCC that can potentially affect the efficacy of RE by altering tumor vascularity or suppressing post-irradiation angiogenesis. The safety and efficacy of sorafenib followed by RE has not been previously reported.Materials and Methods: Patients with HCC who received RE after sorafenib were included in this retrospective review. Overall survival, toxicity, and maximal radiographic response and necrosis criteria were examined.Results: Ten patients (15 RE administrations) fit the inclusion criteria. All were Barcelona Clinic Liver Cancer (BCLC) stage C. Median follow-up was 16.5 weeks. Median overall survival and radiographic progression-free survival were 30 and 28 weeks, respectively. Significant differences in overall survival were seen based on Child-Pugh class (p = 0.002) and radiographic response (p = 0.009). Three patients had partial response, six had stable disease, and one had progressive disease. Grade 1 or 2 acute fatigue, anorexia, and abdominal pain were common. Three patients had Grade 3 ascites in the setting of disease progression. Two patients had Grade 3 biochemical toxicity. One patient was sufficiently downstaged following RE and sorafenib to receive a partial hepatectomy.Conclusion: Yttrium-90 RE in patients with HCC who have received sorafenib demonstrate acceptable toxicity and rates of radiographic response. However, the overall survival is lower than that reported in the literature on RE alone or sorafenib alone. This may be due in part to more patients in this study having advanced disease compared to these other study populations. Larger prospective studies are needed to determine whether the combination of RE and sorafenib is superior to either therapy alone.

Combined Sorafenib and Yttrium-90 Radioembolization for the Treatment of Advanced Hepatocellular Carcinoma

“…Our results, derived from a cohort of patients whose disease, at baseline, was more severe than that experienced by patients in the sharp trial, still showed comparable survival results. However, those survival data contrast with data from a study by Rana et al 53 , who retrospectively reviewed 10 patients receiving sorafenib followed by radioembolization. In their study, which included 7 patients classified as Child-Pugh A and 3 classified as Child-Pugh B, the side effects with combined therapy were similar to those reported here-namely, anorexia, fatigue, gastrointestinal symptoms, and also the more severe side effects related to ascites and liver enzymes-and yet their reported overall survival duration was barely greater than 7 months, which is worse than the survival durations associated with both therapies alone.…”

The emerging questionable benefit of sorafenib as a neo-adjuvant in HCC patients treated with Y-90 radioembolization pending liver transplantation

“…These two observations raise the question whether the pretransplant intolerance to sorafenib and the post-transplant biliary complications and rejection signify a safety signal regarding sorafenib therapy as a neo-adjuvant in patients receiving RE. Doubts regarding the usefulness of adding sorafenib to RE in patients not referred for LT, have already risen following a retrospective analysis of a small study in which 10 HCC patients with BCLC stage C were treated with sorafenib prior to RE [17]. In this study, overall survival of patients with advanced HCC receiving a combination of RE and sorafenib was lower compared to historical data in patients treated with RE or sorafenib alone.…”

Transarterial radioembolization using yttrium-90 microspheres in the treatment of hepatocellular carcinoma: a review on clinical utility and developments

“… 61 This is the fundamental aim of the emerging studies on the combination of TARE and sorafenib. 115 – 117 …”