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.

Keywords: HCC; SIRT; Y90; hepatocellular carcinoma; radioembolization; sorafenib; yttrium-90.

Figure 1

Kaplan–Meier overall survival. Median overall survival (measured from time of first RE and including patients censored because they were alive at the time of analysis) for the entire series was 30 weeks (range 6–42 weeks).

Figure 2

Kaplan–Meier overall survival by Child-Pugh class. The median overall survival was 42 weeks (range 11–42 weeks) for Child-Pugh class A patients and 12 weeks (range 6–17 weeks) for Child-Pugh class B patients (p  = 0.002).

Figure 3

Kaplan–Meier overall survival by radiographic response. Median radiographic follow-up was 17 weeks (range 3–35 weeks). The median overall survival was 6 weeks for the one patient with PD, 30 weeks (range 5–28 weeks) for the six with SD, and it was not reached for the three patients with PR (range 6–35 weeks) (p  = 0.009).

Figure 4

Kaplan–Meier radiographic progression-free survival. Median radiographic progression-free survival of the entire series was 28 weeks (range 3–42 weeks).

Figure 5

Alpha-fetoprotein (AFP) trend per patient. Patients a, f, and h had an elevated pre-RE AFP of >400 ng/mL, all three had a AFP response to RE.

Figure 6

Total bilirubin trend per patient. The spike in total bilirubin seen in patient f was secondary to a resection of the remaining tumor mass 18 weeks after RE, patients b and c had total bilirubin rises in the setting of disease progression.

Figure 7

 T1 MRI with early phase contrast. Pre-radioembolization.

Figure 8

 T1 MRI with early phase contrast. Seven weeks post-RE.

Figure 9

 T1 MRI with early phase contrast. Fifteen weeks post-RE.

Figure 10

 T1 MRI with early phase contrast. Status-post extended left hepatectomy, performed 6 months post-RE.

Figure 11

Micrographs of hematoxylin and eosin-stained sections of the resected liver. Necrotic tumor with microspheres at 40× magnification.

Figure 12

Micrographs of hematoxylin and eosin-stained sections of the resected liver. Viable tumor cells with a microsphere at 200× magnification.

Figure 13

Micrographs of hematoxylin and eosin-stained sections of the resected liver. Viable cirrhotic liver tissue with no microspheres at 100× magnification, typical of the patient’s liver that wasn’t involved with tumor.