Yttrium-90 radioembolization for hepatocellular carcinoma in hepatitis B: commentary on a 103-patient Asian cohort

Y90 radioembolization [also known as selective internal radiation therapy (SIRT)] is recognized as a safe and effective therapy for hepatocellular carcinoma (HCC), with a particular role for Y90 in patients with large tumors and/ or portal vein thrombosis (PVT). Studies from Europe and the United States, comprised of 776 patients in aggregate, have demonstrated comparable results when taking into account cohort differences in terms of baseline Child–Pugh classification and tumor stage defined by the Barcelona Clinic Liver Cancer system (BCLC) [1–4]. These Western studies included patients predominately with hepatitis C and/or alcohol as the underlying cause of liver disease with limited numbers of patients with hepatitis B virus (HBV) (9–30 %). HBV is the leading cause of HCC worldwide, with over 50 % of all causes of HCC attributable to HBV. While there is convincing data from the REVEAL study that the risk of HCC is impacted by the height of the HBV viral load (VL), there has not been conclusive data that achieving an undetectable HBV VL negates the risk of eventual HCC development. This is hypothesized to be related to the integration of cccDNA into the host DNA with a carcinogenetic capacity via genetic instability. Clinical-pathologic differences have been reported between HBV versus Hepatitis C virus (HCV), the former being more commonly associated with larger tumors, younger age and lower cirrhosis rates [5]. Other single center retrospective reports have sought to determine if a difference exists in outcomes with various therapeutic options. Viral etiology was not found to have an impact on outcome among patients treated with transarterial chemoembolization (TACE) [6]. However, the etiology of disease has been apparent in orthotopic liver transplant (OLT), with a significant decrease in overall survival (OS) in HCV due to recurrent HCV post-transplant [7]. Systemic therapy with sorafenib was associated with shorter median OS among Asian patients relative to a Western cohort; however, there was a similar degree of survival benefit associated with sorafenib relative to placebo (hazard ratios 0.69 and 0.68, respectively) [8, 9]. The experienced team from Singapore has reported a retrospective analysis of 103 Asian patients with nearly half (47.6 %) of the patients with HBV-induced HCC treated with Y90 [10]. The tumor characteristics were comparable to the Western cohorts (Table 1). Safety and tolerability were also similar to other cohorts. While the authors demonstrated a comparable median OS of 14.4 months, the time-to-progression (TTP) of 5.3 months was shorter. Progression (using RECIST 1.1 at 3 months after therapy) was available in only half of the entire cohort (potentially affecting the results and lower response rate). Nonetheless, it is of interest that progression was not seen in the treated lesion(s) and the analysis was limited to the first Y90 administration, demonstrating excellent local tumor control; such a pattern of metastases and the high local control rates have been reported previously [11, 12]. However, 38 % of disease control was due to stable disease which, among TACE cohorts, has been found to predict worse outcomes compared to those with complete/partial response [13]. The use of RECIST 1.1, without taking into account presence of necrosis, makes it impossible to L. Kulik Division of Hepatology, Department of Medicine, Northwestern University, Chicago, IL, USA