Gastroenterology

Gastroenterology

Volume 138, Issue 1, January 2010, Pages 52-64
Gastroenterology

Imaging and Advanced Technology
Radioembolization for Hepatocellular Carcinoma Using Yttrium-90 Microspheres: A Comprehensive Report of Long-term Outcomes

https://doi.org/10.1053/j.gastro.2009.09.006Get rights and content

Background & Aims

Hepatocellular carcinoma (HCC) has limited treatment options; long-term outcomes following intra-arterial radiation are unknown. We assessed clinical outcomes of patients treated with intra-arterial yttrium-90 microspheres (Y90).

Methods

Patients with HCC (n = 291) were treated with Y90 as part of a single-center, prospective, longitudinal cohort study. Toxicities were recorded using the Common Terminology Criteria version 3.0. Response rate and time to progression (TTP) were determined using World Health Organization (WHO) and European Association for the Study of the Liver (EASL) guidelines. Survival by stage was assessed. Univariate/multivariate analyses were performed.

Results

A total of 526 treatments were administered (mean, 1.8; range, 1–5). Toxicities included fatigue (57%), pain (23%), and nausea/vomiting (20%); 19% exhibited grade 3/4 bilirubin toxicity. The 30-day mortality rate was 3%. Response rates were 42% and 57% based on WHO and EASL criteria, respectively. The overall TTP was 7.9 months (95% confidence interval, 6–10.3). Survival times differed between patients with Child–Pugh A and B disease (A, 17.2 months; B, 7.7 months; P = .002). Patients with Child–Pugh B disease who had portal vein thrombosis (PVT) survived 5.6 months (95% confidence interval, 4.5–6.7). Baseline age; sex; performance status; presence of portal hypertension; tumor distribution; levels of bilirubin, albumin, and α-fetoprotein; and WHO/EASL response rate predicted survival.

Conclusions

Patients with Child–Pugh A disease, with or without PVT, benefited most from treatment. Patients with Child–Pugh B disease who had PVT had poor outcomes. TTP and overall survival varied by patient stage at baseline. These data can be used to design future Y90 trials and to describe Y90 as a potential treatment option for patients with HCC.

Section snippets

Patient Cohort

Between January 1, 2004, and December 31, 2008, 291 patients with HCC were treated with Y90 at one institution as part of a cohort study. A comprehensive review of toxicity, imaging, and survival outcomes was performed. Data were collected prospectively. The study was Health Insurance Portability and Accountability Act compliant, approved by the institutional review board, and registered (NCT00530010).

Pretreatment Evaluation and Staging

Patients underwent pretreatment assessment, including clinical history, physical examination,

Patient Population

Patient demographics, tumor characteristics, and stage are presented in Table 1. The median age was 65 years (range, 26–90 years), and 22% were 75 years of age or older. Most were male (77%), with hepatitis C (34%) and alcohol (19%) as the most common etiologies. A majority were ECOG 0 (56%) or 1 (36%) and were treatment naive (87%). A total of 51% were confirmed to have HCC by biopsy. Most patients were cirrhotic (87%) and had portal hypertension (69%). A total of 73% exhibited multifocal

Discussion

Significant progress has been made in surgical, locoregional, and systemic treatment options for HCC. Our study includes a comprehensive analysis of TTP using strict imaging criteria in 291 patients with HCC who were treated with Y90. Given that PR and TTP are both prognosticators for survival, our analyses included both parameters.10, 15 Such imaging outcomes of Y90 for HCC obtained in a systematic manner have not been reported and represent the largest reported experience to date. Although it

References (46)

  • J.E. Goin et al.

    Treatment of unresectable hepatocellular carcinoma with intrahepatic yttrium 90 microspheres: factors associated with liver toxicities

    J Vasc Interv Radiol

    (2005)
  • J.E. Goin et al.

    Treatment of unresectable hepatocellular carcinoma with intrahepatic yttrium 90 microspheres: a risk-stratification analysis

    J Vasc Interv Radiol

    (2005)
  • R. Murthy et al.

    Gastrointestinal complications associated with hepatic arterial Yttrium-90 microsphere therapy

    J Vasc Interv Radiol

    (2007)
  • T.K. Rhee et al.

    Tumor response after yttrium-90 radioembolization for hepatocellular carcinoma: comparison of diffusion-weighted functional MR imaging with anatomic MR imaging

    J Vasc Interv Radiol

    (2008)
  • R. Salem et al.

    Treatment of unresectable hepatocellular carcinoma with use of 90Y microspheres (TheraSphere): safety, tumor response, and survival

    J Vasc Interv Radiol

    (2005)
  • C.M. Lo et al.

    Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma

    Hepatology

    (2002)
  • J. Prieto

    Inflammation, HCC and sex: IL-6 in the centre of the triangle

    J Hepatol

    (2008)
  • A.S. Lok et al.

    Incidence of hepatocellular carcinoma and associated risk factors in hepatitis C-related advanced liver disease

    Gastroenterology

    (2009)
  • S. Arii et al.

    Results of surgical and nonsurgical treatment for small-sized hepatocellular carcinomas: a retrospective and nationwide survey in JapanThe Liver Cancer Study Group of Japan

    Hepatology

    (2000)
  • D.M. Parkin et al.

    Global cancer statistics, 2002

    CA Cancer J Clin

    (2005)
  • V. Mazzaferro et al.

    Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis

    N Engl J Med

    (1996)
  • L.M. Kulik et al.

    Yttrium-90 microspheres (TheraSphere(R)) treatment of unresectable hepatocellular carcinoma: downstaging to resection, RFA and bridge to transplantation

    J Surg Oncol

    (2006)
  • D.S. Lu et al.

    Radiofrequency ablation of hepatocellular carcinoma: treatment success as defined by histologic examination of the explanted liver

    Radiology

    (2005)
  • Cited by (829)

    View all citing articles on Scopus

    Conflicts of interest The authors disclose the following: Dr Salem is an advisor to and receives research support from MDS Nordion. Dr Mulcahy and Dr Benson receive research support from MDS Nordion. Dr Lewandowski, Dr Riaz, Dr Ryu, Dr Ibrahim, Dr Atassi, Dr Baker, Dr Gates, Dr Miller, Dr Sato, Dr Wang, Dr Gupta, Dr Newman, Dr Omary, Dr Abecassis, and Dr Kulik disclose no conflicts.

    View full text