Journal Article

Transarterial RAdioembolization versus ChemoEmbolization for the treatment of hepatocellular carcinoma (TRACE): study protocol for a randomized controlled trial

van Vlierberghe, Hans, van Erkel, Arian R, Verkooijen, Helena M, van Erpecum, Karel J, Seinstra, Beatrijs A, Defreyne, Luc, Coenraad, Minneke J, Al Younis, Imad, van den Bosch, Maurice AAJ, van Hoek, Bart, Lam, Marnix GEHH, Lambert, Bieke

2012

Overview

Background Hepatocellular carcinoma is a primary malignant tumor of the liver that accounts for an important health problem worldwide. Only 10 to 15% of hepatocellular carcinoma patients are suitable candidates for treatment with curative intent, such as hepatic resection and liver transplantation. A majority of patients have locally advanced, liver restricted disease (Barcelona Clinic Liver Cancer (BCLC) staging system intermediate stage). Transarterial loco regional treatment modalities offer palliative treatment options for these patients; transarterial chemoembolization (TACE) is the current standard treatment. During TACE, a catheter is advanced into the branches of the hepatic artery supplying the tumor, and a combination of embolic material and chemotherapeutics is delivered through the catheter directly into the tumor. Yttrium-90 radioembolization ( 90 Y-RE) involves the transarterial administration of minimally embolic microspheres loaded with Yttrium-90, a β-emitting isotope, delivering selective internal radiation to the tumor. 90 Y-RE is increasingly used in clinical practice for treatment of intermediate stage hepatocellular carcinoma, but its efficacy has never been prospectively compared to that of the standard treatment (TACE). In this study, we describe the protocol of a multicenter randomized controlled trial aimed at comparing the effectiveness of TACE and 90 Y-RE for treatment of patients with unresectable (BCLC intermediate stage) hepatocellular carcinoma. Methods/design In this pragmatic randomized controlled trial, 140 patients with unresectable (BCLC intermediate stage) hepatocellular carcinoma, with Eastern Cooperative Oncology Group performance status 0 to 1 and Child-Pugh A to B will be randomly assigned to either 90 Y-RE or TACE with drug eluting beads. Patients assigned to 90 Y-RE will first receive a diagnostic angiography, followed by the actual transarterial treatment, which can be divided into two sessions in case of bilobar disease. Patients assigned to TACE will receive a maximum of three consecutive transarterial treatment sessions. Patients will undergo structural follow-up for a timeframe of two years post treatment. Post procedural magnetic resonance imaging (MRI) will be performed at one and three months post trial entry and at three-monthly intervals thereafter for two years to assess tumor response. Primary outcome will be time to progression. Secondary outcomes will be overall survival, tumor response according to the modified RECIST criteria, toxicities/adverse events, treatment related effect on total liver function, quality of life, treatment-related costs and cost-effectiveness. Trial registration NCT01381211

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Ablation / Biomedicine / Cancer therapies / Carcinoma, Hepatocellular - blood supply / Carcinoma, Hepatocellular - diagnostic imaging / Carcinoma, Hepatocellular - mortality / Carcinoma, Hepatocellular - pathology / Carcinoma, Hepatocellular - therapy / Care and treatment / Catheters / Chemoembolization / Chemoembolization, Therapeutic - adverse effects / Chemoembolization, Therapeutic - mortality / Chemotherapy / Clinical trials / Comparative analysis / Cost-Benefit Analysis / Cytotoxicity / Disease Progression / Drug therapy / Embolization, Therapeutic - adverse effects / Embolization, Therapeutic - methods / Embolization, Therapeutic - mortality / Health Care Costs / Health Sciences / Hepatic Artery - diagnostic imaging / Hepatoma / Homeopathy / Humans / Kaplan-Meier Estimate / Liver / Liver cancer / Liver diseases / Liver Neoplasms - blood supply / Liver Neoplasms - diagnostic imaging / Liver Neoplasms - mortality / Liver Neoplasms - pathology / Liver Neoplasms - therapy / Magnetic Resonance Imaging / Materia medica and therapeutics / Medical prognosis / Medicine / Medicine & Public Health / Meta-analysis / Microspheres / Netherlands / Patient outcomes / Patients / Quality of Life / Radiography / Radiopharmaceuticals - administration & dosage / Radiopharmaceuticals - adverse effects / Rare earth metals / Research Design / Statistics for Life Sciences / Study Protocol / Therapeutic embolization / Therapeutics / Thrombosis / Time Factors / Transplantation / Transplants & implants / Treatment Outcome / Veins & arteries / Yttrium Radioisotopes - administration & dosage / Yttrium Radioisotopes - adverse effects