Transarterial radioembolization versus chemoembolization for the treatment of hepatocellular carcinoma (TRACE): study protocol for a randomized controlled trial.
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
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.


BACKGROUND
NCT01381211.
Department of Radiology, University Medical Center Utrecht, Room E.01.132, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands.
Beatrijs A
BA
Seinstra
Luc
L
Defreyne
Bieke
B
Lambert
Marnix G E H
MG
Lam
Helena M
HM
Verkooijen
Karel J
KJ
van Erpecum
Bart
B
van Hoek
Arian R
AR
van Erkel
Minneke J
MJ
Coenraad
Imad
I
Al Younis
Hans
H
van Vlierberghe
Maurice A A J
MA
van den Bosch
D006528:Carcinoma, Hepatocellular / Q000098:blood supply / Q000000981:diagnostic imaging / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D016461:Chemoembolization, Therapeutic / Q000009:adverse effects / Q000401:mortality; D003362:Cost-Benefit Analysis; D018450:Disease Progression; D004621:Embolization, Therapeutic / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D017048:Health Care Costs; D006499:Hepatic Artery / Q000000981:diagnostic imaging; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000098:blood supply / Q000000981:diagnostic imaging / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008279:Magnetic Resonance Imaging; D008863:Microspheres; D009426:Netherlands; D011788:Quality of Life; D011859:Radiography; D019275:Radiopharmaceuticals / Q000008:administration & dosage* / Q000009:adverse effects; D012107:Research Design; D013997:Time Factors; D016896:Treatment Outcome; D015021:Yttrium Radioisotopes / Q000008:administration & dosage* / Q000009:adverse effects
D019275:Radiopharmaceuticals; D015021:Yttrium Radioisotopes