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

Abstract

BackgroundHepatocellular 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 (90Y-RE) involves the transarterial administration of minimally embolic microspheres loaded with Yttrium-90, a β-emitting isotope, delivering selective internal radiation to the tumor. 90Y-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 90Y-RE for treatment of patients with unresectable (BCLC intermediate stage) hepatocellular carcinoma.Methods/designIn 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 90Y-RE or TACE with drug eluting beads. Patients assigned to 90Y-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 registrationNCT01381211

Post‐embolization syndrome as an early predictor of overall survival after transarterial chemoembolization for hepatocellular carcinoma

“…6,14 Although selected patients with poor prognostic factors may benefit from TACE, 40 in addition to the considerations previously discussed, alternative and evolving liver-directed therapies such as transarterial radioembolization should be considered for this high-risk population, particularly given recent data showing equivalent survival and a lower incidence of PES. [41][42][43] Several important limitations should be considered when interpreting our study findings. Given the retrospective nature of our study, some of our findings may be subject to selection bias.…”

“…Finally, patients experiencing a poor survival after TACE, such as those with MVI, are typically not considered good candidates for this therapy, and current guidelines do not recommend it . Although selected patients with poor prognostic factors may benefit from TACE, in addition to the considerations previously discussed, alternative and evolving liver‐directed therapies such as transarterial radioembolization should be considered for this high‐risk population, particularly given recent data showing equivalent survival and a lower incidence of PES …”

Minimal invasive treatments for liver malignancies

“…There was no significant difference in survival between the radioembolization (median 8.0 months) and chemoembolization (median 10.3 months) cohorts (p = 0.33). However, postembolization syndrome was significantly more severe in patients who underwent chemoembolization, which led to increased total hospitalization rates [94]. Y-RE was approved by U.S. Food and Drug Administration for the treatment of CRC liver metastases.…”

Yttrium-90 Microsphere Radioembolization for Hepatocellular Carcinoma

“…Different studies have retrospectively compared the results of TACE with those of Y90-radioembolization [16,17,19,20,22,23,24,25]. Most of these studies are limited by the small number of patients, but one important study by Salem et al retrospectively compared 123 patients treated by Y90-radioembolization with 122 patients treated by TACE [24].…”