Elsevier

Academic Radiology

Volume 25, Issue 4, April 2018, Pages 423-429
Academic Radiology

Original Investigation
Prognostic Factors for Survival After Transarterial Chemoembolization Combined with Sorafenib in the Treatment of BCLC Stage B and C Hepatocellular Carcinomas

https://doi.org/10.1016/j.acra.2017.10.018Get rights and content

Rationale and Objective

The objective of this study was to analyze prognostic factors for survival after transarterial chemoembolization (TACE) combined with sorafenib for hepatocellular carcinoma (HCC) of Barcelona Clinic Liver Cancer (BCLC) stages B and C.

Materials and Methods

Clinical data of 198 patients with BCLC stage B and C HCCs who underwent TACE combined with sorafenib between June 2012 and January 2017 were retrospectively collected and analyzed. Survival curves were detected using log-rank test. Univariate analysis was performed using log-rank test with respect to 11 prognostic factors potentially affecting survival. All statistically significant prognostic factors identified by univariate analysis were entered into a Cox proportion hazards regression model to identify independent predictors of survival. P values were two-sided and P < 0.05 was considered statistically significant.

Results

By the end of this study, the median follow-up duration was 43.6 months. The median overall survival (OS) of the patients was 21.0 months (95% confidence interval [CI]: 16.94–25.05), and the 1-, 2-, 3- and 5-year OS rates were 72%, 43%, 28%, and 4%, respectively. Tumor size (χ2 = 33.607, P < 0.0001), tumor number (χ2 = 4.084, P = 0.043), Child-Pugh class (χ2 = 33.187, P < 0.0001), BCLC stage (χ2 = 50.224, P < 0.0001), portal vein tumor thrombus2 = 88.905, P < 0.0001), Eastern Cooperative Oncology Group (ECOG) performance status (χ2 = 98.007, P < 0.0001), extrahepatic spread (χ2 = 34.980, P < 0.0001), TACE times (χ2 = 8.350, P = 0.015), and sorafenib treatment strategy (χ2 = 81.593, P < 0.0001) were found to be significantly associated with OS by univariate analysis. Multivariate analysis showed that BCLC stage (95% CI: 1.133–3.982, P = 0.019), extrahepatic spread (95% CI: 1.136–2.774, P = 0.012), and sorafenib treatment duration (95% CI: 0.352–0.574, P = 0.000) were independent prognostic factors associated with OS. There were no serious treatment-related adverse events.

Conclusions

This study showed that extrahepatic spread was a risk factor, and sorafenib treatment and superior BCLC stage were protective factors. Therefore, the study indicated that TACE combined with sorafenib was an effective and safe treatment for patients with BCLC stage B HCC without extrahepatic spread.

Introduction

Hepatocellular carcinoma (HCC) is one of the most common malignances. HCC is the third leading causes of cancer mortality worldwide. More than 700,000 new cases are diagnosed as HCC annually and its incidence is increasing in Asia as well as in the rest of the world 1, 2, 3. Nowadays, surgical resection and liver transplantation are still considered as the first-line treatments for patients with very early- or early-stage HCC 4, 5, 6. However, HCC is a highly aggressive liver neoplasm; the majority of patients were diagnosed at the intermediate and advanced stages of tumor growth. The Barcelona Clinic Liver Cancer (BCLC) staging system has been widely accepted as an offer treatment guideline that comprehensively considers the performance status of patients, hepatic function, tumor number, and tumor size. The BCLC staging system has been endorsed by the European Association for the Study of Liver Disease and the American Association for the Study of Liver Disease (AASLD) 4, 7.

According to the BCLC staging system, transarterial chemoembolization (TACE) and sorafenib have been recommended as the standard therapies for patients with HCC of BCLC stages B and C, respectively (8). Sorafenib is a kind of oral multikinase inhibitor with antiproliferative and antiangiogenic effects by blocking the RAF-MEK-ERK signal transduction pathway 9, 10. Theoretically, sorafenib was believed to decrease the angiogenesis of solid tumor by inhibiting the expression level of vascular endothelial growth factor (VEGF) after TACE treatment 9, 10. Hence, sorafenib was expected to improve the clinical efficacy of TACE by decreasing post-TACE angiogenesis in the treatment of HCC. Portal vein tumor thrombus (PVTT) is an important leading cause of BCLC stage C HCC-related deaths. Usually, PVTT can be a cause of tumor spreading, failure of liver function, and portal vein hypertension, which lead to complicated ascites and variceal rupture. According to the available clinical guidelines, sorafenib has been widely recommended as the standard therapy for HCC with PVTT. In recent years, several studies had considered TACE as a palliative treatment choice for patients with BCLC stage C HCC 11, 12, 13, 14, 15. Pan et al., Liu et al., and Liu et al. had reported that TACE was safe and effective in the treatment of advanced HCC with PVTT 13, 14, 15. In Asia, the BCLC stage C HCC is suggested to be an indication for TACE treatment, and an increasing number of clinical trials in the field of combined sorafenib and TACE treatment of HCC are taking place 13, 14, 15, 16, 17, 18.

A large-scale meta-analysis of 1254 patients by Zhang et al. showed that TACE combined with sorafenib was effective and safe in the treatment of BCLC stage B and C HCCs (19). However, few studies were designed to comprehensively analyze overall survival (OS) and its prognostic factors of patients with HCC after combined TACE-sorafenib therapy. Thus, the prognostic factors for survival of patients with BCLC stage B and C HCCs who were treated with combined TACE-sorafenib were not well described. Herein, this retrospective study with 198 patients was designed to evaluate the efficacy and safety of TACE combined with sorafenib and to analyze prognostic factors for survival of the patients. The strengths of the present study were the large sample size. Although the retrospective nature of this study was a limitation, the data regarding survival status and prognostic factors were accurate and well recorded by the reviewers.

Section snippets

Study Population

The clinical data of 198 patients with BCLC stage B and C HCCs were retrospectively collected. All included patients were initially treated with combined TACE-sorafenib in our center between June 2012 and January 2017. In the present study, diagnosis of HCC was based on the recommendations of the AASLD and the European Association for the Study of Liver Disease. All enrolled patients and the treatment methods in the present study were approved by the medical ethics committee of Sun Yat-sen

Patients

Among the included patients, 174 were men and 24 were women, and their age ranged from 24 to 80 years (mean age, 50.6 years). The majority of the patients had hepatitis (hepatitis B or C), and hepatitis-related liver cirrhosis was the most common underlying cause of liver cancer. Hepatitis and liver cirrhosis was diagnosed in 188 (94.9%) and 192 (96.9%) patients, respectively. In this study, 150 patients (75.8%) were associated with a hepatic function of Child-Pugh class A, and 145 patients

Discussion

In the present study, the median OS of all 198 patients was 21.1 months, and the BCLC stage, extrahepatic spread, and sorafenib treatment duration were considered as independent prognostic factors for the survival of patients after combined TACE-sorafenib treatment. The BCLC staging system has been widely accepted as an offer treatment guideline that comprehensively considers patient-related factors (ECOG performance status), tumor-related factors (tumor size and tumor number), and liver

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  • Cited by (0)

    This work was supported by grant [2013]163 from the Key Laboratory of Malignant Tumor Molecular Mechanism and Translational Medicine of Guangzhou Bureau of Science and Information Technology and by grant KLB09001 from the Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes.

    Jia-yan Ni and Jian Kong contributed equally to this work.

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