Hepatocellular carcinoma cases with high levels of c-Raf-1 expression may benefit from postoperative adjuvant sorafenib after hepatic resection even with high risk of recurrence

Oncotarget. 2016 Jul 5;7(27):42598-42607. doi: 10.18632/oncotarget.3799.

Abstract

Background and aims: Liver resection combined with postoperative sorafenib to prevent recurrence remains a controversial approach for cases of hepatocellular carcinoma (HCC), especially cases with a high risk of recurrence. This study aimed to investigate the efficacy and safety of liver resection combined with sorafenib for HCC with a high risk of recurrence.

Results: Most of the cases of HCC were caused by hepatitis B virus (HBV) infection (23 cases, 92%). Most of these tumors (21 cases, 84%) were stage III according to the TNM staging system (12 cases with IIIa, 9 cases with IIIb). In the months after hepatic resection, 19 of the 25 cases (76%) were diagnosed with HCC recurrence or metastasis. Based on the tumor histological biomarker grading system, the group with higher expression levels of c-Raf-1 showed significantly longer overall survival than the group with lower expression of c-Raf-1 (P = 0.012). However, the long-term tumor-free survival advantage disappeared (P = 0.061). Univariate and multivariate analyses indicated that higher expression of c-Raf-1 was significantly associated with better overall survival (hazard ratio [HR]: 1.842; 95% confidence interval [CI]: 1.211-2.542; P = 0.031) and tumor-free survival (HR: 1.319; 95% CI: 1.017-1.543; P = 0.046) in HCC patients who underwent radical hepatic resection.

Patients and methods: We retrospectively collected 25 HCC cases with a high risk of recurrence who underwent radical liver resection and who took sorafenib postoperatively from Jan 2010 to Dec 2012. Factors that might contribute to tumor recurrence and treatment failure such as clinical factors, tumor features, and molecular biomarkers were included in our analysis.

Conclusions: HCC patients with a high risk of post-hepatic resection recurrence may benefit from postoperative sorafenib administered as an adjuvant therapy, especially in cases with high levels of c-Raf-1 expression on histological examination.

Keywords: hepatocellular carcinoma; liver resection; recurrence; risk factors; sorafenib.

MeSH terms

  • Adult
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / surgery
  • Chemotherapy, Adjuvant
  • Disease-Free Survival
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Hepatitis B / drug therapy
  • Hepatitis B / metabolism
  • Hepatitis B / surgery
  • Humans
  • Liver / pathology
  • Liver / surgery
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / surgery
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Metastasis
  • Neoplasm Recurrence, Local
  • Niacinamide / analogs & derivatives*
  • Niacinamide / therapeutic use
  • Phenylurea Compounds / therapeutic use*
  • Postoperative Period
  • Proto-Oncogene Proteins c-raf / metabolism*
  • Recurrence
  • Retrospective Studies
  • Sorafenib

Substances

  • Biomarkers, Tumor
  • Phenylurea Compounds
  • Niacinamide
  • Sorafenib
  • Proto-Oncogene Proteins c-raf