title: Optimal adjuvant therapy for resected hepatocellular carcinoma: a systematic review with network meta-analysis.
abstract: OBJECTIVE
  Major adjuvant therapies (ATs) for resected hepatocellular carcinoma (HCC) include chemotherapy, internal radiation therapy (IRT), interferon therapy (IFNT) and immunotherapy but the optimum regimen remains inconclusive. We aim to compare these therapies in terms of patient survival and recurrence rates.
  
  
  METHODS
  We searched PubMed, EMBASE and Cochrane library databases for randomized trials comparing the above four therapies until 31 March 2014. We estimated the HRs for survival and ORs for overall recurrence among different therapies. Toxic effects were also evaluated.
  
  
  RESULTS
  Fourteen eligible articles were included. IFNT improved 5-year survival greatly (HR 1.81, 95% CI 1.01-3.81, P = 0.034), whereas chemotherapy (HR 0.33, 95% CI 0.03-2.02), IRT (HR 0.31, 95% CI 0.02-3.33) and immunotherapy (HR 0.73, 95% CI 0.05-9.12) all provided a poorer survival outcome after 1-year. Similarly, for 5-year survival rates, although differing, IRT did not provide a significant improvement in survival (HR 1.38, 95% CI 0.34-5.19) compared with IFNT. Chemotherapy (HR 0.49, 95% CI 0.18-1.14) and immunotherapy (HR 0.56, 95% CI 0.17-1.59) did not appear to provide benefit over IFNT. Chemotherapy was ranked the worst in overall recurrence (OR 0.99, 95% CI 0.18-5.38) and most likely to cause toxic effects.
  
  
  CONCLUSIONS
  IFNT was the most efficacious AT regimen both for short and long term survivals. Immunotherapy and IFNT were the most two effective in preventing overall relapse for resected HCC.
authors.affiliation: Department of Infection and Liver Diseases, Liver Research Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.|School of the First Clinical Medical Sciences, Wenzhou Medical University, Wenzhou, China.
authors.forename: Gui-Qi
authors.initials: GQ
authors.lastname: Zhu
authors.affiliation: Department of Infection and Liver Diseases, Liver Research Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.|Institute of Hepatology, Wenzhou Medical University, Wenzhou, China.
authors.forename: Ke-Qing
authors.initials: KQ
authors.lastname: Shi
authors.affiliation: Department of Infection and Liver Diseases, Liver Research Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.|School of the First Clinical Medical Sciences, Wenzhou Medical University, Wenzhou, China.
authors.forename: Hua-Jian
authors.initials: HJ
authors.lastname: Yu
authors.affiliation: Department of Infection and Liver Diseases, Liver Research Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.|School of the First Clinical Medical Sciences, Wenzhou Medical University, Wenzhou, China.
authors.forename: Sun-Yue
authors.initials: SY
authors.lastname: He
authors.affiliation: Global Medicines Development, AstraZeneca R&D, Loughborough, United Kingdom.
authors.forename: Martin
authors.initials: M
authors.lastname: Braddock
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
authors.forename: Meng-Tao
authors.initials: MT
authors.lastname: Zhou
authors.affiliation: Department of Infection and Liver Diseases, Liver Research Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.|Institute of Hepatology, Wenzhou Medical University, Wenzhou, China.
authors.forename: Yong-Ping
authors.initials: YP
authors.lastname: Chen
authors.affiliation: Department of Infection and Liver Diseases, Liver Research Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.|Institute of Hepatology, Wenzhou Medical University, Wenzhou, China.
authors.forename: Ming-Hua
authors.initials: MH
authors.lastname: Zheng
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001499:Bayes Theorem; D006528:Carcinoma, Hepatocellular / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D017024:Chemotherapy, Adjuvant; D018450:Disease Progression; D018572:Disease-Free Survival; D006498:Hepatectomy; D006801:Humans; D007167:Immunotherapy / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D007372:Interferons / Q000009:adverse effects / Q000627:therapeutic use*; D008113:Liver Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008390:Markov Chains; D009010:Monte Carlo Method; D009364:Neoplasm Recurrence, Local; D016017:Odds Ratio; D018714:Radiotherapy, Adjuvant; D012307:Risk Factors; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D007372:Interferons
keywords: adjuvant therapy; hepatocellular carcinoma; indirect comparison; network meta-analysis; toxic effect