Adoptive Immunotherapy For Postoperative Hepatocellular Carcinoma:a Systematic Review

Objective: Adoptive immunotherapy (AIT) can enhance immune function by increasing absolute numbers of effector cells. As an adjuvant therapy for hepatocellular carcinoma (HCC), AIT has made a lot of progress. A systematic review of all randomized clinical trials (RCTs) was performed to evaluate the evidence comparing adoptive immunity based therapy (AIBT) or AIT and therapeutic modalities without AIT.Methods: Ovid Medline,Embase, Cochrane Library, CNKI, CBMdis and VIP were conducted through March 2011 to identify RCTs evaluating postoperative AIBT or AIT for patients with HCC. A fixed-effect model and a random-effect model were used using'intention-to-treat'analysis. There were no language restrictions.Results: Six studies totaling 522 patients met the final inclusion criteria. For the 1-year and 3-year tumor recurrence rate, postoperative AIBT showed statistically significant less incidence of recurrence for patients with HCC [risk ratio (RR)=0.47, 95% confidence intervals (CI)=0.34–0.65, P<0.00001; RR=0.74, 95% CI=0.62-0.88, P=0.0009]. Subgroup analysis showed that AIT was superior to no treatment for the 1-year tumor recurrence rate for HCC patients postoperatively, with a pooled risk ratio of 0.51 (95% CI=0.36-0.71, P=0.0001). After radical resection, the studies were, also favorable for adjuvant AIT for patients with HCC with a pooled risk ratio of 0.50 (95% CI=0.28-0.89, P=0.02). However, for the 1-year and 3-year mortality, postoperative AIBT did not demonstrate statistically significant less incidence (RR=0.50, 95% CI=0.24-1.04, P=0.06; RR=0.71, 95% CI=0.48–1.06, P=0.09). Subgroup analysis for 1-year mortality revealed that radical resection plus AIT was not superior to radical resection alone (RR=0.70, 95% CI= 0.31-1.16, P=0.41). For the 5-year mortality, descriptive analysis showed that HCC patients received no benefits from adjuvant AIT after radical resection. Fever was the main side-effects of AIT. All adverse events were of grade 1 or 2. No treatment-related death was reported.Conclusion: Postoperative AIBT and AIT seem to be a superior model than therapeutic modalities without AIT for patients with HCC but requires further trial.