title: Adoptive immunotherapy to lower postsurgical recurrence rates of hepatocellular carcinoma: a randomised trial.
abstract: BACKGROUND
  Postsurgical recurrence of hepatocellular carcinoma (HCC) is frequent and fatal. Adoptive immunotherapy is active against HCC. We assessed whether postoperative immunotherapy could lower the frequency of recurrence.
  
  
  METHODS
  Between 1992 and 1995, we did a randomised trial in which 150 patients who had undergone curative resection for HCC were assigned adoptive immunotherapy (n=76) or no adjuvant treatment (n=74). Autologous lymphocytes activated vitro with recombinant interleukin-2 and antibody to CD3 were infused five times during the first 6 months. Primary endpoints were time to first recurrence and recurrence-free survival and analyses were by intention to treat.
  
  
  RESULTS
  76 patients received 370 (97%) of 380 scheduled lymphocyte infusions (mean cell number per patient 7.1x10(10) [SD 2.1]; CD3 and HLA-DR cells 78% [16]), and none had grade 3 or 4 adverse events. After a median follow-up of 4.4 years (range 0.2-6.7), adoptive immunotherapy decreased the frequency of recurrence by 18% compared with controls (45 [59%] vs 57 [77%]) [corrected] patients. Time to first recurrence in the immunotherapy group was significantly longer than that in the control group (48% [37-59] vs 33% [22-43] at 3 years, 38% [22-54] vs 22% [11-34] at 5 years; p=0.008). The immunotherapy group had significantly longer recurrence-free survival (p=0.01) and disease-specific survival (p=0.04) than the control group. Overall survival did not differ significantly between groups (p=0.09).
  
  
  CONCLUSIONS
  Adoptive immunotherapy is a safe, feasible treatment that can lower recurrence and improve recurrence-free outcomes after surgery for HCC.
authors.affiliation: Department of Surgery, National Cancer Centre Research Institute, University of Tokyo, Japan. takayamat-2su@h.u-tokyo.ac.jp
authors.forename: T
authors.initials: T
authors.lastname: Takayama
authors.forename: T
authors.initials: T
authors.lastname: Sekine
authors.forename: M
authors.initials: M
authors.lastname: Makuuchi
authors.forename: S
authors.initials: S
authors.lastname: Yamasaki
authors.forename: T
authors.initials: T
authors.lastname: Kosuge
authors.forename: J
authors.initials: J
authors.lastname: Yamamoto
authors.forename: K
authors.initials: K
authors.lastname: Shimada
authors.forename: M
authors.initials: M
authors.lastname: Sakamoto
authors.forename: S
authors.initials: S
authors.lastname: Hirohashi
authors.forename: Y
authors.initials: Y
authors.lastname: Ohashi
authors.forename: T
authors.initials: T
authors.lastname: Kakizoe
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000601:surgery / Q000628:therapy*; D018572:Disease-Free Survival; D006498:Hepatectomy; D006801:Humans; D007167:Immunotherapy / Q000009:adverse effects / Q000379:methods*; D007376:Interleukin-2 / Q000008:administration & dosage / Q000627:therapeutic use; D008113:Liver Neoplasms / Q000601:surgery / Q000628:therapy*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control; D011184:Postoperative Period
chemical_list: D007376:Interleukin-2