title: Intraperitoneal perfusion of cytokine-induced killer cells with local hyperthermia for advanced hepatocellular carcinoma.
abstract: OBJECTIVE
  To study the effect and tolerance of intraperitoneal perfusion of cytokine-induced killer (CIK) cells in combination with local radio frequency (RF) hyperthermia in patients with advanced primary hepatocellular carcinoma (HCC).
  
  
  METHODS
  Patients with advanced primary HCC were included in this study. CIK cells were perfused intraperitoneal twice a week, using 3.2 × 10⁹ to 3.6 × 10⁹ cells each session. Local RF hyperthermia was performed 2 h after intraperitoneal perfusion. Following an interval of one month, the next course of treatment was administered. Patients received treatment until disease progression. Tumor size, immune indices (CD3⁺, CD4⁺, CD3⁺CD8⁺, CD3⁺CD56⁺), alpha-fetoprotein (AFP) level, abdominal circumference and adverse events were recorded. Time to progression and overall survival (OS) were calculated.
  
  
  RESULTS
  From June 2010 to July 2011, 31 patients diagnosed with advanced primary HCC received intraperitoneal perfusion of CIK cells in combination with local RF hyperthermia in our study. Patients received an average of 4.2 ± 0.6 treatment courses (range, 1-8 courses). Patients were followed up for 8.3 ± 0.7 mo (range, 2-12 mo). Following combination treatment, CD4⁺, CD3⁺CD8⁺ and CD3⁺CD56⁺ cells increased from 35.78% ± 3.51%, 24.61% ± 4.19% and 5.94% ± 0.87% to 45.83% ± 2.48% (P = 0.016), 39.67% ± 3.38% (P = 0.008) and 10.72% ± 0.67% (P = 0.001), respectively. AFP decreased from 167.67 ± 22.44 to 99.89 ± 22.05 ng/mL (P = 0.001) and abdominal circumference decreased from 97.50 ± 3.45 cm to 87.17 ± 4.40 cm (P = 0.002). The disease control rate was 67.7%. The most common adverse events were low fever and slight abdominal erubescence, which resolved without treatment. The median time to progression was 6.1 mo. The 3-, 6- and 9-mo and 1-year survival rates were 93.5%, 77.4%, 41.9% and 17.4%, respectively. The median OS was 8.5 mo.
  
  
  CONCLUSIONS
  Intraperitoneal perfusion of CIK cells in combination with local RF hyperthermia is safe, can efficiently improve immunological status, and may prolong survival in HCC patients.
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Jinan University, Guangzhou 510620, Guangdong Province, China.
authors.forename: Xiao-Pu
authors.initials: XP
authors.lastname: Wang
authors.forename: Meng
authors.initials: M
authors.lastname: Xu
authors.forename: Hong-Fei
authors.initials: HF
authors.lastname: Gao
authors.forename: Jian-Fu
authors.initials: JF
authors.lastname: Zhao
authors.forename: Ke-Cheng
authors.initials: KC
authors.lastname: Xu
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D002478:Cells, Cultured; D003131:Combined Modality Therapy; D055612:Cytokine-Induced Killer Cells / Q000276:immunology / Q000637:transplantation*; D018450:Disease Progression; D005260:Female; D006801:Humans; D006979:Hyperthermia, Induced / Q000009:adverse effects; D016219:Immunotherapy, Adoptive / Q000009:adverse effects / Q000379:methods*; D007263:Infusions, Parenteral; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000097:blood / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D047368:Tumor Burden
chemical_list: D014408:Biomarkers, Tumor
keywords: Clinical observation; Cytokine-induced killer cell; Intraperitoneal perfusion; Primary hepatocellular carcinoma; Radio frequency hyperthermia