title: Long-term clinical outcome of phase IIb clinical trial of percutaneous injection with holmium-166/chitosan complex (Milican) for the treatment of small hepatocellular carcinoma.
abstract: OBJECTIVE
  The purpose of this study was to evaluate the long-term tumor response after phase IIb clinical study and the safety of percutaneous holmium-166 ((166)Ho)/chitosan complex injection (PHI) therapy for small hepatocellular carcinoma as a local ablative treatment. (166)Ho is a radioactive isotope derived from natural holmium-165. We developed a (166)Ho/chitosan complex (Milican, Dong Wha Pharmaceutical Co., Seoul, Korea) using chitosan as a vehicle to retain the radioactive material within the tumor.
  
  
  METHODS
  Forty patients with single hepatocellular carcinoma < 3 cm in maximal diameter were enrolled in this study. The patients either had refused surgery or were poor surgical candidates and were treated with only single session of PHI.
  
  
  RESULTS
  Two months after PHI, complete tumor necrosis was achieved in 31 of 40 patients (77.5%) with hepatocellular carcinoma lesions < 3 cm and in 11 of 12 patients (91.7%) with hepatocellular carcinoma < 2 cm. Tumors recurred in 28 patients during the long-term follow-up period, of which 24 recurred at another intrahepatic site. The 1-year and 2-year cumulative local recurrence rates were 18.5% and 34.9%, respectively. The survival rates at 1, 2, and 3 years were 87.2%, 71.8%, and 65.3%, respectively. Transient bone marrow depression was serious adverse event requiring hospitalization in two patients.
  
  
  CONCLUSIONS
  PHI was found to be a safe and novel local ablative procedure for the treatment of small hepatocellular carcinoma and could be used as a bridge to transplantation. A phase III randomized active control trial is clearly warranted among a larger study population.
authors.affiliation: Department of Internal Medicine, Yonsei Institute of Gastroenterology, Yonsei Liver Cancer Study Group, Yonsei University College of Medicine, 134 Shinchoin-dong, Seodaemoon-gu, Seoul, Korea 120-752.
authors.forename: Ja Kyung
authors.initials: JK
authors.lastname: Kim
authors.forename: Kwang-Hyub
authors.initials: KH
authors.lastname: Han
authors.forename: Jong Tae
authors.initials: JT
authors.lastname: Lee
authors.forename: Yong Han
authors.initials: YH
authors.lastname: Paik
authors.forename: Sang Hoon
authors.initials: SH
authors.lastname: Ahn
authors.forename: Jong Doo
authors.initials: JD
authors.lastname: Lee
authors.forename: Kwan Sik
authors.initials: KS
authors.lastname: Lee
authors.forename: Chae Yoon
authors.initials: CY
authors.lastname: Chon
authors.forename: Young Myoung
authors.initials: YM
authors.lastname: Moon
mesh_terms: D000279:Administration, Cutaneous; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000532:radiotherapy*; D048271:Chitosan / Q000627:therapeutic use*; D005260:Female; D006695:Holmium / Q000627:therapeutic use*; D006801:Humans; D008113:Liver Neoplasms / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000532:radiotherapy; D011868:Radioisotopes / Q000627:therapeutic use*; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D011868:Radioisotopes; D048271:Chitosan; D006695:Holmium