title: Unresectable hepatocellular carcinoma: randomized controlled trial of transarterial ethanol ablation versus transcatheter arterial chemoembolization.
abstract: OBJECTIVE
  To compare effectiveness of transarterial ethanol ablation (TEA) and transcatheter arterial chemoembolization (TACE) for unresectable hepatocellular carcinoma and determine whether TEA leads to better overall survival and tumor response than TACE.
  
  
  METHODS
  In this institutional review board-approved preregistered randomized controlled trial (n = 200), informed consent was obtained. Primary outcome was overall survival; secondary outcomes were time to progression (TTP), progression-free survival (PFS), tumor response at computed tomography, and treatment-related toxicity. Eligible patients were randomized at a 1:1 ratio. Treatment included transcatheter delivery of ethiodized oil-ethanol mixture (2:1 ratio by volume up to 60 mL) for TEA and cisplatin-ethiodized oil emulsion (0.5 mg cisplatin per milliliter up to 30 mg), followed by 1-mm gelatin-sponge pellets, for TACE. Study was terminated after interim analysis (n = 98); 90 patients were available for analysis. Overall survival, TTP, and PFS were analyzed with Kaplan-Meier method; differences were compared with log-rank test.
  
  
  RESULTS
  Study was terminated prematurely after interim analysis, which showed no difference in overall survival; this was unlikely to change with further patient accrual. Median overall survival in TEA and TACE was 24.3 months (95% confidence interval [CI]: 12.8, 32.7) and 20.1 months (95% CI: 9.3, 31.2), respectively (P = .358). Median TTP and PFS for intralesional progression were longer with TEA than TACE (TTP, 34.6 months [95% CI: 28.2, 41] vs 26.05 months [95% CI: 18.7, 33.3]; PFS, 14.8 months [95% CI: 10.2, 19.5] vs 9.3 months [95% CI: 7.1, 11.5]) (P = .028 and 0.029, respectively). Complete response rate on a tumor basis was persistently and significantly higher with TEA at 3 months (62 of 88 [70%] vs 39 of 76 [51%], P = .012), 6 months (64 of 88 [73%] vs 41 of 76 [54%], P = .012), and 12 months (66 of 88 [75%] vs 45 of 76 [59%], P = .031).
  
  
  CONCLUSIONS
  Although there was no significant difference in overall survival, TEA demonstrated better complete tumor response, longer time to intralesional progression, and longer PFS.
authors.affiliation: From the Department of Imaging and Interventional Radiology (S.C.H.Y., J.W.Y.H.), Vascular and Interventional Radiology Foundation Clinical Science Center (S.C.H.Y., J.W.Y.H.), Department of Clinical Oncology (S.L.C., F.M., B.M., T.M., W.Y.), and Department of Surgery (P.L.), The Chinese University of Hong Kong, Room 2A061, 2/F, New Extension Block, Prince of Wales Hospital, 30-32 Ngan Shing St, Shatin, New Territories, Hong Kong SAR; and Departments of Clinical Oncology (E.P.H.) and Surgery (K.F.L., J.W.), Prince of Wales Hospital, Shatin, Hong Kong SAR.
authors.forename: Simon Chun Ho
authors.initials: SC
authors.lastname: Yu
authors.forename: Joyce Wai Yi
authors.initials: JW
authors.lastname: Hui
authors.forename: Edwin Pun
authors.initials: EP
authors.lastname: Hui
authors.forename: Stephen Lam
authors.initials: SL
authors.lastname: Chan
authors.forename: Kit Fai
authors.initials: KF
authors.lastname: Lee
authors.forename: Frankie
authors.initials: F
authors.lastname: Mo
authors.forename: John
authors.initials: J
authors.lastname: Wong
authors.forename: Brigette
authors.initials: B
authors.lastname: Ma
authors.forename: Paul
authors.initials: P
authors.lastname: Lai
authors.forename: Tony
authors.initials: T
authors.lastname: Mok
authors.forename: Winnie
authors.initials: W
authors.lastname: Yeo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000628:therapy*; D016461:Chemoembolization, Therapeutic / Q000379:methods*; D000431:Ethanol / Q000008:administration & dosage; D004998:Ethiodized Oil / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000431:Ethanol; D004998:Ethiodized Oil