title: Severity and timing of progression predict refractoriness to transarterial chemoembolization in hepatocellular carcinoma.
abstract: OBJECTIVE
  Patients with hepatocellular carcinoma (HCC) that is refractory to repeated transarterial chemoembolization (TACE) are considered for systemic therapy, but TACE refractoriness is not well defined. The aim of this study was to determine the characteristics of patients whose HCC is refractory to repetitive TACE.
  
  
  METHODS
  We evaluated 264 patients with intermediate-stage HCC who underwent TACE between January 2006 and September 2009. We designated the development of vascular invasion or extrahepatic spread during follow up as "stage progression" (SP), and hypothesized that SP might be the surrogate end-point for TACE refractoriness.
  
  
  RESULTS
  The median follow up was 18.2 months, and median number of TACE was 3.0 (range, 1-13). Median time-to-progression was 5.5 months (95% confidence interval, 4.8-6.2), and median overall survival was 25.3 months (95% confidence interval, 21.6-29.0). We classified the patients according to disease course as: no progressive disease (PD(-); n = 33); PD without SP (PD(+)SP(-); n = 113); PD followed by SP (PD→SP; n = 47); and simultaneous PD and SP (PD&SP; n = 64). PD(-) and PD(+)SP(-) groups showed no difference in overall survival, PD→SP group had worse overall survival than PD(-) and PD(+)SP(-) groups, and PD&SP group had the worst overall survival. The significant prognostic factors for SP-free survival were development of PD and need for three sessions of TACE during the first 6 months.
  
  
  CONCLUSIONS
  SP-free survival can be regarded as an end-point for TACE refractoriness. Development of progression or need for three sessions of TACE within the first 6 months could be predictive of TACE refractoriness.
authors.affiliation: Center for Liver Cancer, National Cancer Center, Goyang, Korea.
authors.forename: Hwi Young
authors.initials: HY
authors.lastname: Kim
authors.forename: Joong-Won
authors.initials: JW
authors.lastname: Park
authors.forename: Jungnam
authors.initials: J
authors.lastname: Joo
authors.forename: Se Jin
authors.initials: SJ
authors.lastname: Jung
authors.forename: Sangbu
authors.initials: S
authors.lastname: An
authors.forename: Sang Myung
authors.initials: SM
authors.lastname: Woo
authors.forename: Hyun Beom
authors.initials: HB
authors.lastname: Kim
authors.forename: Young Hwan
authors.initials: YH
authors.lastname: Koh
authors.forename: Woo Jin
authors.initials: WJ
authors.lastname: Lee
authors.forename: Chang-Min
authors.initials: CM
authors.lastname: Kim
mesh_terms: D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000473:pathology / Q000628:therapy*; D016461:Chemoembolization, Therapeutic / Q000379:methods*; D018450:Disease Progression; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D018579:Patient Selection; D011379:Prognosis; D013997:Time Factors; D017211:Treatment Failure