title: Survival impact of delayed treatment in patients with hepatocellular carcinoma undergoing locoregional therapy: is there a lead-time bias?
abstract: OBJECTIVE
  Many reports indicate the importance of active treatment for hepatocellular carcinoma (HCC), but there are few studies available that address the impact of delayed therapy on survival or take the lead-time bias into account. The objective of this study was to investigate whether patients with delayed locoregional therapy for HCC truly have a shortened survival from the time of diagnosis.
  
  
  METHODS
  Survival rates were compared between 48 HCC patients with treatment delay and 96 age- and gender-matched controls without delay. All patients underwent transarterial chemoembolization or percutaneous ethanol or acetic acid injection for HCC. Treatment delay was defined as a >2 months' time interval between diagnosis and treatment.
  
  
  RESULTS
  Baseline comparison showed that patients with treatment delay had higher scores in the model for endstage liver disease compared with those of patients without delay (12.3+/-1.8 versus 11.1+/-2.5, p=0.01). In the Cox multivariate model, advanced cancer stage (relative risk (RR): 2.66, p=0.001), Child-Turcotte-Pugh class B (RR: 3.81, p<0.001), tumor size >5 cm (RR: 2.02, p=0.011) and treatment delay (RR: 2.91, p=0.001) were independent poor prognostic predictors. Among patients with treatment delay, disease progression was registered in 30 (63%) patients. Patients with prolonged treatment delay (>3 months) were more likely to have tumor progression (p=0.013). In the Cox model, a treatment delay of >3 months independently predicted a poor rate of survival (RR: 3.67, p=0.002).
  
  
  CONCLUSIONS
  Delayed HCC treatment is linked with shortened overall survival unrelated to the lead-time bias in patients undergoing locoregional therapy. Prolonged treatment delay of more than 3 months in these patients may worsen the long-term outcome.
authors: Institute of Pharmacology, National Yang-Ming University School of Medicine, Taipei, Taiwan. tihuo@vghtpe.gov.tw
authors: Teh-Ia
authors: TI
authors: Huo
authors: Yi-Hsiang
authors: YH
authors: Huang
authors: Jen-Huei
authors: JH
authors: Chiang
authors: Jaw-Ching
authors: JC
authors: Wu
authors: Pui-Ching
authors: PC
authors: Lee
authors: Chin-Wen
authors: CW
authors: Chi
authors: Shou-Dong
authors: SD
authors: Lee
mesh_terms: D019342:Acetic Acid / Q000008:administration & dosage*; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D016461:Chemoembolization, Therapeutic; D018450:Disease Progression; D000431:Ethanol / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D015552:Injections, Intralesional; D008113:Liver Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008297:Male; D015996:Survival Rate
chemical_list: D000431:Ethanol; D019342:Acetic Acid