title: Sorafenib off-target effects predict outcomes in patients treated for hepatocellular carcinoma.
abstract: OBJECTIVE
  Sorafenib is the standard of care in advanced hepatocellular carcinoma. This study was aimed to identify clinical parameters that may predict survival in these patients.
  
  
  METHODS
  In this observational study, a training (226 patients) and validation cohorts (54 patients) were analyzed for evaluating pretreatment and on-treatment parameters.
  
  
  RESULTS
  At multivariate analysis, only on-treatment variables (skin toxicity, diarrhea and arterial hypertension - sorafenib off-target effects), alphafetoprotein and radiological responses predicted survival. Using the occurrence of off-target effects, a prognostic index able to distinguish three groups of patients with different survival was constructed and externally validated.
  
  
  CONCLUSIONS
  In hepatocellular carcinoma patients, on-treatment variables are the best predictors of survival. Among these, sorafenib off-target effects may be the most useful indicators for prognostication in field practice.
authors.affiliation: Division of Hepatology, Cardarelli Hospital, Via A Cardarelli 9, 80131, Naples, Italy.
authors.forename: Giovan Giuseppe
authors.initials: GG
authors.lastname: Di Costanzo
authors.forename: Giorgio
authors.initials: G
authors.lastname: de Stefano
authors.forename: Raffaella
authors.initials: R
authors.lastname: Tortora
authors.forename: Nunzia
authors.initials: N
authors.lastname: Farella
authors.forename: Luigi
authors.initials: L
authors.lastname: Addario
authors.forename: Filippo
authors.initials: F
authors.lastname: Lampasi
authors.forename: Alfonso Galeota
authors.initials: AG
authors.lastname: Lanza
authors.forename: Gabriella
authors.initials: G
authors.lastname: Cordone
authors.forename: Michele
authors.initials: M
authors.lastname: Imparato
authors.forename: Nicola
authors.initials: N
authors.lastname: Caporaso
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D015331:Cohort Studies; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009536:Niacinamide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011379:Prognosis; D012307:Risk Factors; D000077157:Sorafenib; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D009536:Niacinamide; D000077157:Sorafenib
keywords: hepatocellular carcinoma; sorafenib; survival prediction