title: Alpha-fetoprotein response correlates with EASL response and survival in solitary hepatocellular carcinoma treated with transarterial therapies: a subgroup analysis.
abstract: OBJECTIVE
  Alpha-fetoprotein (AFP) is a universally recognized tumor marker in hepatocellular carcinoma (HCC). Its utility in assessing response to treatment remains controversial. We sought to study the: (a) correlation between AFP response and imaging response, and (b) ability of AFP, EASL, and WHO response to predict survival outcomes in patients with solitary HCC.
  
  
  METHODS
  Six hundred and twenty-nine HCC patients were treated with transarterial locoregional therapies over an 11-year period. To eliminate confounding factors, we included patients with single tumors, baseline AFP ≥200ng/ml, and no extrahepatic disease; this identified our study cohort of 51 patients. AFP response was defined as>50% decrease from baseline; this was correlated to EASL and WHO response criteria by Kappa agreement, Pearson correlation and receiver operating curves. Survival analyses were performed by Landmark, risk-of-death and Mantel-Byar methodologies. None of the patients received sorafenib.
  
  
  RESULTS
  Three months post-treatment, AFP and EASL response correlated well (Kappa: 0.83; Pearson: 0.84); the sensitivity, specificity, positive and negative predictive values of AFP in predicting EASL response at 3 months were 96.6%, 85.7%, 92.3%, and 93.3%, respectively. Correlation with WHO response was low. From the 3-month landmark, WHO, EASL, and AFP responders survived longer than non-responders (p=0.006, 0.0001, and <0.0001, respectively). The risk of death was lower for EASL and AFP responders by both risk-of-death and Mantel-Byar methodologies (p <0.05).
  
  
  CONCLUSIONS
  Response by AFP and EASL are predictors of survival outcome in patients with solitary HCC. AFP correlates with imaging response assessment by EASL guidelines. Achieving AFP response should be one of the therapeutic intents of locoregional therapies (LRTs).
authors.affiliation: Department of Radiology, Section of Interventional Radiology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, USA.
authors.forename: Khairuddin
authors.initials: K
authors.lastname: Memon
authors.affiliation: Department of Medicine, Division of Hepatology, Northwestern University, Chicago, IL, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Kulik
authors.affiliation: Department of Radiology, Section of Interventional Radiology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Lewandowski
authors.affiliation: Department of Surgery, Division of Transplantation, Comprehensive Transplant Center, Northwestern University, Chicago, IL, USA.
authors.forename: Edward
authors.initials: E
authors.lastname: Wang
authors.affiliation: Department of Radiology, Section of Interventional Radiology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, USA.
authors.forename: Robert K
authors.initials: RK
authors.lastname: Ryu
authors.affiliation: Department of Radiology, Section of Interventional Radiology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, USA.
authors.forename: Ahsun
authors.initials: A
authors.lastname: Riaz
authors.affiliation: Department of Radiology, Section of Interventional Radiology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Nikolaidis
authors.affiliation: Department of Radiology, Section of Interventional Radiology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, USA.
authors.forename: Frank H
authors.initials: FH
authors.lastname: Miller
authors.affiliation: Department of Radiology, Section of Interventional Radiology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, USA.
authors.forename: Vahid
authors.initials: V
authors.lastname: Yaghmai
authors.affiliation: Department of Surgery, Division of Transplantation, Comprehensive Transplant Center, Northwestern University, Chicago, IL, USA.
authors.forename: Talia
authors.initials: T
authors.lastname: Baker
authors.affiliation: Department of Surgery, Division of Transplantation, Comprehensive Transplant Center, Northwestern University, Chicago, IL, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Abecassis
authors.affiliation: Department of Medicine, Division of Hematology and Oncology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, USA.
authors.forename: Al B
authors.initials: AB
authors.lastname: Benson
authors.affiliation: Department of Medicine, Division of Hematology and Oncology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, USA.
authors.forename: Mary F
authors.initials: MF
authors.lastname: Mulcahy
authors.affiliation: Department of Radiology, Section of Interventional Radiology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, USA.
authors.forename: Reed A
authors.initials: RA
authors.lastname: Omary
authors.affiliation: Department of Radiology, Section of Interventional Radiology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, USA; Department of Surgery, Division of Transplantation, Comprehensive Transplant Center, Northwestern University, Chicago, IL, USA; Department of Medicine, Division of Hematology and Oncology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, USA. Electronic address: r-salem@northwestern.edu.
authors.forename: Riad
authors.initials: R
authors.lastname: Salem
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood*; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000188:drug therapy* / Q000401:mortality*; D005060:Europe; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007269:Injections, Intra-Arterial; D008113:Liver Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000401:mortality*; D008297:Male; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D015996:Survival Rate; D016896:Treatment Outcome; D014944:World Health Organization; D000509:alpha-Fetoproteins / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D000509:alpha-Fetoproteins