title: Subclassification of patients with intermediate-stage (Barcelona Clinic Liver Cancer stage-B) hepatocellular carcinoma using the up-to-seven criteria and serum tumor markers.
abstract: BACKGROUND
  Intermediate-stage [Barcelona Clinic Liver Cancer stage-B (BCLC-B)] hepatocellular carcinoma (HCC) comprises of a heterogeneous population of patients with a wide range of tumor burdens. We therefore formulated a subclassification of BCLC-B HCC using the up-to-seven criteria and tumor markers according to the results of a retrospective analysis of these patients.
  
  
  METHODS
  This study included 125 patients newly diagnosed with BCLC-B HCC who underwent transarterial chemoembolization. Among them, 39 and 86 were within or beyond the up-to-seven criteria, respectively. Multivariate Cox proportional hazards analysis was performed to investigate factors that contributed to better prognosis associated with the criteria.
  
  
  RESULTS
  Cumulative overall survival (OS) and disease-free survival rates were significantly higher for patients within the up-to-seven criteria compared with those beyond (p = 0.034 and p = 0.001, respectively). Multivariate analysis revealed that low concentrations of des-γ-carboxy prothrombin (DCP) (<150 mAU/ml) and α-fetoprotein (AFP) (<100 ng/ml) were independent contributors to better OS of patients within or beyond the up-to-seven criteria, respectively. Accordingly, the patients were classified as follows: group A (patients within the up-to-seven criteria with DCP <150 mAU/ml), group C (patients beyond the up-to-seven criteria with AFP ≥100 ng/ml), and group B (other patients). OS differed significantly among groups (p < 0.001), and the median survival times of group A, B, and C were 4.2, 2.7, and 1.5 years, respectively.
  
  
  CONCLUSIONS
  The subclassification system incorporating the up-to-seven criteria combined with DCP and AFP levels may serve as better predictors of prognosis that may guide efforts to improve treatment strategies.
authors.affiliation: Department of Hepatobiliary and Pancreatic Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, 1-3-3, Nakamichi, Higashinari-ku, Osaka, 537-8511, Japan.
authors.forename: Haruki
authors.initials: H
authors.lastname: Kimura
authors.affiliation: Department of Hepatobiliary and Pancreatic Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, 1-3-3, Nakamichi, Higashinari-ku, Osaka, 537-8511, Japan. ohkawa-ka@mc.pref.osaka.jp.
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Ohkawa
authors.affiliation: Department of Hepatobiliary and Pancreatic Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, 1-3-3, Nakamichi, Higashinari-ku, Osaka, 537-8511, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Miyazaki
authors.affiliation: Department of Hepatobiliary and Pancreatic Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, 1-3-3, Nakamichi, Higashinari-ku, Osaka, 537-8511, Japan.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Sakakibara
authors.affiliation: Department of Hepatobiliary and Pancreatic Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, 1-3-3, Nakamichi, Higashinari-ku, Osaka, 537-8511, Japan.
authors.forename: Kazuho
authors.initials: K
authors.lastname: Imanaka
authors.affiliation: Department of Hepatobiliary and Pancreatic Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, 1-3-3, Nakamichi, Higashinari-ku, Osaka, 537-8511, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tamura
authors.affiliation: Department of Hepatobiliary and Pancreatic Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, 1-3-3, Nakamichi, Higashinari-ku, Osaka, 537-8511, Japan.
authors.forename: Hironari
authors.initials: H
authors.lastname: Sueyoshi
authors.affiliation: Department of Hepatobiliary and Pancreatic Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, 1-3-3, Nakamichi, Higashinari-ku, Osaka, 537-8511, Japan.
authors.forename: Ryoji
authors.initials: R
authors.lastname: Takada
authors.affiliation: Department of Hepatobiliary and Pancreatic Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, 1-3-3, Nakamichi, Higashinari-ku, Osaka, 537-8511, Japan.
authors.forename: Nobuyasu
authors.initials: N
authors.lastname: Fukutake
authors.affiliation: Department of Hepatobiliary and Pancreatic Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, 1-3-3, Nakamichi, Higashinari-ku, Osaka, 537-8511, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Uehara
authors.affiliation: Department of Screening for Cancers of Digestive Organs, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan.
authors.forename: Reiko
authors.initials: R
authors.lastname: Ashida
authors.affiliation: Department of Screening for Cancers of Digestive Organs, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Ioka
authors.affiliation: Department of Diagnostic Radiology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Nakazawa
authors.affiliation: Department of Diagnostic Radiology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan.
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Nakanishi
authors.affiliation: Department of Hepatobiliary and Pancreatic Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, 1-3-3, Nakamichi, Higashinari-ku, Osaka, 537-8511, Japan.|Department of Screening for Cancers of Digestive Organs, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Katayama
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000145:classification* / Q000628:therapy*; D016461:Chemoembolization, Therapeutic / Q000379:methods*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000145:classification* / Q000378:metabolism / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D015898:Tomography Scanners, X-Ray Computed; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor
keywords: Barcelona Clinic Liver Cancer intermediate stage; Hepatocellular carcinoma; Overall survival; Up-to-seven criteria