title: A nonrandomized cohort and a randomized study of local control of large hepatocarcinoma by targeting intratumoral lactic acidosis.
abstract: Previous works suggested that neutralizing intratumoral lactic acidosis combined with glucose deprivation may deliver an effective approach to control tumor. We did a pilot clinical investigation, including a nonrandomized (57 patients with large HCC) and a randomized controlled (20 patients with large HCC) study.
  
  
  
  The patients were treated with transarterial chemoembolization (TACE) with or without bicarbonate local infusion into tumor.
  
  
  
  In the nonrandomized controlled study, geometric mean of viable tumor residues (VTR) in TACE with bicarbonate was 6.4-fold lower than that in TACE without bicarbonate (7.1% [95% CI: 4.6%–10.9%] vs 45.6% [28.9%–72.0%]; p<0.0001). This difference was recapitulated by a subsequent randomized controlled study. TACE combined with bicarbonate yielded a 100% objective response rate (ORR), whereas the ORR treated with TACE alone was 44.4% (nonrandomized) and 63.6% (randomized). The survival data suggested that bicarbonate may bring survival benefit.
  
  
  
  Bicarbonate markedly enhances the anticancer activity of TACE.
  
  
  
  Funded by National Natural Science Foundation of China.
  
  
  
  ChiCTR-IOR-14005319.
authors.affiliation: Department of Radiology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Chao
authors.affiliation: Cancer Institute, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Radiology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Jin
authors.affiliation: Department of Radiology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Radiology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Radiology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Guangqiang
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Vanderbilt University Medical Center, Nashville, United States.
authors.forename: Gong
authors.initials: G
authors.lastname: Yang
authors.affiliation: Cancer Institute, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Xun
authors.identifier: 0000-0002-3784-371X
authors.initials: X
authors.lastname: Hu
mesh_terms: D000140:Acidosis, Lactic / Q000188:drug therapy*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001639:Bicarbonates / Q000008:administration & dosage*; D002277:Carcinoma / Q000628:therapy*; D016461:Chemoembolization, Therapeutic / Q000379:methods*; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D001639:Bicarbonates
keywords: bicarbonate; cancer biology; hepatocellular carcinoma; human; lactic acidosis; transarterial chemoembolization