title: Study protocol of the B-CAST study: a multicenter, prospective cohort study investigating the tumor biomarkers in adjuvant chemotherapy for stage III colon cancer.
abstract: BACKGROUND
  Adjuvant chemotherapy for stage III colon cancer is internationally accepted as standard treatment with established efficacy. Several oral fluorouracil (5-FU) derivatives with different properties are available in Japan, but which drug is the most appropriate for each patient has not been established. Although efficacy prediction of 5-FU derivatives using expression of 5-FU activation/metabolism enzymes in tumors has been studied, it has not been clinically applied.
  
  
  METHODS
  The B-CAST study is a multicenter, prospective cohort study aimed to identify the patients who benefit from adjuvant chemotherapy with each 5-FU regimen, through evaluating the relationship between tumor biomarker expression and treatment outcome. The frozen tumor specimens of patients with stage III colon cancer who receives postoperative adjuvant chemotherapy are examined. Protein expression of thymidine phosphorylase (TP), dihydropyrimidine dehydrogenase (DPD), epidermal growth factor receptor (EGFR), and vascular endothelial growth factor (VEGF) are evaluated using enzyme-linked immunosorbent assay (ELISA). mRNA expression of TP, DPD, thymidylate synthase (TS) and orotate phosphoribosyl transferase (OPRT) are evaluated using reverse transcription polymerase chain reaction (RT-PCR). The patients' clinical data reviewed are as follow: demographic and pathological characteristics, regimen, drug doses and treatment duration of adjuvant therapy, types and severity of adverse events, disease free survival, relapse free survival and overall survival. Then, relationships among the protein/mRNA expression, clinicopathological characteristics and the treatment outcomes are analyzed for each 5-FU derivative.
  
  
  CONCLUSIONS
  A total of 2,128 patients from the 217 institutions were enrolled between April 2009 and March 2012. The B-CAST study demonstrated that large-scale, multicenter translational research using frozen samples was feasible when the sample shipment and Web-based data collection were well organized. The results of the study will identify the predictors of benefit from each 5-FU derivative, and will contribute to establish the "personalized therapy" in adjuvant chemotherapy for colon cancer.
  
  
  BACKGROUND
  ClinicalTrials.gov: NCT00918827, UMIN Clinical Trials Registry (UMIN-CTR) UMIN000002013.
authors.affiliation: Department of Surgical Oncology, Tokyo Medical and Dental University, Graduate School, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
authors.forename: Megumi
authors.initials: M
authors.lastname: Ishiguro
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Kotake
authors.forename: Genichi
authors.initials: G
authors.lastname: Nishimura
authors.forename: Naohiro
authors.initials: N
authors.lastname: Tomita
authors.forename: Wataru
authors.initials: W
authors.lastname: Ichikawa
authors.forename: Keiichi
authors.initials: K
authors.lastname: Takahashi
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Watanabe
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Furuhata
authors.forename: Ken
authors.initials: K
authors.lastname: Kondo
authors.forename: Masaki
authors.initials: M
authors.lastname: Mori
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kakeji
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Kanazawa
authors.forename: Michiya
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Masazumi
authors.initials: M
authors.lastname: Okajima
authors.forename: Ichinosuke
authors.initials: I
authors.lastname: Hyodo
authors.forename: Keiko
authors.initials: K
authors.lastname: Miyakoda
authors.forename: Kenichi
authors.initials: K
authors.lastname: Sugihara
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D017024:Chemotherapy, Adjuvant; D002985:Clinical Protocols; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D009367:Neoplasm Staging; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor