title: Determination of the optimal cutoff percentage of residual tumors to define the pathological response rate for gastric cancer treated with preoperative therapy (JCOG1004-A).
abstract: BACKGROUND
  Pathological response rate (pathRR) is a common endpoint used to assess the efficacy of preoperative therapy for gastric cancer. PathRR is estimated based on the percentage of the residual tumor area in the primary tumorous bed. Various cutoff definitions used in previous trials (e.g., 10, 33, 40, 50, 67 %) often impair the comparability of pathRRs between trials.
  
  
  METHODS
  Individual patient data were used from four JCOG trials evaluating preoperative chemotherapy (JCOG0001, JCOG0002, JCOG0210, JCOG0405). Pathological specimens were evaluated from 173 out of 188 patients (92 %) who underwent surgery. Residual tumor area and primary tumorous beds were traced on a virtual microscopic slide by one pathologist and another confirmed these areas. The hazard ratio (HR) in overall survival was calculated for each cutoff percentage by stratified Cox regression analysis, including the study as a stratification factor, and concordance probability estimates (CPE) were calculated.
  
  
  RESULTS
  The numbers of patients with 0%, 1-10 %, 11-33 %, 34-50 %, 51-66 %, and 67-100 % residual tumors were 8, 35, 33, 27, 23, and 47, respectively. HRs in 10, 33, 50, and 67 % cutoffs were 1.91, 1.70, 1.55, and 1.71 for the overall population, and CPEs were 0.56, 0.56, 0.55, and 0.55, respectively. In patients with R0 resection, HRs in 10, 33, 50, and 67 % cutoffs were 1.87, 1.54, 1.24, and 1.38, and CPEs were 0.56, 0.55, 0.52, and 0.52. In subgroup analyses, the 10 % cutoff did not predict survival well for type 4 (linitis plastica) tumors.
  
  
  CONCLUSIONS
  The 10 % cutoff should be the global standard cutoff of %residual tumor to determine pathRR. PathRR might not be recommended for clinical trials where the main subjects are type 4 tumors.
authors: JCOG Data Center/Operations Office, Multi-institutional Clinical Trial Support Center, National Cancer Center, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan, kennakam@ncc.go.jp.
authors: Kenichi
authors: K
authors: Nakamura
authors: Takeshi
authors: T
authors: Kuwata
authors: Tadakazu
authors: T
authors: Shimoda
authors: Junki
authors: J
authors: Mizusawa
authors: Hiroshi
authors: H
authors: Katayama
authors: Ryoji
authors: R
authors: Kushima
authors: Hirokazu
authors: H
authors: Taniguchi
authors: Takeshi
authors: T
authors: Sano
authors: Mitsuru
authors: M
authors: Sasako
authors: Haruhiko
authors: H
authors: Fukuda
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D017322:Clinical Trials, Phase II as Topic; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual; D011300:Preoperative Care; D016016:Proportional Hazards Models; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D016019:Survival Analysis