title: Factors predicting prognosis and recurrence in patients with esophago-gastric adenocarcinoma and histopathological response with less than 10 % residual tumor.
abstract: OBJECTIVE
  Neoadjuvant treatment is an accepted standard approach for treating locally advanced esophago-gastric adenocarcinomas. Despite a response of the primary tumor, a significant percentage dies from tumor recurrence. The aim of this retrospective exploratory study from two academic centers was to identify predictors of survival and recurrence in histopathologically responding patients.
  
  
  METHODS
  Two hundred thirty one patients with adenocarcinomas (esophagus: n = 185, stomach: n = 46, cT3/4, cN0/+, cM0) treated with preoperative chemotherapy (n = 212) or chemoradiotherapy (n = 19) followed by resection achieved a histopathological response (regression 1a: no residual tumor (n = 58), and regression 1b < 10 % residual tumor (n = 173)).
  
  
  RESULTS
  The estimated median overall survival was 92.4 months (5-year survival, 56.6 %) for all patients. For patients with regression 1a, median survival is not reached (5-year survival, 71.6 %) compared to patients with regression 1b with 75.3 months median (5-year survival, 52.2 %) (p = 0.031). Patients with a regression 1a had lymph node metastases in 19.0 versus 33.7 % in regression 1b. The ypT-category (p < 0.001), the M-category (p = 0.005), and the type of treatment (p = 0.04) were found to be independent prognostic factors in R0-resected patients. The recurrence rate was 31.7 % (n = 66) (local, 39.4 %; peritoneal carcinomatosis, 25.7 %; distant metastases, 50 %). Recurrence was predicted by female gender (p = 0.013), ypT-category (p = 0.007), and M-category (p = 0.003) in multivariate analysis.
  
  
  CONCLUSIONS
  Response of the primary tumor does not guarantee recurrence-free long-term survival, but histopathological complete responders have better prognosis compared to partial responders. Established prognostic factors strongly influence the outcome, which could, in the future, be used for stratification of adjuvant treatment approaches. Increasing the rate of histopathological complete responders is a valid endpoint for future clinical trials investigating new drugs.
authors.affiliation: Department of Surgery, University Hospital of Heidelberg, Heidelberg, Germany. katja.ott@med.uni-heidelberg.de
authors.forename: Katja
authors.initials: K
authors.lastname: Ott
authors.forename: Susanne
authors.initials: S
authors.lastname: Blank
authors.forename: Karen
authors.initials: K
authors.lastname: Becker
authors.forename: Rupert
authors.initials: R
authors.lastname: Langer
authors.forename: Wilko
authors.initials: W
authors.lastname: Weichert
authors.forename: Wilfried
authors.initials: W
authors.lastname: Roth
authors.forename: Leila
authors.initials: L
authors.lastname: Sisic
authors.forename: Annika
authors.initials: A
authors.lastname: Stange
authors.forename: Dirk
authors.initials: D
authors.lastname: Jäger
authors.forename: Markus
authors.initials: M
authors.lastname: Büchler
authors.forename: Jörg-Rüdiger
authors.initials: JR
authors.lastname: Siewert
authors.forename: Florian
authors.initials: F
authors.lastname: Lordick
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology* / Q000628:therapy*; D000293:Adolescent; D000328:Adult; D000368:Aged; D059248:Chemoradiotherapy; D016009:Chi-Square Distribution; D003131:Combined Modality Therapy; D004938:Esophageal Neoplasms / Q000473:pathology* / Q000628:therapy*; D016629:Esophagectomy / Q000379:methods; D005260:Female; D006801:Humans; D008197:Lymph Node Excision; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D018365:Neoplasm, Residual / Q000473:pathology / Q000628:therapy*; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D012737:Sex Factors; D013274:Stomach Neoplasms / Q000473:pathology* / Q000628:therapy*; D015996:Survival Rate; D016896:Treatment Outcome