title: Phase III comparison of preoperative chemotherapy compared with chemoradiotherapy in patients with locally advanced adenocarcinoma of the esophagogastric junction.
abstract: OBJECTIVE
  Preoperative chemotherapy is an accepted standard in the treatment of localized esophagogastric adenocarcinoma. Adding radiation therapy to preoperative chemotherapy appears promising, but its definitive value remains unknown.
  
  
  METHODS
  Patients with locally advanced (uT3-4NXM0) adenocarcinoma of the lower esophagus or gastric cardia were randomly allocated to one of two treatment groups: induction chemotherapy (15 weeks) followed by surgery (arm A); or chemotherapy (12 weeks) followed by chemoradiotherapy (3 weeks) followed by surgery (arm B). Primary outcome was overall survival time. A total of 354 patients were needed to detect a 10% increase in 3-year survival from 25% to 35% by addition of radiation therapy. The study was prematurely closed due to low accrual.
  
  
  RESULTS
  The median observation time was 46 months. A total of 126 patients were randomly assigned and 119 eligible patients were evaluated. The number of patients undergoing complete tumor resection was not different between treatment groups (69.5% v 71.5%). Patients in arm B had a significant higher probability of showing pathologic complete response (15.6% v 2.0%) or tumor-free lymph nodes (64.4% v 37.7%) at resection. Preoperative radiation therapy improved 3-year survival rate from 27.7% to 47.4% (log-rank P = .07, hazard ratio adjusted for randomization strata variables 0.67, 95% CI, 0.41 to 1.07). Postoperative mortality was nonsignificantly increased in the chemoradiotherapy group (10.2% v 3.8%; P = .26).
  
  
  CONCLUSIONS
  Although the study was closed early and statistical significance was not achieved, results point to a survival advantage for preoperative chemoradiotherapy compared with preoperative chemotherapy in adenocarcinomas of the esophagogastric junction.
authors.affiliation: Department of Medical Oncology and Hematology, Kliniken Essen-Mitte, Henricistr. 92, D-45136 Essen, Germany. m.stahl@kliniken-essen-mitte.de
authors.forename: Michael
authors.initials: M
authors.lastname: Stahl
authors.forename: Martin K
authors.initials: MK
authors.lastname: Walz
authors.forename: Martin
authors.initials: M
authors.lastname: Stuschke
authors.forename: Nils
authors.initials: N
authors.lastname: Lehmann
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Meyer
authors.forename: Jorge
authors.initials: J
authors.lastname: Riera-Knorrenschild
authors.forename: Peter
authors.initials: P
authors.lastname: Langer
authors.forename: Rita
authors.initials: R
authors.lastname: Engenhart-Cabillic
authors.forename: Michael
authors.initials: M
authors.lastname: Bitzer
authors.forename: Alfred
authors.initials: A
authors.lastname: Königsrainer
authors.forename: Wilfried
authors.initials: W
authors.lastname: Budach
authors.forename: Hansjochen
authors.initials: H
authors.lastname: Wilke
mesh_terms: D000230:Adenocarcinoma / Q000628:therapy*; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D003131:Combined Modality Therapy; D004938:Esophageal Neoplasms / Q000628:therapy*; D004943:Esophagogastric Junction; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D011446:Prospective Studies; D011878:Radiotherapy; D013274:Stomach Neoplasms / Q000628:therapy*
chemical_list: D000970:Antineoplastic Agents