title: Is preoperative chemotherapy followed by surgery the appropriate treatment for signet ring cell containing adenocarcinomas of the esophagogastric junction and stomach?
abstract: BACKGROUND
  Recent data suggest primary resection as the preferable approach in patients with signet ring cell gastric cancer (SRC). The aim of our retrospective exploratory study was to evaluate the influence of SRC on prognosis and response in esophagogastric adenocarcinoma treated with neoadjuvant chemotherapy.
  
  
  METHODS
  A total of 723 locally advanced esophagogastric adenocarcinomas (cT3/4 N any) documented in a prospective database from two academic centers were classified according to the WHO definition for SRC (more than 50 % SRC) and analyzed for their association with response and prognosis after neoadjuvant treatment.
  
  
  RESULTS
  A total of 235 tumors (32.5 %) contained SRC. Median survival of SRC was 26.3 compared with 46.6 months (p < 0.001) for non-SRC. SRC were significantly associated with female gender, gastric localization, advanced ypT and R1/2 categories, and lower risk of surgical complications and anastomotic leakage (each p < 0.001). Clinical (21.1 vs. 33.7 %, p = 0.001) and histopathological response (less than 10 % residual tumor: 16.3 vs. 28.9 %, p < 0.001) were significantly less frequent in SRC. Clinical response (p = 0.003) and complete histopathological response (pCR) (3.4 %) (p = 0.003) were associated with improved prognosis in SRC. Clinical response, surgical complications, ypTN categories, but not SRC were independent prognostic factors in forward Cox regression analysis in R0 resected patients. Risk of peritoneal carcinomatosis was increased (p < 0.001), while local (p = 0.015) and distant metastases (p = 0.02) were less frequent than in non-SRC.
  
  
  CONCLUSIONS
  Prognosis of SRC is unfavorable. Although response to neoadjuvant chemotherapy is rare in SRC, it is associated with improved outcome. Thus, chemotherapy might not generally be abandoned in SRC. A stratification based on SRC should be included in clinical trials.
authors.affiliation: Department of Surgery, Heidelberg University Hospital, University of Heidelberg, Heidelberg, Germany, ulrike.heger@med.uni-heidelberg.de.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Heger
authors.forename: Susanne
authors.initials: S
authors.lastname: Blank
authors.forename: Christiane
authors.initials: C
authors.lastname: Wiecha
authors.forename: Rupert
authors.initials: R
authors.lastname: Langer
authors.forename: Wilko
authors.initials: W
authors.lastname: Weichert
authors.forename: Florian
authors.initials: F
authors.lastname: Lordick
authors.forename: Thomas
authors.initials: T
authors.lastname: Bruckner
authors.forename: Martin
authors.initials: M
authors.lastname: Dobritz
authors.forename: Maria
authors.initials: M
authors.lastname: Burian
authors.forename: Christoph
authors.initials: C
authors.lastname: Springfeld
authors.forename: Lars
authors.initials: L
authors.lastname: Grenacher
authors.forename: Jörg-Rüdiger
authors.initials: JR
authors.lastname: Siewert
authors.forename: Markus
authors.initials: M
authors.lastname: Büchler
authors.forename: Katja
authors.initials: K
authors.lastname: Ott
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000473:pathology / Q000628:therapy; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D018279:Carcinoma, Signet Ring Cell / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000473:pathology / Q000628:therapy; D003131:Combined Modality Therapy; D004938:Esophageal Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D016629:Esophagectomy; D004943:Esophagogastric Junction / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D020360:Neoadjuvant Therapy; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D011183:Postoperative Complications; D011300:Preoperative Care; D011379:Prognosis; D011446:Prospective Studies; D012189:Retrospective Studies; D013274:Stomach Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D015996:Survival Rate