title: High-Grade Toxicity to Neoadjuvant Treatment for Upper Gastrointestinal Carcinomas: What is the Impact on Perioperative and Oncologic Outcomes?
abstract: BACKGROUND
  Perioperative oncologic treatments provide a survival benefit for junctional and gastric adenocarcinoma (JGA) and esophageal cancer (EC). Whether neoadjuvant therapy toxicity (NTT) correlates with increased perioperative risk remains unclear. We aimed to evaluate the impact of grade III/IV NTT on postoperative and oncologic outcomes in resected upper gastrointestinal malignancies.
  
  
  METHODS
  A multicenter retrospective analysis was performed on consecutive patients who benefited from neoadjuvant chemo(radio)therapy followed by surgery between 1997 and 2010 for JGA (first cohort, n = 653) and for EC (second cohort, n = 640). Data between patients who experienced NTT were compared to those who did not.
  
  
  RESULTS
  NTT was associated with higher postoperative mortality after resection of JGA (P = 0.001) and after esophagectomy (P < 0.001), more non-R0 resections (JGA P = 0.019, EC P = 0.024), a decreased administration of adjuvant treatment among the JGA cohort (P = 0.012), and higher surgical morbidity (JGA P = 0.005, EC P = 0.020). Median survival was reduced in patients who experienced NTT in both cohorts (JGA P = 0.018, EC P = 0.037). After adjustment on confounding variables, NTT was independently associated with postoperative mortality in both cohorts (P ≤ 0.007).
  
  
  CONCLUSIONS
  NTT is a predictor of postoperative mortality, correlates with higher postoperative morbidity, and negatively affects oncologic outcomes for upper gastrointestinal carcinomas.
authors: Department of Digestive and Oncological Surgery, University Hospital Claude Huriez, Lille Cedex, France.
authors: William B
authors: WB
authors: Robb
authors: Department of Digestive and Oncological Surgery, University Hospital Claude Huriez, Lille Cedex, France.|University of Lille - Nord de France, Lille, France.|Inserm, UMR837, Jean-Pierre Aubert Research Center, Team 5 Mucins, Epithelial Differentiation and Carcinogenesis, Lille, France.
authors: Mathieu
authors: M
authors: Messager
authors: Department of Digestive and Oncological Surgery, University Hospital Claude Huriez, Lille Cedex, France.|University of Lille - Nord de France, Lille, France.|Inserm, UMR837, Jean-Pierre Aubert Research Center, Team 5 Mucins, Epithelial Differentiation and Carcinogenesis, Lille, France.
authors: Caroline
authors: C
authors: Gronnier
authors: Department of Digestive and Oncological Surgery, University Hospital Claude Huriez, Lille Cedex, France.
authors: Williams
authors: W
authors: Tessier
authors: Department of Digestive and Oncological Surgery, University Hospital Claude Huriez, Lille Cedex, France.
authors: Flora
authors: F
authors: Hec
authors: Department of Digestive and Oncological Surgery, University Hospital Claude Huriez, Lille Cedex, France.|University of Lille - Nord de France, Lille, France.|Inserm, UMR837, Jean-Pierre Aubert Research Center, Team 5 Mucins, Epithelial Differentiation and Carcinogenesis, Lille, France.
authors: Guillaume
authors: G
authors: Piessen
authors: Department of Digestive and Oncological Surgery, University Hospital Claude Huriez, Lille Cedex, France. christophe.mariette@chru-lille.fr.|University of Lille - Nord de France, Lille, France. christophe.mariette@chru-lille.fr.|Inserm, UMR837, Jean-Pierre Aubert Research Center, Team 5 Mucins, Epithelial Differentiation and Carcinogenesis, Lille, France. christophe.mariette@chru-lille.fr.|SIRIC ONCOLille, Lille, France. christophe.mariette@chru-lille.fr.
authors: Christophe
authors: C
authors: Mariette
mesh_terms: D000230:Adenocarcinoma / Q000601:surgery / Q000628:therapy*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects; D059186:Chemoradiotherapy, Adjuvant / Q000009:adverse effects*; D003967:Diarrhea / Q000209:etiology; D019583:Dose Fractionation, Radiation; D004938:Esophageal Neoplasms / Q000601:surgery / Q000628:therapy*; D016629:Esophagectomy / Q000009:adverse effects / Q000401:mortality; D004943:Esophagogastric Junction / Q000601:surgery*; D005260:Female; D005743:Gastrectomy / Q000009:adverse effects / Q000401:mortality; D017052:Hospital Mortality; D006801:Humans; D007970:Leukopenia / Q000209:etiology; D008297:Male; D008875:Middle Aged; D052016:Mucositis / Q000209:etiology; D020360:Neoadjuvant Therapy / Q000009:adverse effects*; D018365:Neoplasm, Residual; D012189:Retrospective Studies; D013274:Stomach Neoplasms / Q000601:surgery / Q000628:therapy*; D015996:Survival Rate; D013921:Thrombocytopenia / Q000209:etiology; D016896:Treatment Outcome; D014839:Vomiting / Q000209:etiology; D055815:Young Adult