title: Impact of neoadjuvant chemoradiation on lymph node status in esophageal cancer: post hoc analysis of a randomized controlled trial.
abstract: OBJECTIVE
  The study objectives were to analyze the impact of the number of lymph nodes (LNs) reported as resected (NLNr) and the number of LNs invaded (NLNi) on the prognosis of esophageal cancer (EC) after neoadjuvant chemoradiotherapy.
  
  
  BACKGROUND
  Pathological LN status is a major disease prognostic factor and marker of surgical quality. The impact of neoadjuvant chemoradiation (nCRT) on LN status remains poorly studied in EC.
  
  
  METHODS
  Post hoc analysis from a phase III randomized controlled trial comparing nCRT and surgery (group nCRT) to surgery alone (group S) in stage I and II EC (NCT00047112). Only patients who underwent surgical resection were considered (n = 170).
  
  
  RESULTS
  nCRT resulted in tumoral downstaging (pT0, 40.7% vs 1.1%, P < 0.001), LN downstaging (pN0, 69.1% vs 47.2%, P = 0.016), and reduction in the median NLNr [16.0 (range, 0-47.0) vs 22.0 (range, 3.0-58.0), P = 0.001] and NLNi [0 (range, 0-25) vs 1.0 (range, 0-25), P = 0.001]. A good histological response (TRG1/2) in the resected esophageal specimen correlated with reduced median NLNi [0 (range, 0-10) vs 1.0 (range, 0-4), P = 0.007]. After adjustment by treatment, NLNi [hazards ratio (HR) (1-3 vs 0) 3.5, 95% confidence interval (CI): 2.3-5.5, and HR (>3 vs 0) 3.5, 95% CI: 2.0-6.2, P < 0.001] correlated with prognosis, whereas NLNr [HR (<15 vs ≥15) 0.95, 95% CI: 0.6-1.4, P = 0.807 and HR (<23 vs ≥23) 1.4, 95% CI: 0.9-2.0, P = 0.131] did not. In Poisson regression analysis, nCRT was an independent predictive variable for reduced NLNr [exp(coefficient) 0.80, 95% CI: 0.66-0.96, P = 0.018].
  
  
  CONCLUSIONS
  nCRT is not only responsible for disease downstaging but also predicts fewer LNs being identified after surgical resection for EC. This has implications for the current quality criteria for surgical resection.
authors.affiliation: *SIRIC ONCOLille and Université Lille-Nord de France †Inserm, UMR837, Team 5 "Mucins, epithelial differentiation and carcinogenesis" Jean Pierre Aubert Research Center, Lille, France ‡Department of Surgical Oncology, Lille University Hospital, Lille, France §Department of Digestive Oncology, La Timone Hospital, Aix-Marseille University, Marseille, France ¶Department of Radiotherapy, Pierre-Bénite Hospital, Lyon, France ‖Department of Biostatistics, Fédération Française de Cancérologie Digestive, Dijon, France **Department of Thoracic Surgery, Hôpital Nord, Marseille, France ††Department of Digestive Surgery, University Hospital, Rennes, France ‡‡Department of Oncology, Gustave Roussy, Villejuif, France §§Department of Oncology, University Hospital, Clermont-Ferrand, France ¶¶Department of Gastroenterology, University Hospital, Limoges, France ‖‖Department of Radiotherapy, University Hospital of Besançon, Besançon, France ***Department of Digestive Surgery, Croix-Rousse University Hospital, Lyon, France †††Department of Gastroenterology, University Hospital of Dijon, Dijon, France.
authors.forename: William B
authors.initials: WB
authors.lastname: Robb
authors.forename: Laetitia
authors.initials: L
authors.lastname: Dahan
authors.forename: Françoise
authors.initials: F
authors.lastname: Mornex
authors.forename: Emilie
authors.initials: E
authors.lastname: Maillard
authors.forename: Pascal-Alexandre
authors.initials: PA
authors.lastname: Thomas
authors.forename: Bernard
authors.initials: B
authors.lastname: Meunier
authors.forename: Valérie
authors.initials: V
authors.lastname: Boige
authors.forename: Denis
authors.initials: D
authors.lastname: Pezet
authors.forename: Valérie
authors.initials: V
authors.lastname: Le Brun-Ly
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Bosset
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Mabrut
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Triboulet
authors.forename: Laurent
authors.initials: L
authors.lastname: Bedenne
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Seitz
authors.forename: Christophe
authors.initials: C
authors.lastname: Mariette
mesh_terms: D000328:Adult; D000368:Aged; D059248:Chemoradiotherapy; D004938:Esophageal Neoplasms / Q000473:pathology* / Q000601:surgery / Q000628:therapy*; D005260:Female; D006801:Humans; D008197:Lymph Node Excision; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D016019:Survival Analysis