title: Multimodality treatment for esophageal adenocarcinoma: multi-center propensity-score matched study.
abstract: The primary aim of this study was to compare survival from neoadjuvant chemoradiotherapy plus surgery (NCRS) versus neoadjuvant chemotherapy plus surgery (NCS) for the treatment of esophageal or junctional adenocarcinoma. The secondary aims were to compare pathological effects, short-term mortality and morbidity, and to evaluate the effect of lymph node harvest upon survival in both treatment groups.
  
  
  
  Data were collected from 10 European centers from 2001 to 2012. Six hundred and eight patients with stage II or III oesophageal or oesophago-gastric junctional adenocarcinoma were included; 301 in the NCRS group and 307 in the NCS group. Propensity score matching and Cox regression analyses were used to compensate for differences in baseline characteristics.
  
  
  
  NCRS resulted in significant pathological benefits with more ypT0 (26.7% versus 5%; P < 0.001), more ypN0 (63.3% versus 32.1%; P < 0.001), and reduced R1/2 resection margins (7.7% versus 21.8%; P < 0.001). Analysis of short-term outcomes showed no statistically significant differences in 30-day or 90-day mortality, but increased incidence of anastomotic leak (23.1% versus 6.8%; P < 0.001) in NCRS patients. There were no statistically significant differences between the groups in 3-year overall survival (57.9% versus 53.4%; Hazard Ratio (HR)= 0.89, 95%C.I. 0.67-1.17, P = 0.391) nor disease-free survival (52.9% versus 48.9%; HR = 0.90, 95%C.I. 0.69-1.18, P = 0.443). The pattern of recurrence was also similar (P = 0.660). There was a higher lymph node harvest in the NCS group (27 versus 14; P < 0.001), which was significantly associated with a lower recurrence rate and improved disease free survival within the NCS group.
  
  
  
  The survival differences between NCRS and NCS maybe modest, if present at all, for the treatment of locally advanced esophageal or junctional adenocarcinoma. Future large-scale randomized trials must control and monitor indicators of the quality of surgery, as the extent of lymphadenectomy appears to influence prognosis in patients treated with NCS, from this large multi-center European study.
authors.affiliation: Department of Surgery & Cancer, Imperial College London, London, UK.
authors.forename: S R
authors.initials: SR
authors.lastname: Markar
authors.affiliation: Department of Surgery, Erasmus MC-University Medical Centre, Rotterdam, Netherlands.
authors.forename: B J
authors.initials: BJ
authors.lastname: Noordman
authors.affiliation: Department of Surgery & Cancer, Imperial College London, London, UK.
authors.forename: H
authors.initials: H
authors.lastname: Mackenzie
authors.affiliation: Oxford Oesophagogastric Centre, Oxford University Hospitals, Oxford, UK.
authors.forename: J M
authors.initials: JM
authors.lastname: Findlay
authors.affiliation: Department of Surgery & Cancer, Imperial College London, London, UK.
authors.forename: P R
authors.initials: PR
authors.lastname: Boshier
authors.affiliation: Department of Surgery & Cancer, Imperial College London, London, UK.
authors.forename: M
authors.initials: M
authors.lastname: Ni
authors.affiliation: Centre for Medical Decision Sciences, Department of Public Health.
authors.forename: E W
authors.initials: EW
authors.lastname: Steyerberg
authors.affiliation: Department of Medical Oncology, Erasmus MC-University Medical Centre, Rotterdam.
authors.forename: A
authors.initials: A
authors.lastname: van der Gaast
authors.affiliation: Department of Radiation Oncology, Academic Medical Centre, Amsterdam.
authors.forename: M C C M
authors.initials: MCCM
authors.lastname: Hulshof
authors.affiliation: Oxford Oesophagogastric Centre, Oxford University Hospitals, Oxford, UK.
authors.forename: N
authors.initials: N
authors.lastname: Maynard
authors.affiliation: Department of Surgery, Academic Medical Centre, Amsterdam, Netherlands.
authors.forename: M I
authors.initials: MI
authors.lastname: van Berge Henegouwen
authors.affiliation: Department of Surgery, Erasmus MC-University Medical Centre, Rotterdam, Netherlands.
authors.forename: B P L
authors.initials: BPL
authors.lastname: Wijnhoven
authors.affiliation: Department of Surgery, Trinity College Dublin and St James's Hospital, Dublin, Ireland.
authors.forename: J V
authors.initials: JV
authors.lastname: Reynolds
authors.affiliation: Department of Surgery, Erasmus MC-University Medical Centre, Rotterdam, Netherlands.
authors.forename: J J B
authors.initials: JJB
authors.lastname: Van Lanschot
authors.affiliation: Department of Surgery & Cancer, Imperial College London, London, UK.
authors.forename: G B
authors.initials: GB
authors.lastname: Hanna
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D059248:Chemoradiotherapy; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D005260:Female; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D011878:Radiotherapy; D016896:Treatment Outcome
keywords: chemotherapy; esophageal neoplasm; neoadjuvant therapy; radiotherapy