title: A randomized clinical trial of neoadjuvant chemotherapy versus neoadjuvant chemoradiotherapy for cancer of the oesophagus or gastro-oesophageal junction.
abstract: BACKGROUND
  Neoadjuvant therapy improves long-term survival after oesophagectomy, treating oesophageal cancer, but the evidence to date is insufficient to determine which of the two main neoadjuvant therapy types, chemotherapy (nCT) or chemoradiotherapy (nCRT), is more beneficial. We aimed to compare the effects of nCT with those of nCRT.
  
  
  METHODS
  This multicentre trial, which was conducted in Sweden and Norway, recruited 181 patients with carcinoma of the oesophagus or the gastro-oesophageal junction who were candidates for curative-intended treatment. The primary end point was histological complete response after neoadjuvant treatment, which has been shown to be correlated with increased long-term survival. Study participants were randomized to nCT or nCRT, followed by surgery with two-field lymphadenectomy. Three cycles of platin/5-fluorouracil were administered in both arms, whereas 40 Gy of concomitant radiotherapy was added in the nCRT arm.
  
  
  RESULTS
  The trial met the primary end point, histological complete response being achieved in 28% after nCRT versus 9% after nCT (P = 0.002). Lymph-node metastases were observed in 62% in the nCT group versus 35% in the nCRT group (P = 0.001). The R0 resection rate was 87% after nCRT and 74% after nCT (P = 0.04). There was no difference in overall survival between the treatment arms.
  
  
  CONCLUSIONS
  The addition of radiotherapy to neoadjuvant chemotherapy results in higher histological complete response rate, higher R0 resection rate, and a lower frequency of lymph-node metastases, without significantly affecting survival.
  
  
  BACKGROUND
  NCT01362127 (https://clinicaltrials.gov; The full study protocol was registered in the Clinical Trials Database).
authors.affiliation: Division of Surgery, Department of Clinical Science Intervention and Technology, Karolinska Institutet and Centre for Digestive Diseases, Karolinska University Hospital, Stockholm fredrik.klevebro@ki.se.
authors.forename: F
authors.initials: F
authors.lastname: Klevebro
authors.affiliation: Departments of Oncology.
authors.forename: G
authors.initials: G
authors.lastname: Alexandersson von Döbeln
authors.affiliation: Pathology, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
authors.forename: N
authors.initials: N
authors.lastname: Wang
authors.affiliation: Department of Gastrointestinal Surgery, St Olavs Hospital, Trondheim University Hospital, Trondheim.
authors.forename: G
authors.initials: G
authors.lastname: Johnsen
authors.affiliation: Department of Oncology, Oslo University Hospital, Oslo.
authors.forename: A-B
authors.initials: AB
authors.lastname: Jacobsen
authors.affiliation: Departments of Oncology.
authors.forename: S
authors.initials: S
authors.lastname: Friesland
authors.affiliation: Department of Oncology, St Olavs Hospital, Trondheim University Hospital, Trondheim.
authors.forename: I
authors.initials: I
authors.lastname: Hatlevoll
authors.affiliation: Department of Oncology, Haukeland University Hospital, Bergen, Norway.
authors.forename: N I
authors.initials: NI
authors.lastname: Glenjen
authors.affiliation: Department of Oncology, Mälarsjukhuset Eskilstuna, Karolinska Institutet, Stockholm, Sweden.
authors.forename: P
authors.initials: P
authors.lastname: Lind
authors.affiliation: Division of Surgery, Department of Clinical Science Intervention and Technology, Karolinska Institutet and Centre for Digestive Diseases, Karolinska University Hospital, Stockholm.
authors.forename: J A
authors.initials: JA
authors.lastname: Tsai
authors.affiliation: Division of Surgery, Department of Clinical Science Intervention and Technology, Karolinska Institutet and Centre for Digestive Diseases, Karolinska University Hospital, Stockholm.
authors.forename: L
authors.initials: L
authors.lastname: Lundell
authors.affiliation: Division of Surgery, Department of Clinical Science Intervention and Technology, Karolinska Institutet and Centre for Digestive Diseases, Karolinska University Hospital, Stockholm.
authors.forename: M
authors.initials: M
authors.lastname: Nilsson
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D000328:Adult; D000368:Aged; D018572:Disease-Free Survival; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D004943:Esophagogastric Junction / Q000473:pathology / Q000601:surgery; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage*; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D009664:Norway; D012074:Remission Induction; D013548:Sweden; D016896:Treatment Outcome
chemical_list: D005472:Fluorouracil
keywords: chemoradiotherapy; chemotherapy; neoadjuvant treatment; oesophageal carcinoma