title: Sequential neoadjuvant chemoradiotherapy (CRT) followed by curative surgery vs. primary surgery alone for resectable, non-metastasized pancreatic adenocarcinoma: NEOPA- a randomized multicenter phase III study (NCT01900327, DRKS00003893, ISRCTN82191749).
abstract: BACKGROUND
  Median OS after surgery in curative intent for non-metastasized pancreas cancer ranges under study conditions from 17.9 months to 23.6 months. Tumor recurrence occurs locally, at distant sites (liver, peritoneum, lungs), or both. Observational and autopsy series report local recurrence rates of up to 87% even after potentially "curative" R0 resection. To achieve better local control, neoadjuvant CRT has been suggested for preoperative tumour downsizing, to elevate the likelihood of curative, margin-negative R0 resection and to increase the OS rate. However, controlled, randomized trials addressing the impact of neoadjuvant CRT survival do not exist.
  
  
  METHODS
  The underlying hypothesis of this randomized, two-armed, open-label, multicenter, phase III trial is that neoadjuvant CRT increases the three-year overall survival by 12% compared to patients undergoing upfront surgery for resectable pancreatic cancer. A rigorous, standardized technique of histopathologically handling Whipple specimens will be applied at all participating centers. Overall, 410 patients (n=205 in each study arm) will be enrolled in the trial, taking into regard an expected drop out rate of 7% and allocated either to receive neoadjuvant CRT prior to surgery or to undergo surgery alone. Circumferential resection margin status, i.e. R0 and R1 rates, respectively, surgical resectability rate, local and distant disease-free and global survival, and first site of tumor recurrence constitute further essential endpoints of the trial.
  
  
  CONCLUSIONS
  For the first time, the NEOPA study investigates the impact of neoadjuvant CRT on survival of resectable pancreas head cancer in a prospectively randomized manner. The results of the study have the potential to change substantially the treatment regimen of pancreas cancer.
  
  
  BACKGROUND
  Clinical Trial gov: NCT01900327, DRKS00003893, ISRCTN82191749.
authors.forename: Michael
authors.initials: M
authors.lastname: Tachezy
authors.forename: Florian
authors.initials: F
authors.lastname: Gebauer
authors.forename: Cordula
authors.initials: C
authors.lastname: Petersen
authors.forename: Dirk
authors.initials: D
authors.lastname: Arnold
authors.forename: Martin
authors.initials: M
authors.lastname: Trepel
authors.forename: Karl
authors.initials: K
authors.lastname: Wegscheider
authors.forename: Phillipe
authors.initials: P
authors.lastname: Schafhausen
authors.forename: Maximilian
authors.initials: M
authors.lastname: Bockhorn
authors.affiliation: Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg Eppendorf, Martinistr, 52, Hamburg 20246, Germany. izbicki@uke.de.
authors.forename: Jakob Robert
authors.initials: JR
authors.lastname: Izbicki
authors.forename: Emre
authors.initials: E
authors.lastname: Yekebas
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols; D059248:Chemoradiotherapy; D059186:Chemoradiotherapy, Adjuvant; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery