title: Patterns of recurrence after surgery alone versus preoperative chemoradiotherapy and surgery in the CROSS trials.
abstract: OBJECTIVE
  To analyze recurrence patterns in patients with cancer of the esophagus or gastroesophageal junction treated with either preoperative chemoradiotherapy (CRT) plus surgery or surgery alone.
  
  
  METHODS
  Recurrence pattern was analyzed in patients from the previously published CROSS I and II trials in relation to radiation target volumes. CRT consisted of five weekly courses of paclitaxel and carboplatin combined with a concurrent radiation dose of 41.4 Gy in 1.8-Gy fractions to the tumor and pathologic lymph nodes with margin.
  
  
  RESULTS
  Of the 422 patients included from 2001 to 2008, 418 were available for analysis. Histology was mostly adenocarcinoma (75%). Of the 374 patients who underwent resection, 86% were allocated to surgery and 92% to CRT plus surgery. On January 1, 2011, after a minimum follow-up of 24 months (median, 45 months), the overall recurrence rate in the surgery arm was 58% versus 35% in the CRT plus surgery arm. Preoperative CRT reduced locoregional recurrence (LRR) from 34% to 14% (P < .001) and peritoneal carcinomatosis from 14% to 4% (P < .001). There was a small but significant effect on hematogenous dissemination in favor of the CRT group (35% v 29%; P = .025). LRR occurred in 5% within the target volume, in 2% in the margins, and in 6% outside the radiation target volume. In 1%, the exact site in relation to the target volume was unclear. Only 1% had an isolated infield recurrence after CRT plus surgery.
  
  
  CONCLUSIONS
  Preoperative CRT in patients with esophageal cancer reduced LRR and peritoneal carcinomatosis. Recurrence within the radiation target volume occurred in only 5%, mostly combined with outfield failures.
authors.affiliation: Vera Oppedijk, Rob van Os, Dick J. Richel, Mark I. van Berge Henegouwen, and Maarten C.C.M. Hulshof, Academic Medical Center, Amsterdam; Patty H. Spruit, Vrije Universiteit Medical Center, Amsterdam; Ate van der Gaast, Jan J.B. van Lanschot, Pieter van Hagen, and Caroline M. van Rij, Erasmus Medical Center, Rotterdam; Maurice J. van der Sangen, Catharina Hospital, Eindhoven; Jannet C. Beukema, University Medical Center, Groningen; Heidi Rütten, Radboud University Medical Center, Nijmegen; and Janny G. Reinders, Arnhems Radiotherapeutisch Instituut, Arnhem, the Netherlands.
authors.forename: Vera
authors.initials: V
authors.lastname: Oppedijk
authors.forename: Ate
authors.initials: A
authors.lastname: van der Gaast
authors.forename: Jan J B
authors.initials: JJ
authors.lastname: van Lanschot
authors.forename: Pieter
authors.initials: P
authors.lastname: van Hagen
authors.forename: Rob
authors.initials: R
authors.lastname: van Os
authors.forename: Caroline M
authors.initials: CM
authors.lastname: van Rij
authors.forename: Maurice J
authors.initials: MJ
authors.lastname: van der Sangen
authors.forename: Jannet C
authors.initials: JC
authors.lastname: Beukema
authors.forename: Heidi
authors.initials: H
authors.lastname: Rütten
authors.forename: Patty H
authors.initials: PH
authors.lastname: Spruit
authors.forename: Janny G
authors.initials: JG
authors.lastname: Reinders
authors.forename: Dick J
authors.initials: DJ
authors.lastname: Richel
authors.forename: Mark I
authors.initials: MI
authors.lastname: van Berge Henegouwen
authors.forename: Maarten C C M
authors.initials: MC
authors.lastname: Hulshof
mesh_terms: D000230:Adenocarcinoma / Q000556:secondary / Q000628:therapy*; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D016190:Carboplatin / Q000008:administration & dosage; D002294:Carcinoma, Squamous Cell / Q000556:secondary / Q000628:therapy*; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects; D019583:Dose Fractionation, Radiation; D004938:Esophageal Neoplasms / Q000473:pathology / Q000628:therapy*; D016629:Esophagectomy / Q000009:adverse effects; D004943:Esophagogastric Junction / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects / Q000601:surgery; D005260:Female; D005743:Gastrectomy / Q000009:adverse effects*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020360:Neoadjuvant Therapy / Q000009:adverse effects; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control*; D017239:Paclitaxel / Q000008:administration & dosage; D016016:Proportional Hazards Models; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000473:pathology / Q000628:therapy*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D016190:Carboplatin; D017239:Paclitaxel