title: The Impact of Preoperative Radiation Therapy on Locoregional Recurrence in Patients with Stage IV Rectal Cancer Treated with Definitive Surgical Resection and Contemporary Chemotherapy.
abstract: OBJECTIVE
  Definitive resection of primary rectal cancers is frequently incorporated, with or without preoperative radiotherapy and perioperative chemotherapy, in the management of selected patients with metastatic rectal adenocarcinoma. This study reviews the impact of preoperative radiotherapy and perioperative chemotherapy on locoregional recurrence and overall survival in these patients.
  
  
  METHODS
  This retrospective study with an Institutional Review Board (IRB) waiver included 109 patients with metastatic rectal adenocarcinoma who underwent definitive primary resection between 1998 and 2011. In addition to resection, 64 patients were treated with preoperative radiotherapy and perioperative chemotherapy and 45 patients were treated with perioperative chemotherapy alone. Radiotherapy dose was typically 50.4 Gy. Baseline variables were compared using chi-square and unpaired t tests. Overall survival was calculated using Kaplan-Meier method. Univariate and multivariate analyses were performed using Cox proportional hazards regression.
  
  
  RESULTS
  There were no significant baseline differences between the two groups. There was no significant difference in locoregional recurrence (10.9 vs. 11.1%; p = 0.90) or overall survival (34.5 vs. 34.8 months; p = 0.89) for patients treated with preoperative radiotherapy compared to those treated with perioperative chemotherapy alone, respectively. Patients who underwent radiotherapy were less likely to have a positive margin (10.9 vs. 20.0%; p = 0.19), lymphovascular invasion (32.8 vs. 53.3%; p = 0.03), and pathologic stage N2 disease (25.0 vs. 42.2%; p = 0.02). Grade 2 postoperative complications were more common in the preoperative radiotherapy group (32.8 vs. 15.6%; p = 0.04). Multivariate analysis demonstrated that patients with poorly differentiated tumors (HR 2.19; p = 0.009) and those that did not undergo liver-directed therapy (HR 2.20; p = 0.005) had inferior survival.
  
  
  CONCLUSIONS
  Locoregional recurrence is modest in patients with metastatic rectal adenocarcinoma receiving definitive primary resection, irrespective of the use of radiotherapy. Preoperative radiotherapy may enhance pathologic downstaging at the expense of increased grade 2 postoperative complications. Its use should be reserved for patients at high risk for locoregional recurrence.
authors.affiliation: Department of Radiation Oncology, Cleveland Clinic, 9500 Euclid Ave - Desk T28, Cleveland, OH, 44195, USA.
authors.forename: Bindu V
authors.initials: BV
authors.lastname: Manyam
authors.forename: Ismail H
authors.initials: IH
authors.lastname: Mallick
authors.forename: May M
authors.initials: MM
authors.lastname: Abdel-Wahab
authors.forename: Chandana A
authors.initials: CA
authors.lastname: Reddy
authors.forename: Feza H
authors.initials: FH
authors.lastname: Remzi
authors.forename: Matthew F
authors.initials: MF
authors.lastname: Kalady
authors.forename: Ian
authors.initials: I
authors.lastname: Lavery
authors.forename: Shlomo A
authors.initials: SA
authors.lastname: Koyfman
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000556:secondary / Q000628:therapy*; D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020360:Neoadjuvant Therapy; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000473:pathology / Q000517:prevention & control*; D009367:Neoplasm Staging; D018714:Radiotherapy, Adjuvant; D012004:Rectal Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D012189:Retrospective Studies