title: Neoadjuvant radiotherapy for rectal cancer: meta-analysis of randomized controlled trials.
abstract: BACKGROUND
  Although neoadjuvant radiotherapy may improve local control of rectal cancer, its clinical value requires further evaluation as a result of potential side effects and advances in surgical technique. A meta-analysis was performed to assess effectiveness and safety of neoadjuvant radiotherapy in the management of rectal cancer.
  
  
  METHODS
  The following databases were searched: the Cochrane Library, Biosis, Web of Science, Embase, ASCO Abstracts and WHO International Clinical Trials Registry Platform. Randomized controlled trials on the following comparisons were included: (1) neoadjuvant therapy versus surgery alone and (2) neoadjuvant chemoradiotherapy versus neoadjuvant radiotherapy.
  
  
  RESULTS
  We identified 17 and 5 relevant trials that enrolled 8,568 and 2,393 patients, respectively. Neoadjuvant radiotherapy improved local control (hazard ratio 0.59; 95 % confidence interval 0.48-0.72) compared to surgery alone even after total mesorectal excision, whereas its benefit in overall survival just failed to reach statistical significance (0.93; 0.85-1.00). However, it was associated with increased perioperative mortality (1.48; 1.08-2.03), in particular if a dose of 5 Gy per fraction was administered (1.85; 1.23-2.78). Chemoradiotherapy improved local control as opposed to radiotherapy (0.53; 0.39-0.72), with no impact on perioperative outcome and long-term survival.
  
  
  CONCLUSIONS
  Neoadjuvant radiotherapy improves local control in patients with rectal cancer, particularly when chemoradiotherapy is administered. The question if the use of more effective chemotherapy protocols improves overall survival warrants further investigation.
authors.affiliation: Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany, nuh.rahbari@googlemail.com.
authors.forename: Nuh N
authors.initials: NN
authors.lastname: Rahbari
authors.forename: Heike
authors.initials: H
authors.lastname: Elbers
authors.forename: Vasileios
authors.initials: V
authors.lastname: Askoxylakis
authors.forename: Edith
authors.initials: E
authors.lastname: Motschall
authors.forename: Ulrich
authors.initials: U
authors.lastname: Bork
authors.forename: Markus W
authors.initials: MW
authors.lastname: Büchler
authors.forename: Jürgen
authors.initials: J
authors.lastname: Weitz
authors.forename: Moritz
authors.initials: M
authors.lastname: Koch
mesh_terms: D006801:Humans; D020360:Neoadjuvant Therapy; D011379:Prognosis; D018714:Radiotherapy, Adjuvant; D016032:Randomized Controlled Trials as Topic; D012004:Rectal Neoplasms / Q000532:radiotherapy*