title: Evaluation of biologic effective dose and schedule of fractionation for preoperative radiotherapy for rectal cancer: meta-analyses and meta-regression.
abstract: OBJECTIVE
  To evaluate whether the risk of local recurrence depends on the biologic effective dose (BED) or fractionation dose in patients with resectable rectal cancer undergoing preoperative radiotherapy (RT) compared with surgery alone.
  
  
  METHODS
  A meta-analysis of randomized controlled trials (RCTs) was performed. The MEDLINE, Embase, CancerLit, and Cochrane Library databases were systematically searched for evidence. To evaluate the dose-response relationship, we conducted a meta-regression analysis. Four subgroups were created: Group 1, RCTs with a BED >30 Gy(10) and a short RT schedule; Group 2, RCTs with BED >30 Gy(10) and a long RT schedule; Group 3, RCTs with BED ≤ 30 Gy(10) and a short RT schedule; and Group 4, RCTs with BED ≤ 30 Gy(10) and a long RT schedule.
  
  
  RESULTS
  Our review identified 21 RCTs, yielding 9,097 patients. The pooled results from these 21 randomized trials of preoperative RT showed a significant reduction in mortality for groups 1 (p = .004) and 2 (p = .03). For local recurrence, the results were also significant in groups 1 (p = .00001) and 2 (p = .00001).The only subgroup that showed a greater sphincter preservation (SP) rate than surgery was group 2 (p = .03). The dose-response curve was linear (p = .006), and RT decreased the risk of local recurrence by about 1.7% for each Gy(10) of BED.
  
  
  CONCLUSIONS
  Our data have shown that RT with a BED of >30 Gy(10) is more efficient in reducing local recurrence and mortality rates than a BED of ≤ 30 Gy(10), independent of the schedule of fractionation used. A long RT schedule with a BED of >30 Gy(10) should be recommended for sphincter preservation.
authors.affiliation: Department of Radiation Oncology, Marília Medicine School, São Paulo, Brazil. gusviani@gmail.com
authors.forename: Gustavo Arruda
authors.initials: GA
authors.lastname: Viani
authors.forename: Eduardo Jose
authors.initials: EJ
authors.lastname: Stefano
authors.forename: Francisco Vendito
authors.initials: FV
authors.lastname: Soares
authors.forename: Sergio Luis
authors.initials: SL
authors.lastname: Afonso
mesh_terms: D019583:Dose Fractionation, Radiation; D006801:Humans; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000517:prevention & control; D011300:Preoperative Care / Q000379:methods; D016032:Randomized Controlled Trials as Topic; D012004:Rectal Neoplasms / Q000401:mortality / Q000517:prevention & control / Q000532:radiotherapy* / Q000601:surgery; D012062:Relative Biological Effectiveness