title: Does para-aortic irradiation reduce the risk of distant metastasis in advanced cervical cancer? A systematic review and meta-analysis of randomized clinical trials.
abstract: OBJECTIVE
  To evaluate the impact of the extension of the radiotherapy field cranially toward para-aortic lymph nodes (EF-RT) in advanced cervical cancer.
  
  
  METHODS
  A systematic search of databases (PubMed, CENTRAL, Clinical Trials) was performed and included studies that were published between 1960 and November 2015 without language restrictions. All randomized clinical trials (RCTs) were analyzed further. All patients must have undergone pelvic radiotherapy and the same systemic therapy in both arms. The primary endpoints were locoregional failure, incidence of distant metastasis, para-aortic failure, and cancer related death. The Mantel-Haenszel method was used in the meta-analysis. The risk of bias analysis was determined using the 7-domain method per the Cochrane Handbook for Systematic Reviews of Interventions V5.1.0. A review of the treatment technique and toxicity was also performed.
  
  
  RESULTS
  A total of 1309 studies were evaluated, 4 RCTs of which met the inclusion criteria; 506 patients were allocated to standard pelvic irradiation, and 494 underwent EF-RT. The risk of bias was considered to be low in nearly 80% of the domains. EF-RT significantly reduced the rate of para-aortic failure (HR 0.35, 95% CI 0.19-0.64; p<0.01) and the incidence of other distant metastases (HR 0.69, 95% CI 0.50-0.96; p=0.03). Locoregional failure and cancer-related death were not significantly altered (OR 1.06 [0.80-1.42]; p=0.67, and 0.68 [0.45-1.01]; p=0.06, respectively). The radiotherapy technique was conventional in 3 studies and conformational in 1 study. In total, 10 treatment-related deaths occurred-4 in pelvic radiation and 6 in EF-RT (OR 2.12 [0.71-6.27]; p=0.18).
  
  
  CONCLUSIONS
  EF-RT that targets the para-aortic lymphatic chain reduces distant metastatic events, but its impact on survival is unknown. Future studies should examine the value of EF-RT using modern radiation techniques.
authors.affiliation: Department of Radiation Oncology, AC Camargo Cancer Center, São Paulo, Brazil. Electronic address: lgsapienza@yahoo.com.br.
authors.forename: Lucas Gomes
authors.initials: LG
authors.lastname: Sapienza
authors.affiliation: Department of Radiation Oncology, Hospital Federal dos Servidores do Estado (HFSE-RJ), Rio de Janeiro, Brazil.
authors.forename: Maria José Leite
authors.initials: MJL
authors.lastname: Gomes
authors.affiliation: Department of Statistics and Epidemiology, AC Camargo Cancer Center, São Paulo, Brazil.
authors.forename: Vinicius Fernando
authors.initials: VF
authors.lastname: Calsavara
authors.affiliation: Division of Gynecology, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, USA.
authors.forename: Mario M
authors.initials: MM
authors.lastname: Leitao
authors.affiliation: Department of Gynecologic Oncology, AC Camargo Cancer Center, São Paulo, Brazil.
authors.forename: Glauco
authors.initials: G
authors.lastname: Baiocchi
mesh_terms: D005260:Female; D006801:Humans; D015182:Lymphatic Irradiation; D008207:Lymphatic Metastasis / Q000517:prevention & control; D016032:Randomized Controlled Trials as Topic; D012306:Risk; D002583:Uterine Cervical Neoplasms / Q000473:pathology / Q000532:radiotherapy*
keywords: Cervical cancer; Extended-field; Para-aortic radiotherapy