title: Radiation therapy targets and the risk of breast cancer-related lymphedema: a systematic review and network meta-analysis.
abstract: New indications have been found for regional nodal irradiation (RNI) in breast cancer treatment, yet the relationship of RNI and lymphedema risk is uncertain. We sought to determine the association of RNI and lymphedema.
  
  
  
  We searched MEDLINE, EMBASE, and Scopus for articles in English on humans published from 1995 to 2015, using search terms breast neoplasm, treatment, and morbidity. Two investigators independently selected articles and extracted information, including manuscripts reporting incidence of lymphedema by radiation targets. Meta-analyses, review papers, case-control studies, matched-pair studies, repetitive datasets, and retrospective studies were excluded. A total of 2399 abstracts were identified and 323 corresponding articles reviewed. Twenty-one studies met inclusion criteria. Data were pooled using a random effects mixed model. Network meta-analyses were performed to determine the association of radiation targets alone and radiation targets plus extent of axillary surgery on incidence of lymphedema.
  
  
  
  The addition of RNI to breast/CW irradiation was associated with an increased incidence of lymphedema (OR 2.85; 95% CI 1.24-6.55). In patients treated with sentinel lymph node biopsy or axillary sampling, there was no association of lymphedema with the addition of RNI to breast/CW irradiation (OR 1.58; 95% CI 0.54-4.66; pooled incidence 5.7 and 4.1%, respectively). Among patients treated with axillary lymph node dissection (ALND), treatment with RNI in addition to breast/CW radiation was associated with a significantly higher risk of lymphedema (OR 2.74; 95% CI 1.38-5.44; pooled incidence 18.2 and 9.4%, respectively).
  
  
  
  RNI is associated with a significantly higher risk of lymphedema than irradiation of the breast/CW, particularly after ALND.
authors.affiliation: Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1202, Houston, TX, 77030, USA. sfshaitelman@mdanderson.org.
authors.forename: Simona F
authors.initials: SF
authors.lastname: Shaitelman
authors.affiliation: Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1484, Houston, TX, 77030, USA.
authors.forename: Yi-Ju
authors.initials: YJ
authors.lastname: Chiang
authors.affiliation: Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1484, Houston, TX, 77030, USA.
authors.forename: Kate D
authors.initials: KD
authors.lastname: Griffin
authors.affiliation: Department of Breast Surgical Oncology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1434, Houston, TX, 77030, USA.
authors.forename: Sarah M
authors.initials: SM
authors.lastname: DeSnyder
authors.affiliation: Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1202, Houston, TX, 77030, USA.
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Smith
authors.affiliation: Department of Plastic Surgery, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1488, Houston, TX, 77030, USA.
authors.forename: Mark V
authors.initials: MV
authors.lastname: Schaverien
authors.affiliation: Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1202, Houston, TX, 77030, USA.
authors.forename: Wendy A
authors.initials: WA
authors.lastname: Woodward
authors.affiliation: Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1484, Houston, TX, 77030, USA.
authors.forename: Janice N
authors.initials: JN
authors.lastname: Cormier
mesh_terms: D001365:Axilla / Q000473:pathology / Q000528:radiation effects; D001943:Breast Neoplasms / Q000150:complications* / Q000175:diagnosis / Q000532:radiotherapy / Q000601:surgery; D005260:Female; D006801:Humans; D015994:Incidence; D008197:Lymph Node Excision; D008198:Lymph Nodes / Q000473:pathology / Q000528:radiation effects; D008209:Lymphedema / Q000453:epidemiology* / Q000209:etiology*; D016017:Odds Ratio; D012306:Risk; D021701:Sentinel Lymph Node Biopsy
keywords: Breast cancer; Lymphedema; Morbidity; Radiation