title: Imaging Radiation Doses and Associated Risks and Benefits in Subjects Participating in Breast Cancer Clinical Trials.
abstract: BACKGROUND
  Medical imaging is commonly required in breast cancer (BC) clinical trials to assess the efficacy and/or safety of study interventions. Despite the lack of definitive epidemiological data linking imaging radiation with cancer development in adults, concerns exist about the risks of imaging radiation-induced malignancies (IRIMs) in subjects exposed to repetitive imaging. We estimated the imaging radiation dose and IRIM risk in subjects participating in BC trials.
  
  
  METHODS
  The imaging protocol requirements in 10 phase III trials in the adjuvant and advanced settings were assessed to estimate the effective radiation dose received by a typical and fully compliant subject in each trial. For each study, the excess lifetime attributable cancer risk (LAR) was calculated using the National Cancer Institute's Radiation Risk Assessment Tool, version 3.7.1. Dose and risk calculations were performed for both imaging intensive and nonintensive approaches to reflect the variability in imaging performed within the studies.
  
  
  RESULTS
  The total effective imaging radiation dose was 0.4-262.2 mSv in adjuvant trials and 26-241.3 mSv in metastatic studies. The dose variability resulted from differing protocol requirements and imaging intensity approaches, with computed tomography, multigated acquisition scans, and bone scans as the major contributors. The mean LAR was 1.87-2,410/100,000 in adjuvant trials (IRIM: 0.0002%-2.41% of randomized subjects) and 6.9-67.3/100,000 in metastatic studies (IRIM: 0.007%-0.067% of subjects).
  
  
  CONCLUSIONS
  IRIMs are infrequent events. In adjuvant trials, aligning the protocol requirements with the clinical guidelines' surveillance recommendations and substituting radiating procedures with equivalent nonradiating ones would reduce IRIM risk. No significant risk has been observed in metastatic trials, and potential concerns on IRIMs are not justified.
  
  
  CONCLUSIONS
  Medical imaging is key in breast cancer (BC) clinical trials. Most of these procedures expose patients to ionizing radiation, and the risk of second cancer development after imaging has prompted recent concerns and controversy. Using accepted calculation models, the number of malignancies were estimated that were potentially attributable to the imaging procedures performed during a patient's participation in BC clinical trials. The results show that for patients participating in metastatic trials, the risk of imaging radiation-induced malignancies is negligible. In adjuvant trials, some second cancers due to imaging could be expected, and measures can be taken to reduce their risk.
authors.affiliation: Medical Lead Department, Translational Research in Oncology, Montevideo, Uruguay; Departamento de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la Republica, Montevideo, Uruguay; Department of Oncology, University of Alberta, Edmonton, Alberta, Canada rodrigo.fresco@trioncology.org.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Fresco
authors.affiliation: Medical Lead Department, Translational Research in Oncology, Montevideo, Uruguay; Departamento de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la Republica, Montevideo, Uruguay; Department of Oncology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Spera
authors.affiliation: Medical Lead Department, Translational Research in Oncology, Montevideo, Uruguay; Departamento de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la Republica, Montevideo, Uruguay; Department of Oncology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Carlos
authors.initials: C
authors.lastname: Meyer
authors.affiliation: Medical Lead Department, Translational Research in Oncology, Montevideo, Uruguay; Departamento de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la Republica, Montevideo, Uruguay; Department of Oncology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Pablo
authors.initials: P
authors.lastname: Cabral
authors.affiliation: Medical Lead Department, Translational Research in Oncology, Montevideo, Uruguay; Departamento de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la Republica, Montevideo, Uruguay; Department of Oncology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: John R
authors.initials: JR
authors.lastname: Mackey
mesh_terms: D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology; D002986:Clinical Trials as Topic; D005260:Female; D006801:Humans; D011829:Radiation Dosage; D011859:Radiography / Q000009:adverse effects*; D011877:Radionuclide Imaging; D012307:Risk Factors
keywords: Breast cancer trials; Imaging radiation; Imaging radiation-induced cancer; Imaging radiation-induced malignancy; Radiation dose; Radiation risks; Radiation-induced cancers