title: Biological dosimetry for breast cancer radiotherapy: a comparison of external beam and intraoperative radiotherapy.
abstract: OBJECTIVE
  External beam radiotherapy (EBRT) is the gold standard adjuvant treatment after breast conserving surgery although a recent phase 3 trial has shown the non-inferiority of intraoperative radiotherapy (IORT). Radiation exposure of the heart and cardiac vessels causes an increase in morbidity and mortality following EBRT for breast cancer. We have used γ-H2AX foci formation in peripheral blood lymphocytes as a surrogate marker of dose delivered to the heart and great vessels and have assessed the feasibility of using this technique for biological dosimetry.
  
  
  METHODS
  34 patients were recruited, having either EBRT or IORT as part of a randomised controlled trial (TARGIT). Blood samples were taken prior to and after first fraction of radiotherapy, and the γ-H2AX biomarker then quantified.
  
  
  RESULTS
  Data were available for 31 patients. Following TARGIT-IORT there was an increase of 0.203 foci per cell (range -1.436 to 1.275) compared with 0.935 foci per cell (range -0.679 to 2.216) in the EBRT group; this difference was highly significant (p = 0.009). As TARGIT-IORT treatment is completed with a single fraction, whilst EBRT requires at least 15 fractions, the actual difference is estimated to be many times more.
  
  
  CONCLUSIONS
  These data show a significantly greater change in γ-H2AX foci number per cell following one fraction of EBRT compared to TARGIT-IORT. This is the first study to demonstrate this effect using a biomarker and demonstrates a proof of concept methodology for similar applications.
authors.affiliation: Department of Academic Oncology, Royal Free Hospital, London, UK.
authors.forename: David K
authors.initials: DK
authors.lastname: Woolf
authors.affiliation: Clinical Trials Group, University College London, London, UK.
authors.forename: Norman R
authors.initials: NR
authors.lastname: Williams
authors.affiliation: The Academic Breast Unit, University College London, London, UK.
authors.forename: Raheleh
authors.initials: R
authors.lastname: Bakshi
authors.affiliation: The Academic Breast Unit, University College London, London, UK.
authors.forename: Seyed Yazdan
authors.initials: SY
authors.lastname: Madani
authors.affiliation: Department of Academic Oncology, Royal Free Hospital, London, UK.
authors.forename: David J
authors.initials: DJ
authors.lastname: Eaton
authors.affiliation: Department of Academic Oncology, Royal Free Hospital, London, UK.
authors.forename: Sara
authors.initials: S
authors.lastname: Fawcitt
authors.affiliation: Department of Academic Oncology, Royal Free Hospital, London, UK.
authors.forename: Katharine
authors.initials: K
authors.lastname: Pigott
authors.affiliation: Leeds Institute of Cancer and Pathology, St James University Hospital, Leeds, UK.
authors.forename: Susan
authors.initials: S
authors.lastname: Short
authors.affiliation: The Academic Breast Unit, University College London, London, UK.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Keshtgar
keywords: Breast cancer; Cardiac toxicity; H2AX; Intraoperative radiotherapy