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@ARTICLE{Dokic:125725,
      author       = {I. Dokic$^*$ and A. Mairani and M. Niklas$^*$ and F.
                      Zimmermann$^*$ and N. Chaudhri and D. Krunic$^*$ and T.
                      Tessonnier and A. Ferrari and K. Parodi and O. Jäkel$^*$
                      and J. Debus and T. Haberer and A. Abdollahi$^*$},
      title        = {{N}ext generation multi-scale biophysical characterization
                      of high precision cancer particle radiotherapy using
                      clinical proton, helium-, carbon- and oxygen ion beams.},
      journal      = {OncoTarget},
      volume       = {7},
      number       = {35},
      issn         = {1949-2553},
      address      = {[S.l.]},
      publisher    = {Impact Journals LLC},
      reportid     = {DKFZ-2017-01851},
      pages        = {56676 - 56689},
      year         = {2016},
      abstract     = {The growing number of particle therapy facilities worldwide
                      landmarks a novel era of precision oncology. Implementation
                      of robust biophysical readouts is urgently needed to assess
                      the efficacy of different radiation qualities. This is the
                      first report on biophysical evaluation of Monte Carlo
                      simulated predictive models of prescribed dose for four
                      particle qualities i.e., proton, helium-, carbon- or oxygen
                      ions using raster-scanning technology and clinical therapy
                      settings at HIT. A high level of agreement was found between
                      the in silico simulations, the physical dosimetry and the
                      clonogenic tumor cell survival. The cell fluorescence ion
                      track hybrid detector (Cell-Fit-HD) technology was employed
                      to detect particle traverse per cell nucleus. Across a panel
                      of radiobiological surrogates studied such as late ROS
                      accumulation and apoptosis (caspase 3/7 activation), the
                      relative biological effectiveness (RBE) chiefly correlated
                      with the radiation species-specific spatio-temporal pattern
                      of DNA double strand break (DSB) formation and repair
                      kinetic. The size and the number of residual nuclear γ-H2AX
                      foci increased as a function of linear energy transfer (LET)
                      and RBE, reminiscent of enhanced DNA-damage complexity and
                      accumulation of non-repairable DSB. These data confirm the
                      high relevance of complex DSB formation as a central
                      determinant of cell fate and reliable biological surrogates
                      for cell survival/ RBE. The multi-scale simulation, physical
                      and radiobiological characterization of novel clinical
                      quality beams presented here constitutes a first step
                      towards development of high precision biologically
                      individualized radiotherapy.},
      cin          = {E210 / W210 / E040 / L101},
      ddc          = {610},
      cid          = {I:(DE-He78)E210-20160331 / I:(DE-He78)W210-20160331 /
                      I:(DE-He78)E040-20160331 / I:(DE-He78)L101-20160331},
      pnm          = {315 - Imaging and radiooncology (POF3-315)},
      pid          = {G:(DE-HGF)POF3-315},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:27494855},
      pmc          = {pmc:PMC5302944},
      doi          = {10.18632/oncotarget.10996},
      url          = {https://inrepo02.dkfz.de/record/125725},
}