% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{DalBello:165889,
      author       = {R. Dal Bello$^*$ and T. Becher$^*$ and Fuss and M. Krämer
                      and J. Seco$^*$},
      title        = {{P}roposal of a chemical mechanism for mini-beam and
                      micro-beam efficacy},
      journal      = {Frontiers of physics},
      volume       = {8},
      issn         = {1673-3487},
      address      = {Heidelberg},
      publisher    = {Springer},
      reportid     = {DKFZ-2020-02458},
      pages        = {564836},
      year         = {2020},
      note         = {#EA:E041#LA:E041#},
      abstract     = {This simulation study proposes a chemical mechanism to
                      define a surrogate to the tumor control during micro- and
                      mini-beam radiation therapy (MBRT). The main focus is
                      proton-MBRT (pMBRT) and the methods developed are applied
                      also to photon-MBRT (MRT). In both cases, the classical
                      interpretation of physical dose cannot be used to explain
                      the observed biological effect and a change of paradigm may
                      be required. MBRT was reported to provide tumor control with
                      reduced side effects when compared to standard dose
                      delivery. The underlying mechanisms leading to a
                      differential response of the normal tissue and the tumor are
                      still unknown. In this work, we propose a chemical mechanism
                      to describe the efficacy of MBRT. The model was developed
                      starting from the observation that pMBRT led to long term
                      survival without significant side effects of rats implanted
                      with a high-grade glioma. We distribution of a generic
                      radiation-induced molecule or radical could be a surrogate
                      to describe the biological effect. The specific mechanisms
                      leading to cell damage were outside the scope of this work.
                      The molecules and radicals were selected according to a set
                      of properties: (i) they should be stable to allow diffusion
                      achieving coverage of the dose-valleys, (ii) they should
                      reach a steady state in production versus removal, (iii)
                      they should be a product of water radiolysis, and (iv) they
                      should have oxidizing capacity. A convolution model was
                      developed to assess the property (i) keeping the analysis as
                      general as possible. The tumor coverage was defined widening
                      the interpretation of the ICRU-62 recommendations. The
                      properties (ii) and (iii) were investigated with the
                      TRAX-CHEM software. The property (iv) was used to exclude
                      not relevant chemical species. The results show that
                      hydrogen peroxide fulfills all the requirements. Moreover,
                      the modeling of its temporal and spatial distributions
                      demonstrate that a uniform coverage of the target by this
                      reactive oxygen specie (ROS) can be achieved during the
                      beam-on time. The model was compared and proven to be
                      compatible with three independent photon micro-beam and
                      proton mini-beam animal experiments. We conclude that
                      hydrogen peroxide is a good candidate to describe the
                      mini-beam and micro-beam efficacy. Further experiments are
                      proposed to experimentally benchmark the model and to
                      correlate the hydrogen peroxide concentration to the tumor
                      control probability.},
      cin          = {E041},
      ddc          = {530},
      cid          = {I:(DE-He78)E041-20160331},
      pnm          = {315 - Imaging and radiooncology (POF3-315)},
      pid          = {G:(DE-HGF)POF3-315},
      typ          = {PUB:(DE-HGF)16},
      doi          = {10.3389/fphy.2020.564836},
      url          = {https://inrepo02.dkfz.de/record/165889},
}