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@ARTICLE{Faddegon:278423,
      author       = {B. Faddegon and E. A. Blakely and L. N. Burigo$^*$ and Y.
                      Censor and I. Dokic$^*$ and N. Domínguez Kondo and R. Ortiz
                      and J. Ramos Méndez and A. Rucinski and K. Schubert and N.
                      Wahl$^*$ and R. Schulte},
      title        = {{I}onization detail parameters and cluster dose: a
                      mathematical model for selection of nanodosimetric
                      quantities for use in treatment planning in charged particle
                      radiotherapy.},
      journal      = {Physics in medicine and biology},
      volume       = {68},
      number       = {17},
      issn         = {0031-9155},
      address      = {Bristol},
      publisher    = {IOP Publ.},
      reportid     = {DKFZ-2023-01657},
      pages        = {175013},
      year         = {2023},
      abstract     = {Objective. To propose a mathematical model for applying
                      ionization detail (ID), the detailed spatial distribution of
                      ionization along a particle track, to proton and ion beam
                      radiotherapy treatment planning (RTP).Approach. Our model
                      provides for selection of preferred ID parameters (Ip) for
                      RTP, that associate closest to biological effects. Cluster
                      dose is proposed to bridge the large gap between
                      nanoscopicIpand macroscopic RTP. Selection ofIpis
                      demonstrated using published cell survival measurements for
                      protons through argon, comparing results for
                      nineteenIp:Nk,k= 2, 3, …, 10, the number of ionizations in
                      clusters ofkor more per particle, andFk,k= 1, 2, …, 10,
                      the number of clusters ofkor more per particle. We then
                      describe application of the model to ID-based RTP and
                      propose a path to clinical translation.Main results. The
                      preferredIpwereN4andF5for aerobic cells,N5andF7for hypoxic
                      cells. Significant differences were found in cell survival
                      for beams having the same LET or the preferredNk.
                      Conversely, there was no significant difference forF5for
                      aerobic cells andF7for hypoxic cells, regardless of ion beam
                      atomic number or energy. Further, cells irradiated with the
                      same cluster dose for theseIphad the same cell survival.
                      Based on these preliminary results and other compelling
                      results in nanodosimetry, it is reasonable to assert
                      thatIpexist that are more closely associated with biological
                      effects than current LET-based approaches and
                      microdosimetric RBE-based models used in particle RTP.
                      However, more biological variables such as cell line and
                      cycle phase, as well as ion beam pulse structure and rate
                      still need investigation.Significance. Our model provides a
                      practical means to select preferredIpfrom radiobiological
                      data, and to convertIpto the macroscopic cluster dose for
                      particle RTP.},
      keywords     = {Relative Biological Effectiveness / Cell Line / Radiation
                      Oncology / Protons / Models, Biological / RBE (Other) /
                      nanodosimetry (Other) / particle therapy (Other) / track
                      structure simulation (Other) / treatment planning (Other) /
                      Protons (NLM Chemicals)},
      cin          = {E040 / E210 / HD01},
      ddc          = {530},
      cid          = {I:(DE-He78)E040-20160331 / I:(DE-He78)E210-20160331 /
                      I:(DE-He78)HD01-20160331},
      pnm          = {315 - Bildgebung und Radioonkologie (POF4-315)},
      pid          = {G:(DE-HGF)POF4-315},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:37489619},
      doi          = {10.1088/1361-6560/acea16},
      url          = {https://inrepo02.dkfz.de/record/278423},
}