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@ARTICLE{Heuchel:284988,
      author       = {L. Heuchel and C. Hahn and J. Ödén and E. Traneus and J.
                      Wulff and B. Timmermann$^*$ and C. Bäumer$^*$ and A. Lühr},
      title        = {{T}he dirty and clean dose concept: {T}owards creating
                      proton therapy treatment plans with a photon-like dose
                      response.},
      journal      = {Medical physics},
      volume       = {51},
      number       = {1},
      issn         = {0094-2405},
      address      = {College Park, Md.},
      publisher    = {AAPM},
      reportid     = {DKFZ-2023-02172},
      pages        = {622-636},
      year         = {2024},
      note         = {2024 Jan;51(1):622-636},
      abstract     = {Applying tolerance doses for organs at risk (OAR) from
                      photon therapy introduces uncertainties in proton therapy
                      when assuming a constant relative biological effectiveness
                      (RBE) of 1.1.This work introduces the novel dirty and clean
                      dose concept, which allows for creating treatment plans with
                      a more photon-like dose response for OAR and, thus, less
                      uncertainties when applying photon-based tolerance doses.The
                      concept divides the 1.1-weighted dose distribution into two
                      parts: the clean and the dirty dose. The clean and dirty
                      dose are deposited by protons with a linear energy transfer
                      (LET) below and above a set LET threshold, respectively. For
                      the former, a photon-like dose response is assumed, while
                      for the latter, the RBE might exceed 1.1. To reduce the
                      dirty dose in OAR, a MaxDirtyDose objective was added in
                      treatment plan optimization. It requires setting two
                      parameters: LET threshold and max dirty dose level. A simple
                      geometry consisting of one target volume and one OAR in
                      water was used to study the reduction in dirty dose in the
                      OAR depending on the choice of the two MaxDirtyDose
                      objective parameters during plan optimization. The best
                      performing parameter combinations were used to create
                      multiple dirty dose optimized (DDopt) treatment plans for
                      two cranial patient cases. For each DDopt plan, 1.1-weighted
                      dose, variable RBE-weighted dose using the Wedenberg RBE
                      model and dose-average LETd distributions as well as
                      resulting normal tissue complication probability (NTCP)
                      values were calculated and compared to the reference plan
                      (RefPlan) without MaxDirtyDose objectives.In the water
                      phantom studies, LET thresholds between 1.5 and 2.5 keV/µm
                      yielded the best plans and were subsequently used. For the
                      patient cases, nearly all DDopt plans led to a reduced
                      Wedenberg dose in critical OAR. This reduction resulted from
                      an LET reduction and translated into an NTCP reduction of up
                      to 19 percentage points compared to the RefPlan. The
                      1.1-weighted dose in the OARs was slightly increased
                      (patient 1: 0.45 Gy(RBE), patient 2: 0.08 Gy(RBE)), but
                      never exceeded clinical tolerance doses. Additionally,
                      slightly increased 1.1-weighted dose in healthy brain tissue
                      was observed (patient 1: 0.81 Gy(RBE), patient 2: 0.53
                      Gy(RBE)). The variation of NTCP values due to variation of
                      α/β from 2 to 3 Gy was much smaller for DDopt (2
                      percentage points (pp)) than for RefPlans (5 pp).The novel
                      dirty and clean dose concept allows for creating
                      biologically more robust proton treatment plans with a more
                      photon-like dose response. The reduced uncertainties in RBE
                      can, therefore, mitigate uncertainties introduced by using
                      photon-based tolerance doses for OAR.},
      keywords     = {clean dose (Other) / dirty dose (Other) / linear energy
                      transfer (LET) (Other) / proton therapy treatment plan
                      optimization (Other) / relative biological effectiveness
                      (RBE) (Other)},
      cin          = {ED01},
      ddc          = {610},
      cid          = {I:(DE-He78)ED01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:37877574},
      doi          = {10.1002/mp.16809},
      url          = {https://inrepo02.dkfz.de/record/284988},
}