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@ARTICLE{Heinzelmann:305654,
      author       = {F. Heinzelmann and S. Peters and A. Quenzer and A. Lühr
                      and S. Löck and S. S. Schleithoff and S. Frisch and C.
                      Bäumer$^*$ and B. Timmermann$^*$},
      title        = {{R}isk modeling of imaging changes after proton beam
                      therapy for childhood brain tumors.},
      journal      = {Radiotherapy and oncology},
      volume       = {nn},
      issn         = {0167-8140},
      address      = {Amsterdam [u.a.]},
      publisher    = {Elsevier Science},
      reportid     = {DKFZ-2025-02286},
      pages        = {nn},
      year         = {2025},
      note         = {epub},
      abstract     = {In childhood brain tumors, minimizing long-term side
                      effects of cancer therapy is a critical objective.
                      Radiation-related imaging changes (ICs), indicative of
                      potential radionecrosis, remain an area of active
                      investigation in proton beam therapy (PBT). This study aimed
                      to identify and correlate post-therapeutic ICs and
                      radio-biological and dosimetric factors, including linear
                      energy transfer (LET) and variable relative biological
                      effectiveness (RBE), as well as clinical factors.A 3:1
                      matched-pair cohort of 93 pediatric PBT patients from a
                      register study was retrospectively analyzed. The cohort
                      comprised various brain tumor entities, with follow-up MRI
                      data available up to 14 months post-treatment. Potential
                      clinical risk factors for therapy-induced ICs in pediatric
                      brains were analyzed using logistic regression at both
                      patient and voxel levels. Dosimetric parameters were
                      evaluated for the entire brain, periventricular region
                      (PVR), and brainstem.A total of 15 cases with
                      post-therapeutic ICs from various childhood tumor entities
                      were identified and localized in the brainstem, the PVR, and
                      other brain regions. At the voxel level, the key parameter
                      linked to increased IC probability was the product of dose D
                      and proton dose-averaged LETd (D· LETdproton)σ=6 mm,
                      excluding voxels below 5 Gy (RBE). The Gaussian filtering
                      with a standard deviation σ of 6 mm served as a practical
                      approach to account for spatial uncertainties. At the
                      patient level, the median dose $(D50\%)$ within the volume
                      of the healthy brain receiving more than 20 Gy (RBE) was
                      most significant.The identified univariate voxel- and
                      patient-level risk factors provide a foundation for
                      predicting post-therapeutic ICs in pediatric CNS tumor
                      patients treated with PBT. Our findings contribute to
                      refining risk prediction models and optimizing treatment
                      planning strategies, ultimately aiming to minimize long-term
                      radiation-induced effects in pediatric brain tumor
                      patients.},
      keywords     = {Adverse effects (Other) / Brain cancer (Other) / Brainstem
                      (Other) / Childhood brain tumors (Other) / Imaging changes
                      (Other) / Linear energy transfer (LET) (Other) / Normal
                      tissue complication probability (NTCP) (Other) /
                      Periventricular region (PVR) (Other) / Proton beam therapy
                      (PBT) (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:41192767},
      doi          = {10.1016/j.radonc.2025.111261},
      url          = {https://inrepo02.dkfz.de/record/305654},
}