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@ARTICLE{Baltazar:282359,
      author       = {F. Baltazar$^*$ and T. Tessonnier and T. Haberer and J.
                      Debus$^*$ and K. Herfarth$^*$ and B. Tawk$^*$ and M.
                      Knoll$^*$ and A. Abdollahi$^*$ and J. Liermann and A.
                      Mairani$^*$},
      title        = {{C}arbon-ion {R}adiotherapy ({CIRT}) as treatment of
                      pancreatic cancer at {HIT}: initial radiation plan analysis
                      of the prospective phase {II} {PACK}-study.},
      journal      = {Radiotherapy and oncology},
      volume       = {188},
      issn         = {0167-8140},
      address      = {Amsterdam [u.a.]},
      publisher    = {Elsevier Science},
      reportid     = {DKFZ-2023-01743},
      pages        = {109872},
      year         = {2023},
      note         = {#EA:E050#LA:E050# / Volume 188, November 2023, 109872},
      abstract     = {To analyze the dose objectives and constraints applied at
                      the prospective phase II PACK-study at Heidelberg ion
                      therapy center (HIT) for different radiobiological
                      models.Treatment plans of 14 patients from the PACK-study
                      were analyzed and recomputed in terms of physical,
                      biological dose and dose-averaged linear energy transfer
                      (LETd). Both LEM-I (local effect model 1) and the adapted
                      NIRS-MKM (microdosimetric kinetic model), were used for
                      relative biological effectiveness (RBE)-weighted dose
                      calculations (DBio|HIT and DBio|NIRS). A new constraint to
                      the gastrointestinal (GI) tract was derived from the
                      National Institute of Radiological Science (NIRS) clinical
                      experience and considered for plan reoptimization
                      $(DBio|NIRS-const_48Gy.$ and $DBio|NIRS-const_50.4Gy).$ The
                      Lyman-Kutcher-Burman (LKB) model of Normal Tissue
                      Complication Probability (NTCP) for GI toxicity endpoints
                      was computed. Furthermore, the computed LETd distribution
                      was evaluated and correlated with Local Control (LC).Only
                      two patients showed a $LETd98\%$ in the GTV greater than 44
                      keV/μm. A HIT-dose constraint to the GI of D 2cm3= 48.6
                      GyRBEHIT was derived from the NIRS experience, in
                      alternative to the standard at HIT Dmax= 45.6 GyRBEHIT. In
                      comparison with the original
                      $DBio|HIT,DBio|NIRS-const_48GyandDBio|NIRS-const_50.4Gy$
                      resulted in an increase in the ITV's $D98\%$ of $8.7\%$ and
                      $11.3\%.$ The NTCP calculation resulted in a probability for
                      gastrointestinal bleeding of $4.5\%,$ $12.3\%$ and $13.0\%,$
                      for DBio|NIRS, $DBio|NIRS-const_48Gy$ and
                      $DBio|NIRS-const_50.4Gy,$ respectively.The results indicate
                      that the current standards applied at HIT for CIRT closely
                      align with the Japanese experience. However, to enhance
                      tumor coverage, a more relaxed constraint on the GI tract
                      may be considered. As the PACK-trial progresses, further
                      analyses of various clinical endpoints are anticipated.},
      keywords     = {Gastrointestinal toxicity (Other) / Pancreatic cancer
                      (Other) / Treatment dose constraints (Other) / carbon ion
                      radiotherapy (Other)},
      cin          = {E050 / E210 / HD01},
      ddc          = {610},
      cid          = {I:(DE-He78)E050-20160331 / 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:37634764},
      doi          = {10.1016/j.radonc.2023.109872},
      url          = {https://inrepo02.dkfz.de/record/282359},
}