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@ARTICLE{Guberina:298610,
      author       = {M. Guberina$^*$ and M. Stuschke$^*$ and D. Flühs and L.
                      Jabbarli and T. Kiefer and E. Biewald and P. Rating and H.
                      Manke and S. Dalbah and C. Hoffmann and N. Guberina$^*$ and
                      C. Pöttgen and M. Fiorentzis and A. Foerster and T.
                      Grunewald and N. Bornfeld and W. Sauerwein and N. Bechrakis
                      and E. Sokolenko},
      title        = {{D}ose response relation for optic nerve atrophy at
                      low-dose rate brachytherapy of uveal melanoma.},
      journal      = {Radiotherapy and oncology},
      volume       = {205},
      issn         = {0167-8140},
      address      = {Amsterdam [u.a.]},
      publisher    = {Elsevier Science},
      reportid     = {DKFZ-2025-00310},
      pages        = {110775},
      year         = {2025},
      note         = {Volume 205, April 2025, 110775},
      abstract     = {Dose-response relationships for optic neuropathy and optic
                      nerve atrophy after brachytherapy for posterior uveal
                      melanoma were poorly defined from previous studies. Here,
                      the outcome differences were analyzed in dependence on
                      dosimetric factors, the applicator type, and tumor dependent
                      variables.Primary objective was to evaluate the association
                      of applied dose and on-set of optic nerve atrophy after
                      brachytherapy for posterior uveal melanoma in order to allow
                      risk estimation for new patients.This retrospective study
                      was performed at a single high volume centre for ocular
                      oncology. Patients receiving brachytherapy with
                      Ruthenium-106 applicators for posterior uveal melanoma with
                      a maximum distance between optic nerve and the nearest tumor
                      margin of 4 optical disc diameters and follow-up with fundus
                      photographs were included. The dose distribution at the
                      optic nerve was reconstructed from the fundus photographs at
                      latest follow-up and the dose-distribution of the applicator
                      using a dedicated software. A first mask with important
                      structural elements such as optic nerve, macula, tumor and
                      vessels was first superimposed on the fundus photograph and
                      adapted to the real contours. In a second step, an
                      applicator contour mask was adapted to the radiation scar in
                      order to calculate the dose distribution in all structures.
                      Dose-response relations were obtained by weighted logistic
                      regression.The maximum dose at the optic disc (ODmax) in
                      this group of 109 patients ranged from 5.8 Gy - 242.2 Gy,
                      median 48.7 Gy. Optic nerve atrophy was observed in
                      29patients. Median time to optic radiation induced optic
                      nerve atrophy was 18 months. Using weighted logistic
                      regression, the dependence of optic nerve atrophy on ODmax
                      was significant (p = 0.0001, chi2 test). There was a
                      considerable interobserver variability in ODmax values (p <
                      0.02, signed rank test). An additional factor influencing
                      the dose-response was the applicator type (p = 0.0315, chi2
                      test). The ODmax for a probability of optic nerve atrophy of
                      50 $\%$ (ED50) were 77.6 Gy ± 7.0 Gy for patients treated
                      with notched COB applicators and 53.2 Gy ± 8.2 Gy for
                      patients with other applicators. Including the applicator
                      type, the area under ROC curve reached a value of 0.857 (95
                      $\%-CI:$ 0.793-0.921) for the logistic model with ODmax. The
                      ED50 for optic nerve neuropathy, classified as grade ≥ 1
                      toxicity, was estimated to be 46.9 Gy ± 4.1 Gy for the
                      maximum dose at the optic disc.Significant dose-response
                      curves were found for optic nerve atrophy at low dose rate
                      brachytherapy. A standard position of COB applicators was
                      identified that allows estimation of the dose-response
                      relation from the scleral dose of the applicator for risk
                      estimation without fundus photographs. This larger data set
                      enhances the knowledge of dose-response relationships for
                      irradiation near the optic nerve.},
      keywords     = {Dose response relation (Other) / Low-dose rate
                      brachytherapy (Other) / Malignant eye tumor (Other) / Optic
                      nerve atrophy (Other) / Optic neuropathy (Other) /
                      Optimizing treatment (Other) / Outcome (Other) / Radiation
                      (Other) / Uveal Melanoma (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:39922315},
      doi          = {10.1016/j.radonc.2025.110775},
      url          = {https://inrepo02.dkfz.de/record/298610},
}