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@ARTICLE{GarrettFernandes:299472,
      author       = {M. Garrett Fernandes and J. Bussink and R. Wijsman and Z.
                      Gouw and A. Weiß$^*$ and N. M. Sijtsema and R. Canters and
                      A. Hope and D. De Ruysscher and E. Troost$^*$ and J.-J.
                      Sonke and B. Stam and R. Monshouwer},
      title        = {{A}ssociation between dose to cardiac structures and
                      overall survival: {A} multivariable analysis in a large,
                      multi-institutional database of stage {III} {NSCLC} patients
                      with external validation.},
      journal      = {Radiotherapy and oncology},
      volume       = {206},
      issn         = {0167-8140},
      address      = {Amsterdam [u.a.]},
      publisher    = {Elsevier Science},
      reportid     = {DKFZ-2025-00432},
      pages        = {110821},
      year         = {2025},
      note         = {Volume 206, May 2025, 110821},
      abstract     = {Inconsistencies in identifying dose-limiting cardiovascular
                      substructures for treating stage III non-small cell lung
                      cancer (NSCLC) have hindered the implementation of cardiac
                      sparing treatment planning guidelines. This study aims to
                      address these inconsistencies by performing a multivariable
                      survival analysis with overall survival as the endpoint
                      using a large, multinational database, followed by external
                      validation.Clinical and dosimetric parameters from 1587
                      stage III NSCLC patients treated at five institutes were
                      analyzed. The whole heart, four cardiac chambers, great
                      vessels and their combinations were considered. The dataset
                      was divided into a training set (four institutes) and a test
                      set (one institute). The optimal parameter set was
                      identified through cross-validation, and the resulting
                      multivariable Cox regression model was externally validated
                      using the test set. Adjusted hazard ratios (aHRs) for all
                      cardiovascular parameters were evaluated.The strongest
                      associations were found for low $Dx\%$ parameters. However,
                      their incremental contribution to model performance,
                      compared to clinical and lung dosimetric parameters only,
                      was low, with small effect sizes. Specifically, the
                      cardiovascular parameter identified by parameter selection
                      was Left Side $D5\%$ (aHR: 1.007 Gy-1, 95 $\%$ CI: 1.004 -
                      1.010 Gy-1, p < 0.0001), which provided a slight improvement
                      in model concordance index of 0.0062 (95 $\%$ CI:
                      0.0000-0.0127) in the training set and 0.0037 (95 $\%$ CI:
                      -0.0200-0.0280) in the test set.Although significant
                      associations between cardiovascular parameters and survival
                      were found, their small effect sizes should be considered
                      when prioritizing cardiac sparing in stage III NSCLC
                      treatment.},
      keywords     = {Cardiotoxicity (Other) / Non-Small-Cell Lung Carcinoma
                      (Other) / Radiotherapy (Other) / Survival (Other) / Survival
                      Analysis (Other)},
      cin          = {DD01},
      ddc          = {610},
      cid          = {I:(DE-He78)DD01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:39993599},
      doi          = {10.1016/j.radonc.2025.110821},
      url          = {https://inrepo02.dkfz.de/record/299472},
}