% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{Herz:302987,
      author       = {A. Herz and M. Guberina$^*$ and C. Pöttgen$^*$ and T.
                      Gauler and T. T. M. Ton and G. Fischedick and L. O. Kiwitt
                      and W. Lübcke and C. Hoffmann and M. Schuler and M.
                      Metzenmacher and B. M. Schaarschmidt and D. Bos and M. Opitz
                      and H. Hautzel and K. Darwiche and S. Bölükbas and K.
                      Grapatsas and V. Jendrossek and L. Gockeln and F.
                      Wirsdörfer and M. Hetzel and E. Mladenov and M.
                      Stuschke$^*$ and N. Guberina$^*$},
      title        = {{T}he effect of durvalumab consolidation after definitive
                      radiochemotherapy for non-operable stage {III} non-small
                      cell lung cancer on the dose effect relation for therapy
                      related pulmonary infiltrates as a risk factor for
                      pneumonitis.},
      journal      = {Translational Lung Cancer Research},
      volume       = {14},
      number       = {6},
      issn         = {2218-6751},
      address      = {[Erscheinungsort nicht ermittelbar]},
      publisher    = {[Verlag nicht ermittelbar]},
      reportid     = {DKFZ-2025-01434},
      pages        = {2074 - 2088},
      year         = {2025},
      abstract     = {Consolidation therapy with the anti-programmed death-ligand
                      1 (PD-L1) antibody durvalumab, or other immune checkpoint
                      inhibitors, has been associated with improved
                      progression-free and overall survival in patients with stage
                      III non-small cell lung cancer (NSCLC) as demonstrated in
                      randomized clinical trials. The purpose of the present study
                      is to evaluate the dose-response relationship for partial
                      lung infiltrate volumes per dose bin after definitive
                      radiochemotherapy as a sensitive end point to detect a
                      durvalumab effect on the lung parenchyma in patients with
                      subclinical or grade ≤2 pneumonitis.Consecutive patients
                      from a prospective registry with inoperable NSCLC stage III
                      who developed no or pneumonitis grade ≤2 after definitive
                      radiochemotherapy with or without durvalumab consolidation
                      were included. Pulmonary infiltrates outside the planning
                      target volumes were contoured in the follow-up computed
                      tomography (CT) at the time of maximum infiltrate
                      expression. Partial lung infiltrate volumes per dose bin
                      were determined over the entire dose range. A mixed random
                      and fixed effect model was used to fit dose response curves
                      stepwise in dose bins of 5 Gy. The Akaike information
                      criterion (AIC) was used for model comparison.Sixty patients
                      with and 44 without durvalumab consolidation were analysed.
                      The step model showed a significant dose response
                      relationship for the pulmonary infiltrates (P<0.001, F-test)
                      that was modified by the durvalumab effect (P<0.001,
                      F-test). There was a significant dependence of the
                      durvalumab effect on radiation dose (P=0.003). The
                      durvalumab effect increased with dose from $0\%$ in the
                      lowest dose bin as reference to $5.2\%±1.2\%$ partial lung
                      infiltrate volume in the highest dose bin. There was
                      significant inter-individual heterogeneity of partial lung
                      infiltrate volumes at each dose bin (P<0.001, F-test). The
                      percentage of lung volume receiving at least 5 Gy (V5) was
                      the most significant characteristic increasing risk of
                      pulmonary infiltrates (P<0.001, F-test). Multivariable
                      proportional hazards Cox-model showed that pulmonary
                      infiltrates at 5-10 and 35-40 Gy dose bins were dominant
                      factors determining the risk of pneumonitis grade 2.The
                      relationship between radiation dose and lung infiltrates
                      observed by follow-up CT scans after radiochemotherapy is
                      sensitive enough to detect factors that systematically
                      increase the radiation dose response. In this case, the
                      focus is on durvalumab consolidation and radiation dose to
                      the lung. The dose-response relationship may help in the
                      prediction of grade 2 pneumonitis. However, further research
                      is needed to understand the biological factors that
                      contribute to the large differences in response to radiation
                      dose between individuals.},
      keywords     = {Pneumonitis (Other) / durvalumab consolidation (Other) /
                      immunotherapy (Other) / lung cancer (Other) / radiation
                      therapy (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:40673077},
      pmc          = {pmc:PMC12261351},
      doi          = {10.21037/tlcr-2024-1284},
      url          = {https://inrepo02.dkfz.de/record/302987},
}