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@ARTICLE{Taugner:305607,
      author       = {J. Taugner and S. Stamer and K. Hofstetter and C. Eze$^*$
                      and L. Käsmann$^*$ and K. Clasen and P. Hartig and W.
                      Spengler and T. Groß and F. Manapov and C. Belka$^*$ and M.
                      Niyazi$^*$},
      title        = {{I}mmune checkpoint inhibition alters patterns of failure
                      in inoperable stage {III} non-small cell lung cancer
                      patients treated with chemoradiotherapy.},
      journal      = {Journal of cancer research and clinical oncology},
      volume       = {151},
      number       = {12},
      issn         = {0301-1585},
      address      = {Heidelberg},
      publisher    = {Springer},
      reportid     = {DKFZ-2025-02257},
      pages        = {313},
      year         = {2025},
      abstract     = {We compared failure patterns in patients with inoperable
                      stage III non-small cell lung cancer (NSCLC) treated with
                      chemoradiotherapy (CRT) alone versus CRT combined with
                      sequential and/or concurrent immune checkpoint inhibitors
                      (CRT-IO).Retrospective real-world data from 221 patients
                      across two German tertiary cancer centers were analyzed. Of
                      these, 74 received CRT-IO, including sequential durvalumab
                      $(85\%)$ and concurrent/sequential nivolumab $(15\%),$ while
                      148 received CRT alone. First failure site and time to
                      failure were compared.Between 2012 and 2022, all patients
                      received thoracic radiotherapy (≥ 60 Gy) and at least two
                      cycles of platinum-based chemotherapy. Induction
                      chemotherapy was administered in $36\%,$ and induction
                      chemo-immunotherapy in $2\%.$ Median follow-up was 51.7
                      months $(95\%$ CI 47.0-56.4). Median overall survival (OS)
                      for the entire cohort was 37.1 months $(95\%$ CI 26.0-48.2),
                      with OS in the CRT-IO group not reached vs. 27.1 months
                      $(95\%$ CI 18.5-25.7) in the CRT group (p < 0.001). Median
                      progression-free survival (PFS) was 22.8 months $(95\%$ CI
                      6.4-39.1) for CRT-IO versus. 9.9 months $(95\%$ CI 7.0-12.8)
                      for CRT (p = 0.001, see Fig. 1). Failure patterns differed
                      significantly. CRT-IO patients had lower loco-regional
                      progression (LRP) rates $(9.5\%$ vs. $21.8\%,$ p = 0.023)
                      and were more frequently alive without progression $(45.9\%$
                      vs. $16.3\%,$ p < 0.001). Brain metastasis (BM) as the first
                      failure, multifocal progression (MFP) and isolated
                      extracranial distant metastasis (ecDM) rates were comparable
                      between the CRT and CRT-IO subgroup. Women had a higher risk
                      of isolated BM $(17.3\%$ vs. $6.8\%,$ p = 0.016), whereas
                      squamous cell carcinoma (SCC) patients had higher LRP rates
                      $(25.3\%$ vs. $13.0\%,$ p = 0.016). Median post-progression
                      survival (PPS) was 19.4 months $(95\%$ CI 16.8-22.0) for
                      CRT-IO and 9.5 months $(95\%$ CI 5.8-13.1) for CRT (p =
                      0.207). PPS was longer after BM (19.9 months) vs. LRP (8.5
                      months, p = 0.076) and significantly better in women (20.7
                      vs. 8.9 months, p = 0.012) and
                      adenocarcinoma/non-otherwise-specified-carcinoma (AC/NOS)
                      vs. SCC (p < 0.001).CRT-IO significantly improves OS, PFS,
                      and LRP control compared to CRT alone. Failure patterns and
                      survival disparities by histology and gender suggest
                      tailored surveillance and treatment strategies are needed.
                      Further studies should optimize management of LRP and
                      long-term outcomes in CRT-IO-treated patients.},
      keywords     = {Humans / Carcinoma, Non-Small-Cell Lung: therapy /
                      Carcinoma, Non-Small-Cell Lung: pathology / Carcinoma,
                      Non-Small-Cell Lung: drug therapy / Carcinoma,
                      Non-Small-Cell Lung: mortality / Carcinoma, Non-Small-Cell
                      Lung: immunology / Female / Male / Immune Checkpoint
                      Inhibitors: therapeutic use / Immune Checkpoint Inhibitors:
                      administration $\&$ dosage / Lung Neoplasms: pathology /
                      Lung Neoplasms: therapy / Lung Neoplasms: drug therapy /
                      Lung Neoplasms: mortality / Lung Neoplasms: immunology /
                      Aged / Middle Aged / Retrospective Studies /
                      Chemoradiotherapy: methods / Neoplasm Staging / Adult /
                      Aged, 80 and over / Treatment Failure / Nivolumab:
                      administration $\&$ dosage / Antineoplastic Combined
                      Chemotherapy Protocols: therapeutic use / Antibodies,
                      Monoclonal / Chemoradiotherapy (Other) / Immunotherapy
                      (Other) / Lung cancer (Other) / NSCLC (Other) /
                      Patterns-of-failure (Other) / Immune Checkpoint Inhibitors
                      (NLM Chemicals) / Nivolumab (NLM Chemicals) / durvalumab
                      (NLM Chemicals) / Antibodies, Monoclonal (NLM Chemicals)},
      cin          = {MU01},
      ddc          = {610},
      cid          = {I:(DE-He78)MU01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:41175229},
      doi          = {10.1007/s00432-025-06355-y},
      url          = {https://inrepo02.dkfz.de/record/305607},
}