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000305607 1001_ $$00000-0003-1473-1202$$aTaugner, Julian$$b0
000305607 245__ $$aImmune checkpoint inhibition alters patterns of failure in inoperable stage III non-small cell lung cancer patients treated with chemoradiotherapy.
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000305607 520__ $$aWe 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.
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000305607 650_7 $$2Other$$aChemoradiotherapy
000305607 650_7 $$2Other$$aImmunotherapy
000305607 650_7 $$2Other$$aLung cancer
000305607 650_7 $$2Other$$aNSCLC
000305607 650_7 $$2Other$$aPatterns-of-failure
000305607 650_7 $$2NLM Chemicals$$aImmune Checkpoint Inhibitors
000305607 650_7 $$031YO63LBSN$$2NLM Chemicals$$aNivolumab
000305607 650_7 $$028X28X9OKV$$2NLM Chemicals$$adurvalumab
000305607 650_7 $$2NLM Chemicals$$aAntibodies, Monoclonal
000305607 650_2 $$2MeSH$$aHumans
000305607 650_2 $$2MeSH$$aCarcinoma, Non-Small-Cell Lung: therapy
000305607 650_2 $$2MeSH$$aCarcinoma, Non-Small-Cell Lung: pathology
000305607 650_2 $$2MeSH$$aCarcinoma, Non-Small-Cell Lung: drug therapy
000305607 650_2 $$2MeSH$$aCarcinoma, Non-Small-Cell Lung: mortality
000305607 650_2 $$2MeSH$$aCarcinoma, Non-Small-Cell Lung: immunology
000305607 650_2 $$2MeSH$$aFemale
000305607 650_2 $$2MeSH$$aMale
000305607 650_2 $$2MeSH$$aImmune Checkpoint Inhibitors: therapeutic use
000305607 650_2 $$2MeSH$$aImmune Checkpoint Inhibitors: administration & dosage
000305607 650_2 $$2MeSH$$aLung Neoplasms: pathology
000305607 650_2 $$2MeSH$$aLung Neoplasms: therapy
000305607 650_2 $$2MeSH$$aLung Neoplasms: drug therapy
000305607 650_2 $$2MeSH$$aLung Neoplasms: mortality
000305607 650_2 $$2MeSH$$aLung Neoplasms: immunology
000305607 650_2 $$2MeSH$$aAged
000305607 650_2 $$2MeSH$$aMiddle Aged
000305607 650_2 $$2MeSH$$aRetrospective Studies
000305607 650_2 $$2MeSH$$aChemoradiotherapy: methods
000305607 650_2 $$2MeSH$$aNeoplasm Staging
000305607 650_2 $$2MeSH$$aAdult
000305607 650_2 $$2MeSH$$aAged, 80 and over
000305607 650_2 $$2MeSH$$aTreatment Failure
000305607 650_2 $$2MeSH$$aNivolumab: administration & dosage
000305607 650_2 $$2MeSH$$aAntineoplastic Combined Chemotherapy Protocols: therapeutic use
000305607 650_2 $$2MeSH$$aAntibodies, Monoclonal
000305607 7001_ $$aStamer, Silja$$b1
000305607 7001_ $$aHofstetter, Kerstin$$b2
000305607 7001_ $$0P:(DE-HGF)0$$aEze, Chukwuka$$b3
000305607 7001_ $$0P:(DE-HGF)0$$aKäsmann, Lukas$$b4
000305607 7001_ $$aClasen, Kerstin$$b5
000305607 7001_ $$aHartig, Philipp$$b6
000305607 7001_ $$aSpengler, Werner$$b7
000305607 7001_ $$aGroß, Thorben$$b8
000305607 7001_ $$aManapov, Farkhad$$b9
000305607 7001_ $$0P:(DE-HGF)0$$aBelka, Claus$$b10
000305607 7001_ $$0P:(DE-HGF)0$$aNiyazi, Maximilian$$b11
000305607 773__ $$0PERI:(DE-600)1459285-X$$a10.1007/s00432-025-06355-y$$gVol. 151, no. 12, p. 313$$n12$$p313$$tJournal of cancer research and clinical oncology$$v151$$x0301-1585$$y2025
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