The 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
Background: 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 rando...
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| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
June 26, 2025
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| In: |
Translational Lung Cancer Research
Year: 2025, Volume: 14, Issue: 6, Pages: 2074-2088 |
| ISSN: | 2226-4477 |
| DOI: | 10.21037/tlcr-2024-1284 |
| Online Access: | Verlag, kostenfrei, Volltext: https://doi.org/10.21037/tlcr-2024-1284 Verlag, kostenfrei, Volltext: https://tlcr.amegroups.org/article/view/102014 
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| Author Notes: | Andreas Herz, Maja Guberina, Christoph Pöttgen, Thomas Gauler, That Truong Mike Ton, Gerrit Fischedick, Lars Oliver Kiwitt, Wolfgang Lübcke, Christian Hoffmann, Martin Schuler, Martin Metzenmacher, Benedikt M. Schaarschmidt, Denise Bos, Marcel Opitz, Hubertus Hautzel, Kaid Darwiche, Servet Bölükbas, Konstantinos Grapatsas, Verena Jendrossek, Lena Gockeln, Florian Wirsdörfer, Mario Hetzel, Emil Mladenov, Martin Stuschke, Nika Guberina |
| Summary: | Background: 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 pneumonitisMethods: Consecutive patients from a prospective registry with inoperable NSCLC stage III whodeveloped no or pneumonitis grade ≤2 after definitive radiochemotherapy with or without durvalumab consolidation were included. Pulmonary infiltrates outside the planning target volumes were contouredin the follow-up computed tomography (CT) at the time of maximum infiltrate expression. Partial lunginfiltrate 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.Results: Sixty patients with and 44 without durvalumab consolidation were analysed. The step modelshowed 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 dosebin 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). |
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| Item Description: | Gesehen am 08.12.2025 |
| Physical Description: | Online Resource |
| ISSN: | 2226-4477 |
| DOI: | 10.21037/tlcr-2024-1284 |