Impact of irae characteristics on efficacy of consolidative immunotherapy following chemoradiotherapy in locally advanced NSCLC

Abstract Background Consolidative PD-L1 inhibitors after concurrent chemoradiotherapy (cCRT) have become standard care in locally advanced non-small cell lung cancer (LA-NSCLC). However, the correlation between immune-related adverse event (irAE) characteristics and patient outcomes remains unclear....

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Main Authors: Xiufen Wang, Xuebing Fu, Qiaohong Liu, Juan Li, Yihui Ge, Jian Zhang, Shuyun Wang, Leirong Wang, Dahai Wang, Yanxin Sun, Yiling Gan, Haodong Sun, Zhen Wang, Yuping Sun, Aiqin Gao
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Language:English
Published: BMC 2025-06-01
Series:BMC Pulmonary Medicine
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Online Access:https://doi.org/10.1186/s12890-025-03742-6
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author Xiufen Wang
Xuebing Fu
Qiaohong Liu
Juan Li
Yihui Ge
Jian Zhang
Shuyun Wang
Leirong Wang
Dahai Wang
Yanxin Sun
Yiling Gan
Haodong Sun
Zhen Wang
Yuping Sun
Aiqin Gao
author_facet Xiufen Wang
Xuebing Fu
Qiaohong Liu
Juan Li
Yihui Ge
Jian Zhang
Shuyun Wang
Leirong Wang
Dahai Wang
Yanxin Sun
Yiling Gan
Haodong Sun
Zhen Wang
Yuping Sun
Aiqin Gao
author_sort Xiufen Wang
collection DOAJ
description Abstract Background Consolidative PD-L1 inhibitors after concurrent chemoradiotherapy (cCRT) have become standard care in locally advanced non-small cell lung cancer (LA-NSCLC). However, the correlation between immune-related adverse event (irAE) characteristics and patient outcomes remains unclear. Methods This retrospective study enrolled LA-NSCLC patients who received consolidative PD-L1 inhibitors after CRT at four cancer centers. Patients who received CRT alone were also included for comparison. Associations between irAE characteristics, frequency, timing, affected systems, and severity, and progression-free survival (PFS) and overall survival (OS) were assessed. Tumor immune microenvironment (TIME) features were analyzed to identify subpopulations at higher risk of severe irAEs. Results Among 107 patients, 59 (55.1%) developed irAEs; 89.8% were grade 1–2 and 10.2% grade 3–4. Patients with irAEs had significantly longer PFS than those without. Late-onset, single-system, endocrine, and mild irAEs predicted better PFS. In contrast, patients with severe irAEs had worse survival than those without ICI consolidation. TIME analysis revealed that severe irAEs were associated with higher CD103+CD8+ T cells infiltration. A > 1.545% cutoff for CD103+CD8+ T cells may help identify patients less likely to benefit from PD-L1 inhibitor consolidation. Conclusions Occurrence of irAEs, particularly late-onset, single-system, or grade 1–2 correlated with greater benefit from consolidative PD-L1 inhibitors in LA-NSCLC. Conversely, severe irAEs predict poorer survival, even compared to no ICI consolidation. Elevated CD103+CD8+ T cell infiltration may serve as a biomarker to identify patients at risk of severe irAEs who may not benefit from immunoconsolidation therapy.
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spelling doaj-art-abed72bfaa18493c94a7241ec74f9a322025-08-20T03:25:15ZengBMCBMC Pulmonary Medicine1471-24662025-06-0125111210.1186/s12890-025-03742-6Impact of irae characteristics on efficacy of consolidative immunotherapy following chemoradiotherapy in locally advanced NSCLCXiufen Wang0Xuebing Fu1Qiaohong Liu2Juan Li3Yihui Ge4Jian Zhang5Shuyun Wang6Leirong Wang7Dahai Wang8Yanxin Sun9Yiling Gan10Haodong Sun11Zhen Wang12Yuping Sun13Aiqin Gao14Phase I Clinical Trail Center, Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical SciencesDepartment of Thoracic Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical SciencesDepartment of Ultrasound, Central Hospital Affiliated to Shandong First Medical UniversityPhase I Clinical Trail Center, Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical SciencesDepartment of Thoracic Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical SciencesPhase I Clinical Trail Center, Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical SciencesDepartment of Thoracic Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical SciencesPhase I Clinical Trail Center, Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical SciencesPhase I Clinical Trail Center, Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical SciencesPhase I Clinical Trail Center, Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical SciencesPhase I Clinical Trail Center, Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical SciencesDepartment of Thoracic Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical SciencesSpecial Inspection Department, Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical SciencesPhase I Clinical Trail Center, Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical SciencesDepartment of Thoracic Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical SciencesAbstract Background Consolidative PD-L1 inhibitors after concurrent chemoradiotherapy (cCRT) have become standard care in locally advanced non-small cell lung cancer (LA-NSCLC). However, the correlation between immune-related adverse event (irAE) characteristics and patient outcomes remains unclear. Methods This retrospective study enrolled LA-NSCLC patients who received consolidative PD-L1 inhibitors after CRT at four cancer centers. Patients who received CRT alone were also included for comparison. Associations between irAE characteristics, frequency, timing, affected systems, and severity, and progression-free survival (PFS) and overall survival (OS) were assessed. Tumor immune microenvironment (TIME) features were analyzed to identify subpopulations at higher risk of severe irAEs. Results Among 107 patients, 59 (55.1%) developed irAEs; 89.8% were grade 1–2 and 10.2% grade 3–4. Patients with irAEs had significantly longer PFS than those without. Late-onset, single-system, endocrine, and mild irAEs predicted better PFS. In contrast, patients with severe irAEs had worse survival than those without ICI consolidation. TIME analysis revealed that severe irAEs were associated with higher CD103+CD8+ T cells infiltration. A > 1.545% cutoff for CD103+CD8+ T cells may help identify patients less likely to benefit from PD-L1 inhibitor consolidation. Conclusions Occurrence of irAEs, particularly late-onset, single-system, or grade 1–2 correlated with greater benefit from consolidative PD-L1 inhibitors in LA-NSCLC. Conversely, severe irAEs predict poorer survival, even compared to no ICI consolidation. Elevated CD103+CD8+ T cell infiltration may serve as a biomarker to identify patients at risk of severe irAEs who may not benefit from immunoconsolidation therapy.https://doi.org/10.1186/s12890-025-03742-6Immune-related adverse eventsLocally advanced non-small cell lung cancerSurvivalConsolidative immunotherapyTumor immune microenvironment
spellingShingle Xiufen Wang
Xuebing Fu
Qiaohong Liu
Juan Li
Yihui Ge
Jian Zhang
Shuyun Wang
Leirong Wang
Dahai Wang
Yanxin Sun
Yiling Gan
Haodong Sun
Zhen Wang
Yuping Sun
Aiqin Gao
Impact of irae characteristics on efficacy of consolidative immunotherapy following chemoradiotherapy in locally advanced NSCLC
BMC Pulmonary Medicine
Immune-related adverse events
Locally advanced non-small cell lung cancer
Survival
Consolidative immunotherapy
Tumor immune microenvironment
title Impact of irae characteristics on efficacy of consolidative immunotherapy following chemoradiotherapy in locally advanced NSCLC
title_full Impact of irae characteristics on efficacy of consolidative immunotherapy following chemoradiotherapy in locally advanced NSCLC
title_fullStr Impact of irae characteristics on efficacy of consolidative immunotherapy following chemoradiotherapy in locally advanced NSCLC
title_full_unstemmed Impact of irae characteristics on efficacy of consolidative immunotherapy following chemoradiotherapy in locally advanced NSCLC
title_short Impact of irae characteristics on efficacy of consolidative immunotherapy following chemoradiotherapy in locally advanced NSCLC
title_sort impact of irae characteristics on efficacy of consolidative immunotherapy following chemoradiotherapy in locally advanced nsclc
topic Immune-related adverse events
Locally advanced non-small cell lung cancer
Survival
Consolidative immunotherapy
Tumor immune microenvironment
url https://doi.org/10.1186/s12890-025-03742-6
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