Cumulative Incidence and Type-Specific Risk Factors of Pneumonitis After Definitive Chemoradiotherapy With or Without Immunotherapy in Locally Advanced Non-Small Cell Lung Cancer

IF 3.9 3区医学 Q2 ONCOLOGY

Clinical lung cancer Pub Date : 2026-03-01 Epub Date: 2025-12-05 DOI:10.1016/j.cllc.2025.11.020

Jiawen Sun , Xin Dong , Zhixue Fu , Sen Han , Yuliang Liu , Anhui Shi , Huiming Yu , Yuting Zhao , Wei Deng , Leilei Jiang , Dan Yang , Xiao Chang , Liuhua Long , Jiayi Yu , Yue Teng , Rong Yu , Weihu Wang

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引用次数: 0

Abstract

Objectives

This study assessed the impact of immune checkpoint inhibitors (ICIs) addition and timing on the incidence of treatment-related pneumonitis (TRP) and explored type-specific risk factors in unresectable locally advanced non-small cell lung cancer (LA-NSCLC) patients receiving definitive chemoradiotherapy (CRT).

Methods

We retrospectively analyzed 449 LA-NSCLC patients receiving definitive CRT±ICIs from January 2019 to December 2021. Patients were grouped by CRT alone (n = 236) or CRT+ICIs (n = 213), with the latter stratified by ICIs timing (induction/concurrent/consolidation) relative to radiotherapy. TRP (including radiation pneumonitis [RP] and checkpoint inhibitor pneumonitis [CIP]) was graded per CTCAE v5.0 through multidisciplinary review. We applied inverse probability of treatment weighting (IPTW) to adjust baseline covariates, Fine-Gray competing-risk model to estimate cumulative incidence and risk factors.

Results

Grade ≥ 2 TRP incidence was significantly increased with CRT+ICIs than CRT (30.6% vs. 9.8%; IPTW-adjusted P < .001), highest with concurrent ICIs (51.5%), followed by induction (32.0%) and consolidation (24.2%). Grade ≥ 2 RP increased to 16.7% with ICIs (IPTW-adjusted P = .004), peaking in the concurrent subgroup (39.1%), while comparable between induction and consolidation (16.1% vs. 12.2%). Independent predictors of grade ≥ 2 RP included ICIs treatment, gemcitabine-based induction chemotherapy, and higher lung dosimetry, with cut-offs of lung V20 (volume receiving ≥ 20 Gy) = 26.8% and mean lung dose (MLD) = 14.05 Gy. Grade ≥ 2 CIP incidence (14.2%) was associated with pre-existing interstitial lung disease or emphysema, PD-1 inhibitors and elevated MLD.

Conclusions

ICIs addition and timing significantly affected TRP risk. Mitigating lung toxicity requires careful selection of ICIs strategy, chemotherapy agents, and optimizing lung radiation dosimetry.

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局部晚期非小细胞肺癌放化疗加或不加免疫治疗后肺炎的累积发病率和类型特异性危险因素

目的本研究评估免疫检查点抑制剂（ICIs）的添加和时间对治疗相关性肺炎（TRP）发病率的影响，并探讨不可切除的局部晚期非小细胞肺癌（LA-NSCLC）患者接受终期放化疗（CRT）的类型特异性危险因素。方法回顾性分析2019年1月至2021年12月接受明确CRT±ICIs的449例LA-NSCLC患者。患者按单独CRT （n = 236）或CRT+ICIs （n = 213）分组，后者按ICIs时间（诱导/同步/巩固）相对于放疗进行分层。TRP（包括放射性肺炎[RP]和检查点抑制剂肺炎[CIP]）通过多学科评价按CTCAE v5.0分级。我们应用治疗加权逆概率（IPTW）来调整基线协变量，使用细灰色竞争风险模型来估计累积发病率和危险因素。结果CRT+ICIs组≥2级TRP发生率明显高于CRT组（30.6% vs. 9.8%； iptw校正P <； 0.001），并发ICIs组发生率最高（51.5%），其次为诱导（32.0%）和巩固（24.2%）。≥2级RP在ICIs组增加到16.7% (iptwr校正P = 0.004)，并发亚组达到峰值（39.1%），而诱导和巩固之间具有可比性（16.1% vs. 12.2%）。≥2级RP的独立预测因子包括ICIs治疗、基于吉西他滨的诱导化疗和更高的肺剂量，肺V20（体积接受≥20 Gy）的临界值= 26.8%，平均肺剂量(MLD) = 14.05 Gy。≥2级CIP发生率（14.2%）与先前存在的间质性肺疾病或肺气肿、PD-1抑制剂和MLD升高相关。结论si的添加量和时间对TRP风险有显著影响。减轻肺毒性需要仔细选择ICIs策略、化疗药物和优化肺辐射剂量测定。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical lung cancer 医学-肿瘤学

CiteScore

7.00

自引率

2.80%

发文量

159

审稿时长

24 days

期刊介绍： Clinical Lung Cancer is a peer-reviewed bimonthly journal that publishes original articles describing various aspects of clinical and translational research of lung cancer. Clinical Lung Cancer is devoted to articles on detection, diagnosis, prevention, and treatment of lung cancer. The main emphasis is on recent scientific developments in all areas related to lung cancer. Specific areas of interest include clinical research and mechanistic approaches; drug sensitivity and resistance; gene and antisense therapy; pathology, markers, and prognostic indicators; chemoprevention strategies; multimodality therapy; and integration of various approaches.