Wang Xueqi, Yang Jingyi, E Jiahui, Liu Fan, Wang Qiliang, Zhang Yuwei, Wang Jing, Liu Ying
Department of Radiology, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer; Key Laboratory of Cancer Immunology and Biotherapy, Tianjin, China.
Department of Lung Cancer Surgery, Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, 300052, China.
BMC Cancer. 2025 Jul 19;25(1):1192. doi: 10.1186/s12885-025-14628-5.
Immune checkpoint inhibitors (ICIs) have demonstrated substantial therapeutic efficacy in the treatment of non-small cell lung cancer (NSCLC); however, their clinical application is associated with unique immune-related adverse effects (irAEs). Among these adverse events, immune checkpoint inhibitor-related pneumonitis (CIP) is rare yet serious, which may potentially result in severe respiratory failure, thereby requiring close clinical monitoring. Research specifically focusing on CIP in NSCLC patients treated with PD-1 inhibitors remain limited. This study targets this distinct cohort to comprehensively investigate the clinical and radiological determinants associated with overall survival, applying time-dependent covariate Cox regression to capture the dynamic impact of prognostic factors over time.
A total of 102 NSCLC participants who received immunotherapy with programmed cell death protein-1 (PD-1) inhibitors and then developed CIP were retrospectively enrolled in this study. Univariate and multivariate time-dependent covariate Cox regression models were constructed to determine associations between CIP features and survival benefits of CIP patients.
The incidence of CIP was 15% (102/680) with a median onset time of 4.6 months. Fifty-one patients (50.0%) were identified as having organizing pneumonia (OP) pattern, followed by nonspecific interstitial pneumonia (NSIP) pattern in 28 patients (27.4%), hypersensitivity pneumonitis (HP) pattern in 6 patients (5.9%), and diffuse alveolar damage (DAD) pattern in 2 patients (2.0%). Additionally, 15 patients (14.7%) were classified as unclassifiable pattern. Kaplan-Meier analysis and Log-rank test indicated that CIP located around the tumor and with reticular opacity were associated with poorer prognosis (P = 0.023, P = 0.013). Compared to those with CIP grades 2-4, patients with CIP grade 1 demonstrated survival benefit with border-line significance (P = 0.049). Multivariate time-dependent covariate Cox regression analysis showed that CIP improvement or not (χ = 6.81, P = 0.009), percentage of neutrophils (χ = 24.13, P < 0.001) and albumin (χ = 31.48, P < 0.001) at the time of CIP diagnosis were independent influencing factors for overall survival (OS) in NSCLC patients with CIP.
CIP without improvement or resolution, a high percentage of neutrophils and elevated albumin level of peripheral blood examination were independent predictors for the prognosis of NSCLC patients, which may have an implication for treatment.
免疫检查点抑制剂(ICI)在非小细胞肺癌(NSCLC)治疗中已显示出显著的治疗效果;然而,其临床应用与独特的免疫相关不良反应(irAE)相关。在这些不良事件中,免疫检查点抑制剂相关肺炎(CIP)虽罕见但严重,可能导致严重呼吸衰竭,因此需要密切临床监测。专门针对接受PD-1抑制剂治疗的NSCLC患者中CIP的研究仍然有限。本研究针对这一独特队列,应用时间依赖性协变量Cox回归来捕捉预后因素随时间的动态影响,全面调查与总生存相关的临床和影像学决定因素。
本研究回顾性纳入了102例接受程序性细胞死亡蛋白1(PD-1)抑制剂免疫治疗后发生CIP的NSCLC参与者。构建单变量和多变量时间依赖性协变量Cox回归模型,以确定CIP特征与CIP患者生存获益之间的关联。
CIP的发生率为15%(102/680),中位发病时间为4.6个月。51例患者(50.0%)被确定为具有机化性肺炎(OP)模式,其次是28例(27.4%)的非特异性间质性肺炎(NSIP)模式、6例(5.9%)的过敏性肺炎(HP)模式和2例(2.0%)的弥漫性肺泡损伤(DAD)模式。此外,15例患者(14.7%)被归类为不可分类模式。Kaplan-Meier分析和Log-rank检验表明,肿瘤周围的CIP和伴有网状模糊影与较差的预后相关(P = 0.023,P = 0.013)。与CIP 2-4级患者相比,CIP 1级患者显示出具有临界意义的生存获益(P = 0.049)。多变量时间依赖性协变量Cox回归分析表明,CIP是否改善(χ = 6.81,P = 0.009)、CIP诊断时的中性粒细胞百分比(χ = 24.13,P < 0.001)和白蛋白(χ = 31.48,P < 0.001)是CIP的NSCLC患者总生存(OS)的独立影响因素。
未改善或未消退的CIP、外周血检查中高百分比的中性粒细胞和升高的白蛋白水平是NSCLC患者预后的独立预测因素,这可能对治疗具有启示意义。