Yang Lan, Wang Haoyu, Tian Panwen, Li Weimin
Department of Pulmonary and Critical Care Medicine State Key Laboratory of Respiratory Health and Multimorbidity West China Hospital of Sichuan University, Precision Medicine Key Laboratory of Sichuan Province, Chengdu, Sichuan, China.
Institute of Respiratory Health, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Front Oncol. 2025 Aug 6;15:1590825. doi: 10.3389/fonc.2025.1590825. eCollection 2025.
The association between smoking status, cumulative smoking dose, and immunotherapy efficacy in non-small cell lung cancer (NSCLC) remains controversial. We sought to integrate the lifetime pack-years with smoking cessation status to identify optimal immunotherapy beneficiaries.
A total of 1,192 immunotherapy-treated NSCLC patients treated between November 2015 and April 2024 were enrolled. Data on demographics, clinical characteristics, pathologic characteristics, treatments, and clinical outcomes were collected. The objective response rate (ORR), disease control rate (DCR), and progression-free survival (PFS) were compared across different smoking statuses (never, current, and former smokers) and cumulative smoking doses (never smokers, non-heavy smokers: <20 pack-years, and heavy smokers: ≥20 pack-years). Multivariate logistic regression and Cox proportional hazards models were used to analyze ORR and PFS, respectively.
Among the 1,192 patients, 377 were never smokers, 499 were current smokers, and 316 were former smokers. In terms of smoking status, former smokers exhibited the longest median PFS (17.0 months, < 0.001), with the highest ORR (46.8%, < 0.001) and DCR (86.7%, = 0.008). Regarding cumulative smoking dose, the heavy smoker group demonstrated the longest median PFS (15.9 months, = 0.001), with the highest ORR (46.6%, < 0.001) and DCR (85.2%, = 0.012). Notably, further multivariate analysis identified former heavy smokers as independent favorable predictors of ORR (OR = 1.93, 95% CI = 1.25-2.99, = 0.003) and PFS (HR = 0.75, 95% CI = 0.57-0.99, = 0.04) in advanced NSCLC patients receiving immunotherapy.
This real-world cohort analysis establishes a clinical stratification combining smoking cessation status with cumulative smoking dose, identifying former heavy smokers as optimal immunotherapy beneficiaries. These findings advocate integrated smoking history documentation and emphasize clinical prioritization of cessation interventions to enhance treatment efficacy in NSCLC.
吸烟状态、累积吸烟量与非小细胞肺癌（NSCLC）免疫治疗疗效之间的关联仍存在争议。我们试图将终生吸烟包年数与戒烟状态相结合，以确定最佳免疫治疗受益者。
共纳入2015年11月至2024年4月期间接受免疫治疗的1192例NSCLC患者。收集了人口统计学、临床特征、病理特征、治疗情况及临床结局的数据。比较了不同吸烟状态（从不吸烟、当前吸烟和既往吸烟）和累积吸烟量（从不吸烟者、非重度吸烟者：<20包年，以及重度吸烟者：≥20包年）下的客观缓解率（ORR）、疾病控制率（DCR）和无进展生存期（PFS）。分别使用多因素逻辑回归和Cox比例风险模型分析ORR和PFS。
在1192例患者中，377例从不吸烟，499例当前吸烟，316例既往吸烟。就吸烟状态而言，既往吸烟者的中位PFS最长（17.0个月，<0.001），ORR最高（46.8%，<0.001），DCR最高（86.7%，=0.008）。关于累积吸烟量，重度吸烟者组的中位PFS最长（15.9个月，=0.001），ORR最高（46.6%，<0.001），DCR最高（85.2%，=0.012）。值得注意的是，进一步的多因素分析确定既往重度吸烟者是接受免疫治疗的晚期NSCLC患者ORR（OR = 1.93，95%CI = 1.25 - 2.99，= 0.003）和PFS（HR = 0.75，95%CI = 0.57 - 0.99，= 0.04）的独立有利预测因素。
这项真实世界队列分析建立了一种将戒烟状态与累积吸烟量相结合的临床分层方法，确定既往重度吸烟者为最佳免疫治疗受益者。这些发现提倡完整记录吸烟史，并强调戒烟干预措施在临床上的优先地位，以提高NSCLC的治疗效果。
