ORIGINAL RESEARCH article
Front. Oncol.
Sec. Cancer Molecular Targets and Therapeutics
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1590825
This article is part of the Research TopicRenewed Insight into Cancer Mechanism and TherapyView all 35 articles
Prognostic Stratification Through Smoking Status and Cumulative Smoking Dose in Advanced Non-Small Cell Lung Cancer Immunotherapy: A Dose-Dependent Real-World Analysis
Provisionally accepted
- West China Hospital, Sichuan University, Chengdu, China
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Background: 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. Methods: A total of 1,192 immunotherapytreated NSCLC patients treated between November 2015 and April 2024 were enrolled. Data of demographic, 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 packyears). Multivariate logistic regression and Cox proportional hazards models were used to analyze ORR and PFS, respectively. Results: 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, P < 0.001), the highest ORR (46.8%, P < 0.001), and DCR (86.7%, P = 0.008). Regarding cumulative smoking dose, the heavy smoker group demonstrated the longest median PFS (15.9 months, P = 0.001), with the highest ORR (46.6%, P < 0.001) and DCR (85.2%, P = 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, P = 0.003) and PFS (HR = 0.75, 95% CI = 0.57-0.99, P = 0.04) in advanced NSCLC patients receiving immunotherapy. Conclusions: 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.
Keywords: Non-small cell lung cancer, immune checkpoint inhibitors, Smoking hygiene, Cumulative smoking dose, Real-world evidence
Received: 10 Mar 2025; Accepted: 15 Jul 2025.
Copyright: © 2025 Yang, Wang, Tian and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Panwen Tian, West China Hospital, Sichuan University, Chengdu, China
Weimin Li, West China Hospital, Sichuan University, Chengdu, China
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