{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T12:31:35Z","timestamp":1789561895915,"version":"build-2803163510"},"reference-count":27,"publisher":"Wiley","issue":"18","license":[{"start":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T00:00:00Z","timestamp":1758067200000},"content-version":"vor","delay-in-days":16,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004391","name":"China Medical University Hospital","doi-asserted-by":"publisher","award":["DMR\u2010114\u2010171"],"award-info":[{"award-number":["DMR\u2010114\u2010171"]}],"id":[{"id":"10.13039\/501100004391","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Thoracic Cancer"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Immune checkpoint inhibitors (ICIs) improve outcomes in non\u2010small cell lung cancer (NSCLC) with high PD\u2010L1 expression, but biomarkers beyond PD\u2010L1 are limited. Smoking\u2010related immune activation may enhance ICI efficacy, yet evidence in non\u2010squamous NSCLC, especially among non\u2010smokers, is sparse.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We retrospectively analyzed 74 patients with Stage <jats:styled-content style=\"fixed-case\">IIIB<\/jats:styled-content>\u2013<jats:styled-content style=\"fixed-case\">IV<\/jats:styled-content> non\u2010squamous <jats:styled-content style=\"fixed-case\">NSCLC<\/jats:styled-content>, <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">L1<\/jats:styled-content> \u2265\u200950%, and no <jats:italic><jats:styled-content style=\"fixed-case\">EGFR<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">ALK<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">ROS1<\/jats:styled-content><\/jats:italic> mutations, treated at a tertiary center in Taiwan (2017\u20132023). Patients were stratified by smoking status. Treatment responses, progression\u2010free survival (<jats:styled-content style=\"fixed-case\">PFS<\/jats:styled-content>), and overall survival (<jats:styled-content style=\"fixed-case\">OS<\/jats:styled-content>) were evaluated using <jats:styled-content style=\"fixed-case\">RECIST<\/jats:styled-content> v1.1, Kaplan\u2013Meier, and Cox regression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among 74 patients, 54 (72.9%) were smokers and 20 (27.1%) were non\u2010smokers. Compared with non\u2010smokers, smokers had a higher partial response rate (66.7% vs. 25.0%, <jats:italic>p<\/jats:italic>\u2009=\u20090.001), longer median PFS (12.8 vs. 1.4\u2009months, <jats:italic>p<\/jats:italic>\u2009=\u20090.001), and improved OS (47.1 vs. 10.0\u2009months, <jats:italic>p<\/jats:italic>\u2009=\u20090.011). In the non\u2010smoker subgroup, chemoimmunotherapy significantly prolonged PFS compared with ICI monotherapy (not reached vs. 1.4\u2009months, <jats:italic>p<\/jats:italic>\u2009=\u20090.034). In multivariate analysis, smoking independently predicted better PFS (HR\u2009=\u20090.234, <jats:italic>p<\/jats:italic>\u2009=\u20090.001) and OS (HR\u2009=\u20090.229, <jats:italic>p<\/jats:italic>\u2009=\u20090.011).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Non\u2010smokers with PD\u2010L1\u2010high non\u2010squamous NSCLC showed significantly poorer outcomes with ICI monotherapy. Chemoimmunotherapy may be preferred in this group. Smoking history may provide a simple and clinically relevant stratification factor when considering ICI\u2010based treatment.<\/jats:p><\/jats:sec>","DOI":"10.1111\/1759-7714.70167","type":"journal-article","created":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T05:18:54Z","timestamp":1758172734000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Real\u2010World Evidence That Non\u2010Smokers With High <scp>PD<\/scp>\u2010<scp>L1<\/scp> Non\u2010Squamous <scp>NSCLC<\/scp> Have Poorer Outcomes With Immune Checkpoint Inhibitors"],"prefix":"10.1111","volume":"16","author":[{"given":"Yu\u2010Chu","family":"Kuo","sequence":"first","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine  Taichung Taiwan"},{"name":"China Medical University Hospital  Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen\u2010Chien","family":"Cheng","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine  Taichung Taiwan"},{"name":"China Medical University Hospital  Taichung Taiwan"},{"name":"School of Medicine, College of Medicine China Medical University  Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsu\u2010Yuan","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine  Taichung Taiwan"},{"name":"China Medical University Hospital  Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun\u2010Ru","family":"Chien","sequence":"additional","affiliation":[{"name":"China Medical University Hospital  Taichung Taiwan"},{"name":"School of Medicine, College of Medicine China Medical University  Taichung Taiwan"},{"name":"Department of Radiation Oncology China Medical University Hospital  Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih\u2010Yen","family":"Tu","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine  Taichung Taiwan"},{"name":"China Medical University Hospital  Taichung Taiwan"},{"name":"School of Medicine, College of Medicine China Medical University  Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6000-9021","authenticated-orcid":false,"given":"Hung\u2010Jen","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine  Taichung Taiwan"},{"name":"China Medical University Hospital  Taichung Taiwan"},{"name":"School of Medicine, College of Medicine China Medical University  Taichung 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