{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T11:35:48Z","timestamp":1784892948749,"version":"3.55.0"},"reference-count":36,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,3,18]],"date-time":"2025-03-18T00:00:00Z","timestamp":1742256000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82272665"],"award-info":[{"award-number":["82272665"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>The association between the spatial heterogeneity of programmed cell death ligand 1 (PD\u2010L1) expression and the efficacy of third\u2010generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR\u2010TKIs) in EGFR\u2010mutant non\u2010small cell lung cancer (NSCLC) remains elusive. This retrospective study analyzed data from 4171 NSCLC patients with EGFR\u2010sensitive mutations treated at Shanghai Chest Hospital from August 2019 to September 2023. Among them, 182 patients receiving third\u2010generation EGFR\u2010TKIs monotherapy as a first\u2010line treatment were enrolled. Patients were categorized by biopsy sites into primary lung lesions (<jats:italic>n<\/jats:italic>\u2009=\u2009112) and metastatic lymph nodes (<jats:italic>n<\/jats:italic>\u2009=\u200970). PD\u2010L1 expression was stratified based on tumor cell proportion score (TPS): &lt;\u20091%, 1%\u201349%, and \u2265\u200950%. The median progression\u2010free survival (PFS) for the entire cohort was 18.33\u2009months. In the PD\u2010L1 TPS group, PFS was 18.87\u2009months for TPS &lt;\u20091%, 17.6\u2009months for TPS 1%\u201349%, and 13.6\u2009months for TPS \u2265\u200950%, with significant differences across groups (<jats:italic>p<\/jats:italic>\u2009=\u20090.026). Moreover, multivariate analysis identified smoking history [HR\u2009=\u20091.653, 95% CI (1.132\u20132.414), <jats:italic>p<\/jats:italic>\u2009=\u20090.009] and TPS \u2265\u200950% [HR\u2009=\u20092.069, 95% CI (1.183\u20133.618), <jats:italic>p<\/jats:italic>\u2009=\u20090.011] as independent risk factors. In primary lesions, the median PFS was 21.93\u2009months for TPS &lt;\u20091%, 18.57\u2009months for TPS 1%\u201349%, and 10.17\u2009months for TPS \u2265\u200950%, with significant differences (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). However, PD\u2010L1 expression in metastatic lymph nodes was not associated with PFS (<jats:italic>p<\/jats:italic>\u2009=\u20090.973). In advanced EGFR\u2010mutant NSCLC, high PD\u2010L1 expression may suggest reduced efficacy of third\u2010generation EGFR\u2010TKIs. The spatial heterogeneity of PD\u2010L1 expression could influence its predictive accuracy for third\u2010generation EGFR\u2010TKI efficacy.<\/jats:p>","DOI":"10.1111\/cas.70060","type":"journal-article","created":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T04:07:51Z","timestamp":1742357271000},"page":"1648-1660","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Spatial Heterogeneity of <scp>PD<\/scp>\u2010<scp>L1<\/scp> Expression as a Biomarker for Third\u2010Generation <scp>EGFR<\/scp>\u2010<scp>TKI<\/scp> Response in Advanced <scp>EGFR<\/scp>\u2010Mutant <scp>NSCLC<\/scp>"],"prefix":"10.1111","volume":"116","author":[{"given":"Yidan","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, Shanghai Chest Hospital Shanghai Jiao Tong University School of Medicine  Shanghai 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