{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T07:47:09Z","timestamp":1781596029752,"version":"3.54.5"},"reference-count":29,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T00:00:00Z","timestamp":1770595200000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Thoracic Cancer"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Epidermal growth factor receptor\u2010mutated (EGFRm) non\u2010small cell lung cancer (NSCLC) responds well to EGFR tyrosine kinase inhibitors (EGFR\u2010TKIs), yet optimal therapy after resistance remains uncertain. Although immune checkpoint inhibitors (ICIs) show limited overall efficacy, heterogeneity in response by programmed cell death ligand 1 (PD\u2010L1) expression exists.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We retrospectively evaluated 90 patients with advanced\/recurrent EGFRm NSCLC treated with first\u2010line EGFR\u2010TKIs (October 2018\u2013October 2023). Clinicopathological and radiologic features were compared by PD\u2010L1 tumor proportion score (&lt;\u200950% vs. \u2265\u200950%). The primary analysis evaluated overall survival from first progression (post\u2010progression OS\/PPS) using a time\u2010varying Cox model with start\u2013stop intervals, modeling ICI as a time\u2010dependent exposure ICI(\n                      <jats:italic>t<\/jats:italic>\n                      ) and testing the ICI(\n                      <jats:italic>t<\/jats:italic>\n                      )\u2009\u00d7\u2009PD\u2010L1 interaction.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The PD\u2010L1\u2009\u2265\u200950% group (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200926) more often had solid histology (62% vs. 8%), solid nodules on computed tomography (96% vs. 52%), and larger tumors (median 42.0 vs. 27.5\u2009mm). Among 68 patients evaluable from\n                      <jats:italic>t<\/jats:italic>\n                      <jats:sub>0<\/jats:sub>\n                      , the ICI(\n                      <jats:italic>t<\/jats:italic>\n                      )\u2009\u00d7\u2009PD\u2010L1 interaction was significant (Wald\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.015; likelihood\u2010ratio\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.036). Stratum\u2010specific adjusted ICI effects suggested a detrimental association in PD\u2010L1\u2009&lt;\u200950% (hazard ratio [HR]: 3.11, 95% confidence interval [CI]: 0.94\u201310.30) but favorable association in PD\u2010L1\u2009\u2265\u200950% (HR: 0.457, 95% CI: 0.138\u20131.512). In exploratory analyses of 22 ICI\u2010treated patients, PD\u2010L1\u2009\u2265\u200950% showed higher response rates (64% vs. 9%) and longer time to treatment failure (3.4 vs. 1.4\u2009months).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>High PD\u2010L1 expression in EGFRm NSCLC is associated with more aggressive morphologic features and modifies the association between post\u2010progression ICI and survival. These findings support PD\u2010L1\u2010informed selection after EGFR\u2010TKI failure, while prospective confirmation is needed.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/1759-7714.70252","type":"journal-article","created":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T00:50:21Z","timestamp":1770684621000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["<scp>PD<\/scp>\n                    \u2010\n                    <scp>L1<\/scp>\n                    Expression and Histopathological Features in\n                    <scp>EGFR<\/scp>\n                    \u2010Mutated Non\u2010Small Cell Lung Cancer: Implications for Immune Checkpoint Inhibitors After\n                    <scp>EGFR<\/scp>\n                    \u2010Tyrosine Kinase Inhibitors Resistance"],"prefix":"10.1111","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2540-5878","authenticated-orcid":false,"given":"Toshiyuki","family":"Sumi","sequence":"first","affiliation":[{"name":"Department of Pulmonary Medicine Hakodate Goryoukaku Hospital  Hakodate Hokkaido Japan"},{"name":"Department of Respiratory Medicine and Allergology Sapporo Medical University School of Medicine  Sapporo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taiki","family":"Ishigooka","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine Hakodate Goryoukaku Hospital  Hakodate Hokkaido Japan"},{"name":"Department of Respiratory Medicine and Allergology Sapporo Medical University School of Medicine  Sapporo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keigo","family":"Matsuura","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine Hakodate Goryoukaku Hospital  Hakodate Hokkaido Japan"},{"name":"Department of Respiratory Medicine and Allergology Sapporo Medical University School of Medicine  Sapporo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takumi","family":"Ikeda","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine Hakodate Goryoukaku Hospital  Hakodate Hokkaido Japan"},{"name":"Department of Respiratory Medicine and Allergology Sapporo Medical University School of Medicine  Sapporo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuichi","family":"Yamada","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine Hakodate Goryoukaku Hospital  Hakodate Hokkaido Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kotomi","family":"Arioka","sequence":"additional","affiliation":[{"name":"Department of Surgical Pathology Hakodate Goryoukaku Hospital  Hakodate Hokkaido Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirofumi","family":"Chiba","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine and Allergology Sapporo Medical University School of Medicine  Sapporo 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