{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T16:37:17Z","timestamp":1790095037043,"version":"4.0.1"},"reference-count":44,"publisher":"Wiley","issue":"29","license":[{"start":{"date-parts":[[2023,8,24]],"date-time":"2023-08-24T00:00:00Z","timestamp":1692835200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Thoracic Cancer"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Risk factors for predicting pneumonitis during durvalumab consolidation after chemoradiotherapy (CRT) in locally advanced non\u2010small cell lung cancer (LA\u2010NSCLC) are still lacking. Extracellular vesicles (EVs) play a crucial role in intercellular communication and are potential diagnostic tools for various diseases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We retrospectively collected predurvalumab treatment serum samples from patients treated with durvalumab for LA\u2010NSCLC, isolated EVs using anti\u2010CD9 and anti\u2010CD63 antibodies, and performed proteomic analyses. We examined EV proteins that could predict the development of symptomatic pneumonitis (SP) during durvalumab treatment. Potential EV\u2010protein biomarkers were validated in an independent cohort.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In the discovery cohort, 73 patients were included, 49 with asymptomatic pneumonitis (AP) and 24 with SP. Of the 5797 proteins detected in circulating EVs, 33 were significantly elevated (fold change [FC]\u2009&gt;\u20091.5, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05) in the SP group, indicating enrichment of the nuclear factor kappa B (NF\u2010\u03baB) pathway. Patients with high levels of EV\u2010RELA, an NF\u2010\u03baB subunit, had a higher incidence of SP than those with low levels of EV\u2010RELA (53.8% vs. 13.4%, <jats:italic>p<\/jats:italic>\u2009=\u20090.0017). In the receiver operating characteristic analysis, EV\u2010RELA demonstrated a higher area under the curve (AUC) than lung V20 (0.76 vs. 0.62) and was identified as an independent risk factor in the multivariate logistic regression analysis (<jats:italic>p<\/jats:italic>\u2009=\u20090.008, odds ratio 7.72). Moreover, high EV\u2010RELA was also a predictor of SP in the validation cohort comprising 43 patients (AUC of 0.80).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Circulating EV\u2010RELA may be a predictive marker for symptomatic pneumonitis in patients with LA\u2010NSCLC treated with durvalumab.<\/jats:p><\/jats:sec>","DOI":"10.1111\/1759-7714.15077","type":"journal-article","created":{"date-parts":[[2023,8,24]],"date-time":"2023-08-24T03:24:52Z","timestamp":1692847492000},"page":"2909-2923","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Exploratory analysis to predict pneumonitis during durvalumab consolidation therapy for patients with locally advanced non\u2010small cell lung cancer from proteomic profiling of circulating extracellular vesicles"],"prefix":"10.1111","volume":"14","author":[{"given":"Masahiro","family":"Torasawa","sequence":"first","affiliation":[{"name":"Department of Thoracic Oncology National Cancer Center Hospital  Tokyo Japan"},{"name":"Department of Respiratory Medicine Juntendo University Graduate School of Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9090-801X","authenticated-orcid":false,"given":"Hidehito","family":"Horinouchi","sequence":"additional","affiliation":[{"name":"Department of Thoracic Oncology National Cancer Center Hospital  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigehiro","family":"Yagishita","sequence":"additional","affiliation":[{"name":"Division of Molecular Pharmacology National Cancer Center Research Institute  Tokyo 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