{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T07:22:03Z","timestamp":1785223323527,"version":"3.55.0"},"reference-count":41,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2011,12,1]],"date-time":"2011-12-01T00:00:00Z","timestamp":1322697600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Respir Res"],"published-print":{"date-parts":[[2011,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>A high incidence of interstitial lung disease (ILD) has been reported in patients with advanced non-small cell lung cancer (NSCLC) treated with epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), particularly in Japanese populations. A previous report from our laboratory demonstrated that KL-6 was a useful serum biomarker to assess the severity of drug-induced pneumonitis. Based on these observations, this study was conducted to evaluate the risk factors of EGFR-TKIs induced ILD and the usefulness of monitoring serum KL-6 levels in patients who developed EGFR-TKIs induced ILD in a large multi-institutional setting.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>We retrospectively reviewed clinical records and radiographies of 341 patients with advanced NSCLCs who were treated with EGFR-TKIs, and analyzed risk factors for the development of EGFR-TKIs induced ILD. Changes of circulating levels of KL-6 were also evaluated in the patients who developed EGFR-TKIs induced ILD.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Among the 341 patients included in this study, 20 (5.9%) developed EGFR-TKIs induced ILD, and 9 (2.6%) died from ILD. Univariate analyses revealed that only preexisting pulmonary fibrosis was a significant risk factor for the development of EGFR-TKIs induced ILD (<jats:italic>p<\/jats:italic> = 0.003). Absolute levels of circulating KL-6 at neither baseline nor the onset of ILD could discriminate between life-threatening and non-life threatening EGFR-TKIs induced ILDs. However, we found that the ratios of serum KL-6 levels just after the onset of EGFR-TKIs induced ILD to those at baseline could quite precisely distinguish survivors from non-survivors (<jats:italic>p<\/jats:italic> = 0.006) as well as acute interstitial pneumonia (AIP) pattern from non-AIP pattern (<jats:italic>p<\/jats:italic> = 0.005).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>The results of this study strongly support the potential of KL-6 as a diagnostic biomarker for life-threatening EGFR-TKIs induced ILD. Monitoring of KL-6 is also useful to evaluate the progression and severity of EGFR-TKIs induced ILD.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1465-9921-12-97","type":"journal-article","created":{"date-parts":[[2011,7,27]],"date-time":"2011-07-27T06:19:11Z","timestamp":1311747551000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Change in serum KL-6 level from baseline is useful for predicting life-threatening EGFR-TKIs induced interstitial lung disease"],"prefix":"10.1186","volume":"12","author":[{"given":"Shigeo","family":"Kawase","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noboru","family":"Hattori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuhisa","family":"Ishikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasushi","family":"Horimasu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazunori","family":"Fujitaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osamu","family":"Furonaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Isobe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seigo","family":"Miyoshi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hironobu","family":"Hamada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Yamane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihito","family":"Yokoyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuoki","family":"Kohno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2011,12,1]]},"reference":[{"key":"1124_CR1","doi-asserted-by":"publisher","first-page":"851","DOI":"10.1097\/CAD.0b013e3283330590","volume":"20","author":"H Modjtahedi","year":"2009","unstructured":"Modjtahedi H, Essapen S: Epidermal growth factor receptor inhibitors in cancer treatment: advances, challenges and opportunities. 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