{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T06:31:08Z","timestamp":1772692268403,"version":"3.50.1"},"reference-count":14,"publisher":"Springer Science and Business Media LLC","issue":"7","license":[{"start":{"date-parts":[[2022,7,28]],"date-time":"2022-07-28T00:00:00Z","timestamp":1658966400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,7,28]],"date-time":"2022-07-28T00:00:00Z","timestamp":1658966400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Cancer Res Clin Oncol"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Purpose<\/jats:title>\n                <jats:p>Immune checkpoint blockade therapy is the standard treatment for metastatic or refractory non-small cell lung cancer (NSCLC). However, it is associated with immune-related adverse events (irAEs). irAEs are sometimes fatal; however, an efficient method for early irAEs detection has not been developed because their onset timing varies. We examined the significance of non-specific symptoms as a prodrome of irAEs in patients with NSCLC.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>We reviewed consecutive patients who received nivolumab at a dosage of 3\u00a0mg\/kg every 2\u00a0weeks for metastatic NSCLC between December 2015 and August 2017. Patient demographics, irAEs and signal symptoms were recorded. Non-specific symptoms (fever and fatigue) occurred 7\u00a0days or earlier before the onset of irAEs were considered signal symptoms. For statistical analyses, the association between irAEs and clinical information, including signal symptoms, was evaluated using Fisher\u2019s exact test and logistic regression.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>A total of 200 patients received nivolumab; 131 (65.5%) were male, their median age was 63\u00a0years (range 30\u201383), 174 (87.0%) had performance status of 0\u20131. Signal symptoms occurred in 38 (19.0%) of the 77 patients (38.5%) who experienced irAEs, and were positively associated with the occurrence of irAEs (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.01). Multivariate analysis showed that the occurrence of irAEs was significantly higher in patients with PS 0\u20131 [odds ratio (OR) 7.01; 95% confidence intervals (CI), 1.69\u201329.13] and patients experienced signal symptoms (OR 17.30; 95% CI, 6.51\u201345.99).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>The occurrence of signal symptoms could be used in the early detection and management of irAEs in patients during immune checkpoint blockade therapy.\n<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00432-022-04205-9","type":"journal-article","created":{"date-parts":[[2022,7,28]],"date-time":"2022-07-28T04:02:29Z","timestamp":1658980949000},"page":"3185-3191","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Non-specific symptoms as a prodrome of immune-related adverse events in patients with non-small cell lung cancer receiving nivolumab: a consecutive analysis of 200 patients"],"prefix":"10.1007","volume":"149","author":[{"given":"Ryoko Inaba","family":"Higashiyama","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9090-801X","authenticated-orcid":false,"given":"Hidehito","family":"Horinouchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aya","family":"Kuchiba","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuji","family":"Matsumoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuji","family":"Murakami","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasushi","family":"Goto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shintaro","family":"Kanda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yutaka","family":"Fujiwara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noboru","family":"Yamamoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuichiro","family":"Ohe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,7,28]]},"reference":[{"issue":"17","key":"4205_CR1","doi-asserted-by":"publisher","first-page":"1627","DOI":"10.1056\/NEJMoa1507643","volume":"373","author":"H Borghaei","year":"2015","unstructured":"Borghaei H, Paz-Ares L, Horn L, Spigel DR, Steins M, Ready NE, Chow LQ, Vokes EE, Felip E, Holgado E, Barlesi F, Kohlhaufl M, Arrieta O, Burgio MA, Fayette J, Lena H, Poddubskaya E, Gerber DE, Gettinger SN, Rudin CM, Rizvi N, Crino L, Blumenschein GR Jr, Antonia SJ, Dorange C, Harbison CT, Graf Finckenstein F, Brahmer JR (2015) Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. 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J Transl Med 16(1):94","journal-title":"J Transl Med"}],"container-title":["Journal of Cancer Research and Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00432-022-04205-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00432-022-04205-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00432-022-04205-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,1]],"date-time":"2023-07-01T12:07:18Z","timestamp":1688213238000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00432-022-04205-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,28]]},"references-count":14,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2023,7]]}},"alternative-id":["4205"],"URL":"https:\/\/doi.org\/10.1007\/s00432-022-04205-9","relation":{},"ISSN":["0171-5216","1432-1335"],"issn-type":[{"value":"0171-5216","type":"print"},{"value":"1432-1335","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,28]]},"assertion":[{"value":"27 June 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 July 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 July 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Dr. Higashiyama has nothing to disclose. Dr. Horinouchi reports grants and personal fees from BMS, grants and personal fees from MSD, grants and personal fees from Chugai, grants and personal fees from Roche, grants and personal fees from Novartis, grants and personal fees from Astra Zeneca, grants from Abbvie, grants from Merck Biophama, grants from Daiichi-Sankyo, grants from Janssen grants from Genomic Health, personal fees from Lilly, personal fees from Kyowa-Kirin, grants and personal fees from Ono, outside the submitted work. Dr. Kuchiba has nothing to disclose. Dr. Matsumoto reports grants from National Cancer Center Research and Development Fund, grants from Grant-in-Aid for Scientific Research on Innovative Areas, grants from Hitachi, Ltd., personal fees from Olympus, personal fees from AstraZeneca, personal fees. from Novartis, personal fees from COOK, personal fees from AMCO INC, personal fees from Thermo Fisher Scientific, personal fees from Erbe Elektromedizin GmbH, personal fees from Fujifilm, personal fees from Chugai, personal fees from Eli Lilly, outside the submitted work. Dr. Murakami reports personal fees from AstraZeneca, personal fees from MSD, personal fees from ONO Pharmaceutical, personal fees from Eli Lilly, personal fees from Chugai Pharmaceutical, personal fees from Novartis, personal fees from MERCK, outside the submitted work. Dr. Goto reports grants and personal fees from Eli Lilly, personal fees from Chugai, grants and personal fees from Taiho Pharmaceutical, personal fees from Boehringer Ingelheim, grants and personal fees from Pfizer, grants and personal fees from Novartis, grants and personal fees from AstraZeneca, personal fees from MSD, personal fees from Guardant Health, grants and personal fees from Ono Pharmaceutical, grants from Kyorin, grants and personal fees from Daiichi Sankyo, personal fees from Illumina, grants and personal fees from Bristol Myers Squibb, grants from Preferred Network, grants from Abbvie, personal fees from Merck, personal fees from Thermo Fischer, outside the submitted work. Dr. Kanda has nothing to disclose. Dr. Fujiwara reports personal fees from Astra Zeneca, personal fees from Daiichi Sankyo, personal fees from ONO Pharmaceutical, personal fees from Otsuka Pharmaceutical, grants and personal fees from Chugai Pharmaceutical, personal fees from Novartis, personal fees from Yakult, grants and personal fees from Bristol-Myers Squibb, personal fees from Pfizer, personal fees from Takeda, grants from AnHeart Therapeutics, grants and personal fees from Eli Lilly, personal fees from Chiome Bioscience, grants from Amgen, outside the submitted work.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"The study was approved by the Institutional Review Board of the National Cancer Center Hospital (No. 2015\u2013355).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Informed consent was obtained from all individual participants included in the study.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"Not required.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publish"}}]}}