{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T22:40:18Z","timestamp":1790721618359,"version":"4.1.0"},"reference-count":40,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","ejcancer.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Cancer"],"published-print":{"date-parts":[[2025,10]]},"DOI":"10.1016\/j.ejca.2025.115748","type":"journal-article","created":{"date-parts":[[2025,8,30]],"date-time":"2025-08-30T15:05:30Z","timestamp":1756566330000},"page":"115748","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":16,"special_numbering":"C","title":["Timing of first pembrolizumab infusion and long-term outcomes in non-small cell lung cancer: A retrospective multicenter study"],"prefix":"10.1016","volume":"228","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-6296-4386","authenticated-orcid":false,"given":"Akihiro","family":"Tsukaguchi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kinnosuke","family":"Matsumoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3599-2583","authenticated-orcid":false,"given":"Akihiro","family":"Tamiya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motohiro","family":"Tamiya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahide","family":"Mori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidekazu","family":"Suzuki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki","family":"Shiroyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akito","family":"Miyazaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiyohide","family":"Komuta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhiro","family":"Mihashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keijiro","family":"Yamauchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kensuke","family":"Kanaoka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9787-1659","authenticated-orcid":false,"given":"Tomoki","family":"Kuge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhei","family":"Kinehara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6506-8992","authenticated-orcid":false,"given":"Koji","family":"Azuma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshie","family":"Niki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koki","family":"Moritomo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshito","family":"Takeda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4749-7117","authenticated-orcid":false,"given":"Atsushi","family":"Kumanogoh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ejca.2025.115748_bib1","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1146\/annurev-physiol-021909-135821","article-title":"The mammalian circadian timing system: organization and coordination of central and peripheral clocks","volume":"72","author":"Dibner","year":"2010","journal-title":"Annu Rev Physiol"},{"key":"10.1016\/j.ejca.2025.115748_bib2","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1177\/0748730415577723","article-title":"Circadian clocks in the immune system","volume":"30","author":"Labrecque","year":"2015","journal-title":"J Biol Rhythms"},{"key":"10.1016\/j.ejca.2025.115748_bib3","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1124\/pr.116.013441","article-title":"Systems chronotherapeutics","volume":"69","author":"Ballesta","year":"2017","journal-title":"Pharm Rev"},{"key":"10.1016\/j.ejca.2025.115748_bib4","first-page":"321","article-title":"Circadian rhythms: influence on physiology, pharmacology, and therapeutic interventions","volume":"48","author":"Ayyar","year":"2021","journal-title":"J Pharm Pharm"},{"key":"10.1016\/j.ejca.2025.115748_bib5","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1146\/annurev.pharmtox.48.113006.094626","article-title":"Circadian timing in cancer treatments","volume":"50","author":"L\u00e9vi","year":"2010","journal-title":"Annu Rev Pharm Toxicol"},{"key":"10.1016\/j.ejca.2025.115748_bib6","doi-asserted-by":"crossref","first-page":"e129","DOI":"10.1016\/S1470-2045(21)00639-2","article-title":"Toxicity and efficacy of chronomodulated chemotherapy: a systematic review","volume":"23","author":"Printezi","year":"2022","journal-title":"Lancet Oncol"},{"key":"10.1016\/j.ejca.2025.115748_bib7","doi-asserted-by":"crossref","first-page":"1819","DOI":"10.1016\/S0140-6736(18)32409-7","article-title":"Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial","volume":"393","author":"Mok","year":"2019","journal-title":"Lancet"},{"key":"10.1016\/j.ejca.2025.115748_bib8","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1038\/s41416-024-02704-9","article-title":"Why does circadian timing of administration matter for immune checkpoint inhibitors\u2019 efficacy?","volume":"131","author":"Karabou\u00e9","year":"2024","journal-title":"Br J Cancer"},{"key":"10.1016\/j.ejca.2025.115748_bib9","doi-asserted-by":"crossref","first-page":"1777","DOI":"10.1016\/S1470-2045(21)00546-5","article-title":"Effect of immunotherapy time-of-day infusion on overall survival among patients with advanced melanoma in the USA (MEMOIR): a propensity score-matched analysis of a single-centre, longitudinal study","volume":"22","author":"Qian","year":"2021","journal-title":"Lancet Oncol"},{"key":"10.1016\/j.ejca.2025.115748_bib10","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2024.1512972","article-title":"Effect of immune checkpoint inhibitor time-of-day infusion on survival in advanced biliary tract cancer: a propensity score-matched analysis","volume":"15","author":"Zheng","year":"2024","journal-title":"Front Immunol"},{"key":"10.1016\/j.ejca.2025.115748_bib11","doi-asserted-by":"crossref","first-page":"463","DOI":"10.3892\/ol.2024.14596","article-title":"Efficacy of timing\u2011dependent infusion of nivolumab in patients with advanced gastric cancer","volume":"28","author":"Tanaka","year":"2024","journal-title":"Oncol Lett"},{"key":"10.1016\/j.ejca.2025.115748_bib12","doi-asserted-by":"crossref","DOI":"10.1016\/j.ebiom.2025.105607","article-title":"Overall survival according to time-of-day of combined immuno-chemotherapy for advanced non-small cell lung cancer: a bicentric bicontinental study","volume":"113","author":"Huang","year":"2025","journal-title":"EBiomedicine"},{"key":"10.1016\/j.ejca.2025.115748_bib13","doi-asserted-by":"crossref","first-page":"2690","DOI":"10.1016\/j.cell.2024.04.015","article-title":"Circadian tumor infiltration and function of CD8+ t cells dictate immunotherapy efficacy","volume":"187","author":"Wang","year":"2024","journal-title":"Cell"},{"key":"10.1016\/j.ejca.2025.115748_bib14","doi-asserted-by":"crossref","first-page":"972","DOI":"10.1158\/1541-7786.MCR-21-0786","article-title":"Diurnal expression of PD-1 on tumor-associated macrophages underlies the dosing time-dependent antitumor effects of the PD-1\/PD-L1 inhibitor BMS-1 in B16\/BL6 melanoma-bearing mice","volume":"20","author":"Tsuruta","year":"2022","journal-title":"Mol Cancer Res"},{"key":"10.1016\/j.ejca.2025.115748_bib15","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1038\/s41586-022-05605-0","article-title":"Dendritic cells direct circadian anti-tumour immune responses","volume":"614","author":"Wang","year":"2023","journal-title":"Nature"},{"key":"10.1016\/j.ejca.2025.115748_bib16","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1038\/s41590-024-01859-0","article-title":"Circadian control of tumor immunosuppression affects efficacy of immune checkpoint blockade","volume":"25","author":"Fortin","year":"2024","journal-title":"Nat Immunol"},{"key":"10.1016\/j.ejca.2025.115748_bib17","doi-asserted-by":"crossref","first-page":"2144","DOI":"10.1158\/1078-0432.CCR-18-1449","article-title":"The first-week proliferative response of peripheral blood PD-1+CD8+ t cells predicts the response to anti-PD-1 therapy in solid tumors","volume":"25","author":"Kim","year":"2019","journal-title":"Clin Cancer Res"},{"key":"10.1016\/j.ejca.2025.115748_bib18","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1038\/nature22079","article-title":"T-cell invigoration to tumour burden ratio associated with anti-PD-1 response","volume":"545","author":"Huang","year":"2017","journal-title":"Nature"},{"key":"10.1016\/j.ejca.2025.115748_bib19","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1016\/j.annonc.2022.07.1851","article-title":"A multicentre study of pembrolizumab time-of-day infusion patterns and clinical outcomes in non-small-cell lung cancer: too soon to promote morning infusions","volume":"33","author":"Cortellini","year":"2022","journal-title":"Ann Oncol"},{"key":"10.1016\/j.ejca.2025.115748_bib20","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.ejca.2023.01.007","article-title":"Clinical outcomes by infusion timing of immune checkpoint inhibitors in patients with advanced non-small cell lung cancer","volume":"182","author":"Rousseau","year":"2023","journal-title":"Eur J Cancer"},{"key":"10.1016\/j.ejca.2025.115748_bib21","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.ejca.2008.10.026","article-title":"New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1)","volume":"45","author":"Eisenhauer","year":"2009","journal-title":"Eur J Cancer"},{"key":"10.1016\/j.ejca.2025.115748_bib22","unstructured":"Cancer Institute N. Common terminology criteria for adverse events (CTCAE). v5.0. Published online; 2017, https:\/\/ctep.cancer.gov\/protocolDevelopment\/electronic_applications\/ctc.htm#ctc_50, [Accessed April 19, 2025]."},{"key":"10.1016\/j.ejca.2025.115748_bib23","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1002\/pst.433","article-title":"Optimal caliper widths for propensity-score matching when estimating differences in means and differences in proportions in observational studies","volume":"10","author":"Austin","year":"2011","journal-title":"Pharm Stat"},{"key":"10.1016\/j.ejca.2025.115748_bib24","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1080\/03610910902859574","article-title":"Using the standardized difference to compare the prevalence of a binary variable between two groups in observational research","volume":"38","author":"Austin","year":"2009","journal-title":"Commun Stat Simul Comput"},{"key":"10.1016\/j.ejca.2025.115748_bib25","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1056\/NEJMoa1614362","article-title":"Health effects of overweight and obesity in 195 countries over 25 years","volume":"377","author":"GBD","year":"2017","journal-title":"N Engl J Med"},{"key":"10.1016\/j.ejca.2025.115748_bib26","doi-asserted-by":"crossref","DOI":"10.1038\/srep12493","article-title":"Prognostic significance of neutrophil-to-lymphocyte ratio in non-small cell lung cancer: a meta-analysis","volume":"5","author":"Gu","year":"2015","journal-title":"Sci Rep"},{"key":"10.1016\/j.ejca.2025.115748_bib27","doi-asserted-by":"crossref","DOI":"10.1200\/JCO.2023.41.16_suppl.e21055","article-title":"Improved survival on morning pembrolizumab with or without chemotherapy during initial treatment for stage IV non-small cell lung cancer","volume":"41","author":"Karabou\u00e9","year":"2023","journal-title":"J Clin Oncol"},{"key":"10.1016\/j.ejca.2025.115748_bib28","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1200\/JCO.21.01570","article-title":"Adaptive dosing of nivolumab + ipilimumab immunotherapy based upon early, interim radiographic assessment in advanced melanoma (The ADAPT-IT Study)","volume":"40","author":"Postow","year":"2022","journal-title":"J Clin Oncol"},{"key":"10.1016\/j.ejca.2025.115748_bib29","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1038\/s43018-025-00981-8","article-title":"The diverse roles of the circadian clock in cancer","volume":"6","author":"Fortin","year":"2025","journal-title":"Nat Cancer"},{"key":"10.1016\/j.ejca.2025.115748_bib30","doi-asserted-by":"crossref","DOI":"10.1016\/j.esmoop.2023.102220","article-title":"Effect of immunotherapy-infusion time of day on survival of patients with advanced cancers: a study-level meta-analysis","volume":"9","author":"Landr\u00e9","year":"2024","journal-title":"ESMO Open"},{"key":"10.1016\/j.ejca.2025.115748_bib31","doi-asserted-by":"crossref","first-page":"2268","DOI":"10.1158\/1078-0432.CCR-17-1902","article-title":"Evaluation of overall response rate and progression-free survival as potential surrogate endpoints for overall survival in immunotherapy trials","volume":"24","author":"Mushti","year":"2018","journal-title":"Clin Cancer Res"},{"key":"10.1016\/j.ejca.2025.115748_bib32","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1158\/1078-0432.CCR-12-2625","article-title":"Durable cancer regression off-treatment and effective reinduction therapy with an anti-PD-1 antibody","volume":"19","author":"Lipson","year":"2013","journal-title":"Clin Cancer Res"},{"key":"10.1016\/j.ejca.2025.115748_bib33","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1001\/jamaoncol.2017.1588","article-title":"Nivolumab for patients with advanced melanoma treated beyond progression: analysis of 2 phase 3 clinical trials","volume":"3","author":"Long","year":"2017","journal-title":"JAMA Oncol"},{"key":"10.1016\/j.ejca.2025.115748_bib34","doi-asserted-by":"crossref","first-page":"3541","DOI":"10.1200\/JCO.2015.61.6870","article-title":"Pseudoprogression and immune-related response in solid tumors","volume":"33","author":"Chiou","year":"2015","journal-title":"J Clin Oncol"},{"key":"10.1016\/j.ejca.2025.115748_bib35","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejca.2024.113571","article-title":"Early morning immune checkpoint blockade and overall survival of patients with metastatic cancer: an In-depth chronotherapeutic study","volume":"199","author":"Catozzi","year":"2024","journal-title":"Eur J Cancer"},{"key":"10.1016\/j.ejca.2025.115748_bib36","doi-asserted-by":"crossref","DOI":"10.3389\/fonc.2023.1240284","article-title":"Circadian rhythm disorders in patients with advanced cancer: a scoping review","volume":"13","author":"Gouldthorpe","year":"2023","journal-title":"Front Oncol"},{"key":"10.1016\/j.ejca.2025.115748_bib37","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1038\/sj.bjc.6602859","article-title":"Circadian function in patients with advanced non-small-cell lung cancer","volume":"93","author":"Levin","year":"2005","journal-title":"Br J Cancer"},{"key":"10.1016\/j.ejca.2025.115748_bib38","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1161\/HYPERTENSIONAHA.116.06588","article-title":"Keeping up with the clock: circadian disruption and obesity risk","volume":"68","author":"Covassin","year":"2016","journal-title":"Hypertension"},{"key":"10.1016\/j.ejca.2025.115748_bib39","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1210\/jc.2015-3924","article-title":"Effects of the internal circadian system and circadian misalignment on glucose tolerance in chronic shift workers","volume":"101","author":"Morris","year":"2016","journal-title":"J Clin Endocrinol Metab"},{"key":"10.1016\/j.ejca.2025.115748_bib40","doi-asserted-by":"crossref","first-page":"846","DOI":"10.7326\/0003-4819-141-11-200412070-00008","article-title":"Brief communication: sleep curtailment in healthy young men is associated with decreased leptin levels, elevated ghrelin levels, and increased hunger and appetite","volume":"141","author":"Spiegel","year":"2004","journal-title":"Ann Intern Med"}],"updated-by":[{"DOI":"10.1016\/j.ejca.2025.116010","type":"erratum","label":"Erratum","source":"publisher","updated":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T00:00:00Z","timestamp":1763337600000}}],"container-title":["European Journal of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0959804925005337?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0959804925005337?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T09:43:13Z","timestamp":1779702193000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0959804925005337"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10]]},"references-count":40,"alternative-id":["S0959804925005337"],"URL":"https:\/\/doi.org\/10.1016\/j.ejca.2025.115748","relation":{},"ISSN":["0959-8049"],"issn-type":[{"value":"0959-8049","type":"print"}],"subject":[],"published":{"date-parts":[[2025,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Timing of first pembrolizumab infusion and long-term outcomes in non-small cell lung cancer: A retrospective multicenter study","name":"articletitle","label":"Article Title"},{"value":"European Journal of Cancer","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejca.2025.115748","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"115748"}}