{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T08:25:04Z","timestamp":1786955104728,"version":"build-2736575974"},"reference-count":18,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["LTGY23H160011"],"award-info":[{"award-number":["LTGY23H160011"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["LTGY24H010003"],"award-info":[{"award-number":["LTGY24H010003"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Program of Province TCM Sci-Tech Plan","award":["2024ZL298"],"award-info":[{"award-number":["2024ZL298"]}]},{"DOI":"10.13039\/100007219","name":"Natural Science Foundation of Shanghai Municipality","doi-asserted-by":"publisher","award":["25ZR1402449"],"award-info":[{"award-number":["25ZR1402449"]}],"id":[{"id":"10.13039\/100007219","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Ther Adv Med Oncol"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Esophageal squamous cell carcinoma (ESCC) is a highly lethal malignancy for which immune checkpoint inhibitors (ICIs) have improved outcomes, yet significant inter-patient variability in response persists. Emerging evidence suggests that circadian rhythms modulate anti-tumor immunity, but the impact of ICI infusion timing on ESCC prognosis remains unexplored.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To determine whether the timing of ICI infusion impacts survival outcomes in patients with advanced ESCC and to identify an optimal infusion time window.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>A single-center, retrospective cohort study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We included 339 patients with advanced ESCC who received ICI therapy at Zhejiang Cancer Hospital between June 2018 and September 2022. Infusion timing was examined using two metrics: (i) first infusion time, and (ii) average infusion time across the first three cycles. Restricted cubic spline models were applied to explore dose-response relationships with infusion time as a continuous variable. Patients were categorized as early (before 14:00) or late (at or after 14:00) for each metric. Survival outcomes were analyzed using univariate and multivariate Cox proportional hazards models and Kaplan-Meier methods. Sensitivity analyses included an alternative 13:30 cutoff and a subgroup analysis of patients receiving ICI monotherapy. The study was conducted in compliance with the STROBE guidelines.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In the primary analysis of first infusion time, each one-hour delay was associated with increased risks of disease progression (HR=1.049, 95% CI: 1.003\u20131.097, P=0.036) and mortality (HR=1.062, 95% CI: 1.014\u20131.112, P=0.010). Kaplan-Meier analysis showed significantly better median PFS (6.2 vs. 5.3 months, P=0.010) and OS (13.3 vs. 12.4 months, P=0.026) in the Early-first versus Late-first group. In the secondary analysis of average infusion time during the first three cycles, each one-hour delay increased progression risk (HR=1.073, 95% CI: 1.001\u20131.151, P=0.027) and mortality risk (HR=1.092, 95% CI: 1.017\u20131.172, P=0.015), with Kaplan-Meier analysis showing a trend toward improved median PFS (6.2 vs. 5.6 months, P=0.098) and OS (13.4 vs. 12.1 months, P=0.057) in the Early-3M versus Late-3M group. Restricted cubic spline analysis revealed a nearly linear dose-response relationship (nonlinearity P&gt;0.05).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The timing of ICIs infusions may be an independent prognostic factor for survival in advanced ESCC. Administration before 14:00 was associated with improved PFS and OS.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/17588359261473570","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T04:58:44Z","timestamp":1786683524000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Timing of immune checkpoint inhibitor infusion predicts survival in advanced esophageal squamous cell carcinoma: A retrospective cohort study"],"prefix":"10.1177","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-9361-3334","authenticated-orcid":false,"given":"Wenjing","family":"Wang","sequence":"first","affiliation":[{"name":"Zhejiang Cancer Hospital"},{"name":"Hangzhou Institute of Medicine (HIM)"},{"name":"Shanghai Pulmonary Hospital School of Medicine Tongji 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