{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T10:55:53Z","timestamp":1791284153045,"version":"4.1.0"},"reference-count":29,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl Journal of Cancer"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    While first\u2010line immune checkpoint inhibitors (ICIs) combined with chemoradiotherapy (CRT) represent a crucial advancement for unresectable locally advanced esophageal squamous cell carcinoma (ESCC), the optimal sequencing of these modalities remains unresolved. To evaluate the efficacy and safety of induction, concurrent, and consolidation ICI strategies, this multicenter real\u2010world cohort study enrolled 662 patients with Stage II\u2013IVA unresectable ESCC across 12 cancer centers. Patients were categorized into induction (IC\u2010CRT), concurrent (ICRT), and consolidation (CRT\u2010IC) groups, with inverse probability of treatment weighting (IPTW) applied to balance baseline characteristics. Following IPTW adjustment, the median overall survival (OS) in the IC\u2010CRT, ICRT, and CRT\u2010IC groups was 34.7\u2009months, not reached, and 23.1\u2009months, respectively (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.016), while the corresponding median progression\u2010free survival (PFS) times were 20.1, 25.3, and 12.9\u2009months, respectively (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.014). Among the three sequencing strategies, ICRT achieved the most favorable survival outcomes, followed by IC\u2010CRT and CRT\u2010IC. Multivariable Cox regression confirmed that ICRT was associated with a significantly reduced risk of mortality compared with IC\u2010CRT (HR\u2009=\u20090.71,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.046) and CRT\u2010IC (HR\u2009=\u20090.53, adjusted\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001). Safety profiles indicated that ICRT carried the highest burden of Grade 3\u20134 treatment\u2010related pneumonitis (7.7%). In conclusion, ICRT as a first\u2010line treatment for locally advanced ESCC showed the most favorable survival profile compared with induction or consolidation sequencing, although its higher toxicity profile necessitates careful patient selection and proactive clinical management. In contrast, the CRT\u2010IC strategy exhibited the best tolerability but the least favorable survival outcome.\n                  <\/jats:p>","DOI":"10.1002\/ijc.70740","type":"journal-article","created":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T10:40:37Z","timestamp":1791283237000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Optimal Sequencing of First\u2010Line Immune Checkpoint Inhibitors With Definitive Chemoradiotherapy: A Multicenter Real\u2010World Cohort Study Comparing Induction, Concurrent, and Consolidation Strategies for Unresectable Locally Advanced Esophageal Squamous Cell Carcinoma"],"prefix":"10.1002","author":[{"given":"Xiaohan","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology The Fourth Hospital of Hebei Medical University  Shijiazhuang 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9993-6663","authenticated-orcid":false,"given":"Chenyu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Anyang Tumor Hospital The Affiliated Anyang Tumor Hospital of Henan University of Science and Technology  Anyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4351-5325","authenticated-orcid":false,"given":"Yatian","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology Nanjing Medical University Affiliated Cancer Hospital &amp; Jiangsu Cancer Hospital &amp; Jiangsu Institute of Cancer Research  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pudong","family":"Qian","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology Nanjing Medical University Affiliated Cancer Hospital &amp; Jiangsu Cancer Hospital &amp; Jiangsu Institute of Cancer Research  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianzhong","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology Shanxi Province Cancer Hospital, Cancer Hospital Affiliated to Shanxi Medical University  Taiyuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Hou","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology Shanxi Province Cancer Hospital, Cancer Hospital Affiliated to Shanxi Medical University  Taiyuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanji","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital  Fuzhou 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