{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T19:12:22Z","timestamp":1791573142916,"version":"4.3.4"},"reference-count":31,"publisher":"BMJ","issue":"8","license":[{"start":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T00:00:00Z","timestamp":1756425600000},"content-version":"unspecified","delay-in-days":28,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004829","name":"Science and Technology Department of Sichuan Province","doi-asserted-by":"publisher","award":["2025ZNSFSC0045"],"award-info":[{"award-number":["2025ZNSFSC0045"]}],"id":[{"id":"10.13039\/501100004829","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82373021"],"award-info":[{"award-number":["82373021"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"1\u00b73\u00b75 Project for Disciplines of Excellence, West China Hospital, Sichuan University","award":["ZYJC21003"],"award-info":[{"award-number":["ZYJC21003"]}]},{"name":"1\u00b73\u00b75 Project for Disciplines of Excellence, West China Hospital, Sichuan University","award":["ZYYC23010"],"award-info":[{"award-number":["ZYYC23010"]}]},{"DOI":"10.13039\/100018904","name":"Beijing Xisike Clinical Oncology Research Foundation","doi-asserted-by":"crossref","award":["(Y-HS202202-0094 and Y-2024AZ(NSCLC)ZD-0267)"],"award-info":[{"award-number":["(Y-HS202202-0094 and Y-2024AZ(NSCLC)ZD-0267)"]}],"id":[{"id":"10.13039\/100018904","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2025,7,4]]},"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Lung cancer remains a leading cause of cancer-related deaths worldwide, with squamous lung cancer representing a significant subtype. Despite advancements in chemotherapy and immunotherapy, outcomes for patients with advanced squamous lung cancer remain suboptimal. Recent studies have shown that immunotherapy, particularly with programmed death receptor 1 (PD-1)\/programmed death-ligand 1 (PD-L1) inhibitors, can improve survival rates, but challenges persist in achieving durable responses. Combining immunotherapy with radiotherapy has emerged as a promising strategy. Stereotactic body radiotherapy (SBRT) can enhance the immune response by inducing tumour-specific antigen release and promoting systemic immune activation, while low-dose radiation (LDRT) may further potentiate these effects by modulating the immune environment. This study explores a novel triple-combination approach using SBRT, LDRT, sintilimab and chemotherapy to optimise therapeutic efficacy and improve outcomes in locally advanced or metastatic squamous non-small cell lung cancer (sqNSCLC).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>This is a randomised, controlled, open-label, multicentre phase II clinical trial involving patients with locally advanced or metastatic sqNSCLC. Participants are randomised 1:1 into two arms: the experimental arm receives SBRT and LDRT combined with sintilimab and chemotherapy, while the control arm receives sintilimab with chemotherapy alone. Randomisation is stratified by PD-L1 expression and the presence of brain metastases. The primary endpoint is the objective response rate. Secondary endpoints include disease control rate, progression-free survival, overall survival and safety. Based on an expected ORR of 75% for the experimental group and 55% for the control, with a 20% difference detection at 80.1% power and a two-sided \u03b1 level of 0.2, a total of 114 patients (57 per group, accounting for a 10% dropout rate) is required.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>The study protocol was approved by the Ethics Commission of Sichuan University West China Hospital (2023\u20131582), Medical Ethics Committee of Affiliated Hospital of North Sichuan Medical College (2024ER543-1), Ethics Committee of The Second Affiliated Hospital of Chongqing Medical University (2024-54-2), Ethics Committee of Union Hospital (Tongji Medical College, Huazhong University of Science and Technology) (2024-1052-02), Ethics Committee of Sichuan Cancer Hospital (SCCHEC-02-2025-069), Clinical Trial Ethics Committee of Deyang People's Hospital (2025-03-012-H01), and Ethics Committee of Guizhou Provincial People's Hospital (2025-108). Results will be submitted for publication in a peer-reviewed journal.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT06121505\">NCT06121505<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2024-094859","type":"journal-article","created":{"date-parts":[[2025,8,31]],"date-time":"2025-08-31T19:15:12Z","timestamp":1756667712000},"page":"e094859","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":4,"title":["Low-dose radiation and stereotactic body radiotherapy with PD-1 inhibitor sintilimab and chemotherapy for first-line treatment of locally advanced or metastatic squamous lung cancer: protocol for a randomised phase II trial (IHC002 study)"],"prefix":"10.1136","volume":"15","clinical-trial-number":[{"clinical-trial-number":"nct06121505","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct06121505","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-7740-3358","authenticated-orcid":false,"given":"Ruoxi","family":"Zhang","sequence":"first","affiliation":[{"name":"Division of Thoracic Tumor Multimodality Treatment, Cancer Center and State Key Laboratory of Biotherapy, and The National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mi","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Thoracic Tumor Multimodality Treatment, Cancer Center and State Key Laboratory of Biotherapy, and The National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China"},{"name":"Department of Oncology, The Third Hospital of Mianyang, Sichuan Mental Health Center, Mianyang, Sichuan, People's Republic of China\u200c"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nanhao","family":"Yin","sequence":"additional","affiliation":[{"name":"Division of Thoracic Tumor Multimodality Treatment, Cancer Center and State Key Laboratory of Biotherapy, and The National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianxin","family":"Xue","sequence":"additional","affiliation":[{"name":"Division of Thoracic Tumor Multimodality Treatment, Cancer Center and State Key Laboratory of Biotherapy, and The National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China"},{"name":"Laboratory of Clinical Cell Therapy, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2025,8,31]]},"reference":[{"key":"2025123106480739000_15.8.e094859.1","doi-asserted-by":"publisher","DOI":"10.3322\/CAAC.21834"},{"key":"2025123106480739000_15.8.e094859.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jncc.2024.01.006"},{"key":"2025123106480739000_15.8.e094859.3","doi-asserted-by":"publisher","DOI":"10.1016\/S2468-2667(23)00211-6"},{"key":"2025123106480739000_15.8.e094859.4","doi-asserted-by":"publisher","DOI":"10.1097\/JTO.0000000000000630"},{"key":"2025123106480739000_15.8.e094859.5","doi-asserted-by":"crossref","first-page":"1512","DOI":"10.1038\/s41467-024-45769-z","article-title":"Sintilimab with two cycles of chemotherapy for the treatment of advanced squamous non-small cell lung cancer: a phase 2 clinical trial","volume":"15","author":"Zhang","year":"2024","journal-title":"Nat Commun"},{"key":"2025123106480739000_15.8.e094859.6","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(23)00444-8"},{"key":"2025123106480739000_15.8.e094859.7","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.18.00149"},{"key":"2025123106480739000_15.8.e094859.8","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)32409-7"},{"key":"2025123106480739000_15.8.e094859.9","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1810865"},{"key":"2025123106480739000_15.8.e094859.10","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1001\/jamaoncol.2021.0366","article-title":"Tislelizumab plus chemotherapy vs chemotherapy alone as first-line treatment for advanced squamous non\u2013small-cell lung cancer","volume":"7","author":"Wang","year":"2021","journal-title":"JAMA Oncol"},{"key":"2025123106480739000_15.8.e094859.11","doi-asserted-by":"crossref","unstructured":"Zhou C , Wu L , Fan Y , et al . 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