{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T18:13:41Z","timestamp":1788459221965,"version":"build-2803163510"},"reference-count":31,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003787","name":"Natural Science Foundation of Hebei Province","doi-asserted-by":"publisher","award":["H2024102003"],"award-info":[{"award-number":["H2024102003"]}],"id":[{"id":"10.13039\/501100003787","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Radiation-induced lung injury (RILI) is a common and dose-limiting complication in patients with non-small cell lung cancer (NSCLC) receiving radiotherapy, especially in combination with chemotherapy and\/or immunotherapy. RILI encompasses acute radiation pneumonitis (RP) and chronic pulmonary fibrosis, significantly impacting patients\u2019 quality of life and treatment outcomes. Preclinical and clinical evidence suggests that nintedanib, a tyrosine kinase inhibitor approved for idiopathic pulmonary fibrosis (IPF), may have preventive effects against RILI due to shared fibrotic pathways. However, prospective data on its prophylactic use remain limited.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This is a randomized, multicenter, unblinded, controlled trial designed to evaluate the efficacy and safety of nintedanib in preventing RILI. A total of 66 patients with unresectable stage II-III NSCLC scheduled to receive CCRT will be enrolled from three centers in China. Eligible participants will be randomized 1:1 to either the nintedanib group or the control group. Randomization is stratified by concurrent chemotherapy regimen (etoposide-based vs. taxane-based vs. pemetrexed-based). The nintedanib group will receive oral nintedanib 150 mg twice daily, initiated 1\u20132 weeks before radiotherapy and continued for 12 weeks, followed by a voluntary treatment period from week 13 to week 24. The control group will receive CCRT alone without nintedanib. All patients will undergo standardized CCRT comprising platinum-based doublet chemotherapy (cisplatin or carboplatin combined with etoposide, taxanes, or pemetrexed) and radiotherapy (60 Gy\/30 fractions). Immunotherapy consolidation is permitted as a viable treatment option per guideline recommendations. Primary endpoint: The incidence of grade \u22652 RILI (according to CTCAE v5.0) within 6 months after radiotherapy initiation. Secondary endpoints: Time to radiological lung injury; changes in pulmonary function (FVC%, FEV1%, DLco%); tumor response outcomes (OS, PFS, ORR); safety and tolerability; and patient-reported outcomes. This trial will provide the first prospective evidence on the efficacy of nintedanib for preventing RILI in patients with unresectable stage II-III NSCLC undergoing CCRT. The results may inform clinical practice and guide future prophylactic strategies for RILI.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>\n                      This study was registered on April 16, 2025, at the Chinese Clinical Trial Registry (No. Chi\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/CTR2500100845\" xlink:type=\"simple\">CTR2500100845<\/jats:ext-link>\n                      ).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Reporting guideline<\/jats:title>\n                    <jats:p>This protocol was developed in accordance with the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guidelines.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0356205","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T17:22:57Z","timestamp":1788456177000},"page":"e0356205","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Nintedanib in the prevention of radiation-induced lung injury in patients with unresectable stage II-III NSCLC: A protocol for a randomized, multicenter, control group study"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3849-0650","authenticated-orcid":true,"given":"Ai","family":"Cui","sequence":"first","affiliation":[{"name":"Beijing Chao-Yang Hospital, Capital Medical University","place":["Beijing, P.R. China"],"department":["Department of Pulmonary and Critical Care Medicine"]},{"name":"The First Hospital of Zhangjiakou","place":["Zhangjiakou, Hebei, P.R. China"],"department":["Department of Respiratory and Critical Care Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anhui","family":"Shi","sequence":"additional","affiliation":[{"name":"Beijing Cancer Hospital","place":["Beijing, P.R. China"],"department":["Department of Radiation Oncology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Deng","sequence":"additional","affiliation":[{"name":"Cancer Hospital Chinese Academy of Medical Sciences","place":["Beijing, P.R. China"],"department":["Department of Radiation Oncology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanyan","family":"Sun","sequence":"additional","affiliation":[{"name":"Beijing Chao-Yang Hospital, Capital Medical University","place":["Beijing, P.R. China"],"department":["Department of Pulmonary and Critical Care Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayi","family":"Yu","sequence":"additional","affiliation":[{"name":"Beijing Cancer Hospital","place":["Beijing, P.R. China"],"department":["Department of Radiation Oncology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinrong","family":"Lian","sequence":"additional","affiliation":[{"name":"Cancer Hospital Chinese Academy of Medical Sciences","place":["Beijing, P.R. China"],"department":["Department of Radiation Oncology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyue","family":"Zhao","sequence":"additional","affiliation":[{"name":"The First Hospital of Zhangjiakou","place":["Zhangjiakou, Hebei, P.R. 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