{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T05:13:32Z","timestamp":1789535612244,"version":"build-2803163510"},"reference-count":30,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T00:00:00Z","timestamp":1778457600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      To comprehensively evaluate the efficacy and safety of three-dimensional (3D)-printed template-assisted CT-guided\n                      <jats:sup>125<\/jats:sup>\n                      I seed implantation for refractory bone metastases in a multicenter cohort, to explore its impact on systemic immune function and to identify potential mechanisms.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This retrospective analysis was conducted on 253 patients with refractory bone metastases who were continuously admitted to Affiliated Zhongshan Hospital of Dalian University, Linyi Cancer Hospital, The Affiliated Hospital of Xuzhou Medical University, Dalian Public Health Clinical Center, and The Second Hospital of Dalian Medical University. The onset time and the duration of pain relief were recorded. The therapeutic efficacy was evaluated by comparing pre- and postoperative Daily Oral Morphine Equivalent Consumption (OMEC), Numerical Rating Scale (NRS) for pain, Quality of Life (QOL) scores, and Karnofsky Performance Status (KPS) scores, as well as by measuring the quantitative changes in target lesion volume and Hounsfield unit (HU) values on imaging before and after the procedure. According to Response Evaluation Criteria in Solid Tumors version 1.1, the objective response rate (ORR) and disease control rate (DCR) were calculated to evaluate tumor response. Flow cytometry was used to detect and compare pre- and postoperative proportions of CD3\n                      <jats:sup>+<\/jats:sup>\n                      CD16\n                      <jats:sup>+<\/jats:sup>\n                      \/CD56\n                      <jats:sup>+<\/jats:sup>\n                      natural killer-like T (NKT) cells and CD3\n                      <jats:sup>\u2212<\/jats:sup>\n                      CD16\n                      <jats:sup>+<\/jats:sup>\n                      \/CD56\n                      <jats:sup>+<\/jats:sup>\n                      NK cells, interleukin (IL)-17A level, and CD4\n                      <jats:sup>+<\/jats:sup>\n                      \/CD8\n                      <jats:sup>+<\/jats:sup>\n                      T-cell ratio, to assess the changes in host immune function after treatment. Local progression-free survival (LPFS) and overall survival (OS) were calculated, and adverse events were documented.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      All patients completed 3D-printed template-assisted CT-guided\n                      <jats:sup>125<\/jats:sup>\n                      I seed implantation, with a procedural success rate of 100%. The clinical symptoms improved after treatment; the median onset time to pain relief was 3.5 days, and the median duration of relief was 10.7 months. The OMEC values and the NRS scores were significantly lower than those before procedure (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.05), whereas QOL and KPS scores were significantly higher (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.05). The radiologic evaluation showed that ORR and DCR were 42.29% and 69.56%, and 79.05% and 88.93%, respectively, at 1 and 6 months after implantation. The target lesion volumes reduced significantly (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.05), whereas the HU value increased significantly (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.05), indicating tumor necrosis and osteoblastic repair. The median LPFS was 14.1 months, and the median OS was 19.5 months. The immune function analysis revealed enhanced antitumor immune response, reflected by significant increases in the proportions of NKT cells, NK cells, and CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells, a decrease in IL-17A level, and a trend toward normalization of the CD4\n                      <jats:sup>+<\/jats:sup>\n                      \/CD8\n                      <jats:sup>+<\/jats:sup>\n                      ratio (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.05). Adverse events mainly consisted of transient local pain of Common Terminology Criteria for Adverse Events grades 1\u20132. No uncontrollable major bleeding, needle-track seeding, or other severe complication, and no treatment-related death occurred.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      The 3D-printed template-assisted CT-guided\n                      <jats:sup>125<\/jats:sup>\n                      I seed implantation was a safe and effective treatment for refractory bone metastases. It provided durable local tumor control and pain relief, and was accompanied by systemic immunological changes. These changes correlated with clinical improvements, suggesting a potential immunological component to the therapeutic effect. This therapy therefore provided a promising treatment strategy for refractory bone metastases.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0347893","type":"journal-article","created":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T17:40:42Z","timestamp":1778521242000},"page":"e0347893","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["The radioactive 3D-printed template-assisted CT-guided 125I seed implantation for refractory bone metastases: A multicenter retrospective analysis of efficacy, safety, and immune function changes"],"prefix":"10.1371","volume":"21","author":[{"given":"Guang Sheng","family":"Zhao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hou Ze","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiu Shi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin Yu","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin Bo","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruo Yu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0171-9263","authenticated-orcid":true,"given":"Jun","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bu Qiang","family":"Zhuang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,5,11]]},"reference":[{"issue":"10","key":"pone.0347893.ref001","doi-asserted-by":"crossref","first-page":"1647","DOI":"10.1016\/j.jtho.2020.06.011","article-title":"A Randomized Open-Label Phase III Trial Evaluating the Addition of Denosumab to Standard First-Line Treatment in Advanced NSCLC: The European Thoracic Oncology Platform (ETOP) and European Organisation for Research and Treatment of Cancer (EORTC) SPLENDOUR Trial","volume":"15","author":"S Peters","year":"2020","journal-title":"J Thorac Oncol"},{"issue":"2","key":"pone.0347893.ref002","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1007\/s10549-020-05712-4","article-title":"Risk factors for skeletal-related events in patients with bone metastasis from breast cancer undergoing treatment with zoledronate","volume":"182","author":"H Miyashita","year":"2020","journal-title":"Breast Cancer Res Treat"},{"issue":"4","key":"pone.0347893.ref003","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1007\/s10147-019-01589-6","article-title":"A randomized, double-blind, comparison of radium-223 and placebo, in combination with abiraterone acetate and prednisolone, in castration-resistant metastatic prostate cancer: subgroup analysis of Japanese patients in the ERA 223 study","volume":"25","author":"N Matsubara","year":"2020","journal-title":"Int J Clin Oncol"},{"issue":"5","key":"pone.0347893.ref004","doi-asserted-by":"crossref","first-page":"621","DOI":"10.3892\/br.2015.483","article-title":"Advances in the clinical research of the minimally invasive treatment for the posterior edge of vertebral-body defects by spinal metastases","volume":"3","author":"X Liu","year":"2015","journal-title":"Biomed Rep"},{"key":"pone.0347893.ref005","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0234927","article-title":"Bone metastasis and skeletal-related events in patients with solid cancer: A Korean nationwide health insurance database study","volume":"15","author":"S Hong","year":"2020","journal-title":"PLoS One"},{"issue":"8","key":"pone.0347893.ref006","doi-asserted-by":"crossref","first-page":"6337","DOI":"10.1007\/s11033-020-05684-0","article-title":"Bone metastases: a comprehensive review of the literature","volume":"47","author":"F Migliorini","year":"2020","journal-title":"Mol Biol Rep"},{"issue":"23","key":"pone.0347893.ref007","doi-asserted-by":"crossref","first-page":"6047","DOI":"10.3390\/ijms20236047","article-title":"Bone Pain in Cancer Patients: Mechanisms and Current Treatment","volume":"220","author":"R Zaj\u0105czkowska","year":"2019","journal-title":"Int J Mol Sci"},{"issue":"2","key":"pone.0347893.ref008","first-page":"57","article-title":"Expert consensus on the diagnosis and treatment of bone metastasis in lung cancer (2014 version)","volume":"17","author":"Y Sun","year":"2014","journal-title":"Zhongguo Fei Ai Za Zhi"},{"issue":"11","key":"pone.0347893.ref009","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1200\/JCO.2006.09.5281","article-title":"Palliative radiotherapy trials for bone metastases: a systematic review","volume":"25","author":"E Chow","year":"2007","journal-title":"J Clin Oncol"},{"issue":"5","key":"pone.0347893.ref010","doi-asserted-by":"crossref","first-page":"742","DOI":"10.4103\/jcrt.JCRT_399_17","article-title":"Brachytherapy with iodine 125 seeds for bone metastases","volume":"13","author":"W Wang","year":"2017","journal-title":"J Cancer Res Ther"},{"key":"pone.0347893.ref011","doi-asserted-by":"crossref","first-page":"101618","DOI":"10.1016\/j.suronc.2021.101618","article-title":"Iodine-125 radioactive seed brachytherapy as a treatment for spine and bone metastases: A systematic review and meta-analysis","volume":"38","author":"R Sharma","year":"2021","journal-title":"Surg Oncol"},{"issue":"1","key":"pone.0347893.ref012","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1186\/s12885-020-07223-3","article-title":"Evaluation of radioactive 125I seed implantation for the treatment of refractory malignant tumours based on a CT-guided 3D template-assisted technique: efficacy and safety","volume":"20","author":"GS Zhao","year":"2020","journal-title":"BMC Cancer"},{"key":"pone.0347893.ref013","doi-asserted-by":"crossref","first-page":"1667205","DOI":"10.3389\/fonc.2025.1667205","article-title":"Analysis of short-term clinical efficacy and immune function changes of advanced non-small cell lung cancer after radiotherapy or chemotherapy under CT-guided 125I seed implantation","volume":"15","author":"S Chen","year":"2025","journal-title":"Front Oncol"},{"issue":"2","key":"pone.0347893.ref014","article-title":"Stereotactic Body and Conventional Radiotherapy for Painful Bone Metastases: A Systematic Review and Meta-Analysis","volume":"7","author":"BJJ Bindels","year":"2024","journal-title":"JAMA Netw Open"},{"issue":"1","key":"pone.0347893.ref015","article-title":"Hemibody Irradiation for Bone Metastases: A Systematic Review and Meta-Analysis","volume":"16","author":"L Berk","year":"2024","journal-title":"Cureus"},{"key":"pone.0347893.ref016","first-page":"147","article-title":"3D-printed template and optical needle navigation in CT-guided iodine-125 permanent seed implantation","volume":"85","author":"S Liu","year":"2021","journal-title":"Polski Przeglad Radiologiczny"},{"key":"pone.0347893.ref017","first-page":"723","article-title":"125I seed brachytherapy versus external beam radiotherapy for painful bone metastases from lung cancer: a retrospective study","volume":"62","author":"J Xiang","year":"2021","journal-title":"J Pain Symptom Manage"},{"issue":"6","key":"pone.0347893.ref018","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1001\/jamaoncol.2019.0192","article-title":"Single-Fraction Stereotactic vs Conventional Multifraction Radiotherapy for Pain Relief in Patients With Predominantly Nonspine Bone Metastases: A Randomized Phase 2 Trial","volume":"5","author":"Q-N Nguyen","year":"2019","journal-title":"JAMA Oncol"},{"issue":"2","key":"pone.0347893.ref019","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1016\/j.ijrobp.2020.11.060","article-title":"Pain Response After Stereotactic Body Radiation Therapy Versus Conventional Radiation Therapy in Patients With Bone Metastases-A Phase 2 Randomized Controlled Trial Within a Prospective Cohort","volume":"110","author":"BJ Pielkenrood","year":"2021","journal-title":"Int J Radiat Oncol Biol Phys"},{"issue":"1","key":"pone.0347893.ref020","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1136\/bmjspcare-2021-003285","article-title":"Bone pain from spinal metastases: Iodine-125 brachytherapy","volume":"15","author":"H Shao","year":"2024","journal-title":"BMJ Support Palliat Care"},{"issue":"10","key":"pone.0347893.ref021","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.1007\/s00256-017-2706-6","article-title":"Quantitative contrast-enhanced CT attenuation evaluation of osseous metastases following chemotherapy","volume":"46","author":"CY Chang","year":"2017","journal-title":"Skeletal Radiol"},{"issue":"3","key":"pone.0347893.ref022","doi-asserted-by":"crossref","DOI":"10.1002\/acm2.13840","article-title":"Characteristics of preplan-based three-dimensional individual template-guided brachytherapy compared to freehand implantation","volume":"24","author":"B Zhang","year":"2023","journal-title":"J Appl Clin Med Phys"},{"issue":"7","key":"pone.0347893.ref023","doi-asserted-by":"crossref","first-page":"1430","DOI":"10.4103\/jcrt.JCRT_434_19","article-title":"Expert consensus on computed tomography-assisted three-dimensional-printed coplanar template guidance for interstitial permanent radioactive 125I seed implantation therapy","volume":"15","author":"J Wang","year":"2019","journal-title":"J Cancer Res Ther"},{"issue":"5","key":"pone.0347893.ref024","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1007\/s00066-021-01748-7","article-title":"Cumulative dose, toxicity, and outcomes of spinal metastases re-irradiation\u00a0: Systematic review on behalf of the Re-Irradiation Working Group of the Italian Association of Radiotherapy and Clinical Oncology (AIRO)","volume":"197","author":"A Pontoriero","year":"2021","journal-title":"Strahlenther Onkol"},{"issue":"1","key":"pone.0347893.ref025","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1269\/jrr.06048","article-title":"Effects of low-dose irradiation on enhancement of immunity by dendritic cells","volume":"48","author":"A Shigematsu","year":"2007","journal-title":"J Radiat Res"},{"issue":"1","key":"pone.0347893.ref026","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1158\/2159-8290.CD-21-0003","article-title":"Low-Dose Radiotherapy Reverses Tumor Immune Desertification and Resistance to Immunotherapy","volume":"12","author":"FG Herrera","year":"2022","journal-title":"Cancer Discov"},{"key":"pone.0347893.ref027","doi-asserted-by":"crossref","first-page":"2561","DOI":"10.2147\/OTT.S137491","article-title":"Analysis of immune status after iodine-125 permanent brachytherapy in prostate cancer","volume":"10","author":"E Du","year":"2017","journal-title":"Onco Targets Ther"},{"key":"pone.0347893.ref028","doi-asserted-by":"crossref","first-page":"1084904","DOI":"10.3389\/fonc.2023.1084904","article-title":"Efficacy and safety of CT-guided 125I seed implantation by coplanar template as a salvage therapy for vertebral metastases after failure of external beam radiation therapy: a retrospective study","volume":"13","author":"P Li","year":"2023","journal-title":"Front Oncol"},{"issue":"1","key":"pone.0347893.ref029","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1186\/s12957-016-1050-y","article-title":"Palliative treatment of pelvic bone tumors using radioiodine (125I) brachytherapy","volume":"14","author":"C Wang","year":"2016","journal-title":"World J Surg Oncol"},{"issue":"8","key":"pone.0347893.ref030","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.3390\/cells11081309","article-title":"Translational Strategies to Target Metastatic Bone Disease","volume":"11","author":"GM Pagnotti","year":"2022","journal-title":"Cells"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0347893","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T17:40:48Z","timestamp":1778521248000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0347893"}},"subtitle":[],"editor":[{"given":"Xing-Xiong","family":"An","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,5,11]]},"references-count":30,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,5,11]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0347893","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,11]]}}}