Clinical outcomes of radioactive 125 I seed brachytherapy for recurrent refractory differentiated thyroid cancers

Clinical outcomes of radioactive 125 I seed brachytherapy for recurrent refractory differentiated thyroid cancers | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Clinical outcomes of radioactive 125 I seed brachytherapy for recurrent refractory differentiated thyroid cancers Zhen Gao, Yixing Li, Jinzhao Dai, Xuemin Di, Zezhou Liu, Huimin Yu, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5869645/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract [ Objective: ]The purpose of this research was to evaluate the feasibility and efficacy of 125I seed brachytherapy for recurrent refractory differentiated thyroid cancers. [ Methods ]:Between August 2005 and March 2023 33 patients with recurrence refractory of differentiated thyroid cancer were treated with 125I seed brachytherapy. 125I seeds were implanted into the tumor under the guidance of CT and/or 3D-printed template images with the median prescription dose of 126 Gy (range, 90-155 Gy). The median seed number was 54 (range 8-214). Clinical efficacy was evaluated with Response Evaluation Criteria in Solid Tumors. Follow-up Survival and adverse events were analyzed. [ Results: ] 125 I seeds were successfully implanted in 44 lesions among 33 patients. Lesions included 34 cervical lymph node metastases, 2 cases of recurrent thyroid lesions, 2 cases of pulmonary metastases, 3 cases of bone metastases,1 cases of pleural metastases, 1 case of mediastinal lymph node involvement, and 1 case of back soft tissue metastasis. Patients were monitored for 6–96 months. Six months postoperatively, CT images revealed 26 cases of CR, 14 cases of PR, and 4 cases of Stable Disease (SD). The ORR was 90.9% (40/44), and the LCR reached 100% (44/44) at 6 months. The median OS was 40.7 months, with 1-year,2-year,3-year, 4-year and 5-year survival rates of 91%, 88%, 74%,64.5%,and 51%, respectively.14 patients had died due to systemic metastases.No severe complications occurred. [ Conclusions: ]CT-guided iodine-125 brachytherapy provided a safe and effective choice for recurrent refractory differentiated thyroid cancers with significant local therapeutic effects and minor complications. thyroid cancer recurrence refractory brachytherapy efficacy evaluation iodine-125 seeds Figures Figure 1 INTRODUCTION The incidence of thyroid cancer has consistently been increasing over the past years [ 1 ] . Differentiated thyroid carcinoma (DTC), arising from thyroid follicular epithelial cells, accounts for 90% of these cases [ 2 ] . Despite the good prognosis of DTC following standardized surgery, radioactive iodine-131 ( 131 I) seed therapy, and thyroid hormone suppression, disease progression or recurrence occurs in 14.9% of these patients [ 3 ] , leading to locally advanced DTC. This manifests as invasion of vital peripheral structures, such as the recurrent laryngeal nerve, trachea, esophagus, larynx, cervical large vessels, superior mediastinum, and skin muscles, requiring repeated surgical resections and repairs, which leads to tissue injury and impacts organ function. During postoperative 131 I seed therapy, 30% of the patients develop 131 I resistance, leading to iodine refractory DTC [ 4 , 5 ] and a poor overall prognosis . Tyrosine kinase inhibitors (TKIs) have demonstrated activity in radioiodine refractory differentiated thyroid carcinoma (RR-DTC),but the lack of long-term survival data and the relatively indolent nature of DTC make it difficult to determine the appropriate time for initiating TKI therapy [ 6 ] . Localized treatment plays an important role in local recurrence and/or metastases in RR-DTC. Locoregional metastases in DTC have historically been treated surgically, but repeated neck excisions are associated with a high risk of complications [ 7 , 8 ] . There is a lack of standard treatment options for recurrent or refractory DTCs. Therefore, it is desirable to develop less invasive alternatives to repeated surgeries as part of multimodal DTC treatment. Iodine-125 ( 125 I) seed implantation with low-dose rate (LDR) is a type of brachytherapy characterized by a sharp drop in the fall off dose, allowing accurate dose delivery and sparing the normal tissues, which is not possible with EBRT. It has previously been used as a standard therapy for localized prostate carcinomas [ 9 , 10 ] . An increasing number of studies have demonstrated adequate efficacy of 125 I brachytherapy in several solid tumors [ 11 – 13 ] . However, the use of this technique for the local control of DTC foci has rarely been reported. Therefore, we conducted a retrospective study to evaluate the efficacy and safety of 125 I brachytherapy for the treatment of recurrent refractory DTCs, providing a reference for clinical practice and future research. MATERIALS AND METHODS Clinical Information The present study investigated cases of recurrence refractory DTCs treated with 125 I brachytherapy. The data, combining information from three medical centers, was retrospectively screened from August 2005 to March 2023. Specifically, there were 10 cases from the Department of Nuclear Medicine at the First College of Clinical Medical Science, China Three Gorges University; 6 cases from the Department of Nuclear Medicine at the Affiliated Qingdao Central Hospital of Qingdao University; and 17 cases from the Department of Oncology at Hebei General Hospital. Inclusion criteria for the participants were: 1) pathologically confirmed diagnosis of DTC; 2) inability to tolerate or refusal of surgical resection and external radiotherapy, or iodine-resistant thyroid cancer; 3) Karnofsky Performance Score (KPS) of ≥ 60; 4) normal blood routine examination and coagulation function; and 5) expected survival of ≥ 3 months. Exclusion criteria included severe organ dysfunction, coagulation dysfunction (with anticoagulant therapy cessation at least 5–7 days before implantation), poor general condition or cachexia, and lack of CT and other imaging data after 125 I seed implantation. The decision to deliver brachytherapy was discussed in a multidisciplinary tumor board for all cases. If treatment was recommended, patients were informed of the benefits and potential risks of brachytherapy, and written consent was obtained before participation in the protocol. Detailed patient and tumor characteristics are summarized in Table 1. Table 1. Clinical characteristics of the patients treated with 125 I-seed implantation Parameter Characteristics No. of patients Percentage（%） Sex Male 15 45% Female 18 55% Age <55 years 10 30% ≥55years 23 70% DTC subtype PTC 31 94% FTC 2 6% Previous treatment regimen Surgery 29 88% RAI-131 27 81% External radiotherapy 2 6% Targeted therapy 3 9% Ablation therapy 1 3% Endotracheal stent implant 1 3% Surgery location Neck lymph nodes 34 77% Recurrent thyroid lesions 2 5% Bone 3 7% Pulmonary 2 5% Pleura 1 2% Mediastinal lymph nodes 1 2% Back soft tissue metastasis 1 2% Initial tumor volume (cm 3 ) <50 34 77% ≥50 10 23% Implant and guide technique CT and US 3D 38 6 86% 14% Instruments and equipment Mick Radio-Nuclear company (USA) supplied the 18-G implantation needles and seed implant applicator for this study. The 125 I seeds (ZHIBO Bio-Medical Tech Ltd., Beijing, China) were cylindrical, measuring 4.5 mm in length and 0.8 mm in diameter. The seeds had an activity range of 0.3–3.0 mCi and a half-life of 59.4 days, emitting g-ray energy at 27–35 keV. The tissue half-value layer was 1.7 cm, and approximately 93–97% of the seed’s energy was delivered into the tumor after 8–10 months. For treatment planning, the Panther Brachy version 5.0 (Prowess Inc., Concord, CA, USA) treatment planning system (TPS) was utilized. The RM-905a radioactivity meter, provided by the Chinese Institute of Metrology, was used for measurements. Imaging involved performing PET-CT (Discovery CT750 HD, GE, USA). 125 I seed implantation Preoperative preparation: One week prior to surgery, enhanced CT scan with a slice thickness of 5 mm was conducted. The images were transmitted to the TPS to create a preoperative plan. The prescribed dose for 125 I seed implantation involved D90, V100, and V150, covering the Planning Treatment Volume (PTV). The PTV included the entire Gross Tumor Volume (GTV) along with 0.5- to 1.0-cm margins. Operation procedure: Intraoperatively, the position remained consistent with the preoperative design. Local anesthesia with 1% lidocaine was administered. CT and ultrasound localization scans were performed to determine the puncture point, angle, and depth from the body surface. Following the preoperative plan, particles were sparsely implanted at 0.5–1.0 cm intervals. Immediate postoperative CT scans were obtained to observe the spatial distribution of particles, and re-implantation was performed in areas with dosimetric cold spots. Postoperative treatment: Postoperative CT scan images were verified for quality by transferring them to the TPS. The actual dose to the tumor was determined using the Dose-Volume Histogram (DVH). Follow-up and clinical efficacy evaluation Follow-up CT scans were conducted at 1 month, 3 months, 6 months, and subsequently every 3 months after the procedure. The primary endpoints were the Objective Response Rate (ORR) and Tumor Local Control Rate (LCR). ORR was defined as the proportion of patients achieving Complete Response (CR) and Partial Response (PR). LCR was calculated as (CR + PR + SD/total cases)%. Secondary endpoints comprised Overall Survival (OS) and the incidence of adverse events. The clinical efficacy of 125 I brachytherapy was evaluated using the Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1). OS was defined as the duration between 125 I brachytherapy and the last follow-up or death. Adverse reactions were evaluated following the new classification of the Society of Interventional Radiology. Complications The patients were observed for complications, including fever, bleeding, bone marrow suppression, liver and kidney dysfunction, radioactive skin and mucosal reactions, and particle displacement, after seed implantation. The skin-mucosal response was assessed according to the Radiological Collaboration in Oncology/ European Research and Treatment in Oncology (RTOC/EORTC) radiological injury grading criteria. Statistical analysis Data analysis was performed using SPSS (version 24.0). Continuous variables were expressed as means ± SD. Survival analysis was performed using the Kaplan-Meier method. A p-value < 0.05 was considered statistically significant. RESULTS 125 I implantation and dosimetry A total of 33 patients received 125 I seed implantation to meet the TPS criteria, followed by postoperative dose evaluation. The seed activity was 0.3–3.0 mCi, and the median number of 125 I seeds implanted was 54 (range: 8–214) with a median dose 90 (D90) of 126 Gy (range: 90–155 Gy) Clinical efficacy evaluation and OS According to the initial plan, 125 I seeds were successfully implanted in 44 lesions among 33 patients. Lesions included 34 cervical lymph node metastases, 2 cases of recurrent thyroid lesions, 2 cases of pulmonary metastases, 3 cases of bone metastases,1 cases of pleural metastases, 1 case of mediastinal lymph node involvement, and 1 case of back soft tissue metastasis. All patients tolerated the procedure well. Patients were monitored for 6–96 months. Six months postoperatively, CT images revealed 26 cases of CR, 14 cases of PR, and 4 cases of Stable Disease (SD). The ORR was 90.9% (40/44), and the LCR reached 100% (44/44) at 6 months. Survival analysis spanned 6–96 months. The median OS was 40.7 months, with 1-year,2-year,3-year, 4-year and 5-year survival rates of 91%, 88%, 74%,64.5%,and 51%, respectively. Figure 1 illustrates the actuarial curve for OS. At the last follow-up, 14 patients had died due to systemic metastases. Adverse events There were no complications, including fever, hemorrhage, bone marrow suppression, liver and kidney dysfunction, radioactive skin and mucous membrane reactions, and particle displacement, during the follow-up period in any of the patients. Furthermore, no RTOG/EORTC grade > 2 complications were observed. Six patients experienced mild pain after implantation, which resolved spontaneously. DISCUSSION Thyroid cancer typically exhibits a benign biological behavior, resulting in an excellent prognosis for the majority of patients. However, 15–30% of the patients may develop lymph node metastasis, predominantly in cervical lymph nodes. Recurrent DTCs often respond well to salvage treatment, involving radioactive iodine (RAI), additional surgery, and hormone suppression [ 14 , 15 ] . Despite these interventions, approximately one-third of the patients experience dedifferentiation during initial or ongoing treatment due to various driver gene changes. This dedifferentiation leads to the loss of iodine uptake capacity in cervical lymph node metastases, transforming them into radioactive iodine-refractory differentiated thyroid carcinomas (RAIR-DTCs). A subset of patients may face challenges with local metastasis, unsuitable for repeated neck surgery and resistant to RAI ablation. Addressing refractory recurrences and metastases poses a significant challenge in DTC management. Limited treatment options exist, with TKIs, specifically oral antiangiogenic multitargeted TKIs, demonstrating a progression-free survival benefit in phase 3 trials [ 16 , 17 ] . However, these drugs carry substantial toxicities that can impact quality of life, and some individuals cannot tolerate them [ 18 , 19 ] . The 2015 ATA guidelines propose ablative therapy, external radiation therapy, and particle implantation as considerations for patients with inoperable, progressive, or symptomatic metastases (exhibiting tracheal or esophageal invasion, recurrent laryngeal nerve compression, or local pain). These therapies aim to enhance survival rates and provide palliative care [ 2 ] . Despite these recommendations, there is no universally accepted treatment for refractory thyroid cancer recurrence. External beam radiotherapy may be considered for unresectable tumors, though its role in DTC remains debated due to potential severe damage to normal tissues and functions [ 20 ] . In recent years, interventional therapy techniques have gained attention. Commonly used methods include thermal ablation, anhydrous ethanol ablation, and 125 I particle implantation. Each technique has its own advantages and limitations. Ethanol injection is generally recommended for lesions with a diameter exceeding 10 mm, often requiring repeated treatments [ 21 , 22 ] . Laser ablation is suitable for lesions with a maximum diameter less than 10 mm [ 23 , 24 ] . Radiofrequency ablation and microwave ablation have specific site requirements due to intraoperative heat conduction and thermal damage [ 25 , 26 ] . 125 I seed implantation, a LDR brachytherapy, releases low-energy gamma rays continuously, ensuring safety with a sharp dose drop-off. Only a 1.7-cm soft tissue thickness is sufficient to shield half the radiation dosage [ 27 ] . This approach has emerged as a salvage method for various tumors, including recurrent gliomas, retroperitoneal recurrent carcinoma, and recurrent cancers in the head, neck, and ovaries [ 28 – 31 ] . In our center, 125 I seed implantation has proven effective and safe for numerous solid tumors, including lung cancer [ 32 ] , skin squamous cell carcinoma [ 33 ] , malignant solitary fibrous tumor [ 34 ] , and as a salvage treatment for lymph metastases or locoregional recurrence [ 35 , 36 ] . However, limited studies have addressed recurrent refractory thyroid cancer patients. Previous research has assessed the therapeutic efficacy of 125 I seed implantation for thyroid cancer, achieving 1-, 2-, 3-, 4-, and 5-year local control rates of 92.9%, 83.3%, 54.6%, 45.5%, and 40.0%, respectively [ 36 ] . The present study conducted a preliminary analysis of the clinical efficacy and safety of 125 I seed implantation in treating 33 cases of recurrent refractory thyroid cancer patients. Results indicated that the ORR and LCR at 6 months post- 125 I seed implantation therapy were 90.9% and 100%, respectively, outperforming our research center’s previous study [ 36 ] . This improvement may be attributed to the differentiated nature of all cases and their inert biological characteristics. The study’s reliability was enhanced by its multi-center design, reinforcing the earlier findings. In this investigation, cases with 125 I seed implants exhibited a broad lesion volume range (7.9–448 cm 3 ) and various lesion locations. No procedure failed, indicating the method’s wide applicability and good tolerance. However, based on our experience, permanent implantation of 125 I seeds in a large tumor carries a risk of loss of control and complications. In this study, 10 patients with tumors larger than 50 cm 3 underwent successful implantation without technical failure, demonstrating the method’s repeatability and operability. Four cases with tumors accompanied by liquefaction necrosis suggested draining the necrotic region first, maintaining unobstructed drainage, changing medicine promptly, and then implanting seeds into the solid part of the tumor multiple times. To date, the dose and activity choice for 125 I seed implantation remain controversial, lacking standard guidelines. Our previous study indicated the safety of 125 I seed brachytherapy with a dose (EQD2) of 85–123.25 Gy for previously treated patients. In this study, the median prescription dose was 126 Gy (range: 90–155 Gy), higher than in previous studies, but without serious complications, affirming its safety. Compared to EBRT, the key advantage of 125 I seed brachytherapy lies in enhancing the target dose while reducing the dose to organs at risk, potentially yielding improved results. Additionally, multiple salvage 125 I seed treatments after local failure further add to the therapy’s advantages. Despite these promising findings, the study had limitations. It was a retrospective, multi-center clinical study, and future prospective investigations are required to minimize bias. The relatively small patient cohort suggests the need for larger studies to confirm our findings. Being a single-arm study without parallel controls, only external historical data could be used for comparison, introducing potential bias in result evaluation. In conclusion, CT-guided 125 I seed implantation brachytherapy emerged as a safe and effective radiation technique for recurrent thyroid cancers, demonstrating a definite curative local therapeutic effect and safety. This therapy holds promise as a new strategy for thyroid cancer recurrence, particularly in elderly patients with complications ineligible for surgical resection or not benefiting from EBRT and systemic therapy. Declarations Acknowledgements The authors would like to thank all the patients who participated in the study. Authors' contributions Zhen Gao and Hongtao Zhang drafted the paper and conducted the literature review. Yixing,Li and Jinzhao Dai completed the operation of seed implantation.Huimin Yu and and Xuemin Di revised the manuscript by making the required corrections.Zezhou Liu and Juan Wang designed the pre-plan . Xiaoli Liu is the oncologist who follows the patient. All authors reviewed the manuscript. Funding All authors declare that they have no competing interest. Availability of data and materials The datasets in this retrospective study are available from corresponding author on reasonable request. The confidential patient data should not be shared. Ethics approval and consent to participate This retrospective study was approved by the Ethics Committee of Hebei Provincial People's Hospital. Written informed consent was obtained from all individual participants included in the study. Consent for publication Not applicable. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5869645","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":405722648,"identity":"c9b07e43-1d5f-473a-b0e3-0808590ca789","order_by":0,"name":"Zhen Gao","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAzUlEQVRIiWNgGAWjYJACZiCWsz/e2PjwAylajBnOHG42liBFSyLDjfQ2AR5ilMu7Hz78uaDiTgLjzIdtDBIMdnK6DQS0GJ5JSzCeceZZHrN0YtuDAoZkY7MDhLQ05Bgk87YdLmaTTmw3kGA4kLiNoJb+NwaHef8dTuyRPNgmwUOMFnmJHMNm3obDiTMkGInUYiDxLJmZ59hhYwOeRGAgGxDhF/n+5MOfeWoOyxmwH3/48EOFnRxBLQaoCgwIKAfb0kCEolEwCkbBKBjhAAAUF0NDrEb4TAAAAABJRU5ErkJggg==","orcid":"","institution":"Hebei General Hospital","correspondingAuthor":true,"prefix":"","firstName":"Zhen","middleName":"","lastName":"Gao","suffix":""},{"id":405722649,"identity":"f04a7a4e-4f1f-4707-af80-1029809d1022","order_by":1,"name":"Yixing Li","email":"","orcid":"","institution":"The First College of Clinical Medical Science of Three Gorges University, Yichang Central Peoples Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yixing","middleName":"","lastName":"Li","suffix":""},{"id":405722650,"identity":"8ecc5d98-981b-41ad-b29c-a1c934c6750b","order_by":2,"name":"Jinzhao Dai","email":"","orcid":"","institution":"Affiliated Qingdao Central Hospital of Qingdao University, Qingdao Cancer Hospital","correspondingAuthor":false,"prefix":"","firstName":"Jinzhao","middleName":"","lastName":"Dai","suffix":""},{"id":405722651,"identity":"8108934d-bd2b-470d-bac9-17ffd1b1ea36","order_by":3,"name":"Xuemin Di","email":"","orcid":"","institution":"Hebei General Hospital","correspondingAuthor":false,"prefix":"","firstName":"Xuemin","middleName":"","lastName":"Di","suffix":""},{"id":405722652,"identity":"d533b292-8190-4163-87b1-1a03e3d3c479","order_by":4,"name":"Zezhou Liu","email":"","orcid":"","institution":"Hebei General Hospital","correspondingAuthor":false,"prefix":"","firstName":"Zezhou","middleName":"","lastName":"Liu","suffix":""},{"id":405722653,"identity":"b1976d0c-732c-4fc1-8f0d-943feed179df","order_by":5,"name":"Huimin Yu","email":"","orcid":"","institution":"Hebei General Hospital","correspondingAuthor":false,"prefix":"","firstName":"Huimin","middleName":"","lastName":"Yu","suffix":""},{"id":405722654,"identity":"11cec8ab-fe1b-4f03-9ea7-90cecd19c70e","order_by":6,"name":"Xiaoli Liu","email":"","orcid":"","institution":"Hebei General Hospital","correspondingAuthor":false,"prefix":"","firstName":"Xiaoli","middleName":"","lastName":"Liu","suffix":""},{"id":405722655,"identity":"d0087af7-cc75-4bcf-aad7-502a67e9e98a","order_by":7,"name":"Juan Wang","email":"","orcid":"","institution":"Hebei General Hospital","correspondingAuthor":false,"prefix":"","firstName":"Juan","middleName":"","lastName":"Wang","suffix":""},{"id":405722656,"identity":"e57f1ac2-12c7-4563-bca1-bd036e47c8f8","order_by":8,"name":"Hongtao Zhang","email":"","orcid":"","institution":"Hebei General Hospital","correspondingAuthor":false,"prefix":"","firstName":"Hongtao","middleName":"","lastName":"Zhang","suffix":""}],"badges":[],"createdAt":"2025-01-21 03:08:10","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5869645/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5869645/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":74588845,"identity":"5cedfc54-b1c7-47a0-a8f6-ca6035be37fb","added_by":"auto","created_at":"2025-01-23 17:20:05","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":34861,"visible":true,"origin":"","legend":"\u003cp\u003eThe overall survival rates of the patients after 125I seed brachytherapy\u003c/p\u003e","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5869645/v1/8de0f24e22d674ea45374896.jpg"},{"id":74645923,"identity":"ba6a1532-c55b-4548-a465-79f3222f8a93","added_by":"auto","created_at":"2025-01-24 09:54:13","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":616895,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5869645/v1/4dcae9b1-9b38-4e4a-b700-cda6e1a3f967.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Clinical outcomes of radioactive 125 I seed brachytherapy for recurrent refractory differentiated thyroid cancers","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eThe incidence of thyroid cancer has consistently been increasing over the past years\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e. Differentiated thyroid carcinoma (DTC), arising from thyroid follicular epithelial cells, accounts for 90% of these cases\u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e. Despite the good prognosis of DTC following standardized surgery, radioactive iodine-131 (\u003csup\u003e131\u003c/sup\u003eI) seed therapy, and thyroid hormone suppression, disease progression or recurrence occurs in 14.9% of these patients\u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e, leading to locally advanced DTC. This manifests as invasion of vital peripheral structures, such as the recurrent laryngeal nerve, trachea, esophagus, larynx, cervical large vessels, superior mediastinum, and skin muscles, requiring repeated surgical resections and repairs, which leads to tissue injury and impacts organ function. During postoperative \u003csup\u003e131\u003c/sup\u003eI seed therapy, 30% of the patients develop \u003csup\u003e131\u003c/sup\u003eI resistance, leading to iodine refractory DTC\u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e and a poor overall prognosis .\u003c/p\u003e \u003cp\u003eTyrosine kinase inhibitors (TKIs) have demonstrated activity in radioiodine refractory differentiated thyroid carcinoma (RR-DTC),but the lack of long-term survival data and the relatively indolent nature of DTC make it difficult to determine the appropriate time for initiating TKI therapy\u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e. Localized treatment plays an important role in local recurrence and/or metastases in RR-DTC. Locoregional metastases in DTC have historically been treated surgically, but repeated neck excisions are associated with a high risk of complications\u003csup\u003e[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e. There is a lack of standard treatment options for recurrent or refractory DTCs. Therefore, it is desirable to develop less invasive alternatives to repeated surgeries as part of multimodal DTC treatment.\u003c/p\u003e \u003cp\u003eIodine-125 (\u003csup\u003e125\u003c/sup\u003eI) seed implantation with low-dose rate (LDR) is a type of brachytherapy characterized by a sharp drop in the fall off dose, allowing accurate dose delivery and sparing the normal tissues, which is not possible with EBRT. It has previously been used as a standard therapy for localized prostate carcinomas\u003csup\u003e[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e. An increasing number of studies have demonstrated adequate efficacy of \u003csup\u003e125\u003c/sup\u003eI brachytherapy in several solid tumors\u003csup\u003e[\u003cspan additionalcitationids=\"CR12\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e. However, the use of this technique for the local control of DTC foci has rarely been reported. Therefore, we conducted a retrospective study to evaluate the efficacy and safety of \u003csup\u003e125\u003c/sup\u003eI brachytherapy for the treatment of recurrent refractory DTCs, providing a reference for clinical practice and future research.\u003c/p\u003e"},{"header":"MATERIALS AND METHODS","content":"\u003cp\u003e\u003cstrong\u003eClinical Information\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe present study investigated cases of recurrence refractory DTCs treated with\u0026nbsp;\u003csup\u003e125\u003c/sup\u003eI brachytherapy. The data, combining information from three medical centers, was retrospectively screened from August 2005 to March 2023.\u0026nbsp;Specifically, there were 10 cases from the Department of Nuclear Medicine at the First College of Clinical Medical Science, China Three Gorges University; 6 cases from the Department of Nuclear Medicine at the Affiliated Qingdao Central Hospital of Qingdao University; and\u0026nbsp;17 cases from the Department of Oncology at Hebei General Hospital.\u003c/p\u003e\n\u003cp\u003eInclusion criteria for the participants were: 1) pathologically confirmed diagnosis of DTC;\u0026nbsp;2) inability to tolerate or refusal of surgical resection and external radiotherapy, or iodine-resistant thyroid cancer; 3) Karnofsky Performance Score (KPS) of \u0026ge; 60; 4) normal blood routine examination and coagulation function; and 5) expected survival of \u0026ge; 3 months.\u003c/p\u003e\n\u003cp\u003eExclusion criteria included severe organ dysfunction, coagulation dysfunction (with anticoagulant therapy cessation at least 5\u0026ndash;7 days before implantation), poor general condition or cachexia, and lack of CT and other imaging data after\u0026nbsp;\u003csup\u003e125\u003c/sup\u003eI seed implantation. The decision to deliver brachytherapy was discussed in a multidisciplinary tumor board for all cases. If treatment was recommended, patients were informed of the benefits and potential risks of brachytherapy, and written consent was obtained before participation in the protocol. Detailed patient and tumor characteristics are summarized in Table 1.\u003c/p\u003e\n\u003cp\u003eTable 1. Clinical characteristics of the patients treated with \u003csup\u003e125\u003c/sup\u003eI-seed implantation\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" align=\"\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eParameter\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eCharacteristics\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eNo. of patients \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003ePercentage（%）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eSex\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e45%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e55%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eAge\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026lt;55 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e30%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026ge;55years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e70%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eDTC subtype\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003ePTC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e94%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eFTC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e6%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003ePrevious treatment regimen\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eSurgery\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e88%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eRAI-131\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e81%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eExternal radiotherapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e6%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eTargeted therapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e9%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eAblation therapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e3%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eEndotracheal stent implant\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e3%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eSurgery location\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eNeck lymph nodes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e77%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eRecurrent thyroid lesions\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e5%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eBone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e7%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003ePulmonary\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e5%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003ePleura\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e2%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eMediastinal lymph nodes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e2%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eBack soft tissue metastasis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e2%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eInitial tumor volume (cm\u003csup\u003e3\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026lt;50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e77%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026ge;50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e23%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eImplant and guide\u0026nbsp;\u003c/p\u003e\n \u003cp\u003etechnique\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eCT and US\u003c/p\u003e\n \u003cp\u003e3D\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e38\u003c/p\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e86%\u003c/p\u003e\n \u003cp\u003e14%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eInstruments and equipment\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMick Radio-Nuclear company (USA) supplied the 18-G implantation needles and seed implant applicator for this study. The \u003csup\u003e125\u003c/sup\u003eI seeds (ZHIBO Bio-Medical Tech Ltd., Beijing, China) were cylindrical, measuring 4.5 mm in length and 0.8 mm in diameter. The seeds had an activity range of 0.3\u0026ndash;3.0 mCi and a half-life of 59.4 days, emitting g-ray energy at 27\u0026ndash;35 keV. The tissue half-value layer was 1.7 cm, and approximately 93\u0026ndash;97% of the seed\u0026rsquo;s energy was delivered into the tumor after 8\u0026ndash;10 months. For treatment planning, the Panther Brachy version 5.0 (Prowess Inc., Concord, CA, USA) treatment planning system (TPS) was utilized. The RM-905a radioactivity meter, provided by the Chinese Institute of Metrology, was used for measurements. Imaging involved performing PET-CT (Discovery CT750 HD, GE, USA).\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e\u003cstrong\u003e125\u003c/strong\u003e\u003c/sup\u003e\u003cstrong\u003eI seed implantation\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePreoperative preparation: One week prior to surgery, enhanced CT scan with a slice thickness of 5 mm was conducted. The images were transmitted to the TPS to create a preoperative plan. The prescribed dose for\u0026nbsp;\u003csup\u003e125\u003c/sup\u003eI seed implantation involved D90, V100, and V150, covering the Planning Treatment Volume (PTV). The PTV included the entire Gross Tumor Volume (GTV) along with 0.5- to 1.0-cm margins.\u003c/p\u003e\n\u003cp\u003eOperation procedure: Intraoperatively, the position remained consistent with the preoperative design. Local anesthesia with 1% lidocaine was administered. CT and ultrasound localization scans were performed to determine the puncture point, angle, and depth from the body surface. Following the preoperative plan, particles were sparsely implanted at 0.5\u0026ndash;1.0 cm intervals. Immediate postoperative CT scans were obtained to observe the spatial distribution of particles, and re-implantation was performed in areas with dosimetric cold spots.\u003c/p\u003e\n\u003cp\u003ePostoperative treatment: Postoperative CT scan images were verified for quality by transferring them to the TPS. The actual dose to the tumor was determined using the Dose-Volume Histogram (DVH).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFollow-up and clinical efficacy evaluation \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFollow-up CT scans were conducted at 1 month, 3 months, 6 months, and subsequently every 3 months after the procedure. The primary endpoints were the Objective Response Rate (ORR) and Tumor Local Control Rate (LCR). ORR was defined as the proportion of patients achieving Complete Response (CR) and Partial Response (PR). LCR was calculated as (CR + PR + SD/total cases)%. Secondary endpoints comprised Overall Survival (OS) and the incidence of adverse events. The clinical efficacy of\u0026nbsp;\u003csup\u003e125\u003c/sup\u003eI brachytherapy was evaluated using the Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1). OS was defined as the duration between\u0026nbsp;\u003csup\u003e125\u003c/sup\u003eI brachytherapy and the last follow-up or death. Adverse reactions were evaluated following the new classification of the Society of Interventional Radiology.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eComplications \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe patients were observed for complications, including fever, bleeding, bone marrow suppression, liver and kidney dysfunction, radioactive skin and mucosal reactions, and particle displacement, after seed implantation. The skin-mucosal response was assessed according to the Radiological Collaboration in Oncology/ European Research and Treatment in Oncology (RTOC/EORTC) radiological injury grading criteria.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical analysis \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData analysis was performed using SPSS (version 24.0). Continuous variables were expressed as means \u0026plusmn; SD. Survival analysis was performed using the Kaplan-Meier method. A p-value \u0026lt; 0.05 was considered statistically significant.\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cp\u003e\u003csup\u003e\u003cstrong\u003e125\u003c/strong\u003e\u003c/sup\u003e\u003cstrong\u003eI implantation and dosimetry\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA total of 33 patients received \u003csup\u003e125\u003c/sup\u003eI seed implantation to meet the TPS criteria, followed by postoperative dose evaluation. The seed activity was 0.3\u0026ndash;3.0 mCi, and the median number of \u003csup\u003e125\u003c/sup\u003eI seeds implanted was 54 (range: 8\u0026ndash;214) with a median dose 90 (D90) of 126 Gy (range: 90\u0026ndash;155 Gy) \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical efficacy evaluation and OS \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAccording to the initial plan, \u003csup\u003e125\u003c/sup\u003eI seeds were successfully implanted in 44 lesions among 33 patients. Lesions included 34 cervical lymph node metastases, 2 cases of recurrent thyroid lesions, 2 cases of pulmonary metastases, 3 cases of bone metastases,1 cases of pleural metastases, 1 case of mediastinal lymph node involvement, and 1 case of back soft tissue metastasis. All patients tolerated the procedure well. Patients were monitored for 6\u0026ndash;96 months. Six months postoperatively, CT images revealed 26 cases of CR, 14 cases of PR, and 4 cases of Stable Disease (SD). The ORR was 90.9% (40/44), and the LCR reached 100% (44/44) at 6 months. Survival analysis spanned 6\u0026ndash;96 months. The median OS was 40.7 months, with 1-year,2-year,3-year, 4-year and 5-year survival rates of 91%, 88%, 74%,64.5%,and 51%, respectively. Figure 1 illustrates the actuarial curve for OS. At the last follow-up, 14 patients had died due to systemic metastases.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAdverse events\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThere were no complications, including fever, hemorrhage, bone marrow suppression, liver and kidney dysfunction, radioactive skin and mucous membrane reactions, and particle displacement, during the follow-up period in any of the patients. Furthermore, no RTOG/EORTC grade \u0026gt; 2 complications were observed. Six patients experienced mild pain after implantation, which resolved spontaneously.\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eThyroid cancer typically exhibits a benign biological behavior, resulting in an excellent prognosis for the majority of patients. However, 15\u0026ndash;30% of the patients may develop lymph node metastasis, predominantly in cervical lymph nodes. Recurrent DTCs often respond well to salvage treatment, involving radioactive iodine (RAI), additional surgery, and hormone suppression\u003csup\u003e[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/sup\u003e. Despite these interventions, approximately one-third of the patients experience dedifferentiation during initial or ongoing treatment due to various driver gene changes. This dedifferentiation leads to the loss of iodine uptake capacity in cervical lymph node metastases, transforming them into radioactive iodine-refractory differentiated thyroid carcinomas (RAIR-DTCs). A subset of patients may face challenges with local metastasis, unsuitable for repeated neck surgery and resistant to RAI ablation. Addressing refractory recurrences and metastases poses a significant challenge in DTC management.\u003c/p\u003e \u003cp\u003eLimited treatment options exist, with TKIs, specifically oral antiangiogenic multitargeted TKIs, demonstrating a progression-free survival benefit in phase 3 trials\u003csup\u003e[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/sup\u003e. However, these drugs carry substantial toxicities that can impact quality of life, and some individuals cannot tolerate them\u003csup\u003e[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/sup\u003e. The 2015 ATA guidelines propose ablative therapy, external radiation therapy, and particle implantation as considerations for patients with inoperable, progressive, or symptomatic metastases (exhibiting tracheal or esophageal invasion, recurrent laryngeal nerve compression, or local pain). These therapies aim to enhance survival rates and provide palliative care\u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e. Despite these recommendations, there is no universally accepted treatment for refractory thyroid cancer recurrence. External beam radiotherapy may be considered for unresectable tumors, though its role in DTC remains debated due to potential severe damage to normal tissues and functions\u003csup\u003e[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIn recent years, interventional therapy techniques have gained attention. Commonly used methods include thermal ablation, anhydrous ethanol ablation, and \u003csup\u003e125\u003c/sup\u003eI particle implantation. Each technique has its own advantages and limitations. Ethanol injection is generally recommended for lesions with a diameter exceeding 10 mm, often requiring repeated treatments\u003csup\u003e[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/sup\u003e. Laser ablation is suitable for lesions with a maximum diameter less than 10 mm\u003csup\u003e[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/sup\u003e. Radiofrequency ablation and microwave ablation have specific site requirements due to intraoperative heat conduction and thermal damage\u003csup\u003e[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003e \u003csup\u003e125\u003c/sup\u003eI seed implantation, a LDR brachytherapy, releases low-energy gamma rays continuously, ensuring safety with a sharp dose drop-off. Only a 1.7-cm soft tissue thickness is sufficient to shield half the radiation dosage\u003csup\u003e[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]\u003c/sup\u003e. This approach has emerged as a salvage method for various tumors, including recurrent gliomas, retroperitoneal recurrent carcinoma, and recurrent cancers in the head, neck, and ovaries\u003csup\u003e[\u003cspan additionalcitationids=\"CR29 CR30\" citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]\u003c/sup\u003e. In our center, \u003csup\u003e125\u003c/sup\u003eI seed implantation has proven effective and safe for numerous solid tumors, including lung cancer\u003csup\u003e[\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]\u003c/sup\u003e, skin squamous cell carcinoma\u003csup\u003e[\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]\u003c/sup\u003e, malignant solitary fibrous tumor\u003csup\u003e[\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]\u003c/sup\u003e, and as a salvage treatment for lymph metastases or locoregional recurrence\u003csup\u003e[\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]\u003c/sup\u003e. However, limited studies have addressed recurrent refractory thyroid cancer patients.\u003c/p\u003e \u003cp\u003ePrevious research has assessed the therapeutic efficacy of \u003csup\u003e125\u003c/sup\u003eI seed implantation for thyroid cancer, achieving 1-, 2-, 3-, 4-, and 5-year local control rates of 92.9%, 83.3%, 54.6%, 45.5%, and 40.0%, respectively\u003csup\u003e[\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]\u003c/sup\u003e. The present study conducted a preliminary analysis of the clinical efficacy and safety of \u003csup\u003e125\u003c/sup\u003eI seed implantation in treating 33 cases of recurrent refractory thyroid cancer patients. Results indicated that the ORR and LCR at 6 months post-\u003csup\u003e125\u003c/sup\u003eI seed implantation therapy were 90.9% and 100%, respectively, outperforming our research center\u0026rsquo;s previous study\u003csup\u003e[\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]\u003c/sup\u003e. This improvement may be attributed to the differentiated nature of all cases and their inert biological characteristics. The study\u0026rsquo;s reliability was enhanced by its multi-center design, reinforcing the earlier findings.\u003c/p\u003e \u003cp\u003eIn this investigation, cases with \u003csup\u003e125\u003c/sup\u003eI seed implants exhibited a broad lesion volume range (7.9\u0026ndash;448 cm\u003csup\u003e3\u003c/sup\u003e) and various lesion locations. No procedure failed, indicating the method\u0026rsquo;s wide applicability and good tolerance. However, based on our experience, permanent implantation of \u003csup\u003e125\u003c/sup\u003eI seeds in a large tumor carries a risk of loss of control and complications. In this study, 10 patients with tumors larger than 50 cm\u003csup\u003e3\u003c/sup\u003e underwent successful implantation without technical failure, demonstrating the method\u0026rsquo;s repeatability and operability. Four cases with tumors accompanied by liquefaction necrosis suggested draining the necrotic region first, maintaining unobstructed drainage, changing medicine promptly, and then implanting seeds into the solid part of the tumor multiple times.\u003c/p\u003e \u003cp\u003eTo date, the dose and activity choice for \u003csup\u003e125\u003c/sup\u003eI seed implantation remain controversial, lacking standard guidelines. Our previous study indicated the safety of \u003csup\u003e125\u003c/sup\u003eI seed brachytherapy with a dose (EQD2) of 85\u0026ndash;123.25 Gy for previously treated patients. In this study, the median prescription dose was 126 Gy (range: 90\u0026ndash;155 Gy), higher than in previous studies, but without serious complications, affirming its safety. Compared to EBRT, the key advantage of \u003csup\u003e125\u003c/sup\u003eI seed brachytherapy lies in enhancing the target dose while reducing the dose to organs at risk, potentially yielding improved results. Additionally, multiple salvage \u003csup\u003e125\u003c/sup\u003eI seed treatments after local failure further add to the therapy\u0026rsquo;s advantages.\u003c/p\u003e \u003cp\u003eDespite these promising findings, the study had limitations. It was a retrospective, multi-center clinical study, and future prospective investigations are required to minimize bias. The relatively small patient cohort suggests the need for larger studies to confirm our findings. Being a single-arm study without parallel controls, only external historical data could be used for comparison, introducing potential bias in result evaluation.\u003c/p\u003e \u003cp\u003eIn conclusion, CT-guided \u003csup\u003e125\u003c/sup\u003eI seed implantation brachytherapy emerged as a safe and effective radiation technique for recurrent thyroid cancers, demonstrating a definite curative local therapeutic effect and safety. This therapy holds promise as a new strategy for thyroid cancer recurrence, particularly in elderly patients with complications ineligible for surgical resection or not benefiting from EBRT and systemic therapy.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors would like to thank all the patients who participated in the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eZhen Gao and Hongtao Zhang drafted the paper and conducted the literature review. Yixing,Li and Jinzhao Dai completed the operation of seed implantation.Huimin Yu and and Xuemin Di revised the manuscript by making the required corrections.Zezhou Liu and \u0026nbsp;Juan Wang designed the pre-plan . Xiaoli Liu is the oncologist who follows the patient. All authors reviewed the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors declare that they have no competing interest.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets in this retrospective study are available from corresponding author on reasonable request. The confidential patient data should not be shared.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis retrospective study was approved by the Ethics Committee of Hebei Provincial People\u0026apos;s Hospital.\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from all individual participants included in the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors declare that they have no competing interest.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eBray F, Ferlay J, Soerjomataram I, et al. 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Eur Arch Otorhinolaryngol. 2017;274(9):3497\u0026ndash;501.DOI:10.1007/s00405-017-4660-2.\u003c/li\u003e\n\u003cli\u003eFontenot TE, Deniwar A, Bhatia P,et al. Percutaneous ethanol injection vs reoperation for locally recurrent papillary thyroid cancer: a systematic review and pooled analysis. JAMA Otolaryngol Head Neck Surg. 2015;141(6):512\u0026ndash;8. DOI:10.1001/jamaoto.2015.0596. \u003c/li\u003e\n\u003cli\u003eZhang L, Zhou W, Zhan W. Role of ultrasound in the assessment of percutaneous laser ablation of cervical metastatic lymph nodes from thyroid carcinoma. Acta Radiol. 2018;59(4):434\u0026ndash;40. DOI:10.1177/02 84185117721261. \u003c/li\u003e\n\u003cli\u003eMauri G, Cova L, Ierace T,et al. Treatment of metastatic lymph nodes in the neck from papillary thyroid carcinoma with percutaneous laser ablation. Cardiovasc Intervent Radiol. 2016;39(7): 1023\u0026ndash;30.DOI:10.1007/s00270-016-1313-6.\u003c/li\u003e\n\u003cli\u003eGuang Y, Luo Y, Zhang Y, et al. 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Analysis of the efficacy and safety of iodine-125 seeds implantation in the treatment of patients with inoperable early-stage non-small cell lung cancer. J Contemp Brachyther (2021) 13(3):347\u0026ndash;57. DOI: 10.5114/jcb.2021.106241.\u003c/li\u003e\n\u003cli\u003eLiang Y, Di X, Liu Z, et al. 125I seeds implantation for an elderly patient of skin squamous cell carcinomas with ulcer guided by ultrasound. J Cancer Res Ther (2018) 14(7):1660\u0026ndash;4. DOI: 10.4103/jcrt.JCRT_1032_17. \u003c/li\u003e\n\u003cli\u003eGao Z, Yu H, Di X, et al. Case report: 125I seed implantation for rare malignant solitary fibrous tumor in the pelvic cavity: a case report. Front Oncol (2022) 12:884491.DOI:10.3389/fonc.2022.884491. \u003c/li\u003e\n\u003cli\u003eZhang Y, Liu Z, Liang Y, et al. The effectiveness and prognostic factors of radioactive iodine-125 seed implantation for the treatment of cervical lymph node recurrence of esophageal squamous cell carcinoma after external beam radiation therapy. J Contemp Brachyther (2020) 12(6):579\u0026ndash;85. DOI: 10.5114/jcb.2020.101691. \u003c/li\u003e\n\u003cli\u003eYu H, Zhang H, Gao Z, et al. 125I seed brachytherapy for refractory loco-regional recurrence of non-anaplastic thyroid cancer. Front Oncol (2022) 12:773708. DOI: 10.3389/fonc.2022.773708.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"thyroid cancer, recurrence, refractory, brachytherapy, efficacy evaluation, iodine-125 seeds","lastPublishedDoi":"10.21203/rs.3.rs-5869645/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5869645/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e[\u003cstrong\u003eObjective:\u003c/strong\u003e]The purpose of this research was to evaluate the feasibility and efficacy of 125I seed brachytherapy for recurrent refractory differentiated thyroid cancers.\u003c/p\u003e\n\u003cp\u003e[\u003cstrong\u003eMethods\u003c/strong\u003e]:Between August 2005 and March 2023 33 patients with recurrence refractory of\u003c/p\u003e\n\u003cp\u003edifferentiated thyroid cancer were treated with 125I seed brachytherapy. 125I seeds were implanted into the tumor under the guidance of CT and/or 3D-printed template images with the median prescription dose of 126 Gy (range, 90-155 Gy). The median seed number was 54 (range 8-214). Clinical efficacy was evaluated with Response Evaluation Criteria in Solid Tumors. Follow-up\u003c/p\u003e\n\u003cp\u003eSurvival and adverse events were analyzed.\u003c/p\u003e\n\u003cp\u003e[\u003cstrong\u003eResults:\u003c/strong\u003e]\u003csup\u003e125\u003c/sup\u003eI seeds were successfully implanted in 44 lesions among 33 patients. Lesions included 34 cervical lymph node metastases, 2 cases of recurrent thyroid lesions, 2 cases of pulmonary metastases, 3 cases of bone metastases,1 cases of pleural metastases, 1 case of mediastinal lymph node involvement, and 1 case of back soft tissue metastasis. Patients were monitored for 6–96 months. Six months postoperatively, CT images revealed 26 cases of CR, 14 cases of PR, and 4 cases of Stable Disease (SD). The ORR was 90.9% (40/44), and the LCR reached 100% (44/44) at 6 months. The median OS was 40.7 months, with 1-year,2-year,3-year, 4-year and 5-year survival rates of 91%, 88%, 74%,64.5%,and 51%, respectively.14 patients had died due to systemic metastases.No severe complications occurred.\u003c/p\u003e\n\u003cp\u003e[\u003cstrong\u003eConclusions:\u003c/strong\u003e]CT-guided iodine-125 brachytherapy provided a safe and effective choice for \u0026nbsp;recurrent refractory differentiated thyroid cancers with significant local therapeutic effects and minor complications.\u003c/p\u003e","manuscriptTitle":"Clinical outcomes of radioactive 125 I seed brachytherapy for recurrent refractory differentiated thyroid cancers","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-01-23 17:12:00","doi":"10.21203/rs.3.rs-5869645/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"c6853d34-33f4-4d2a-bf3b-a6db4913e1ae","owner":[],"postedDate":"January 23rd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-01-24T09:54:05+00:00","versionOfRecord":[],"versionCreatedAt":"2025-01-23 17:12:00","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5869645","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5869645","identity":"rs-5869645","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}