{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T13:34:52Z","timestamp":1785418492798,"version":"3.56.0"},"reference-count":31,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T00:00:00Z","timestamp":1784937600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Tianjin Medical University Cancer Institute & Hospital \u201c358 Project\u201d","award":["358-2022-11"],"award-info":[{"award-number":["358-2022-11"]}]},{"name":"Tianjin Medical University Cancer Institute & Hospital \u201c358 Project\u201d","award":["358-2023-3"],"award-info":[{"award-number":["358-2023-3"]}]},{"award":["358-2022-11"],"award-info":[{"award-number":["358-2022-11"]}],"id":[{"id":"https:\/\/ror.org\/0152hn881","id-type":"ROR","asserted-by":"publisher"}]},{"award":["358-2023-3"],"award-info":[{"award-number":["358-2023-3"]}],"id":[{"id":"https:\/\/ror.org\/0152hn881","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: Image-guided adaptive brachytherapy is a core component of definitive treatment for locally advanced cervical cancer (LACC). However, implantation remains challenging in bulky, asymmetric, or anatomically complex tumors, where standard applicator geometry or purely straight interstitial trajectories may be insufficient for individualized target coverage. This study evaluated the real-world implementation of a patient-specific 3D-printed template-guided adaptive brachytherapy workflow for complex LACC. Methods: We retrospectively reviewed 120 consecutive patients with FIGO 2018 stage IB3\u2013IVA cervical cancer treated with definitive chemoradiotherapy followed by high-dose-rate image-guided brachytherapy between March 2023 and March 2025. All patients were treated using a patient-specific 3D-printed template-guided hybrid intracavitary\/interstitial workflow integrating CT\/MRI-based target assessment, individualized catheter trajectory planning, template fabrication, implantation verification, and adaptive treatment planning. Straight-channel or curved-channel guidance was selected according to residual tumor geometry and pelvic anatomy, with flexible plastic interstitial catheters used for curved or anatomically constrained trajectories. Procedural deliverability, dosimetry, toxicity, early clinical outcomes, and exploratory dose\u2013outcome patterns were analyzed. Results: The median HR-CTV volume was 55.9 cm3, and the median HR-CTV D90 was 92.9 Gy EQD2. Median organ-at-risk D2cc values remained within contemporary institutional and guideline-consistent constraints. A total of 555 template-guided HDR brachytherapy fractions were delivered. The median applicator-and-catheter placement time was 4.21 min per fraction, with a median of 7.25 implanted channels. Minor and major insertion-related bleeding occurred in 10.8% and 1.7% of patients, respectively. At a median follow-up of 20.1 months, estimated 3-year overall survival, progression-free survival, local recurrence-free survival, regional recurrence-free survival, and distant metastasis-free survival were 77.9%, 76.8%, 94.3%, 98.0%, and 86.2%, respectively. Late grade \u2265 3 gastrointestinal and genitourinary toxicities occurred in 2.5% and 1.7% of patients, respectively, with no grade 4\u20135 events. Exploratory dose\u2013outcome analyses suggested hypothesis-generating dose\u2013outcome patterns, but these findings were not intended to define or validate a clinical dose threshold. Conclusions: This real-world implementation study supports the feasibility of patient-specific 3D-printed template-guided adaptive brachytherapy for complex LACC. By translating CT\/MRI-based individualized trajectory planning into template-guided intracavitary\/interstitial catheter placement, this workflow achieved guideline-consistent target coverage, acceptable organ-at-risk doses, efficient procedural delivery, and low severe toxicity within the available follow-up. Dose\u2013outcome findings remain exploratory and require validation in more mature cohorts.<\/jats:p>","DOI":"10.3390\/cancers18152399","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T05:49:27Z","timestamp":1785131367000},"page":"2399","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Image-Guided Adaptive Brachytherapy Using Patient-Specific 3D-Printed Templates for Complex Locally Advanced Cervical Cancer: A Real-World Implementation Study"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6748-5629","authenticated-orcid":false,"given":"Yuanjie","family":"Cao","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology, Tianjin Medical University Cancer Institute & Hospital, Tianjin\u2019s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin 300060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0649-8797","authenticated-orcid":false,"given":"Imashi Sandupama","family":"Wickramage","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Tianjin Medical University Cancer Institute & Hospital, Tianjin Medical University, Tianjin 300060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Tianjin Medical University Cancer Institute & Hospital, Tianjin\u2019s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin 300060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youheng","family":"Tan","sequence":"additional","affiliation":[{"name":"School of Automation, Central South University, Changsha 410083, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenwen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Tianjin Medical University Cancer Institute & Hospital, Tianjin\u2019s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin 300060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingsong","family":"Pang","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Tianjin Medical University Cancer Institute & Hospital, Tianjin\u2019s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin 300060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Tianjin Medical University Cancer Institute & Hospital, Tianjin\u2019s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin 300060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,25]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1056\/NEJMra2404457","article-title":"Cervical Cancer","volume":"392","author":"Tewari","year":"2025","journal-title":"N. Engl. J. Med."},{"key":"ref_3","unstructured":"International Commission on Radiation Units & Measurements (2016). ICRU Report 89: Prescribing, Recording, and Reporting Brachytherapy for Cancer of the Cervix, Oxford University Press on behalf of the ICRU."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.radonc.2005.11.014","article-title":"Recommendations from gynaecological (GYN) GEC ESTRO working group (II): Concepts and terms in 3D image-based treatment planning in cervix cancer brachytherapy-3D dose volume parameters and aspects of 3D image-based anatomy, radiation physics, radiobiology","volume":"78","author":"Barillot","year":"2006","journal-title":"Radiother. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.radonc.2004.12.015","article-title":"Recommendations from Gynaecological (GYN) GEC-ESTRO Working Group (I): Concepts and terms in 3D image based 3D treatment planning in cervix cancer brachytherapy with emphasis on MRI assessment of GTV and CTV","volume":"74","author":"Briot","year":"2005","journal-title":"Radiother. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.radonc.2021.05.010","article-title":"IBS-GEC ESTRO-ABS recommendations for CT based contouring in image guided adaptive brachytherapy for cervical cancer","volume":"160","author":"Mahantshetty","year":"2021","journal-title":"Radiother. Oncol."},{"key":"ref_7","first-page":"48","article-title":"The EMBRACE II study: The outcome and prospect of two decades of evolution within the GEC-ESTRO GYN working group and the EMBRACE studies","volume":"9","author":"Tanderup","year":"2018","journal-title":"Clin. Transl. Radiat. Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1016\/j.radonc.2016.03.011","article-title":"Image guided brachytherapy in locally advanced cervical cancer: Improved pelvic control and survival in RetroEMBRACE, a multicenter cohort study","volume":"120","author":"Sturdza","year":"2016","journal-title":"Radiother. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1016\/j.radonc.2016.06.006","article-title":"Dose-volume effect relationships for late rectal morbidity in patients treated with chemoradiation and MRI-guided adaptive brachytherapy for locally advanced cervical cancer: Results from the prospective multicenter EMBRACE study","volume":"120","author":"Mazeron","year":"2016","journal-title":"Radiother. Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.ijrobp.2008.10.033","article-title":"Dose-volume histogram parameters and local tumor control in magnetic resonance image-guided cervical cancer brachytherapy","volume":"75","author":"Dimopoulos","year":"2009","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/j.radonc.2016.08.007","article-title":"Image Guided Adaptive Brachytherapy in cervix cancer: A new paradigm changing clinical practice and outcome","volume":"120","author":"Tanderup","year":"2016","journal-title":"Radiother. Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1016\/j.ygyno.2022.06.019","article-title":"Clinical outcome of combined intracavitary\/interstitial brachytherapy using a hybrid applicator in locally advanced cervical cancer","volume":"166","author":"Rogowski","year":"2022","journal-title":"Gynecol. Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Yang, X., Ren, H., Li, Z., and Fu, J. (2024). Brachytherapy for cervical cancer: From intracavitary to interstitial technique. Front. Oncol., 14.","DOI":"10.3389\/fonc.2024.1442712"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Cordoba, A., Gesta, E., Escande, A., Noeuveglise, A., Cayez, R., Halty, A., Ladjimi, M.T., Narducci, F., Hudry, D., and Martinez Gomez, C. (2024). Interstitial needles versus intracavitary applicators only for locally advanced cervical cancer: Results from real-life dosimetric comparisons. Front. Oncol., 14.","DOI":"10.3389\/fonc.2024.1347727"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.radonc.2013.01.010","article-title":"Clinical feasibility of combined intracavitary\/interstitial brachytherapy in locally advanced cervical cancer employing MRI with a tandem\/ring applicator in situ and virtual preplanning of the interstitial component","volume":"107","author":"Fokdal","year":"2013","journal-title":"Radiother. Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1016\/j.radonc.2016.03.020","article-title":"Image guided adaptive brachytherapy with combined intracavitary and interstitial technique improves the therapeutic ratio in locally advanced cervical cancer: Analysis from the retroEMBRACE study","volume":"120","author":"Fokdal","year":"2016","journal-title":"Radiother. Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/j.brachy.2025.05.001","article-title":"The American Brachytherapy Society (ABS) consensus guidance for hybrid intracavitary interstitial brachytherapy for locally advanced cervical cancer","volume":"24","author":"Chino","year":"2025","journal-title":"Brachytherapy"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1002\/mp.17424","article-title":"Individual curved-needle interstitial template created using three-dimensional printing for brachytherapy for distal parauterine tumor recurrence","volume":"52","author":"Zhang","year":"2025","journal-title":"Med. Phys."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1016\/j.brachy.2024.05.004","article-title":"3D-printed individual template brachytherapy for the treatment of intractable central pelvic recurrent cervical cancer: A single institution experience","volume":"23","author":"Zhu","year":"2024","journal-title":"Brachytherapy"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1016\/j.brachy.2023.07.001","article-title":"A practical guide to hybrid interstitial\/intracavitary brachytherapy for locally-advanced cervical cancer","volume":"22","author":"Ladbury","year":"2023","journal-title":"Brachytherapy"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"368","DOI":"10.5114\/jcb.2025.158456","article-title":"Precision brachytherapy for bulky cervical tumors: Clinical implementation of a 3D-printed template and curved needle system","volume":"17","author":"Cao","year":"2025","journal-title":"J. Contemp. Brachytherapy"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.radonc.2015.12.012","article-title":"Individualised 3D printed vaginal template for MRI guided brachytherapy in locally advanced cervical cancer","volume":"118","author":"Lindegaard","year":"2016","journal-title":"Radiother. Oncol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"4053","DOI":"10.1002\/mp.14888","article-title":"Design and evaluation of 3D printable patient-specific applicators for gynecologic HDR brachytherapy","volume":"48","author":"Semeniuk","year":"2021","journal-title":"Med. Phys."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.ijrobp.2022.05.027","article-title":"Applying 3D-Printed Templates in High-Dose-Rate Brachytherapy for Cervix Cancer: Simplified Needle Insertion for Optimized Dosimetry","volume":"114","author":"Marar","year":"2022","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1470","DOI":"10.1080\/0284186X.2023.2246642","article-title":"Clinical outcomes using a 3D printed tandem-needle-template and the EMBRACE-II planning aims for image guided adaptive brachytherapy in locally advanced cervical cancer","volume":"62","author":"Cobussen","year":"2023","journal-title":"Acta Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1016\/j.brachy.2023.02.002","article-title":"3D printing in brachytherapy: A systematic review of gynecological applications","volume":"22","author":"Fahimian","year":"2023","journal-title":"Brachytherapy"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"453","DOI":"10.5114\/jcb.2023.133676","article-title":"The Montreal split ring applicator: Towards highly adaptive gynecological brachytherapy using 3D-printed biocompatible patient-specific interstitial caps","volume":"15","author":"Kamio","year":"2023","journal-title":"J. Contemp. Brachytherapy"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1016\/j.brachy.2024.05.003","article-title":"Evaluation and improvement of the safety of 3D-printed template assisted intracavitary\/interstitial brachytherapy for cervical cancer using repeat FMEA","volume":"23","author":"Shen","year":"2024","journal-title":"Brachytherapy"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1016\/j.ijrobp.2019.03.020","article-title":"Importance of Technique, Target Selection, Contouring, Dose Prescription, and Dose-Planning in External Beam Radiation Therapy for Cervical Cancer: Evolution of Practice From EMBRACE-I to II","volume":"104","author":"Berger","year":"2019","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.semradonc.2020.05.008","article-title":"Evidence-Based Dose Planning Aims and Dose Prescription in Image-Guided Brachytherapy Combined With Radiochemotherapy in Locally Advanced Cervical Cancer","volume":"30","author":"Tanderup","year":"2020","journal-title":"Semin. Radiat. Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1016\/S1470-2045(20)30753-1","article-title":"MRI-guided adaptive brachytherapy in locally advanced cervical cancer (EMBRACE-I): A multicentre prospective cohort study","volume":"22","author":"Tanderup","year":"2021","journal-title":"Lancet Oncol."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/15\/2399\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T06:03:12Z","timestamp":1785132192000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/15\/2399"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,25]]},"references-count":31,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["cancers18152399"],"URL":"https:\/\/doi.org\/10.3390\/cancers18152399","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,25]]}}}