{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T16:45:56Z","timestamp":1791909956073,"version":"4.3.4"},"reference-count":47,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T00:00:00Z","timestamp":1745366400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Despite the development of advanced cancer therapies, achieving cancer eradication remains challenging. Radioimmunotherapy (RIT) is an innovative approach that combines radionuclides with monoclonal antibodies targeting tumour-associated antigens or those expressed by the tumour microenvironment. Over the past two decades, RIT has been extensively researched, along with two RIT products\u201490Y-ibritumomab tiuxetan and 131I-tositumomab. However, despite its demonstrated efficacy in non-solid tumours, RIT\u2019s clinical use remains limited, and its effectiveness in solid tumours is inconclusive. This study aimed to analyse randomised controlled trials (RCTs) to evaluate the overall clinical effectiveness of RIT across different cancer types and its impact on treatment outcomes. Methods: A systematic search of PubMed, EMBASE, Scopus, CENTRAL, and Google Scholar was conducted from January 2000 to October 2024 in accordance with PRISMA guidelines and the PICOS framework. Studies were included if they were RCTs evaluating RIT for cancer treatment and reported treatment outcomes such as overall survival (OS), progression-free survival (PFS), disease-free survival, or time to progression (TTP). Data extraction was performed using a standardised Excel form, and study quality was assessed with the Joanna Briggs Institute Critical Appraisal Tool for RCTs. A narrative synthesis of the data was complemented by meta-analyses where feasible, particularly for progression- and survival-related endpoints. Results: Out of 2241 records identified, 20 RCTs encompassing approximately 3562 patients were included. The majority of trials focused on non-solid tumours, particularly non-Hodgkin\u2019s lymphoma (NHL), while a smaller subset evaluated solid tumours such as lung, pancreatic, ovarian, and prostate cancers. Most non-solid tumour studies employed 90Y-ibritumomab tiuxetan or 131I-tositumomab, targeting the CD20 antigen, whereas limited evidence exists for RIT efficacy in solid tumours. Meta-analysis of progression-related outcomes yielded a pooled hazard ratio (HR) of 0.48 (95% CI: 0.39\u20130.59), indicating a 52% reduction in the risk of progression. In contrast, overall survival outcomes were more variable, with a pooled OS HR of 0.80 (95% CI: 0.60\u20131.07). Adverse events, predominantly haematological and nonhaematological toxicities, were common yet generally reversible. The findings suggest that RIT, especially when used as part of combination regimens, significantly improves treatment outcomes in non-solid tumours but has an inconsistent effect in solid tumour settings. Conclusions: The results underscore the clinical promise of RIT in treating non-solid tumours like NHL, where combination regimens yield superior outcomes compared to monotherapy. However, the inconclusive evidence in solid tumours highlights the need for further large-scale, well-designed RCTs to define the optimal use, dosing, and patient selection for RIT in these settings. Additionally, standardisation in outcome reporting and longer follow-up periods are essential for more accurate economic and clinical assessments. Overall, RIT represents a valuable therapeutic modality, yet its integration into cancer treatment regimens should be guided by further research aimed at mitigating toxicity and optimising combination strategies.<\/jats:p>","DOI":"10.3390\/cancers17091413","type":"journal-article","created":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T10:40:48Z","timestamp":1745404848000},"page":"1413","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Assessing the Clinical Effectiveness of Radioimmunotherapy with Combined Radionuclide\/Monoclonal Antibody Conjugates in Cancer Treatment: Insights from Randomised Clinical Trials"],"prefix":"10.3390","volume":"17","author":[{"given":"Yifu","family":"Chen","sequence":"first","affiliation":[{"name":"School of Public Health, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2006, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5978-3762","authenticated-orcid":false,"given":"Padam Kanta","family":"Dahal","sequence":"additional","affiliation":[{"name":"School of Health, Medical and Applied Sciences, Central Queensland University, Sydney Campus, Sydney, NSW 2000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parvez","family":"Mosharaf","sequence":"additional","affiliation":[{"name":"School of Business, Faculty of Business, Education, Law and Arts, Centre for Health Research, University of Southern Queensland, Toowoomba, QLD 4350, Australia"},{"name":"Bioinformatics Laboratory, Department of Statistics, University of Rajshahi, Rajshahi 6205, Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2218-8433","authenticated-orcid":false,"given":"Md.","family":"Shahjalal","sequence":"additional","affiliation":[{"name":"Department of Public Health, North South University, Dhaka 1212, Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rashidul Alam","family":"Mahumud","sequence":"additional","affiliation":[{"name":"NHRMC Clinical Trials Centre, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2006, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1038\/nrc3925","article-title":"Radioimmunotherapy of human tumours","volume":"15","author":"Larson","year":"2015","journal-title":"Nat. Rev. Cancer"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Rondon, A., Rouanet, J., and Degoul, F. (2021). Radioimmunotherapy in Oncology: Overview of the Last Decade Clinical Trials. Cancers, 13.","DOI":"10.3390\/cancers13215570"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1038\/nrclinonc.2011.160","article-title":"Clinical radioimmunotherapy\u2014The role of radiobiology","volume":"8","author":"Pouget","year":"2011","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"S79","DOI":"10.1016\/j.chest.2020.03.013","article-title":"Randomized Controlled Trials","volume":"158","author":"Zabor","year":"2020","journal-title":"Chest"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1093\/oncolo\/oyad333","article-title":"A Systematic Review of Clinical Applications of Anti-CD20 Radioimmunotherapy for Lymphoma","volume":"29","author":"Durando","year":"2024","journal-title":"Oncologist"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"208","DOI":"10.37349\/etat.2024.00213","article-title":"Recent preclinical and clinical advances in radioimmunotherapy for non-Hodgkin\u2019s lymphoma","volume":"5","author":"Goto","year":"2024","journal-title":"Explor. Target. Anti-Tumor Ther."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Hull, A., Li, Y., Bartholomeusz, D., Hsieh, W., Allen, B., and Bezak, E. (2020). Radioimmunotherapy of Pancreatic Ductal Adenocarcinoma: A Review of the Current Status of Literature. Cancers, 12.","DOI":"10.3390\/cancers12020481"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"103395","DOI":"10.1016\/j.critrevonc.2021.103395","article-title":"Radioimmunotherapy of glioblastoma multiforme\u2014Current status and future prospects","volume":"163","author":"Li","year":"2021","journal-title":"Crit. Rev. Oncol.\/Hematol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e1230","DOI":"10.1002\/cl2.1230","article-title":"PRISMA2020: An R package and Shiny app for producing PRISMA 2020-compliant flow diagrams, with interactivity for optimised digital transparency and Open Synthesis","volume":"18","author":"Haddaway","year":"2022","journal-title":"Campbell. Syst. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Higgins, J.P.T. (2019). Cochrane Handbook for Systematic Reviews of Interventions, 2nd ed, Wiley-Blackwell.","DOI":"10.1002\/9781119536604"},{"key":"ref_11","first-page":"494","article-title":"The revised JBI critical appraisal tool for the assessment of risk of bias for randomized controlled trials","volume":"21","author":"Barker","year":"2023","journal-title":"JBI Evid. Synth."},{"key":"ref_12","unstructured":"Akers, J., Aguiar-Ib\u00e1\u00f1ez, R., and Baba-Akbari, A. (2009). Systematic Reviews: CRD\u2019s Guidance for Undertaking Reviews in Health Care, University of New York, Center for Reviews and Dissemination."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2453","DOI":"10.1200\/JCO.2002.11.076","article-title":"Randomized controlled trial of yttrium-90-labeled ibritumomab tiuxetan radioimmunotherapy versus rituximab immunotherapy for patients with relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin\u2019s lymphoma","volume":"20","author":"Witzig","year":"2002","journal-title":"J. Clin. Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"7792","DOI":"10.1158\/1078-0432.CCR-04-0756","article-title":"The radioisotope contributes significantly to the activity of radioimmunotherapy","volume":"10","author":"Davis","year":"2004","journal-title":"Clin. Cancer Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1200\/JCO.2005.02.5973","article-title":"Phase III trial of intraperitoneal therapy with yttrium-90-labeled HMFG1 murine monoclonal antibody in patients with epithelial ovarian cancer after a surgically defined complete remission","volume":"24","author":"Verheijen","year":"2006","journal-title":"J. Clin. Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1089\/hyb.2006.25.125","article-title":"Use of monoclonal anti-EGFR antibody in the radioimmunotherapy of malignant gliomas in the context of EGFR expression in grade III and IV tumors","volume":"25","author":"Wygoda","year":"2006","journal-title":"Hybridoma"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1002\/hep.21465","article-title":"A randomized controlled trial of Licartin for preventing hepatoma recurrence after liver transplantation","volume":"45","author":"Xu","year":"2007","journal-title":"Hepatology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"5156","DOI":"10.1200\/JCO.2008.17.2015","article-title":"Phase III trial of consolidation therapy with yttrium-90-ibritumomab tiuxetan compared with no additional therapy after first remission in advanced follicular lymphoma","volume":"26","author":"Morschhauser","year":"2008","journal-title":"J. Clin. Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"6094","DOI":"10.1200\/JCO.2009.22.6258","article-title":"Quantitative PCR analysis for Bcl-2\/IgH in a phase III study of Yttrium-90 Ibritumomab Tiuxetan as consolidation of first remission in patients with follicular lymphoma","volume":"27","author":"Goff","year":"2009","journal-title":"J. Clin. Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Sultana, A., Shore, S., Raraty, M.G., Vinjamuri, S., Evans, J.E., Smith, C.T., Lane, S., Chauhan, S., Bosonnet, L., and Garvey, C. (2009). Randomised Phase I\/II trial assessing the safety and efficacy of radiolabelled anti-carcinoembryonic antigen I(131) KAb201 antibodies given intra-arterially or intravenously in patients with unresectable pancreatic adenocarcinoma. BMC Cancer, 9.","DOI":"10.1186\/1471-2407-9-66"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4706","DOI":"10.1002\/cncr.27418","article-title":"A randomized study comparing yttrium-90 ibritumomab tiuxetan (Zevalin) and high-dose BEAM chemotherapy versus BEAM alone as the conditioning regimen before autologous stem cell transplantation in patients with aggressive lymphoma","volume":"118","author":"Shimoni","year":"2012","journal-title":"Cancer"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1200\/JCO.2012.42.4101","article-title":"Phase III randomized intergroup trial of CHOP plus rituximab compared with CHOP chemotherapy plus (131)iodine-tositumomab for previously untreated follicular non-Hodgkin lymphoma: SWOG S0016","volume":"31","author":"Press","year":"2013","journal-title":"J. Clin. Oncol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1662","DOI":"10.1200\/JCO.2012.45.9453","article-title":"Phase III Randomized Study of Rituximab\/Carmustine, Etopo-side, Cytarabine, and Melphalan (BEAM) Compared With Iodine-131 Tositumomab\/BEAM With Autologous Hematopoietic Cell Transplantation for Relapsed Diffuse Large B-Cell Lymphoma: Results From the BMT CTN 0401 Trial","volume":"31","author":"Vose","year":"2013","journal-title":"J. Clin. Oncol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"dju239","DOI":"10.1093\/jnci\/dju239","article-title":"Randomized trial of [131I] metuximab in treatment of hepatocellular carcinoma after percutaneous radiofrequency ablation","volume":"106","author":"Bian","year":"2014","journal-title":"J. Natl. Cancer. Inst."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"779","DOI":"10.3109\/10428194.2014.927461","article-title":"Patients with relapsed follicular lymphoma treated with rituximab versus tositumomab and iodine I-131 tositumomab","volume":"56","author":"Quackenbush","year":"2015","journal-title":"Leuk. Lymphoma"},{"key":"ref_26","first-page":"326","article-title":"A randomized study comparing the effectiveness of microwave ablation radioimmunotherapy and postoperative adjuvant chemoradiation in the treatment of non-small cell lung cancer","volume":"21","author":"Zhao","year":"2016","journal-title":"J. Buon."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1016\/S2468-1253(19)30422-4","article-title":"Adjuvant (131)I-metuximab for hepatocellular carcinoma after liver resection: A randomised, controlled, multicentre, open-label, phase 2 trial","volume":"5","author":"Li","year":"2020","journal-title":"Lancet. Gastroenterol. Hepatol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1080\/10428194.2021.1971216","article-title":"A randomized phase II study comparing consolidation with a single dose of 90Y ibritumomab tiuxetan vs. maintenance with rituximab for two years in patients with newly diagnosed follicular lymphoma responding to R-CHOP. Long-term follow-up results","volume":"63","author":"Canales","year":"2022","journal-title":"Leuk. Lymphoma"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"LBA21","DOI":"10.1200\/JCO.2023.41.6_suppl.LBA21","article-title":"Randomized, double-blinded phase II study of ketoconazole (keto), hydrocortisone (HC), and anti-PSMA antibody J591 labeled with 177Lu or 111In in patients (pts) with high-risk non-metastatic (met) castration-resistant prostate cancer (M0 CRPC)","volume":"41","author":"Tagawa","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1200\/JCO.23.02018","article-title":"Randomized Phase III SIERRA Trial of <sup>131<\/sup>I-Apamistamab Before Allogeneic Hematopoietic Cell Transplantation Versus Conventional Care for Relapsed\/Refractory AML","volume":"43","author":"Gyurkocza","year":"2024","journal-title":"J. Clin. Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.annonc.2023.10.095","article-title":"Radioimmunotherapy versus autologous hematopoietic stem cell transplantation in relapsed\/refractory follicular lymphoma: A Fondazione Italiana Linfomi multicenter, randomized, phase III trial","volume":"35","author":"Ladetto","year":"2024","journal-title":"Ann. Oncol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1080\/10428194.2023.2295792","article-title":"The asymptomatic follicular lymphoma (AFL) trial: Single-agent rituximab immunotherapy versus 90Y-ibritumomab tiuxetan radioimmunotherapy (RIT) for patients with new, untreated follicular lymphoma","volume":"65","author":"Laoruangroj","year":"2024","journal-title":"Leuk. Lymphoma"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/S1526-9655(11)70259-7","article-title":"Updated results of a Phase III trial comparing ibritumomab tiuxetan with rituximab in previously treated patients with non-Hodgkin\u2019s lymphoma","volume":"3","author":"Gibson","year":"2002","journal-title":"Clin. Lymphoma"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"98","DOI":"10.3816\/CLM.2004.n.015","article-title":"Yttrium 90-labeled ibritumomab tiuxetan radioimmunotherapy produces high response rates and durable remissions in patients with previously treated B-cell lymphoma","volume":"5","author":"Gordon","year":"2004","journal-title":"Clin. Lymphoma"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2710","DOI":"10.1002\/ijc.22663","article-title":"Decreased intraperitoneal disease recurrence in epithelial ovarian cancer patients receiving intraperitoneal consolidation treatment with yttrium-90-labeled murine HMFG1 without improvement in overall survival","volume":"120","author":"Oei","year":"2007","journal-title":"Int. J. Cancer"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1977","DOI":"10.1200\/JCO.2012.45.6400","article-title":"90Yttrium-ibritumomab tiuxetan consolidation of first remission in advanced-stage follicular non-Hodgkin lymphoma: Updated results after a median follow-up of 7.3 years from the International, Randomized, Phase III First-LineIndolent trial","volume":"31","author":"Morschhauser","year":"2013","journal-title":"J. Clin. Oncol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1200\/JCO.2017.74.5083","article-title":"Continued Excellent Outcomes in Previously Untreated Patients With Follicular Lymphoma After Treatment With CHOP Plus Rituximab or CHOP Plus 131I-Tositumomab: Long-Term Follow-Up of Phase III Randomized Study SWOG-S0016","volume":"36","author":"Shadman","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"349","DOI":"10.2217\/imt.10.114","article-title":"Cancer Radioimmunotherapy","volume":"3","author":"Sharkey","year":"2011","journal-title":"Immunotherapy"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"492061","DOI":"10.1155\/2014\/492061","article-title":"Radioimmunotherapy: A specific treatment protocol for cancer by cytotoxic radioisotopes conjugated to antibodies","volume":"2014","author":"Kawashima","year":"2014","journal-title":"ScientificWorldJournal"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2035","DOI":"10.1200\/jco.2011.29.15_suppl.2035","article-title":"Open-label, dose confirmation study of interstitial 131I-chTNT-1\/b mab for the treatment of glioblastoma multiforme (GBM) at first relapse: Interim results","volume":"29","author":"Shapiro","year":"2011","journal-title":"J. Clin. Oncol."},{"key":"ref_41","first-page":"445","article-title":"Dosimetry of phase I interstitial 131I-chTNT-1\/B MAb (Cotara) for the treatment of recurrent glioma","volume":"50","author":"Shen","year":"2009","journal-title":"J. Nucl. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1055\/a-1429-1967","article-title":"Intracranial 131I-chTNT Brachytherapy in Patients with Deep-Seated Glioma: A Single-center Experience with 10-Year Follow-up from China","volume":"60","author":"Zhao","year":"2021","journal-title":"Nuklearmedizin"},{"key":"ref_43","unstructured":"Euctr, P.L. (2023, September 17). Radioimmunotherapy with 90Y-Clivatizumab Tetraxetan Plus Low Dose Gemcitabine Versus Placebo Plus Low-Dose Gemcitabine. Available online: https:\/\/trialsearch.who.int\/Trial2.aspx?TrialID=EUCTR2013-004516-21-PL."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"192","DOI":"10.3171\/2010.2.JNS091211","article-title":"A Phase II study of anti-epidermal growth factor receptor radioimmunotherapy in the treatment of glioblastoma multiforme","volume":"113","author":"Li","year":"2010","journal-title":"J. Neurosurg."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1056\/NEJMoa2107322","article-title":"Lutetium-177\u2013PSMA-617 for Metastatic Castration-Resistant Prostate Cancer","volume":"385","author":"Sartor","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1016\/bs.seda.2015.08.007","article-title":"Chapter 40\u2014Thyroid Hormones, Iodine and Iodides, and Antithyroid Drugs","volume":"Volume 37","author":"Ray","year":"2015","journal-title":"Side Effects of Drugs Annual"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1081\/CNV-120016421","article-title":"Comparative physical and pharmacologic characteristics of iodine-131 and yttrium-90: Implications for radioimmunotherapy for patients with non-Hodgkin\u2019s lymphoma","volume":"21","author":"Leonard","year":"2003","journal-title":"Cancer Investig."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/9\/1413\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:20:17Z","timestamp":1760030417000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/9\/1413"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,23]]},"references-count":47,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,5]]}},"alternative-id":["cancers17091413"],"URL":"https:\/\/doi.org\/10.3390\/cancers17091413","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,23]]}}}