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Selective internal radiation therapy (SIRT) allows selective delivery of high dose radiation to liver tumours and has shown promise in the management of NENs. We determined the safety and efficacy of SIRT for inoperable liver metastases secondary to NENs. Dose-response and dose-toxicity relationship were assessed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A prospective, multicentre, phase 2 study was conducted. Primary outcomes were objective response rate (ORR) in the treated liver volume according to RECIST 1.1 and mRECIST criteria, incidence and severity of adverse events (AEs) at 6 months. Secondary outcomes were hepatic specific progression free survival, PFS, overall survival (OS), change in quality of life (QoL). Tumour dose-response relationship was derived retrospectively from post therapy yttrium-90 bremsstrahlung single photon emission computed tomography\/CT for both the tumour and perfused normal liver.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      21 patients were analysed; majority had grade 2 NEN (67%) and were heavily pretreated, 76% having received prior systemic therapy including peptide receptor radiotherapy (33%). ORR by RECIST 1.1 and mRECIST were 14% and 45%, respectively. Median hepatic specific PFS, PFS and OS were 48.1, 13.3 and 49.9 months respectively. Only 3 patients experienced grade 3 AEs; 2 radiation-induced liver disease that resolved without sequelae and one arterial plug migration. No significant deterioration in QoL was observed following SIRT. Dosimetry analysis found a clear tumour dose\/response relationship for 3-month ORR. Mean tumour dose in responders was 372\u00a0Gy versus 173\u00a0Gy in non-responders (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). We identified a threshold tumour absorbed dose of 164\u00a0Gy for PFS 48.1months compared to 8.8months (HR 0.2, 95%CI 0.05\u20130.96.\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.03).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In a prospective study of heavily pretreated patients, we have demonstrated clinical efficacy of SIRT for the management of liver metastases secondary to NENs. A tumour dose-response relationship was demonstrated and a threshold tumour dose for survival outcome. This work lends prospective evidence for personalised dosimetry in NENs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00259-026-07762-0","type":"journal-article","created":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T00:59:40Z","timestamp":1771289980000},"page":"4521-4531","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Efficacy and evaluation of dose-response relationship of selective internal radiation therapy for the management of liver metastases in neuroendocrine neoplasia"],"prefix":"10.1007","volume":"53","author":[{"given":"Qasim","family":"Ahmed","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolaos","family":"Doumanoglou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne","family":"Evans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Martinez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Ward","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hooshang","family":"Izadi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Wernig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Bray-Parry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuldip","family":"Nijran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Perry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neva","family":"Patel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chloe","family":"Bowen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Alsafi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rob","family":"Thomas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tahir","family":"Shah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priten","family":"Khagram","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Tait","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rohini","family":"Sharma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,17]]},"reference":[{"issue":"2","key":"7762_CR1","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1159\/000335597","volume":"95","author":"M Pavel","year":"2012","unstructured":"Pavel M, Baudin E, Couvelard A, Krenning E, Oberg K, Steinmuller T, et al. 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J Vasc Interv Radiol. 2013;24(8):1147\u201353. https:\/\/doi.org\/10.1016\/j.jvir.2013.04.018.","journal-title":"J Vasc Interv Radiol"}],"container-title":["European Journal of Nuclear Medicine and Molecular Imaging"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00259-026-07762-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00259-026-07762-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00259-026-07762-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T04:09:24Z","timestamp":1779422964000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00259-026-07762-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,17]]},"references-count":32,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["7762"],"URL":"https:\/\/doi.org\/10.1007\/s00259-026-07762-0","relation":{},"ISSN":["1619-7070","1619-7089"],"issn-type":[{"value":"1619-7070","type":"print"},{"value":"1619-7089","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,17]]},"assertion":[{"value":"23 September 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 January 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 February 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Bloomsbury Research NHS Ethics Committee (18\/LO\/0761) and the UK Health Research Authority (IRAS ID 231087). The administration of radioactivity was approved by the Administration of Radioactive Substances Advisory Committee, U.K (R190).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Written informed consent was obtained from all individual participants included in the study.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}