{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T20:28:54Z","timestamp":1787862534667,"version":"build-2784847793"},"reference-count":26,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,4,29]],"date-time":"2025-04-29T00:00:00Z","timestamp":1745884800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008645","name":"Terumo","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008645","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Neuroendocrinology"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Patients with bulky neuroendocrine liver metastases (NELM) undergoing PRRT with [<jats:sup>177<\/jats:sup>Lu]Lu\u2010DOTATATE have a worse survival than patients with limited liver metastases. Previously, the safety and efficacy of additional selective internal radiotherapy (SIRT), using holmium\u2010166 (<jats:sup>166<\/jats:sup>Ho)\u2010microspheres, directly following PRRT in patients with NELM were confirmed in the prospective HEPAR PLuS study. The aim of the current study was to provide insight into the efficacy and survival benefit of PRRT\u2009+\u2009<jats:sup>166<\/jats:sup>Ho\u2010SIRT over PRRT\u2010only by means of a propensity score matched historical cohort. A multicenter retrospective data collection was performed to match patients treated with PRRT\u2010only to the prospectively collected HEPAR PLuS study patients. Demographic, clinical, laboratory, and imaging data were collected. The primary endpoint was the proportion of patients with progression\u2010free survival (PFS) at 2\u2009years after the start of PRRT. Secondary endpoints included the proportion of patients with 2\u2010year hepatic PFS (hPFS), general PFS and hPFS, objective response rates (ORR), and overall survival (OS). Twenty\u2010four patients were 1:1 matched and included in the analysis. All key matching criteria were balanced between cohorts if feasible. The proportion of patients with PFS and hPFS at 2\u2009years was 68% and 82% after PRRT\u2009+\u2009<jats:sup>166<\/jats:sup>Ho\u2010SIRT versus 55% and 50% after PRRT only. Time to median PFS was comparable (31 vs. 30\u2009months). An initial delay in hepatic progression or death of any cause was observed in PRRT\u2009+\u2009<jats:sup>166<\/jats:sup>Ho\u2010SIRT mNET patients (75% probability of PFS at 27 vs. 22\u2009months), most notably in intestinal tumors (75% probability of PFS at 26 vs. 15\u2009months). Best ORR was 71% after PRRT\u2009+\u2009<jats:sup>166<\/jats:sup>Ho\u2010SIRT versus 25% after PRRT only. This study showed that <jats:sup>166<\/jats:sup>Ho\u2010SIRT after PRRT (vs. PRRT\u2010only) had a positive effect on the liver disease progression in patients with NELM, increasing the 2\u2010year hPFS rate and tumor response and delaying hepatic progression or death. However, this effect did not translate into improving general PFS and OS.<\/jats:p>","DOI":"10.1111\/jne.70034","type":"journal-article","created":{"date-parts":[[2025,4,30]],"date-time":"2025-04-30T02:24:33Z","timestamp":1745979873000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["<scp>PRRT<\/scp> plus holmium\u2010166\u2010<scp>SIRT<\/scp> (<scp>HEPAR PLuS<\/scp>) versus <scp>PRRT<\/scp>\u2010only in patients with metastatic neuroendocrine tumors: A propensity\u2010score matched analysis"],"prefix":"10.1111","volume":"37","author":[{"given":"W. B.","family":"Veldhuis","sequence":"first","affiliation":[{"name":"Department of Radiology and Nuclear Medicine University Medical Center Utrecht  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4199-4561","authenticated-orcid":false,"given":"T.","family":"Walter","sequence":"additional","affiliation":[{"name":"Department of Oncology Hospices Civils de Lyon  Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. M. V.","family":"de Vries\u2010Huizing","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine Netherlands Cancer Institute  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Theysohn","sequence":"additional","affiliation":[{"name":"Department of Diagnostic and Interventional Radiology and Neuroradiology University Hospital Essen, University Duisburg\u2010Essen  Essen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Barton","sequence":"additional","affiliation":[{"name":"Barton Biostatistics Ltd  Essex UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. D.","family":"Ekkelenkamp","sequence":"additional","affiliation":[{"name":"Medical Affairs Interventional Oncology Terumo Europe NV  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.","family":"Lachachi","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine Hospices Civils de Lyon  Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. J. G.","family":"de Jong","sequence":"additional","affiliation":[{"name":"Medical Affairs Interventional Oncology Terumo Europe NV  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L. W.","family":"van Golen","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine Netherlands Cancer Institute  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Lanzafame","sequence":"additional","affiliation":[{"name":"Clinic for Nuclear Medicine University Hospital Essen, University Duisburg\u2010Essen  Essen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Milot","sequence":"additional","affiliation":[{"name":"Department of Radiology Hospices Civils de Lyon  Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Lahner","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism Division of Laboratory Research, University Hospital Essen, University Duisburg\u2010Essen  Essen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. E. G. H.","family":"Lam","sequence":"additional","affiliation":[{"name":"Department of Radiology and Nuclear Medicine University Medical Center Utrecht  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. E. T.","family":"Tesselaar","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal and Medical Oncology Netherlands Cancer Institute  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8824-8697","authenticated-orcid":false,"given":"A. J. A. 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