{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T02:51:52Z","timestamp":1772160712197,"version":"3.50.1"},"reference-count":30,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,6,21]],"date-time":"2023-06-21T00:00:00Z","timestamp":1687305600000},"content-version":"vor","delay-in-days":20,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Neuroendocrinology"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>\n                      RECIST 1.1 criteria are commonly used with computed tomography (CT) to evaluate the efficacy of systemic treatments in patients with neuroendocrine tumors (NETs) and liver metastases (LMs), but their relevance is questioned in this setting. We aimed to explore alternative criteria using different numbers of measured LMs and thresholds of size and density variation. We retrospectively studied patients with advanced pancreatic or small intestine NETs with LMs, treated with systemic treatment in the first\u2010and\/or second\u2010line, without early progression, in 14 European expert centers. We compared time to treatment failure (TTF) between responders and non\u2010responders according to various criteria defined by 0%, 10%, 20% or 30% decrease in the sum of LM size, and\/or by 10%, 15% or 20% decrease in LM density, measured on two, three or five LMs, on baseline (\u22641\u2009month before treatment initiation) and first revaluation (\u22646\u2009months) contrast\u2010enhanced CT scans. Multivariable Cox proportional hazard models were performed to adjust the association between response criteria and TTF on prognostic factors. We included 129 systemic treatments (long\u2010acting somatostatin analogs 41.9%, chemotherapy 26.4%, targeted therapies 31.8%), administered as first\u2010line (53.5%) or second\u2010line therapies (46.5%) in 91 patients. A decrease \u226510% in the size of three LMs was the response criterion that best predicted prolonged TTF, with significance at multivariable analysis (HR 1.90; 95% CI: 1.06\u20133.40;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u2009.03). Conversely, response defined by RECIST 1.1 did not predict prolonged TTF (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u2009.91), and neither did criteria based on changes in LM density. A \u226510% decrease in size of three LMs could be a more clinically relevant criterion than the current 30% threshold utilized by RECIST 1.1 for the evaluation of treatment efficacy in patients with advanced NETs. Its implementation in clinical trials is mandatory for prospective validation. Criteria based on changes in LM density were not predictive of treatment efficacy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Trial Registration<\/jats:title>\n                    <jats:p>Registered  at CNIL\u2010CERB, Assistance publique hopitaux de Paris as \u201cE\u2010NETNET\u2010L\u2010E\u2010CT\u201d July 2018. No number was assigned. Approved by the Medical Ethics Review Board of University Medical Center Groningen.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jne.13311","type":"journal-article","created":{"date-parts":[[2023,5,30]],"date-time":"2023-05-30T09:33:19Z","timestamp":1685439199000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Proposal of early\n                    <scp>CT<\/scp>\n                    morphological criteria for response of liver metastases to systemic treatments in gastroenteropancreatic neuroendocrine tumors: Alternatives to\n                    <scp>RECIST<\/scp>"],"prefix":"10.1111","volume":"35","author":[{"given":"Louis","family":"de Mestier","sequence":"first","affiliation":[{"name":"Department of Pancreatology and Digestive Oncology Universit\u00e9 Paris\u2010Cit\u00e9, INSERM U1149, Beaujon University Hospital  Clichy France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthieu","family":"Resche\u2010Rigon","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics Universit\u00e9 Paris\u2010Cit\u00e9, Saint\u2010Louis Hospital  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2999-1958","authenticated-orcid":false,"given":"Clarisse","family":"Dromain","sequence":"additional","affiliation":[{"name":"Department of Radiology Lausanne University Hospital (CHUV) and University of Lausanne (UNIL)  Lausanne Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela","family":"Lamarca","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology The Christie Hospital  Manchester UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"La Salvia","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Hospital Universitario 12 de Octubre  Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lesley","family":"de Baker","sequence":"additional","affiliation":[{"name":"Department of Radiology Universitair Ziekenhuis Antwerpen  Edegem Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3622-3268","authenticated-orcid":false,"given":"Uli","family":"Fehrenbach","sequence":"additional","affiliation":[{"name":"Department of Radiology Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin  Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Pusceddu","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Fondazione IRCCS Istituto Nazionale dei Tumori  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annamaria","family":"Colao","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Department of Clinical Medicine and Surgery Universit\u00e0 Federico II di Napoli  Naples Italy"},{"name":"Endocrinology Unit, Department of Clinical and Molecular Medicine Sapienza University of Rome, Sant'Andrea Hospital, ENETS Center of Excellence  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7598-214X","authenticated-orcid":false,"given":"Ivan","family":"Borbath","sequence":"additional","affiliation":[{"name":"Department of Hepatology and Gastroenterology University Hospital St Luc\/UCLouvain  Woluwe Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robbert","family":"de Haas","sequence":"additional","affiliation":[{"name":"Department of Radiology University of Groningen, University Medical Center Groningen  Groningen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Rinzivillo","sequence":"additional","affiliation":[{"name":"Digestive Disease Unit Sant'Andrea University Hospital, ENETS Center of Excellence  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandro","family":"Zerbi","sequence":"additional","affiliation":[{"name":"Pancreatic Surgery Humanitas Clinical and Research Center, Rozzano\u2010  Milano Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luigi","family":"Funicelli","sequence":"additional","affiliation":[{"name":"Division of Radiology, IEO European Institute of Oncology IRCCS  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1463-5165","authenticated-orcid":false,"given":"Wouter W.","family":"de Herder","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Erasmus MC and Erasmus MC Cancer Institute  Rotterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6545-7023","authenticated-orcid":false,"given":"Andreas","family":"Selberherr","sequence":"additional","affiliation":[{"name":"Division of General Surgery, Department of Surgery Medical University  Vienna Austria"},{"name":"Department of General and Visceral Surgery Evangelisches Krankenhaus Wien  Vienna Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna Dorothea","family":"Wagner","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Lausanne University Hospital (CHUV) and University of Lausanne (UNIL)  Lausanne Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Prakash","family":"Manoharan","sequence":"additional","affiliation":[{"name":"Department of Radiology and Nuclear Medicine The Christie  Manchester UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"De Cima","sequence":"additional","affiliation":[{"name":"Department of Radiology Hospital Universitario 12 de Octubre  Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Willem","family":"Lybaert","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Universitair Ziekenhuis Antwerpen  Edegem Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henning","family":"Jann","sequence":"additional","affiliation":[{"name":"Department of Hepatology and Gastroenterology Charit\u00e9\u2010University, Charit\u00e9\u2010Universit\u00e4tsmedizin  Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalie","family":"Prinzi","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Fondazione IRCCS Istituto Nazionale dei Tumori  Milan 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Italy"},{"name":"Department of Medical\u2010Surgical Sciences and Translational Medicine Sapienza University of Rome, ENETS Center of Excellence  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vittorio","family":"Pedicini","sequence":"additional","affiliation":[{"name":"Department of Radiology Humanitas Clinical and Research Center  Rozzano\u2010Milano Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Giovanna","family":"Pitoni","sequence":"additional","affiliation":[{"name":"Post\u2010graduate School in Radiodiagnostics University of Milan  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander","family":"Siebenhuener","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology University of Zurich, University Hospital Zurich  Zurich Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marius 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