{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T18:59:53Z","timestamp":1793213993439,"version":"4.5.0"},"reference-count":14,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T00:00:00Z","timestamp":1744675200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Peptide receptor radionuclide therapy (PRRT) is a well-established treatment option for neuroendocrine tumors (NET), yet randomized controlled trials have not provided data on its impact on overall survival. The real-world efficacy of PRRT and its association with tumor functionality and grading in pancreatic neuroendocrine tumors (PanNET) remains underexplored.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A retrospective analysis of 166 patients with histologically confirmed metastatic PanNET was performed. Subgroup analyses examined progression-free survival (PFS) and overall survival (OS) following PRRT cycles, stratified by tumor grading, tumor functionality and bone metastases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of 166 patients, 100 (60.2%) received PRRT with a median of four cycles. In the PRRT cohort, 68% of patients had deceased. PFS after four and eight consecutive cycles was 20 and 18 months, respectively (p=0.4). OS for the entire cohort was 79 months, with patients receiving 4+ cycles of PRRT having an OS of 87 months and those receiving 5+ cycles achieving an OS of 100 months. Patients with grade 1 or 2 tumors had a significantly longer median OS of 97 months compared to 74.5 months for grade 3 tumors (p = 0.0055). There was no significant difference in OS between functioning and non-functioning tumors after PRRT. Patients with bone metastases who received PRRT had a significantly shorter OS than those without (74 vs. 89 months, p = 0.013). In 19% of patients who received PRRT, therapy was discontinued due to progressive disease, toxicity or death.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Patients receiving extended cycles of PRRT showed improved survival outcomes in metastatic PanNET, particularly in patients with lower tumor grades and without bone metastases. No survival difference was seen between functioning and non-functioning PanNET, while patients with grade 3 tumors and bone metastases had significantly shorter survival despite PRRT.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2025.1526470","type":"journal-article","created":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T04:12:41Z","timestamp":1744690361000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Impact of functionality and grading on survival in pancreatic neuroendocrine tumor patients receiving peptide receptor radionuclide therapy"],"prefix":"10.3389","volume":"16","author":[{"given":"Annie","family":"Mathew","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Kersting","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang P.","family":"Fendler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna","family":"Braegelmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dagmar","family":"Fuhrer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harald","family":"Lahner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,4,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1607427","article-title":"Phase 3 trial of (177)Lu-dotatate for midgut neuroendocrine tumors","volume":"376","author":"Strosberg","year":"2017","journal-title":"N Engl J Med"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(24)00701-3","article-title":"all the, [(177)Lu]Lu-DOTA-TATE plus long-acting octreotide versus 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Neuroendocrine Tumor Society 2023 guidance paper for functioning pancreatic neuroendocrine tumour syndromes","author":"Hofland","year":"2023","journal-title":"J Neuroendocrinol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"e13138","DOI":"10.1111\/jne.13138","article-title":"Real-world efficacy of lutetium peptide receptor radionuclide therapy in patients with neuroendocrine tumours","volume":"34","author":"Almeamar","year":"2022","journal-title":"J Neuroendocrinol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0298824","article-title":"Safety and efficacy of peptide receptor radionuclide therapy in neuroendocrine tumors: A single center experience","volume":"19","author":"Sukrithan","year":"2024","journal-title":"PloS One"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1007\/s12022-022-09708-2","article-title":"Overview of the 2022 WHO classification of neuroendocrine 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