{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T20:59:25Z","timestamp":1791925165458,"version":"4.3.4"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T00:00:00Z","timestamp":1747267200000},"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>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Peptide receptor radionuclide therapy (PRRT) is an effective and well-tolerated treatment for advanced neuroendocrine tumors (NETs). However, persistent thrombocytopenia (PT) has been reported and may compromise further therapies and outcomes. This study aimed to identify predictive factors for PT defined as a platelet count &amp;lt;100 x 10\n                      <jats:sup>9<\/jats:sup>\n                      \/L, 2 months after the end of PRRT.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed a single-center retrospective analysis of clinical, biological, and imaging parameters of metastatic NET patients undergoing [177Lu]Lu-DOTATATE therapy. Bone metastatic volume was quantitatively measured and converted into an Osteo-Medullary Invasion Score (OMIS). The initial decline of platelet count (IDPC) was defined as the relative change (%) in platelet count between the baseline and the nadir value before the second cycle.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In total, 47 patients (25 women, 22 men, median age 68 years) were included. Fifteen patients (31.9%) had bone metastases, and five (10.6%) had an OMIS \u2265 30%. Six patients (15.4%) presented with a spleen length \u2265 100 mm. Median follow-up was 50.1 months. Median IDPC was 26%. Eight patients (17%) presented with PT. PT was associated with an OMIS \u2265 30% (p &amp;lt; 0.001; odds ratio not estimable), a spleen length \u2265 100 mm (p = 0.04; odds ratio = 7), and an IDPC \u2265 30% (p= 0.014: odds ratio = 15.8), and was unrelated to age, gender, previous cancer, previous therapies, and cumulative activity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>We found that 17% of PT incidence correlated with relatively high bone metastatic burden and spleen length. Physicians should be vigilant in the event of a significant drop in platelet count after the first cycle of PRRT.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2025.1568243","type":"journal-article","created":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T00:10:44Z","timestamp":1747267844000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Predictive factors for persistent thrombocytopenia after peptide receptor radioligand therapy in enteropancreatic neuroendocrine tumors"],"prefix":"10.3389","volume":"16","author":[{"given":"Romain","family":"Ferrara","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Zemmour","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thibaut","family":"Reichert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Ouk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Niccoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jemima","family":"Maniry-Quellier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Brenot-Rossi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Charrier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandrine","family":"Oziel-Taieb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,5,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.15.4377","article-title":"One hundred years after \u201ccarcinoid\u201d: epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States","volume":"26","author":"Yao","year":"2008","journal-title":"J Clin Oncol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2017.0589","article-title":"Trends in the incidence, prevalence, and survival outcomes in patients with neuroendocrine tumors in the United States","volume":"3","author":"Dasari","year":"2017","journal-title":"JAMA Oncol"},{"key":"B3","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":"B4","doi-asserted-by":"publisher","DOI":"10.3390\/ph12030114","article-title":"Lutathera((R)): the first FDA- and EMA-approved radiopharmaceutical for peptide receptor radionuclide therapy","volume":"12","author":"Hennrich","year":"2019","journal-title":"Pharmaceut (Basel)"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-16-2743","article-title":"Long-term efficacy, survival, and safety of [(177)Lu-DOTA(0),Tyr(3)]octreotate in patients with gastroenteropancreatic and bronchial neuroendocrine tumors","volume":"23","author":"Brabander","year":"2017","journal-title":"Clin Cancer Res"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1007\/s00259-015-3193-4","article-title":"Subacute haematotoxicity after PRRT with (177)Lu-DOTA-octreotate: prognostic factors, incidence and course","volume":"43","author":"Bergsma","year":"2016","journal-title":"Eur J Nucl Med Mol Imag"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1007\/s00259-022-05833-6","article-title":"177Lu]Lu-DOTATATE peptide receptor radionuclide therapy\u2013associated myeloid neoplasms: insights from the WHO pharmacovigilance database","volume":"49","author":"vigne","year":"2022","journal-title":"Eur J Nuclear Med Mol Imag"},{"key":"B8","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1007\/s00259-014-2893-5","article-title":"Long-term tolerability of PRRT in 807 patients with neuroendocrine tumours: the value and limitations of clinical factors","volume":"42","author":"Bodei","year":"2015","journal-title":"Eur J Nucl Med Mol Imag"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.117.189712","article-title":"Persistent hematologic dysfunction after peptide receptor radionuclide therapy with (177)Lu-DOTATATE: incidence, course, and predicting factors in patients with gastroenteropancreatic neuroendocrine tumors","volume":"59","author":"Bergsma","year":"2018","journal-title":"J Nucl Med"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3413\/Nukmed-0614-13-08","article-title":"Can peptide receptor radionuclide therapy be safely applied in florid bone metastases? A pilot analysis of late stage osseous involvement","volume":"53","author":"Sabet","year":"2014","journal-title":"Nuklearmedizin"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1097\/RLU.0000000000004130","article-title":"Severe thrombocytopenia in patients with advanced neuroendocrine tumor treated with peptide receptor radioligand therapy","volume":"47","author":"Naveed Ahmad","year":"2022","journal-title":"Clin Nucl Med"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1097\/RLU.0000000000004671","article-title":"Safety and efficacy of 177 lu-DOTATATE in neuroendocrine tumor patients with extensive bone disease","volume":"48","author":"Alsadik","year":"2023","journal-title":"Clin Nucl Med"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.112.119347","article-title":"Long-term hematotoxicity after peptide receptor radionuclide therapy with 177Lu-octreotate","volume":"54","author":"Sabet","year":"2013","journal-title":"J Nucl Med"},{"key":"B14","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/j.mednuc.2019.12.002","article-title":"Investigation of risk factors for 177Lu-DOTATATE-induced thrombocytopenia in routine follow-up","volume":"44","author":"Ferrara NC","year":"2020","journal-title":"Med Nucl"},{"key":"B15","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1088\/0031-9155\/26\/3\/003","article-title":"Active bone marrow distribution as a function of age in humans","volume":"26","author":"Cristy","year":"1981","journal-title":"Phys Med Biol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.2214\/ajr.184.5.01841510","article-title":"Determination of splenomegaly by CT: is there a place for a single measurement","volume":"184","author":"Bezerra","year":"2005","journal-title":"AJR Am J Roentgenol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.15.2553","article-title":"Treatment with the radiolabeled somatostatin analog [177 Lu-DOTA 0,Tyr3]octreotate: toxicity, efficacy, and survival","volume":"26","author":"Kwekkeboom","year":"2008","journal-title":"J Clin Oncol"},{"key":"B18","doi-asserted-by":"publisher","first-page":"e0260073","DOI":"10.1371\/journal.pone.0260073","article-title":"Haematotoxicity during peptide receptor radionuclide therapy: Baseline parameters differences and effect on patient\u2019s therapy course","volume":"16","author":"de Vries-Huizing","year":"2021","journal-title":"PLoS One"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1007\/s00259-013-2677-3","article-title":"Outcome of peptide receptor radionuclide therapy with 177Lu-octreotate in advanced grade 1\/2 pancreatic neuroendocrine tumours","volume":"41","author":"Ezziddin","year":"2014","journal-title":"Eur J Nucl Med Mol Imag"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1007\/s00259-018-4209-7","article-title":"Personalized (177)Lu-octreotate peptide receptor radionuclide therapy of neuroendocrine tumours: initial results from the P-PRRT trial","volume":"46","author":"Del Prete","year":"2019","journal-title":"Eur J Nucl Med Mol Imag"},{"key":"B21","unstructured":"Advanced Accelerator Applications USA I. LUTATHERA (lutetium Lu 177 dotatate) injection, for intravenous use: U.S. Food and Drug Administration\n          \n          2024"},{"key":"B22","article-title":"Distribution of somatostatin receptors in normal and neoplastic human tissues: recent advances and potential relevance","volume":"70","author":"Reubi","year":"1997","journal-title":"Yale J Biol Med"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.123.265484","article-title":"Specific uptake in the bone marrow causes high absorbed red marrow doses during [(177)Lu]Lu-DOTATATE treatment","volume":"64","author":"Hemmingsson","year":"2023","journal-title":"J Nucl Med"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.113.120600","article-title":"Comparative biodistribution and radiation dosimetry of 68Ga-DOTATOC and 68Ga-DOTATATE in patients with neuroendocrine tumors","volume":"54","author":"Sandstrom","year":"2013","journal-title":"J Nucl Med"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01126","article-title":"Generation of myeloid cells in cancer: the spleen matters","volume":"11","author":"Wu","year":"2020","journal-title":"Front Immunol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.123.267023","article-title":"Absorbed dose-response relationship in patients with gastroenteropancreatic neuroendocrine tumors treated with [(177)Lu]Lu-DOTATATE: one step closer to personalized medicine","volume":"65","author":"Hebert","year":"2024","journal-title":"J Nucl Med"},{"key":"B27","doi-asserted-by":"publisher","first-page":"e32212","DOI":"10.1097\/MD.0000000000032212","article-title":"Predicting subacute hematological toxicity of 177Lu-DOTATATE therapy using healthy organs\u2019 uptake on post-treatment quantitative SPECT: A pilot study","volume":"101","author":"Morland","year":"2022","journal-title":"Med (Baltimore)"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-27994-2_33","article-title":"Is there a correlation between peptide receptor radionuclide therapy-associated hematological toxicity and spleen dose","volume":"194","author":"Kulkarni","year":"2013","journal-title":"Recent Results Cancer Res"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1159\/000506746","article-title":"177Lu-DOTATATE therapy of advanced pancreatic neuroendocrine tumors heavily pretreated with chemotherapy: analysis of outcome, safety, and their determinants","volume":"111","author":"Fross-Baron","year":"2021","journal-title":"Neuroendocrinology"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1007\/s00259-013-2547-z","article-title":"Outcome and toxicity of salvage therapy with 177Lu-octreotate in patients with metastatic gastroenteropancreatic neuroendocrine tumours","volume":"41","author":"Sabet","year":"2014","journal-title":"Eur J Nucl Med Mol Imag"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1007\/s00259-018-4158-1","article-title":"Salvage peptide receptor radionuclide therapy with [(177)Lu-DOTA,Tyr(3)]octreotate in patients with bronchial and gastroenteropancreatic neuroendocrine tumours","volume":"46","author":"van der Zwan","year":"2019","journal-title":"Eur J Nucl Med Mol Imag"},{"key":"B32","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1097\/RLU.0000000000004203","article-title":"Dose-limiting bone marrow toxicities after peptide receptor radionuclide therapy are more prevalent in women than in men","volume":"47","author":"Minczeles","year":"2022","journal-title":"Clin Nucl Med"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(21)00572-6","article-title":"(177)Lu-Dotatate plus long-acting octreotide versus high\u2212dose long-acting octreotide in patients with midgut neuroendocrine tumours (NETTER-1): final overall survival and long-term safety results from an open-label, randomised, controlled, phase 3 trial","volume":"22","author":"Strosberg","year":"2021","journal-title":"Lancet Oncol"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2025.1568243\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T00:10:47Z","timestamp":1747267847000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2025.1568243\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,15]]},"references-count":33,"alternative-id":["10.3389\/fendo.2025.1568243"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2025.1568243","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,15]]},"article-number":"1568243"}}