{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T05:24:39Z","timestamp":1772601879972,"version":"3.50.1"},"reference-count":26,"publisher":"Bentham Science Publishers Ltd.","issue":"2","license":[{"start":{"date-parts":[[2022,4,27]],"date-time":"2022-04-27T00:00:00Z","timestamp":1651017600000},"content-version":"vor","delay-in-days":57,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/legalcode"}],"funder":[{"DOI":"10.13039\/100009142","name":"Cancer Care Ontario CCO Canada","doi-asserted-by":"publisher","award":["172567"],"award-info":[{"award-number":["172567"]}],"id":[{"id":"10.13039\/100009142","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["eurekaselect.com"],"crossmark-restriction":true},"short-container-title":["CRP"],"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:sec>\n<jats:title>Background:<\/jats:title>\n<jats:p>Peptide receptor radionuclide therapy (PRRT) has been recently approved\nfor advanced, metastatic, or progressive neuroendocrine tumors (NETs).<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Objectives:<\/jats:title>\n<jats:p>This study reports the adverse events (AEs) observed with patient-tailored administered\nactivity.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Methods:<\/jats:title>\n<jats:p>Fifty-two PRRT naive patients were treated with 177Lu-DOTATATE. The administered\nactivity ranges between 2.78 and 5.55 GBq\/cycle using the patient's unique characteristics (age,\nsymptoms, blood work, and biomarkers).<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Results:<\/jats:title>\n<jats:p>The protocol was well tolerated with the overwhelming majority of participants being forty-\nsix (88%), completing all 4 induction therapy cycles. The median cumulative administered activity\nwas 19.6 GBq (ranged 3.8-22.3 GBq). A total of 42\/52 (81%) reported at least one symptom,\nand 43\/52 (83%) had evidence of biochemical abnormality at enrollment that would meet grade 1\nor 2 criteria for AEs. These symptoms only slightly increase with treatment to 50\/52 (96%) and\n51\/52 (98%), respectively. The most common symptoms were mild fatigue (62%), shortness of\nbreath (50%), nausea (44%), abdominal pain (38%), and musculoskeletal pain (37%). The most\ncommon biomarker abnormalities were mild anemia (81%), reduced estimated glomerular filtration\nrate (eGFR) (58%), increased alkaline phosphatase (ALP) (50%), and leukopenia (37%). Of\ncritical importance, no 177Lu-DOTATATE related grade 3 or 4 AEs were observed.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Conclusion:<\/jats:title>\n<jats:p>Tailoring the administered activity of 177Lu-DOTATATE to the individual patient\nwith a variety of NETs is both safe and well-tolerated. No patient developed severe grade 3 or 4\nAEs. Most patients exhibit symptoms or biochemical abnormality before treatment and this only\nslightly worsens following induction therapy.<\/jats:p>\n<\/jats:sec>","DOI":"10.2174\/1874471014666210810100435","type":"journal-article","created":{"date-parts":[[2021,9,6]],"date-time":"2021-09-06T18:00:52Z","timestamp":1630951252000},"page":"123-133","update-policy":"https:\/\/doi.org\/10.2174\/bsp_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Toxicity and Tolerability of 177Lu-DOTA-TATE PRRT with a Modified Administered\nActivity Protocol in NETs of Variable Origin \u2013 A Phase 2 Registry\nStudy"],"prefix":"10.2174","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6320-7565","authenticated-orcid":true,"given":"Alireza","family":"Khatami","sequence":"first","affiliation":[{"name":"Division of Nuclear Medicine, Department of Medical Imaging, Western University, London, ON N645C1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Golmehr","family":"Sistani","sequence":"additional","affiliation":[{"name":"Division of Nuclear Medicine, Department of Medical Imaging, Western University, London, ON N645C1, Canada"},{"name":"Division of Radiology, Department of Medical Imaging, Western University, London, ON, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Duncan E. K.","family":"Sutherland","sequence":"additional","affiliation":[{"name":"Division of Nuclear Medicine, Department of Medical Imaging, Western University, London, ON N645C1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"DeBrabandere","sequence":"additional","affiliation":[{"name":"Division of Nuclear Medicine, Department of Medical Imaging, Western University, London, ON N645C1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert H.","family":"Reid","sequence":"additional","affiliation":[{"name":"Division of Nuclear Medicine, Department of Medical Imaging, Western University, London, ON N645C1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David T.","family":"Laidley","sequence":"additional","affiliation":[{"name":"Division of Nuclear Medicine, Department of Medical Imaging, Western University, London, ON N645C1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"965","reference":[{"key":"ref=1","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1053\/j.semnuclmed.2015.12.003","volume":"46","author":"Bodei L.","year":"2016","unstructured":"Bodei L.; Kwekkeboom D.J.; Kidd M.; Modlin I.M.; Krenning E.P.; Radiolabeled somatostatin analogue therapy of gastroenteropancreatic cancer. Semin Nucl Med 2016,46(3),225-238","journal-title":"Semin Nucl Med"},{"key":"ref=2","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1530\/ERC-16-0099","volume":"23","author":"Childs A.","year":"2016","unstructured":"Childs A.; Kirkwood A.; Edeline J.; Luong T.V.; Watkins J.; Lamarca A.; Alrifai D.; Nsiah-Sarbeng P.; Gillmore R.; Mayer A.; Thirlwell C.; Sarker D.; Valle J.W.; Meyer T.; Ki-67 index and response to chemotherapy in patients with neuroendocrine tumours. Endocr Relat Cancer 2016,23(7),563-570","journal-title":"Endocr Relat Cancer"},{"key":"ref=3","doi-asserted-by":"publisher","first-page":"324","DOI":"10.1097\/01.pas.0000149706.74216.b6","volume":"29","author":"Schmid K.","year":"2005","unstructured":"Schmid K.; Birner P.; Gravenhorst V.; End A.; Geleff S.; Prognostic value of lymphatic and blood vessel invasion in neuroendocrine tumors of the lung. Am J Surg Pathol 2005,29(3),324-328","journal-title":"Am J Surg Pathol"},{"key":"ref=4","doi-asserted-by":"publisher","first-page":"3063","DOI":"10.1200\/JCO.2007.15.4377","volume":"26","author":"Yao J.C.","year":"2008","unstructured":"Yao J.C.; Hassan M.; Phan A.; Dagohoy C.; Leary C.; Mares J.E.; Abdalla E.K.; Fleming J.B.; Vauthey J.N.; Rashid A.; Evans D.B.; One hundred years after \u201ccarcinoid\u201d: Epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. J Clin Oncol 2008,26(18),3063-3072","journal-title":"J Clin Oncol"},{"key":"ref=5","doi-asserted-by":"publisher","first-page":"1335","DOI":"10.1001\/jamaoncol.2017.0589","volume":"3","author":"Dasari A.","year":"2017","unstructured":"Dasari A.; Shen C.; Halperin D.; Zhao B.; Zhou S.; Xu Y.; Shih T.; Yao J.C.; Trends in the incidence, prevalence, and survival outcomes in patients with neuroendocrine tumors in the United States. JAMA Oncol 2017,3(10),1335-1342","journal-title":"JAMA Oncol"},{"key":"ref=6","doi-asserted-by":"publisher","first-page":"934","DOI":"10.1002\/cncr.11105","volume":"97","author":"Modlin I.M.","year":"2003","unstructured":"Modlin I.M.; Lye K.D.; Kidd M.; A 5-decade analysis of 13,715 carcinoid tumors. Cancer 2003,97(4),934-959","journal-title":"Cancer"},{"key":"ref=7","year":"2020","unstructured":"American Cancer Society2020"},{"key":"ref=8","doi-asserted-by":"publisher","first-page":"4656","DOI":"10.1200\/JCO.2009.22.8510","volume":"27","author":"Rinke A.","year":"2009","unstructured":"Rinke A.; M\u00fcller H.H.; Schade-Brittinger C.; Klose K.J.; Barth P.; Wied M.; Mayer C.; Aminossadati B.; Pape U.F.; Bl\u00e4ker M.; Harder J.; Arnold C.; Gress T.; Arnold R.; Placebo-controlled, double-blind, prospective, randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors: A report from the PROMID Study Group. J Clin Oncol 2009,27(28),4656-4663","journal-title":"J Clin Oncol"},{"key":"ref=9","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1056\/NEJMoa1316158","volume":"371","author":"Caplin M.E.","year":"2014","unstructured":"Caplin M.E.; Pavel M.; \u0106wik\u0142a J.B.; Phan A.T.; Raderer M.; Sedl\u00e1\u010dkov\u00e1 E.; Cadiot G.; Wolin E.M.; Capdevila J.; Wall L.; Rindi G.; Langley A.; Martinez S.; Blumberg J.; Ruszniewski P.; Lanreotide in metastatic enteropancreatic neuroendocrine tumors. N Engl J Med 2014,371(3),224-233","journal-title":"N Engl J Med"},{"key":"ref=10","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1038\/nrendo.2009.105","volume":"5","author":"van Essen M.","year":"2009","unstructured":"van Essen M.; Krenning E.P.; Kam B.L.R.; de Jong M.; Valkema R.; Kwekkeboom D.J.; Peptide-receptor radionuclide therapy for endocrine tumors. Nat Rev Endocrinol 2009,5(7),382-393","journal-title":"Nat Rev Endocrinol"},{"key":"ref=11","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1007\/978-3-030-56267-0_4","author":"Civelek A.C.","year":"2021","unstructured":"Civelek A.C.; Wong F.C.L.;  Locoregional radionuclide cancer therapy clinical and scientific aspects 2021,61-87","journal-title":"Locoregional radionuclide cancer therapy clinical and scientific aspects"},{"key":"ref=12","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1056\/NEJMoa1607427","volume":"376","author":"Strosberg J.","year":"2017","unstructured":"Strosberg J.; El-Haddad G.; Wolin E.; Hendifar A.; Yao J.; Chasen B.; Mittra E.; Kunz P.L.; Kulke M.H.; Jacene H.; Bushnell D.; O\u2019Dorisio T.M.; Baum R.P.; Kulkarni H.R.; Caplin M.; Lebtahi R.; Hobday T.; Delpassand E.; Van Cutsem E.; Benson A.; Srirajaskanthan R.; Pavel M.; Mora J.; Berlin J.; Grande E.; Reed N.; Seregni E.; \u00d6berg K.; Lopera Sierra M.; Santoro P.; Thevenet T.; Erion J.L.; Ruszniewski P.; Kwekkeboom D.; Krenning E.; Phase 3 trial of lu-dotatate for midgut neuroendocrine tumors. N Engl J Med 2017,376(2),125-135","journal-title":"N Engl J Med"},{"key":"ref=13","doi-asserted-by":"publisher","first-page":"970","DOI":"10.1007\/s00259-018-3945-z","volume":"45","author":"Garske-Rom\u00e1n U.","year":"2018","unstructured":"Garske-Rom\u00e1n U.; Sandstr\u00f6m M.; Fr\u00f6ss Baron K.; Lundin L.; Hellman P.; Welin S.; Johansson S.; Khan T.; Lundqvist H.; Eriksson B.; Sundin A.; Granberg D.; Prospective observational study of Lu-DOTA-octreotate therapy in 200 patients with advanced metastasized neuroendocrine tumours (NETs): Feasibility and impact of a dosimetry-guided study protocol on outcome and toxicity. Eur J Nucl Med Mol Imaging 2018,45(6),970-988","journal-title":"Eur J Nucl Med Mol Imaging"},{"key":"ref=14","doi-asserted-by":"publisher","first-page":"2124","DOI":"10.1200\/JCO.2007.15.2553","volume":"26","author":"Kwekkeboom D.J.","year":"2008","unstructured":"Kwekkeboom D.J.; de Herder W.W.; Kam B.L.; van Eijck C.H.; van Essen M.; Kooij P.P.; Feelders R.A.; van Aken M.O.; Krenning E.P.; Treatment with the radiolabeled somatostatin analog [177 Lu-DOTA 0,Tyr3]octreotate: Toxicity, efficacy, and survival. J Clin Oncol 2008,26(13),2124-2130","journal-title":"J Clin Oncol"},{"key":"ref=15","doi-asserted-by":"publisher","first-page":"2125","DOI":"10.1007\/s00259-011-1902-1","volume":"38","author":"Bodei L.","year":"2011","unstructured":"Bodei L.; Cremonesi M.; Grana C.M.; Fazio N.; Iodice S.; Baio S.M.; Bartolomei M.; Lombardo D.; Ferrari M.E.; Sansovini M.; Chinol M.; Paganelli G.; Peptide receptor radionuclide therapy with Lu-DOTATATE: The IEO phase I-II study. Eur J Nucl Med Mol Imaging 2011,38(12),2125-2135","journal-title":"Eur J Nucl Med Mol Imaging"},{"key":"ref=16","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/j.lungcan.2020.10.005","volume":"150","author":"Mirvis E.","year":"2020","unstructured":"Mirvis E.; Toumpanakis C.; Mandair D.; Gnanasegaran G.; Caplin M.; Navalkissoor S.; Efficacy and tolerability of peptide receptor radionuclide therapy (PRRT) in advanced metastatic bronchial neuroendocrine tumours (NETs). Lung Cancer 2020,150,70-75","journal-title":"Lung Cancer"},{"key":"ref=17","doi-asserted-by":"publisher","first-page":"909","DOI":"10.3390\/cancers11070909","volume":"11","author":"Vyakaranam A.R.","year":"2019","unstructured":"Vyakaranam A.R.; Crona J.; Norl\u00e9n O.; Granberg D.; Garske-Rom\u00e1n U.; Sandstr\u00f6m M.; Fr\u00f6ss-Baron K.; Thiis-Evensen E.; Hellman P.; Sundin A.; Favorable outcome in patients with pheochromocytoma and paraganglioma treated with lu-dotatate. Cancers (Basel) 2019,11(7),909","journal-title":"Cancers (Basel)"},{"key":"ref=18","doi-asserted-by":"publisher","first-page":"718","DOI":"10.1007\/s00259-018-4196-8","volume":"46","author":"Kong G.","year":"2019","unstructured":"Kong G.; Grozinsky-Glasberg S.; Hofman M.S.; Akhurst T.; Meirovitz A.; Maimon O.; Krausz Y.; Godefroy J.; Michael M.; Gross D.J.; Hicks R.J.; Highly favourable outcomes with peptide receptor radionuclide therapy (PRRT) for metastatic rectal neuroendocrine neoplasia (NEN). Eur J Nucl Med Mol Imaging 2019,46(3),718-727","journal-title":"Eur J Nucl Med Mol Imaging"},{"key":"ref=19","year":"2010","unstructured":"Common Terminology Criteria for Adverse Events (CTCAE)Version 403 United States, Department of Health and Human Services, National Institutes of Health, National Cancer Institute, National Cancer Therapy Evaluation Program (CTEP)Available at: https:\/\/evs.nci.nih.gov\/ftp1\/CTCAE\/CTCAE_4.03\/CTCAE_4.03_2010-06-14_QuickReference_8.5x11.pdf; 2010","journal-title":"Common Terminology Criteria for Adverse Events (CTCAE)Version 403"},{"key":"ref=20","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1007\/s00259-014-2893-5","volume":"42","author":"Bodei L.","year":"2015","unstructured":"Bodei L.; Kidd M.; Paganelli G.; Grana C.M.; Drozdov I.; Cremonesi M.; Lepensky C.; Kwekkeboom D.J.; Baum R.P.; Krenning E.P.; Modlin I.M.; Long-term tolerability of PRRT in 807 patients with neuroendocrine tumours: The value and limitations of clinical factors. Eur J Nucl Med Mol Imaging 2015,42(1),5-19","journal-title":"Eur J Nucl Med Mol Imaging"},{"key":"ref=21","doi-asserted-by":"publisher","first-page":"1857","DOI":"10.2967\/jnumed.112.119347","volume":"54","author":"Sabet A.","year":"2013","unstructured":"Sabet A.; Ezziddin K.; Pape U.F.; Ahmadzadehfar H.; Mayer K.; P\u00f6ppel T.; Guhlke S.; Biersack H.J.; Ezziddin S.; Long-term hematotoxicity after peptide receptor radionuclide therapy with 177Lu-octreotate. J Nucl Med 2013,54(11),1857-1861","journal-title":"J Nucl Med"},{"key":"ref=22","doi-asserted-by":"publisher","first-page":"115","DOI":"10.3390\/curroncol28010015","volume":"28","author":"Sistani G.","year":"2020","unstructured":"Sistani G.; Sutherland D.E.K.; Mujoomdar A.; Wiseman D.P.; Khatami A.; Tsvetkova E.; Reid R.H.; Laidley D.T.; Efficacy of lu-dotatate induction and maintenance therapy of various types of neuroendocrine tumors: A phase II registry study. Curr Oncol 2020,28(1),115-127","journal-title":"Curr Oncol"},{"key":"ref=23","doi-asserted-by":"publisher","first-page":"16932","DOI":"10.18632\/oncotarget.24524","volume":"9","author":"Baum R.P.","year":"2018","unstructured":"Baum R.P.; Kulkarni H.R.; Singh A.; Kaemmerer D.; Mueller D.; Prasad V.; Hommann M.; Robiller F.C.; Niepsch K.; Franz H.; Jochems A.; Lambin P.; H\u00f6rsch D.; Results and adverse events of personalized peptide receptor radionuclide therapy with Yttrium and Lutetium in 1048 patients with neuroendocrine neoplasms. Oncotarget 2018,9(24),16932-16950","journal-title":"Oncotarget"},{"key":"ref=24","doi-asserted-by":"publisher","first-page":"4617","DOI":"10.1158\/1078-0432.CCR-16-2743","volume":"23","author":"Brabander T.","year":"2017","unstructured":"Brabander T.; van der Zwan W.A.; Teunissen J.J.M.; Kam B.L.R.; Feelders R.A.; de Herder W.W.; van Eijck C.H.J.; Franssen G.J.H.; Krenning E.P.; Kwekkeboom D.J.; Long-term efficacy, survival, and safety of [177Lu-DOTA0, Tyr3]octreotate in patients with gastroenteropancreatic and bronchial neuroendocrine tumors. Clin Cancer Res 2017,23(16),4617-4624","journal-title":"Clin Cancer Res"},{"key":"ref=25","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1053\/j.seminoncol.2018.08.004","volume":"45","author":"Ramage J.","year":"2018","unstructured":"Ramage J.; Naraev B.G.; Halfdanarson T.R.; Peptide receptor radionuclide therapy for patients with advanced pancreatic neuroendocrine tumors. Semin Oncol 2018,45(4),236-248","journal-title":"Semin Oncol"},{"key":"ref=26","doi-asserted-by":"publisher","first-page":"2989","DOI":"10.1158\/1078-0432.CCR-20-3703","volume":"27","author":"Jha A.","year":"2021","unstructured":"Jha A.; Ta\u00efeb D.; Carrasquillo J.A.; Pryma D.A.; Patel M.; Millo C.; de Herder W.W.; Del Rivero J.; Crona J.; Shulkin B.L.; Virgolini I.; Chen A.P.; Mittal B.R.; Basu S.; Dillon J.S.; Hope T.A.; Mari Aparici C.; Iagaru A.H.; Hicks R.J.; Avram A.M.; Strosberg J.R.; Civelek A.C.; Lin F.I.; Pandit-Taskar N.; Pacak K.; High-specific-activity 131I-MIBG vs. 177Lu-DOTATATE targeted radionuclide therapy for metastatic pheochromocytoma and paraganglioma. Clin Cancer Res 2021,27(11),2989-2995","journal-title":"Clin Cancer Res"}],"container-title":["Current Radiopharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.eurekaselect.com\/article\/download?doi=10.2174\/1874471014666210810100435","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.eurekaselect.com\/195474\/article","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.eurekaselect.com\/article\/download?doi=10.2174\/1874471014666210810100435","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,27]],"date-time":"2022-10-27T16:31:53Z","timestamp":1666888313000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.eurekaselect.com\/195474\/article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3]]},"references-count":26,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2022,3]]}},"alternative-id":["LiveAll1"],"URL":"https:\/\/doi.org\/10.2174\/1874471014666210810100435","relation":{},"ISSN":["1874-4710"],"issn-type":[{"value":"1874-4710","type":"print"}],"subject":[],"published":{"date-parts":[[2022,3]]},"assertion":[{"value":"Peer Reviewed","order":0,"name":"review_status","label":"Review Status","group":{"name":"peer_review_details","label":"Peer Review Details"}},{"value":"Single blind","order":1,"name":"review_process","label":"Review Process","group":{"name":"peer_review_details","label":"Peer Review Details"}},{"value":"Checked with iThenticate","order":0,"name":"screening_status","label":"Screening Status","group":{"name":"plagiarism_screening","label":"Plagiarism Screening"}},{"value":"2021-03-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-05-21","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-05-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-04-27","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}