{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T19:30:03Z","timestamp":1790623803164,"version":"4.1.0"},"reference-count":26,"publisher":"Springer Science and Business Media LLC","issue":"10","license":[{"start":{"date-parts":[[2025,3,26]],"date-time":"2025-03-26T00:00:00Z","timestamp":1742947200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,3,26]],"date-time":"2025-03-26T00:00:00Z","timestamp":1742947200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001782","name":"University of Melbourne","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001782","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur J Nucl Med Mol Imaging"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>\n                      Patients with gastro-entero-pancreatic neuroendocrine tumours (GEP NET) who retain somatostatin receptor (SSTR) expression after initial response to [\n                      <jats:sup>177<\/jats:sup>\n                      Lu]Lu-DOTA-Octreotate (LuTate) peptide receptor radionuclide therapy (PRRT) are amenable to re-treatment (R-PRRT) upon progression. We assessed the safety and efficacy of R-PRRT in patients with progressive metastatic GEP NET.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>\n                      A retrospective analysis, approved by institutional ethics board, was performed in patients with GEP NET who received R-PRRT for either symptomatically or radiologically progressive disease. Safety was assessed by renal and haematological parameters at 3 months post R-PRRT (CTCAE v5.0). Molecular imaging response was evaluated on [\n                      <jats:sup>68<\/jats:sup>\n                      Ga]Ga-DOTA-Octreotate (GaTate) PET\/CT using pre-defined criteria. RECIST 1.1 responses 3 months post R-PRRT were documented when feasible. Progression-free and overall survival analysis were performed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 63 patients had R1-PRRT (1\u20133 cycles). The majority (70%) had Grade 2 NET and small intestinal primary (51%). A second re-treatment course (R2-PRRT) was given in 20 patients and a third course (R3-PRRT) in 6 patients. Glomerular filtration rate (GFR) was stable following R1-PRRT. Following R2-PRRT, worsening GFR from CTCAE G2 to G3 was seen in 10% (2\/20) of patients, but none after R3-PRRT. Grade 3 thrombocytopenia occurred in 2 patients after R1-PRRT and in 1 patient after R3-PRRT. Grade 4 thrombocytopenia was observed in 1 patient post R1-PRRT. Following R1-PRRT, RECIST 1.1 responses CR, PR, SD was 0%, 10%, 76%, respectively. Disease control rate on GaTate PET\/CT was 52\/58 (89%) post R1-PRRT. Median progression free survival (PFS) following R1-PRRT was 1.6 years (95% CI:1.2\u20132.3).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>R-PRRT is feasible, tolerable and efficacious in achieving disease control in patients with progressive GEP NET.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00259-025-07235-w","type":"journal-article","created":{"date-parts":[[2025,3,29]],"date-time":"2025-03-29T10:11:11Z","timestamp":1743243071000},"page":"3672-3681","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Safety and efficacy of re-treatment with [177Lu]Lu-DOTA-Octreotate radionuclide therapy in progressive gastro-entero-pancreatic neuroendocrine tumours \u2013 a single centre experience"],"prefix":"10.1007","volume":"52","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1007-974X","authenticated-orcid":false,"given":"Raghava","family":"Kashyap","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramin","family":"Alipour","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Boehm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerry","family":"Jewell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aravind S.","family":"RaviKumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Cardin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javad","family":"Saghebi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael S.","family":"Hofman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael T.","family":"Fahey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Michael","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"Akhurst","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodney J.","family":"Hicks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace","family":"Kong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,3,26]]},"reference":[{"key":"7235_CR1","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1267\/ahc.12006","volume":"45","author":"G Mizutani","year":"2012","unstructured":"Mizutani G, Nakanishi Y, Watanabe N, Honma T, Obana Y, Seki T, et al. Expression of somatostatin receptor (SSTR) subtypes (SSTR-1, 2A, 3, 4 and 5) in neuroendocrine tumors using Real-time RT-PCR method and immunohistochemistry. Acta Histochem Cytochem. 2012;45:167\u201376.","journal-title":"Acta Histochem Cytochem"},{"key":"7235_CR2","doi-asserted-by":"publisher","first-page":"S61","DOI":"10.2967\/jnumed.116.186783","volume":"58","author":"M Fani","year":"2017","unstructured":"Fani M, Nicolas GP, Wild D. Somatostatin receptor antagonists for imaging and therapy. J Nucl Med. 2017;58:S61\u20136.","journal-title":"J Nucl Med"},{"key":"7235_CR3","doi-asserted-by":"publisher","first-page":"R53","DOI":"10.1677\/ERC-09-0078","volume":"17","author":"DJ Kwekkeboom","year":"2010","unstructured":"Kwekkeboom DJ, Kam BL, van Essen M, Teunissen JJ, van Eijck CH, Valkema R, et al. Somatostatin-receptor-based imaging and therapy of gastroenteropancreatic neuroendocrine tumors. Endocr Relat Cancer. 2010;17:R53\u201373.","journal-title":"Endocr Relat Cancer"},{"key":"7235_CR4","doi-asserted-by":"publisher","first-page":"500","DOI":"10.1148\/rg.352140164","volume":"35","author":"MS Hofman","year":"2015","unstructured":"Hofman MS, Lau WF, Hicks RJ. Somatostatin receptor imaging with 68Ga DOTATATE PET\/CT: clinical utility, normal patterns, pearls, and pitfalls in interpretation. Radiographics. 2015;35:500\u201316.","journal-title":"Radiographics"},{"key":"7235_CR5","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1016\/j.hoc.2015.09.009","volume":"30","author":"DJ Kwekkeboom","year":"2016","unstructured":"Kwekkeboom DJ, Krenning EP. Peptide receptor radionuclide therapy in the treatment of neuroendocrine tumors. Hematol Oncol Clin North Am. 2016;30:179\u201391.","journal-title":"Hematol Oncol Clin North Am"},{"key":"7235_CR6","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1053\/j.semnuclmed.2015.12.003","volume":"46","author":"L Bodei","year":"2016","unstructured":"Bodei L, Kwekkeboom DJ, Kidd M, Modlin IM, Krenning EP. Radiolabeled somatostatin analogue therapy of gastroenteropancreatic cancer. Semin Nucl Med. 2016;46:225\u201338.","journal-title":"Semin Nucl Med"},{"key":"7235_CR7","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1056\/NEJMoa1607427","volume":"376","author":"J Strosberg","year":"2017","unstructured":"Strosberg J, El-Haddad G, Wolin E, Hendifar A, Yao J, Chasen B, et al. Phase 3 trial of (177)Lu-Dotatate for midgut neuroendocrine tumors. N Engl J Med. 2017;376:125\u201335.","journal-title":"N Engl J Med"},{"key":"7235_CR8","doi-asserted-by":"publisher","first-page":"2578","DOI":"10.1200\/JCO.2018.78.5865","volume":"36","author":"J Strosberg","year":"2018","unstructured":"Strosberg J, Wolin E, Chasen B, Kulke M, Bushnell D, Caplin M, et al. Health-related quality of life in patients with progressive midgut neuroendocrine tumors treated with 177Lu-Dotatate in the phase III NETTER-1 trial. J Clin Oncol. 2018;36:2578\u201384.","journal-title":"J Clin Oncol"},{"key":"7235_CR9","doi-asserted-by":"publisher","first-page":"2807","DOI":"10.1016\/S0140-6736(24)00701-3","volume":"403","author":"S Singh","year":"2024","unstructured":"Singh S, Halperin D, Myrehaug S, Herrmann K, Pavel M, Kunz PL, et al. [177Lu]Lu-DOTA-TATE plus long-acting octreotide versus high\u2013dose long-acting octreotide for the treatment of newly diagnosed, advanced grade 2\u20133, well-differentiated, gastroenteropancreatic neuroendocrine tumours (NETTER-2): an open-label, randomised, phase 3 study. Lancet. 2024;403:2807\u201317.","journal-title":"Lancet"},{"key":"7235_CR10","doi-asserted-by":"publisher","first-page":"937","DOI":"10.2967\/jnumed.118.230607","volume":"60","author":"TA Hope","year":"2019","unstructured":"Hope TA, Abbott A, Colucci K, Bushnell DL, Gardner L, Graham WS, et al. NANETS\/SNMMI procedure standard for somatostatin receptor\u2013Based peptide receptor radionuclide therapy with 177Lu-DOTATATE. J Nucl Med. 2019;60:937\u201343.","journal-title":"J Nucl Med"},{"key":"7235_CR11","doi-asserted-by":"publisher","first-page":"1955","DOI":"10.1007\/s00259-015-3105-7","volume":"42","author":"S Severi","year":"2015","unstructured":"Severi S, Sansovini M, Ianniello A, Bodei L, Nicolini S, Ibrahim T, et al. Feasibility and utility of re-treatment with (177)Lu-DOTATATE in GEP-NENs relapsed after treatment with (90)Y-DOTATOC. Eur J Nucl Med Mol Imaging. 2015;42:1955\u201363.","journal-title":"Eur J Nucl Med Mol Imaging"},{"key":"7235_CR12","doi-asserted-by":"publisher","first-page":"704","DOI":"10.1007\/s00259-018-4158-1","volume":"46","author":"WA van der Zwan","year":"2019","unstructured":"van der Zwan WA, Brabander T, Kam BLR, Teunissen JJM, Feelders RA, Hofland J, et al. Salvage peptide receptor radionuclide therapy with [(177)Lu-DOTA,Tyr(3)]octreotate in patients with bronchial and gastroenteropancreatic neuroendocrine tumours. Eur J Nucl Med Mol Imaging. 2019;46:704\u201317.","journal-title":"Eur J Nucl Med Mol Imaging"},{"key":"7235_CR13","doi-asserted-by":"publisher","first-page":"383","DOI":"10.2967\/jnumed.109.068957","volume":"51","author":"M van Essen","year":"2010","unstructured":"van Essen M, Krenning EP, Kam BLR, de Herder WW, Feelders RA, Kwekkeboom DJ. Salvage therapy with (177)Lu-octreotate in patients with bronchial and gastroenteropancreatic neuroendocrine tumors. J Nucl Med. 2010;51:383\u201390.","journal-title":"J Nucl Med"},{"key":"7235_CR14","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1007\/s00259-013-2547-z","volume":"41","author":"A Sabet","year":"2014","unstructured":"Sabet A, Haslerud T, Pape UF, Sabet A, Ahmadzadehfar H, Grunwald F, et al. Outcome and toxicity of salvage therapy with 177Lu-octreotate in patients with metastatic gastroenteropancreatic neuroendocrine tumours. Eur J Nucl Med Mol Imaging. 2014;41:205\u201310.","journal-title":"Eur J Nucl Med Mol Imaging"},{"key":"7235_CR15","doi-asserted-by":"publisher","first-page":"20180041","DOI":"10.1259\/bjr.20180041","volume":"91","author":"E Vaughan","year":"2018","unstructured":"Vaughan E, Machta J, Walker M, Toumpanakis C, Caplin M, Navalkissoor S. Retreatment with peptide receptor radionuclide therapy in patients with progressing neuroendocrine tumours: efficacy and prognostic factors for response. Br J Radiol. 2018;91:20180041.","journal-title":"Br J Radiol"},{"key":"7235_CR16","first-page":"e47506","volume":"15","author":"MM Silva","year":"2023","unstructured":"Silva MM, Canha M, Salazar D, Neves JS, Ferreira G, Carvalho D, et al. Efficacy, toxicity, and prognostic factors of Re-treatment with [177Lu]Lu-DOTA-TATE in patients with progressing neuroendocrine tumors: the experience of a single center. Cureus. 2023;15:e47506.","journal-title":"Cureus"},{"key":"7235_CR17","doi-asserted-by":"publisher","first-page":"746","DOI":"10.2967\/jnumed.123.265703","volume":"65","author":"ES Delpassand","year":"2024","unstructured":"Delpassand ES, Yazdi SM, Ghantoji S, Nakasato A, Strickland C, Nunez R, et al. Effectiveness and safety of retreatment with 177Lu-DOTATATE in patients with progressive neuroendocrine tumors: A retrospective Real-World study in the united States. J Nucl Med. 2024;65:746\u201352.","journal-title":"J Nucl Med"},{"key":"7235_CR18","doi-asserted-by":"publisher","first-page":"6615511","DOI":"10.1155\/2021\/6615511","volume":"2021","author":"A Zemczak","year":"2021","unstructured":"Zemczak A, Gut P, Pawlak D, Kolodziej M, Krolicki L, Kos-Kudla B, et al. The safety and efficacy of the repeated PRRT with [(90)Y]Y\/[(177)Lu]Lu-DOTATATE in patients with NET. Int J Endocrinol. 2021;2021:6615511.","journal-title":"Int J Endocrinol"},{"key":"7235_CR19","doi-asserted-by":"publisher","first-page":"788","DOI":"10.1186\/s12885-019-6000-y","volume":"19","author":"S Rudisile","year":"2019","unstructured":"Rudisile S, Gosewisch A, Wenter V, Unterrainer M, Boning G, Gildehaus FJ, et al. Salvage PRRT with (177)Lu-DOTA-octreotate in extensively pretreated patients with metastatic neuroendocrine tumor (NET): dosimetry, toxicity, efficacy, and survival. BMC Cancer. 2019;19:788.","journal-title":"BMC Cancer"},{"key":"7235_CR20","doi-asserted-by":"publisher","first-page":"115","DOI":"10.3390\/curroncol28010015","volume":"28","author":"G Sistani","year":"2020","unstructured":"Sistani G, Sutherland DEK, Mujoomdar A, Wiseman DP, Khatami A, Tsvetkova E, et al. Efficacy of (177)Lu-Dotatate induction and maintenance therapy of various types of neuroendocrine tumors: A phase II registry study. Curr Oncol. 2020;28:115\u201327.","journal-title":"Curr Oncol"},{"key":"7235_CR21","doi-asserted-by":"crossref","unstructured":"Kashyap R, Jackson P, Ms H, Eu P, Jm B, Zannino D, et al. Rapid blood clearance and lack of long-term renal toxicity of 177Lu-DOTATATE enables shortening of renoprotective amino acid infusion. 2013. Available from: http:\/\/europepmc.org\/abstract\/med\/23864305","DOI":"10.1007\/s00259-013-2504-x"},{"key":"7235_CR22","doi-asserted-by":"publisher","first-page":"2997","DOI":"10.1007\/s00259-023-06257-6","volume":"50","author":"R Alipour","year":"2023","unstructured":"Alipour R, Jackson P, Bressel M, Hogg A, Callahan J, Hicks RJ, et al. The relationship between tumour dosimetry, response, and overall survival in patients with unresectable neuroendocrine neoplasms (NEN) treated with 177Lu DOTATATE (LuTate). Eur J Nucl Med Mol Imaging. 2023;50:2997\u20133010.","journal-title":"Eur J Nucl Med Mol Imaging"},{"key":"7235_CR23","doi-asserted-by":"publisher","unstructured":"Prasad V, Koumarianou A, Denecke T, Sundin A, Deroose CM, Pavel M, et al. Challenges in developing response evaluation criteria for peptide receptor radionuclide therapy: A consensus report from the European neuroendocrine tumor society advisory board meeting 2022 and the ENETS theranostics task force. J Neuroendocrinol. 2025 Feb;37(2):e13479. https:\/\/doi.org\/10.1111\/jne.13479. Epub 2024 Dec 9.","DOI":"10.1111\/jne.13479"},{"key":"7235_CR24","doi-asserted-by":"publisher","first-page":"218","DOI":"10.2967\/jnumed.120.260760","volume":"63","author":"L Zidan","year":"2022","unstructured":"Zidan L, Iravani A, Oleinikov K, Ben-Haim S, Gross DJ, Meirovitz A, et al. Efficacy and safety of 177Lu-DOTATATE in lung neuroendocrine tumors: A bicenter study. J Nucl Med. 2022;63:218\u201325.","journal-title":"J Nucl Med"},{"key":"7235_CR25","doi-asserted-by":"publisher","first-page":"1147","DOI":"10.1002\/sim.8829","volume":"40","author":"MP Fay","year":"2021","unstructured":"Fay MP, Lumbard K. Confidence intervals for difference in proportions for matched pairs compatible with exact McNemar\u2019s or sign tests. Stat Med. 2021;40:1147\u201359.","journal-title":"Stat Med"},{"key":"7235_CR26","doi-asserted-by":"publisher","first-page":"1902","DOI":"10.1007\/s00259-019-04389-2","volume":"46","author":"I Goncalves","year":"2019","unstructured":"Goncalves I, Burbury K, Michael M, Iravani A, Ravi Kumar AS, Akhurst T, et al. Characteristics and outcomes of therapy-related myeloid neoplasms after peptide receptor radionuclide\/chemoradionuclide therapy (PRRT\/PRCRT) for metastatic neuroendocrine neoplasia: a single-institution series. Eur J Nucl Med Mol Imaging. 2019;46:1902\u201310.","journal-title":"Eur J Nucl Med Mol Imaging"}],"container-title":["European Journal of Nuclear Medicine and Molecular Imaging"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00259-025-07235-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00259-025-07235-w\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00259-025-07235-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,6]],"date-time":"2025-09-06T08:12:25Z","timestamp":1757146345000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00259-025-07235-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,26]]},"references-count":26,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2025,8]]}},"alternative-id":["7235"],"URL":"https:\/\/doi.org\/10.1007\/s00259-025-07235-w","relation":{},"ISSN":["1619-7070","1619-7089"],"issn-type":[{"value":"1619-7070","type":"print"},{"value":"1619-7089","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,26]]},"assertion":[{"value":"10 February 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 March 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 March 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Human ethics and consent to participate declarations"}},{"value":"No direct conflicts of interests with the current research work.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}