AIMN, ITANET, SIE joint position paper for the recognition, prevention and management of NET carcinoid syndrome and crises during peptide receptor radionuclide therapy

Riccardo Laudicella¹, Antongiulio Faggiano², Valeria Pirro³, Rexhep Durmo⁴, Pierpaolo Salsi⁵, Roberta Modica⁶, Luca Urso^{7

8}, Chiara Maria Grana⁹, Daniele Sances¹⁰, Maria Rinzivillo¹¹, Manuela Albertelli^{12

13}, Francesca Spada¹⁴, Stefano Partelli^{15

16}, Francesco Ferraù¹⁷, Nicola Fazio¹⁴, Salvatore Tafuto¹⁸, Marco Maccauro¹⁹, Mirco Bartolomei⁸, Francesco Panzuto²⁰, Maria Luisa De Rimini²¹, Secondo Lastoria²², Angelina Filice²³

Affiliations

¹ Nuclear Medicine, Department of Biomedical and Dental Sciences and Morpho-Functional Imaging, University of Messina, Messina, Italy.
² Unit of Endocrinology, Department of Clinical and Molecular Medicine, Sant 'Andrea University Hospital, ENETS Center of Excellence, Sapienza University of Rome, Rome, Italy.
³ Department of Nuclear Medicine, Ordine Mauriziano Hospital, Turin, Italy.
⁴ Nuclear Medicine Unit, Azienda Unità Sanitaria Locale-IRCCS Di Reggio Emilia, Viale Risorgimento, 80, 42123, Reggio Emilia, Italy. rexhep.durmo@ausl.re.it.
⁵ ICU Department of General and Specialist Surgery, Azienda Unità Sanitaria Locale - IRCCS Di Reggio Emilia, Reggio Emilia, Italy.
⁶ Endocrinology, Diabetology and Andrology Unit, Department of Clinical Medicine and Surgery, Federico II University of Naples, Naples, Italy.
⁷ Department of Translational Medicine, University of Ferrara, Ferrara, Italy.
⁸ Nuclear Medicine Unit, Onco-Hematology Department, University Hospital of Ferrara, Ferrara, Italy.
⁹ Division of Nuclear Medicine, Istituto Europeo Di Oncologia, IRCCS, Milan, Italy.
¹⁰ Division of Anesthesia and Intensive Care, Istituto Europeo Di Oncologia, IRCCS, Milan, Italy.
¹¹ Digestive Disease Unit, Department of Surgical-Medical Sciences and Translational Medicine, Sant'Andrea University Hospital, ENETS Center of Excellence, Sapienza University of Rome, Rome, Italy.
¹² Endocrinology, Department of Internal Medicine and Medical Specialties (DiMI), University of Genova, Genoa, Italy.
¹³ Endocrinology, IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
¹⁴ Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, IEO, European Institute of Oncology IRCCS, Milan, Italy.
¹⁵ School of Medicine, Vita-Salute San Raffaele University, Milan, Italy.
¹⁶ Pancreas Translational and Clinical Research Centre, Pancreatic and Transplant Surgery Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.
¹⁷ Department of Human Pathology of Adulthood and Childhood 'G. Barresi', University of Messina, Messina, Italy.
¹⁸ Sarcomas and Rare Tumors Unit, Istituto Nazionale Tumori, IRCCS Fondazione "G. Pascale", Naples, Italy.
¹⁹ Nuclear Medicine Department, Foundation IRCCS, Istituto Nazionale Tumori, Milan, Italy.
²⁰ Department of Medical-Surgical Sciences and Translational Medicine, Digestive Disease Unit, ENETS Center of Excellence Sant'Andrea University Hospital, Sapienza University of Rome, Rome, Italy.
²¹ Nuclear Medicine - PET and Therapy Unit, Department of Health Services AORN Dei Colli, Naples, Italy.
²² IRCCS National Cancer Institute, Fondazione Senatore G. Pascale, Naples, Italy.
²³ Nuclear Medicine Unit, Azienda Unità Sanitaria Locale-IRCCS Di Reggio Emilia, Viale Risorgimento, 80, 42123, Reggio Emilia, Italy.

PMID: 41055768
DOI: 10.1007/s00259-025-07596-2

Review

AIMN, ITANET, SIE joint position paper for the recognition, prevention and management of NET carcinoid syndrome and crises during peptide receptor radionuclide therapy

Riccardo Laudicella et al. Eur J Nucl Med Mol Imaging. 2025.

. 2025 Oct 7.

doi: 10.1007/s00259-025-07596-2. Online ahead of print.

Authors

Affiliations

¹ Nuclear Medicine, Department of Biomedical and Dental Sciences and Morpho-Functional Imaging, University of Messina, Messina, Italy.
² Unit of Endocrinology, Department of Clinical and Molecular Medicine, Sant 'Andrea University Hospital, ENETS Center of Excellence, Sapienza University of Rome, Rome, Italy.
³ Department of Nuclear Medicine, Ordine Mauriziano Hospital, Turin, Italy.
⁴ Nuclear Medicine Unit, Azienda Unità Sanitaria Locale-IRCCS Di Reggio Emilia, Viale Risorgimento, 80, 42123, Reggio Emilia, Italy. rexhep.durmo@ausl.re.it.
⁵ ICU Department of General and Specialist Surgery, Azienda Unità Sanitaria Locale - IRCCS Di Reggio Emilia, Reggio Emilia, Italy.
⁶ Endocrinology, Diabetology and Andrology Unit, Department of Clinical Medicine and Surgery, Federico II University of Naples, Naples, Italy.
⁷ Department of Translational Medicine, University of Ferrara, Ferrara, Italy.
⁸ Nuclear Medicine Unit, Onco-Hematology Department, University Hospital of Ferrara, Ferrara, Italy.
⁹ Division of Nuclear Medicine, Istituto Europeo Di Oncologia, IRCCS, Milan, Italy.
¹⁰ Division of Anesthesia and Intensive Care, Istituto Europeo Di Oncologia, IRCCS, Milan, Italy.
¹¹ Digestive Disease Unit, Department of Surgical-Medical Sciences and Translational Medicine, Sant'Andrea University Hospital, ENETS Center of Excellence, Sapienza University of Rome, Rome, Italy.
¹² Endocrinology, Department of Internal Medicine and Medical Specialties (DiMI), University of Genova, Genoa, Italy.
¹³ Endocrinology, IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
¹⁴ Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, IEO, European Institute of Oncology IRCCS, Milan, Italy.
¹⁵ School of Medicine, Vita-Salute San Raffaele University, Milan, Italy.
¹⁶ Pancreas Translational and Clinical Research Centre, Pancreatic and Transplant Surgery Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.
¹⁷ Department of Human Pathology of Adulthood and Childhood 'G. Barresi', University of Messina, Messina, Italy.
¹⁸ Sarcomas and Rare Tumors Unit, Istituto Nazionale Tumori, IRCCS Fondazione "G. Pascale", Naples, Italy.
¹⁹ Nuclear Medicine Department, Foundation IRCCS, Istituto Nazionale Tumori, Milan, Italy.
²⁰ Department of Medical-Surgical Sciences and Translational Medicine, Digestive Disease Unit, ENETS Center of Excellence Sant'Andrea University Hospital, Sapienza University of Rome, Rome, Italy.
²¹ Nuclear Medicine - PET and Therapy Unit, Department of Health Services AORN Dei Colli, Naples, Italy.
²² IRCCS National Cancer Institute, Fondazione Senatore G. Pascale, Naples, Italy.
²³ Nuclear Medicine Unit, Azienda Unità Sanitaria Locale-IRCCS Di Reggio Emilia, Viale Risorgimento, 80, 42123, Reggio Emilia, Italy.

PMID: 41055768
DOI: 10.1007/s00259-025-07596-2

Abstract

Purpose: Carcinoid syndrome (CS) is the most frequent neuroendocrine tumor (NET)-related syndrome with variable presentations related to hormonal discharge and long-term complications, such as carcinoid heart disease (CHD). Carcinoid crisis (CC) is an acute and serious CS complication, due to a massive release of vasoactive hormones and biologically active substances, which may occur during stressogenic procedures such as peptide receptor radionuclide therapy (PRRT). CC is an emergency and life-threatening condition that needs to be prevented, promptly recognized, and managed. The purpose of this joint Italian multidisciplinary position paper is to support the involved personnel in delivering [177Lu]Lu-based PRRT to syndromic NET patients, focusing on CC management.

Methods: The literature evidence regarding CS, CHD, and CC during/after PRRT and the knowledge of 22 Italian NET experts in Anesthesiology, Endocrinology, Gastroenterology, Nuclear Medicine, Oncology, and Surgery involved in PRRT were the basis for the present document.

Results: The expert panel expressed several recommendations regarding: 1) CC high-risk patients identification; 2) CC prevention, including considerations of the behavioral and nutritional status, and somatostatin analogue therapy; 3) how to implement PRRT premedication in CC high-risk patients; 4) how to manage CC during PRRT, including post-PRRT monitoring, and radiation protection considerations.

Conclusion: This practical guide summarizes the views and experience in CS, CHD, and CC in relation to PRRT of a joint NET-dedicated Italian multidisciplinary team. These recommendations should be taken into the context of Nuclear Medicine good practice and do not substitute any national and International legal or regulatory provisions.

Keywords: CC; CS; Carcinoid heart disease; Lutetium; Neuroendocrine tumor; PRRT; RLT; RPT.

PubMed Disclaimer

Conflict of interest statement

Declarations. Ethical approval: This is a practical guide and therefore no ethical approval is required. Consent to publish: Informed consent for the publication of images was received from the participants who appeared in the manuscript. Competing interests: The authors have no relevant financial or non-financial interests to disclose.

References

1. Halperin DM, Shen C, Dasari A, Xu Y, Chu Y, Zhou S, et al. Frequency of carcinoid syndrome at neuroendocrine tumour diagnosis: a population-based study. Lancet Oncol. 2017;18:525–34. https://doi.org/10.1016/S1470-2045(17)30110-9 . - DOI - PubMed - PMC
1. Grozinsky-Glasberg S, Davar J, Hofland J, Dobson R, Prasad V, Pascher A, et al. European neuroendocrine tumor society (ENETS) 2022 guidance paper for carcinoid syndrome and carcinoid heart disease. J Neuroendocrinol. 2022;34:e13146. https://doi.org/10.1111/jne.13146 . - DOI - PubMed - PMC
1. Oleinikov K, Avniel-Polak S, Gross DJ, Grozinsky-Glasberg S. Carcinoid syndrome: updates and review of current therapy. Curr Treat Options Oncol. 2019;20(9):70. https://doi.org/10.1007/s11864-019-0671-0 . - DOI - PubMed
1. Grimaldi F, Fazio N, Attanasio R, Frasoldati A, Papini E, Angelini F, et al. Italian association of clinical endocrinologists (AME) position statement: a stepwise clinical approach to the diagnosis of gastroenteropancreatic neuroendocrine neoplasms. J Endocrinol Invest. 2014;37(9):875–909. https://doi.org/10.1007/s40618-014-0119-0 . - DOI - PubMed - PMC
1. Laskaratos FM, Rombouts K, Caplin M, Toumpanakis C, Thirlwell C, Mandair D. Neuroendocrine tumors and fibrosis: an unsolved mystery? Cancer. 2017;123(24):4770–90. https://doi.org/10.1002/cncr.31079 . - DOI - PubMed

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AIMN, ITANET, SIE joint position paper for the recognition, prevention and management of NET carcinoid syndrome and crises during peptide receptor radionuclide therapy

Affiliations

AIMN, ITANET, SIE joint position paper for the recognition, prevention and management of NET carcinoid syndrome and crises during peptide receptor radionuclide therapy

Authors

Affiliations

Abstract

Conflict of interest statement

References

Publication types

LinkOut - more resources

Full Text Sources

Miscellaneous