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Purpose: This paper outlines the consensus of the Italian Association for Neuroendocrine Tumors(Itanet), the Italian Association of Nuclear Medicine (AIMN), the Italian Society of Endocrinology (SIE), and the Italian Association of Medical Oncology (AIOM) on treating neuroendocrine neoplasms (NENs)with radioligand therapy (RLT)., Methods: A list of 10 questions regarding using RLT ingastroenteropancreatic neuroendocrine tumors (GEP-NETs) was addressed after a careful review of theavailable literature. compiling information from the MEDLINE database, augmented with expert opinionsand recommendations, aligns with the latest scientific research and the author's extensive knowledge.The recommendations are evaluated using the GRADE system, showcasing the level of evidence andthe strength of the recommendations., Results and Conclusions: Specifically, this paper focuses on thesubcategories of well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs) thatexpress somatostatin receptors and are considered suitable for RLT, according to internationalguidelines., Competing Interests: Declarations. Conflict of interest: MA received honoraria as consultants from AAA, Novartis and Recordati outside the submitted work, CMG received honoraria as consultants from Novartis and ITM outside the submitted work, MC received honoraria as consultants from AAA, Novartis, Advanz, Harpoon Therapeutics, Merck, Harbour Biomedical outside the submitted work, AF received honoraria as support for research project and scientific organization from Novartis and Ipsen, NF received honoraria as consultants and speakers from Novartis and ITM outside the submitted work, FS received honoraria as consultants and speakers from AAA, outside the submitted work, MM received honoraria as consultants and speakers from AAA, outside the submitted work. The other authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of this manuscript., (© 2024. The Author(s).)

Purpose: Pre-treatment [ 99m Tc]TcMAA-based radioembolization treatment planning using multicompartment dosimetry involves the definition of the tumor and normal tissue compartments and calculation of the prescribed absorbed doses. The aim was to compare the real-world utility of anatomic and [ 99m Tc]TcMAA-based segmentation of tumor and normal tissue compartments., Materials and Methods: Included patients had HCC treated by glass [ 90 Y]yttrium microspheres, ≥ 1 tumor, ≥ 3 cm diameter and [ 99m Tc]TcMAA SPECT/CT imaging before treatment. Segmentation was performed retrospectively using dedicated dosimetry software: (1) anatomic (diagnostic CT/MRI-based), and (2) [ 99m Tc]TcMAA threshold-based (i.e., using an activity-isocontour threshold). CT/MRI was co-registered with [ 99m Tc]TcMAA SPECT/CT. Logistic regression and Cox regression, respectively, were used to evaluate relationships between total perfused tumor absorbed dose (TAD) and objective response rate (ORR) and overall survival (OS). In a subset-analysis pre- and post-treatment dosimetry were compared using Bland-Altman analysis and Pearson's correlation coefficient., Results: A total of 209 patients were enrolled. Total perfused tumor and normal tissue volumes were larger when using anatomic versus [ 99m Tc]TcMAA threshold segmentation, resulting in lower absorbed doses. mRECIST ORR was higher with increasing total perfused TAD (odds ratio per 100 Gy TAD increase was 1.22 (95% CI: 1.01-1.49; p = 0.044) for anatomic and 1.19 (95% CI: 1.04-1.37; p = 0.012) for [ 99m Tc]TcMAA threshold segmentation. Higher total perfused TAD was associated with improved OS (hazard ratio per 100 Gy TAD increase was 0.826 (95% CI: 0.714-0.954; p = 0.009) and 0.847 (95% CI: 0.765-0.936; p = 0.001) for anatomic and [ 99m Tc]TcMAA threshold segmentation, respectively). For pre- vs. post-treatment dosimetry comparison, the average bias for total perfused TAD was + 11.5 Gy (95% limits of agreement: -227.0 to 250.0) with a strong positive correlation (Pearson's correlation coefficient = 0.80)., Conclusion: Real-world data support [ 99m Tc]TcMAA imaging to estimate absorbed doses prior to treatment of HCC with glass [ 90 Y]yttrium microspheres. Both anatomic and [ 99m Tc]TcMAA threshold methods were suitable for treatment planning., Trial Registration Number: NCT03295006., Competing Interests: Declarations. Conflicts of Interest/Competing interests: Marnix Lam, MD, PhD: Is a consultant for Boston Scientific, Terumo and Quirem Medical. He receives research support from Boston Scientific, Terumo and Quirem Medical. The UMC Utrecht receives royalties from Quirem Medical. Etienne Garin, MD, PhD: Serves as a consultant for Boston Scientific. Paul Haste, MD: Is a consultant for Boston Scientific. Alban Denys, MD, MSc: Is a consultant for Cook, Neuwave, and received grants from Johnson and Johnson. Brian Geller, MD: Nothing to disclose. S. Cheenu Kappadath, PhD: Is a consultant for Boston Scientific, Sirtex Medical, and Terumo Medical. He receives research support from Boston Scientific, Sirtex Medical and ABK Biomedical. Cuneyt Turkmen, MD: Is a consultant for Boston Scientific. Daniel Y Sze, MD, PhD: Was a consultant for Argon, Artio Medical, Astra-Zeneca, Bayer, BlackSwan Vascular, Boston Scientific, Bristol Meyers Squibb, Eisai, FludX, W.L. Gore, Guerbet, Koli, Sirtex, Terumo, TriSalus, and Varian; received institutional research support from Boston Scientific, W.L. Gore, Merit Medical, and Sirtex; held equity in BlackSwan Vascular, Confluent Medical, Koli, Proteus Digital Health, Radiaction, and TriSalus; and serves on data safety monitoring boards for W.L. Gore and Replimune. Hamad Saleh Alsuhaibani, MD: Nothing to disclose. Ken Herrmann, MD: Reports personal fees from Bayer, personal fees and other from Sofie Bioscienes, personal fees from SIRTEX, non-financial support from ABX, personal fees from Adacap, personal fees from Curium, personal fees from Endocyte, grants and personal fees from Boston Scientific, personal fees from IPSEN, personal fees from Siemens Healthineers, personal fees from GE Healthcare, personal fees from Amgen, personal fees from Novartis, personal fees from ymabs, personal fees from Aktis Oncology, personal fees from Theragnostics, personal fees from Pharma15, outside the submitted work. Marco Maccauro, MD: Nothing to disclose. Murat Cantasdemir, MD: Is a consultant for Boston Scientific. Matthew Dreher, PhD: Works for Boston Scientific. Kirk D. Fowers, PhD: Works for Boston Scientific. Vanessa Gates, PhD: Is a consultant for Boston Scientific. Riad Salem, MD: Is a consultant for Boston Scientific, AstraZeneca, Genentech, Sirtex, Cook, Eisai, Bard and QED Therapeutics. Ethics approval: Not Applicable. Consent to participate: Not Applicable., (© 2024. The Author(s).)