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Lisa Bodei Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York, USA
LuGenIum Consortium for Independent Research, Milan, Rotterdam, Bad Berka, London

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Irvin M Modlin LuGenIum Consortium for Independent Research, Milan, Rotterdam, Bad Berka, London
Emeritus Professor Gastroenterological Surgery, Yale University, School of Medicine, New Haven, Connecticut, USA

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Markus Luster Department of Nuclear Medicine, University Hospital Marburg, Marburg, Germany

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Flavio Forrer Nuclear Medicine, Cantonal Hospital, St. Gallen, Switzerland

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Marta Cremonesi Division of Health Physics, European Institute of Oncology, Milan, Italy

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Rodney J Hicks Centre for Cancer Imaging, The Peter MacCallum Cancer Centre, St Andrew’s Place, East Melbourne, Australia

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Samer Ezziddin Department of Nuclear Medicine, Saarland University Hospital, Homburg, Saarland, Germany

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Mark Kidd Wren Laboratories, Branford, Connecticut, USA

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Arturo Chiti Humanitas University, Milan, Italy

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Peptide receptor radionuclide therapy (PRRT) with 90Y-octreotide or 177Lu-octreotate is an effective treatment for inoperable or metastatic neuroendocrine tumors (NETs), particularly well-differentiated gastroenteropancreatic or bronchopulmonary NETs. PRRT is generally extremely well tolerated, with modest toxicity to target organs, kidney and bone marrow. Nevertheless, a priori concerns regarding long-term effects lead clinicians such as Brieau and coworkers, in this ERC issue, to ascribe to the combination of alkylating agents and PRRT the apparently high occurrence (n=4) of myeloproliferative events (therapy-related myeloid neoplasms (t-MNs)) in a small cohort of 20 progressive, advanced digestive NETs treated with PRRT after chemotherapy. Anecdotal reports of myelotoxic events should be placed in the correct perspective of larger series, where the reported incidence of these events is ~2%, with the aim of promoting a balanced awareness of the issue and unbiased and reasonable overall conclusions. For a comprehensive definition of the issue, we provide an evaluation of the occurrence of t-MN in patients treated with various myelotoxic treatments.

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Michela Perrino Endocrine-Diabetological Unit, Endocrine Surgery Unit, Nuclear Medicine Unit, Department of Medical Sciences, University of Milan

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Guia Vannucchi Endocrine-Diabetological Unit, Endocrine Surgery Unit, Nuclear Medicine Unit, Department of Medical Sciences, University of Milan

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Leonardo Vicentini Endocrine-Diabetological Unit, Endocrine Surgery Unit, Nuclear Medicine Unit, Department of Medical Sciences, University of Milan

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Gianmaria Cantoni Endocrine-Diabetological Unit, Endocrine Surgery Unit, Nuclear Medicine Unit, Department of Medical Sciences, University of Milan

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Davide Dazzi Endocrine-Diabetological Unit, Endocrine Surgery Unit, Nuclear Medicine Unit, Department of Medical Sciences, University of Milan

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Carla Colombo Endocrine-Diabetological Unit, Endocrine Surgery Unit, Nuclear Medicine Unit, Department of Medical Sciences, University of Milan

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Marcello Rodari Endocrine-Diabetological Unit, Endocrine Surgery Unit, Nuclear Medicine Unit, Department of Medical Sciences, University of Milan

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Arturo Chiti Endocrine-Diabetological Unit, Endocrine Surgery Unit, Nuclear Medicine Unit, Department of Medical Sciences, University of Milan

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Paolo Beck-Peccoz Endocrine-Diabetological Unit, Endocrine Surgery Unit, Nuclear Medicine Unit, Department of Medical Sciences, University of Milan

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Laura Fugazzola Endocrine-Diabetological Unit, Endocrine Surgery Unit, Nuclear Medicine Unit, Department of Medical Sciences, University of Milan

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The incidence of papillary thyroid cancer (PTC) is rapidly growing, the recorded increase being mainly related to tumors ≤2 cm. The re-classification of tumors >1 and ≤2 cm limited to the thyroid from the T2 to the T1 category triggered some concerns about their best management. In order to identify possible predictors of disease outcome, several clinico-pathological features were analyzed by uni- and multivariate analyses in a retrospective consecutive series of 251 PTCs ≤2 cm. Moreover, since 37% of cases were submitted to prophylactic central compartment node dissection (CLND, VI–VII levels) and radioiodine ablation was performed only when the tumor had an extrathyroidal extension, the impact of these therapeutic tools on the final outcome was evaluated. Among all outcome predictors analyzed, only lymph node metastases and extracapsular invasion were strongly associated with persistence/recurrence. It is worth noting that neither age nor tumor size was a significant indicator of the outcome. Interestingly, as far as the therapeutic interventions are concerned, CLND was strongly associated with remission, whereas radioiodine ablation did not influence the outcome. In conclusion, present results confirm the prognostic influence of node metastases and extra-thyroidal invasion, indicating the need for aggressive treatment in tumors extending beyond the capsule. On the contrary, all pT1N0 tumors, regardless of the diameter, the number of intrathyroidal foci, and the age can be effectively treated only by surgery. The major impact of prophylactic CLND on prognosis suggests to routinely associate it to total thyroidectomy in cases with a preoperative diagnosis of malignancy.

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