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  • Author: Paolo Piaggi x
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Alessandro Brancatella Endocrinology Unit, Department of Clinical and Experimental Medicine, University Hospital of Pisa, Pisa, Italy

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Laura Pierotti Endocrinology Unit, Department of Clinical and Experimental Medicine, University Hospital of Pisa, Pisa, Italy

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Nicola Viola Endocrinology Unit, Department of Clinical and Experimental Medicine, University Hospital of Pisa, Pisa, Italy

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Isabella Lupi Endocrinology Unit, Department of Clinical and Experimental Medicine, University Hospital of Pisa, Pisa, Italy

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Lucia Montanelli Endocrinology Unit, Department of Clinical and Experimental Medicine, University Hospital of Pisa, Pisa, Italy

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Chiara Cremolini Oncology Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy

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Paolo Piaggi Department of Information Engineering, University of Pisa, Pisa, Italy

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Antonio Chella Pneumology Unit, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy

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Andrea Antonuzzo Oncology Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy

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Daniele Sgrò Endocrinology Unit, Department of Clinical and Experimental Medicine, University Hospital of Pisa, Pisa, Italy

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Lucia Antonangeli Endocrinology Unit, Department of Clinical and Experimental Medicine, University Hospital of Pisa, Pisa, Italy

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Chiara Sardella Endocrinology Unit, Department of Clinical and Experimental Medicine, University Hospital of Pisa, Pisa, Italy

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Sandra Brogioni Endocrinology Unit, Department of Clinical and Experimental Medicine, University Hospital of Pisa, Pisa, Italy

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Claudio Marcocci Endocrinology Unit, Department of Clinical and Experimental Medicine, University Hospital of Pisa, Pisa, Italy

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Ferruccio Santini Endocrinology Unit, Department of Clinical and Experimental Medicine, University Hospital of Pisa, Pisa, Italy

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Francesco Latrofa Endocrinology Unit, Department of Clinical and Experimental Medicine, University Hospital of Pisa, Pisa, Italy

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Objective

Destructive thyroiditis is the most common endocrine immune-related adverse event (iRAEs) in patients treated with anti-PD1/PD-L1 agents. Given its self-limited course, current guidelines recommend no treatment for this iRAE. Nevertheless, in patients with enlarged thyroid volume and a poor performance status, thyrotoxicosis may be particularly severe and harmful. The aim of the study is to evaluate if steroid treatment might be useful in improving thyrotoxicosis in subjects with a poor performance status.

Methods

We conducted a retrospective study, comparing the course of thyrotoxicosis of four patients treated with oral prednisone at the dosage of 25 mg/day (tapered to discontinuation in 3 weeks) and an enlarged thyroid volume to that of eight patients with similar thyroid volume who were left untreated.

Results

The levels of thyroid hormones were lower in subjects treated compared to those untreated at time of 7, 14, 21, 28, 35, 42, 60 and 90 days (P  < 0.05 at each time). The time to remission of thyrotoxicosis was 24 days in patients treated with steroids and 120 days in untreated patients (P  < 0.001). At 6 months, the rate of evolution to hypothyroidism was similar in the two groups (4/4 in the steroid group vs 7/8 in the untreated group, P  = 0.74) and no difference was found in tumor progression (P  = 0.89).

Conclusions

Our preliminary data suggest that in patients with a poor performance status experiencing a severe destructive thyrotoxicosis induced by PD-1 blockade, a short period of administration of oral prednisone is effective in obtaining a quick reduction of the levels of thyroid hormones.

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Luciana Puleo Endocrine Unit, Department of Clinical and Experimental Medicine

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Laura Agate Endocrine Unit, Department of Clinical and Experimental Medicine

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Irene Bargellini Department of Vascular and Interventional Radiology

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Giuseppe Boni Regional Center of Nuclear Medicine

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Paolo Piaggi Endocrine Unit, Department of Clinical and Experimental Medicine

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Claudio Traino Regional Center of Nuclear Medicine

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Tommaso Depalo Regional Center of Nuclear Medicine

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Giulia Lorenzoni Department of Vascular and Interventional Radiology

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Francesca Bianchi Regional Center of Nuclear Medicine

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Duccio Volterrani Regional Center of Nuclear Medicine

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Sandra Brogioni Endocrine Unit, Department of Clinical and Experimental Medicine

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Valeria Bottici Endocrine Unit, Department of Clinical and Experimental Medicine

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Maurizia Rossana Brunetto Hepatology Unit, University of Pisa, Pisa, Italy

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Barbara Coco Hepatology Unit, University of Pisa, Pisa, Italy

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Eleonora Molinaro Endocrine Unit, Department of Clinical and Experimental Medicine

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Rossella Elisei Endocrine Unit, Department of Clinical and Experimental Medicine

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Objectives

Liver metastases occur in 45% of patients with advanced metastatic medullary thyroid cancer (MTC). Transarterial radioembolization (TARE) has been proposed to treat liver metastases (LM), especially in neuroendocrine tumors. The aim of this study was to investigate the biochemical (calcitonin and carcino-embryonic antigen) and objective response of liver metastases from MTC to TARE.

Methods

TARE is an internal radiotherapy in which microspheres loaded with β-emitting yttrium-90 (90Y) are delivered into the hepatic arteries that supply blood to LM. Eight patients with progressive multiple LM underwent TARE and were followed prospectively. They were clinically, biochemically and radiologically evaluated at 1, 4, 12 and 18 months after TARE.

Results

Two patients were excluded from the analysis due to severe liver injury and death due to extrahepatic disease progression, respectively. One month after TARE, a statistically significant (P = 0.02) reduction of calcitonin was observed in all patients and remained clinically relevant during follow-up; reduction of CEA, although not significant, was found in all patients. Significant reduction of liver tumor mass was observed 1, 4 and 12 months after TARE (P = 0.007, P = 0.004, P = 0.002, respectively). After 1 month, three of six patients showed partial response (PR) and three of six stable disease (SD) according to RECIST 1.1, while five of six patients had a PR and one of six a SD according to mRECIST. The clinical response remained relevant 18 months after TARE. Excluding one patient, all others showed only a slight and transient increase in liver enzymes.

Conclusions

TARE is effective in LM treatment of MTC. The absence of severe complications and the good tolerability make TARE a valid therapeutic strategy when liver LM are multiple and progressive.

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