Search Results
Search for other papers by Furio Pacini in
Google Scholar
PubMed
Search for other papers by Dagmar Fuhrer in
Google Scholar
PubMed
Search for other papers by Rossella Elisei in
Google Scholar
PubMed
Search for other papers by Daria Handkiewicz-Junak in
Google Scholar
PubMed
Search for other papers by Sophie Leboulleux in
Google Scholar
PubMed
Search for other papers by Markus Luster in
Google Scholar
PubMed
Search for other papers by Martin Schlumberger in
Google Scholar
PubMed
Search for other papers by Johannes W Smit in
Google Scholar
PubMed
Modern use of post-operative radioactive iodine (RAI) treatment for differentiated thyroid cancer (DTC) should be implemented in line with patients’ risk stratification. Although beneficial effects of radioiodine are undisputed in high-risk patients, controversy remains in intermediate-risk and some low-risk patients. Since the last consensus on post-surgical use of RAI in DTC patients, new retrospective data and results of prospective randomized trials have been published, which have allowed the development of a new European Thyroid Association (ETA) statement for the indications of post-surgical RAI therapy in DTC. Questions about which patients are candidates for RAI therapy, which activities of RAI can be used, and which modalities of pre-treatment patient preparation should be used are addressed in the present guidelines.
Search for other papers by Laura Valerio in
Google Scholar
PubMed
Search for other papers by Carlotta Giani in
Google Scholar
PubMed
Search for other papers by Laura Agate in
Google Scholar
PubMed
Search for other papers by Eleonora Molinaro in
Google Scholar
PubMed
Search for other papers by David Viola in
Google Scholar
PubMed
Search for other papers by Valeria Bottici in
Google Scholar
PubMed
Search for other papers by Antonio Matrone in
Google Scholar
PubMed
Search for other papers by Luciana Puleo in
Google Scholar
PubMed
Search for other papers by Loredana Lorusso in
Google Scholar
PubMed
Search for other papers by Virginia Cappagli in
Google Scholar
PubMed
Search for other papers by Alessandro Ribechini in
Google Scholar
PubMed
Search for other papers by Rossella Elisei in
Google Scholar
PubMed
Introduction: Tyrosine kinase inhibitors represent a better treatment in patients with radioiodine-refractory differentiated thyroid cancer (RAI-R DTC). Lenvatinib is usually well-tolerated, but sometimes, it is associated with serious and even life-threatening side effects. The aim of this study was to evaluate the prevalence of and the potential risk factors for fistula and/or organ perforation in RAI-R DTC patients treated with lenvatinib. Methods: This study included data from advanced and progressive RAI-R DTC patients treated with lenvatinib from February 2011 to February 2020 who were followed up at a single center. The clinical-pathological features and the biochemical and morphological results of the patients were collected at the time of starting lenvatinib and during the follow-up. Results: Fourteen of 95 (14.7%) locally advanced or metastatic RAI-R DTC patients treated with lenvatinib developed a fistula or organ perforation. Nine of 14 (64.3%) patients had tumor infiltration of the trachea, bronchus, esophagus, pleura, or bladder. Five of 14 (35.7%) had a bowel perforation, but only 2 had preexisting diverticulosis. Evaluation of the risk factors for developing a fistula or organ perforation showed that the presence of tumor infiltration and the tumor histology (papillary and poorly differentiated vs. follicular and Hurthle thyroid cancer) were significantly correlated with the development of a fistula or organ perforation (p = 0.003 and p = 0.02, respectively). In the subgroup of patients with tumor infiltration, we found that the papillary thyroid cancer histotype was the only potential predictor of fistula development. External beam radiation therapy (EBRT), the starting dose of lenvatinib, and the duration of treatment were not relevant for the development of fistula. Conclusions: In metastatic thyroid cancer patients treated with lenvatinib, the presence of tumor infiltration and histological type should be considered as potential risk factors for the development of fistula or organ perforation, although they do not represent an absolute contraindication. Although EBRT and the presence of diverticulosis were not significantly associated with the development of fistula and organ perforation, they should be regarded as potential additional reasons for the development of these complications. According to our findings, there is no reason to start lenvatinib at a lower daily dose when tumor infiltration is present.
Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
Search for other papers by Laura Fugazzola in
Google Scholar
PubMed
Search for other papers by Rossella Elisei in
Google Scholar
PubMed
Search for other papers by Dagmar Fuhrer in
Google Scholar
PubMed
Search for other papers by Barbara Jarzab in
Google Scholar
PubMed
Search for other papers by Sophie Leboulleux in
Google Scholar
PubMed
Search for other papers by Kate Newbold in
Google Scholar
PubMed
Search for other papers by Jan Smit in
Google Scholar
PubMed
The vast majority of thyroid cancers of follicular origin (TC) have a very favourable outcome, but 5–10% of cases will develop metastatic disease. Around 60–70% of this subset, hence less than 5% of all patients with TC, will become radioiodine refractory (RAI-R), with a significant negative impact on prognosis and a mean life expectancy of 3–5 years. Since no European expert consensus or guidance for this challenging condition is currently available, a task force of TC experts was nominated by the European Thyroid Association (ETA) to prepare this document based on the principles of clinical evidence. The task force started to work in September 2018 and after several revision rounds, prepared a list of recommendations to support the treatment and follow-up of patients with advanced TC. Criteria for advanced RAI-R TC were proposed, and the most appropriate diagnostic tools and the local, systemic and palliative treatments are described. Systemic therapy with multikinase inhibitors is fully discussed, including recommendations on how to start it and at which dosage, on the duration of treatment, and on the management of side effects. The appropriate relationship between the specialist and the patient/family as well as ethical issues are covered. Based on the available studies and on personal experience, the experts provided 39 recommendations aimed to improve the management of advanced RAI-R TCs. Above all of them is the indication to treat and follow these patients in a specialized setting which allows the interaction between several specialists in a multidisciplinary team.
Search for other papers by Laura Agate in
Google Scholar
PubMed
Search for other papers by Francesca Bianchi in
Google Scholar
PubMed
Search for other papers by Federica Brozzi in
Google Scholar
PubMed
Search for other papers by Pierina Santini in
Google Scholar
PubMed
Search for other papers by Eleonora Molinaro in
Google Scholar
PubMed
Search for other papers by Valeria Bottici in
Google Scholar
PubMed
Search for other papers by David Viola in
Google Scholar
PubMed
Search for other papers by Loredana Lorusso in
Google Scholar
PubMed
Search for other papers by Paolo Vitti in
Google Scholar
PubMed
Search for other papers by Rossella Elisei in
Google Scholar
PubMed
Background: Recently, there has been a trend to reduce the use of radioiodine remnant ablation (RRA) in patients with low-risk (LR) and intermediate-risk (IR) differentiated thyroid cancer (DTC). Objectives: The aim of this paper was to evaluate the diagnostic role of whole-body scan (ptWBS) performed after RRA in LR and IR DTC patients. Methods: We analyzed 545 DTC patients treated with total thyroidectomy and RRA in hypothyroidism followed by a ptWBS. Neck ultrasound (US) and serum thyroglobulin measurement were performed. According to the American Thyroid Association guidelines, patients were classified as LR (n = 345) and IR (n = 200). Results: In addition to the thyroid remnant, the ptWBS showed the presence of further areas of <sup>131</sup>I uptake in 16/545 (2.9%) cases. ptWBS showed laterocervical lymph node metastases in 11/16 patients (10/11 were also detected by US), mediastinal uptake in 1/16, lung metastases in 3/16, and bone metastases in 1/16. Only 6/545 (1.1%) metastases were detected by ptWBS alone. After 7.8 years, 8/16 patients were free of disease, and 8 had persistent disease: 4 “biochemical” and 4 “structural.” Remission was achieved in 3 cases after one single <sup>131</sup>I course, in 1 case after surgery, and in the last 4 cases after several <sup>131</sup>I courses. Conclusions: The ptWBS diagnostic role was clinically relevant for the therapeutic strategies of our patients only in 1.1% of the cases. The cost-effectiveness of performing RRA and ptWBS in all LR and IR patients to find 1–2% of the cases with distant metastases remains controversial.
Search for other papers by Luigino Dal Maso in
Google Scholar
PubMed
Search for other papers by Daniela Pierannunzio in
Google Scholar
PubMed
Search for other papers by Silvia Francisci in
Google Scholar
PubMed
Search for other papers by Angela De Paoli in
Google Scholar
PubMed
Search for other papers by Federica Toffolutti in
Google Scholar
PubMed
Search for other papers by Salvatore Vaccarella in
Google Scholar
PubMed
Search for other papers by Silvia Franceschi in
Google Scholar
PubMed
Search for other papers by Rossella Elisei in
Google Scholar
PubMed
Search for other papers by Ugo Fedeli in
Google Scholar
PubMed
Objective
A decrease in the use of radioactive iodine (RAI) treatment for thyroid cancer has been described in the last decade in the US following subsequent updates of the American Thyroid Association guidelines. By contrast, population-based data from European countries are lacking. The study aims to assess the frequency and long-term trends in the use of RAI in Italy.
Methods
From the Italian national hospital discharge database, the proportion of RAI treatment after total thyroidectomy with thyroid cancer diagnosis has been assessed by sex and age class during 2001–2018.
Results
Throughout the whole study period, RAI was performed after 58% of 149,419 total thyroidectomies. The use of RAI was higher for men and younger patients; it peaked in 2007 (64% in women and 68% in men) and declined thereafter (2018: 46% in women and 53% in men), with a similar pattern observed across all ages and areas.
Conclusion
National data show that in Italy trends in RAI treatment paraleled those observed in the US. Further monitoring of the use of RAI is warranted in Italy, as elsewhere, to assess the impact of international guidelines on real-life clinical management of thyroid cancer.
Search for other papers by Francesca Orsolini in
Google Scholar
PubMed
Search for other papers by Alessandro Prete in
Google Scholar
PubMed
Search for other papers by Pierpaolo Falcetta in
Google Scholar
PubMed
Search for other papers by Domenico Canale in
Google Scholar
PubMed
Search for other papers by Fulvio Basolo in
Google Scholar
PubMed
Search for other papers by Greta Alì in
Google Scholar
PubMed
Search for other papers by Francesca Manassero in
Google Scholar
PubMed
Search for other papers by Paolo Vitti in
Google Scholar
PubMed
Search for other papers by Rossella Elisei in
Google Scholar
PubMed
Search for other papers by Eleonora Molinaro in
Google Scholar
PubMed
Introduction
Medullary thyroid cancer (MTC) is a rare endocrine tumor, which can be sporadic or familial, as a component of multiple endocrine neoplasia 2 (MEN2). Overall, 10% of MTC cases have already developed at presentation or will develop metastasis during follow-up. Testicular metastases are exceptional and only one case of unilateral testis involvement by metastatic MTC has been already reported in literature. We described the first known case of asymptomatic bilateral testicular MTC metastases, discovered incidentally at testicular ultrasound (US) performed for unrelated reasons.
Case presentation
A Latin American 32-year-old man with MEN 2A syndrome and metastatic MTC underwent andrological and urological examination due to premature ejaculation. US imaging showed two symmetrical hypoechoic lesions involving both testes. Suspecting a bilateral testicular cancer, the patient underwent excision biopsy of both testicular lesions. Histopathology and immunohistochemical examinations documented metastatic MTC of both testicular lesions.
Conclusion
Beyond its rarity, testis should be considered as a potential metastatic site of MTC, especially in patients with advanced disease.
Established facts
-
Distant metastases are present at the diagnosis in 10–15% of patients with medullary thyroid carcinoma (MTC).
-
Testicular metastases are anecdotal. Only one case of unilateral testis involvement by metastatic MTC has been reported in the literature.
Novel insights
-
Testis should be considered as a possible site of metastases in patients with diffuse metastatic MTC.
-
Testicular ultrasound could be considered as an useful tool for the evaluation and follow-up of metastatic MTC.
Search for other papers by Carla Gambale in
Google Scholar
PubMed
Search for other papers by Alessandro Prete in
Google Scholar
PubMed
Search for other papers by Lea Contartese in
Google Scholar
PubMed
Search for other papers by Liborio Torregrossa in
Google Scholar
PubMed
Search for other papers by Francesca Bianchi in
Google Scholar
PubMed
Search for other papers by Eleonora Molinaro in
Google Scholar
PubMed
Search for other papers by Gabriele Materazzi in
Google Scholar
PubMed
Search for other papers by Rossella Elisei in
Google Scholar
PubMed
Search for other papers by Antonio Matrone in
Google Scholar
PubMed
Background
Second 131I treatment is commonly performed in clinical practice in patients with differentiated thyroid cancer and biochemical incomplete or indeterminate response (BiR/InR) after initial treatment.
Objective
The objective of the is study is to evaluate the clinical impact of the second 131I treatment in BiR/InR patients and analyze the predictive factors for structural incomplete response (SiR).
Patients and methods
One hundred fifty-three BiR/InR patients after initial treatment who received a second 131I treatment were included in the study. The clinical response in a short- and medium- long-term follow-up was evaluated.
Results
After the second 131I treatment (median 8 months), 11.8% patients showed excellent response (ER), 17% SiR, while BiR/InR persisted in 71.2%. Less than half (38.5%) of SiR patients had radioiodine-avid metastases. Patients who, following the second 131I treatment, experienced SiR had larger tumor size and more frequently aggressive histology and vascular invasion than those experienced BiR/InR and ER. Also, the median values of thyroglobulin on levothyroxine therapy (LT4-Tg), Tg peak after recombinant human TSH stimulation (rhTSH-Tg) and thyroglobulin antibodies (TgAb) were significantly higher in patients who developed SiR. At last evaluation (median: 9.9 years), BiR/InR persisted in 57.5%, while 26.2% and 16.3% of the patients showed ER and SiR, respectively. About half of BiR/InR patients (71/153 (46.4%)) received further treatments after the second 131I treatment.
Conclusions
Radioiodine-avid metastatic disease detected by the second 131I is an infrequent finding in patients with BiR/InR after initial treatment. However, specific pathologic and biochemical features allow to better identify those cases with higher probability of developing SiR, thus improving the clinical effectiveness of performing a second 131I treatment.
Search for other papers by Lars Bastholt in
Google Scholar
PubMed
Department of Nuclear Medicine, University Hospital Würzburg, Würzburg
Search for other papers by Michael C. Kreissl in
Google Scholar
PubMed
Search for other papers by Dagmar Führer in
Google Scholar
PubMed
Search for other papers by Ana L. Maia in
Google Scholar
PubMed
Search for other papers by Laura D. Locati in
Google Scholar
PubMed
Search for other papers by Léa Maciel in
Google Scholar
PubMed
Search for other papers by Yi Wu in
Google Scholar
PubMed
Search for other papers by Kevin N. Heller in
Google Scholar
PubMed
Search for other papers by Alan Webster in
Google Scholar
PubMed
Search for other papers by Rossella Elisei in
Google Scholar
PubMed
Objectives: Effective management of adverse events (AEs) following vandetanib treatment is important to maximize clinical benefits. We examined whether more frequent contact with vandetanib-treated patients reduced AEs of CTCAE grade 2 or higher. Study Design: In this open-label, multicentre, phase III study, patients with locally advanced or metastatic medullary thyroid cancer were randomized to a patient outreach programme (outreach) or a standard AE monitoring schedule (vandetanib control) for 52 weeks. In addition to standard AE monitoring, patients in the outreach arm were contacted every 2 weeks by telephone/during their clinic visit for specific AE questioning related to diarrhoea, nausea, vomiting, fatigue, headache and rash. Patients received vandetanib at 200 or 300 mg/day, depending on the creatinine levels at screening. Results: Altogether, 205 patients were randomized (outreach, n = 103; vandetanib control, n = 102). This study did not meet its primary objective; the mean percentage of time patients experienced at least one AE of grade 2 or higher was higher for the outreach group (51.65%) than for the vandetanib control group (45.19%); the difference was not statistically significant (t statistic: 1.29; 95% CI -3.44 to 16.37%; p = 0.199). The most frequently reported AEs were diarrhoea (56.9% for the outreach group vs. 46.6% for the vandetanib controls), hypertension (36.3 vs. 31.1%), rash (25.5 vs. 24.3%) and nausea (25.5% vs. 18.4%), and the most frequently reported AEs of grade 2 or higher were hypertension (33.3 vs. 23.3%), diarrhoea (26.5 vs. 24.3%) and dermatitis acneiform (11.8 vs. 9.7%). Conclusions: Additional outreach to patients treated with vandetanib had no impact on the rate or severity of AEs compared to the standard AE monitoring schedule. AEs were consistent with the known safety profile of vandetanib.
Search for other papers by Luciana Puleo in
Google Scholar
PubMed
Search for other papers by Laura Agate in
Google Scholar
PubMed
Search for other papers by Irene Bargellini in
Google Scholar
PubMed
Search for other papers by Giuseppe Boni in
Google Scholar
PubMed
Search for other papers by Paolo Piaggi in
Google Scholar
PubMed
Search for other papers by Claudio Traino in
Google Scholar
PubMed
Search for other papers by Tommaso Depalo in
Google Scholar
PubMed
Search for other papers by Giulia Lorenzoni in
Google Scholar
PubMed
Search for other papers by Francesca Bianchi in
Google Scholar
PubMed
Search for other papers by Duccio Volterrani in
Google Scholar
PubMed
Search for other papers by Sandra Brogioni in
Google Scholar
PubMed
Search for other papers by Valeria Bottici in
Google Scholar
PubMed
Search for other papers by Maurizia Rossana Brunetto in
Google Scholar
PubMed
Search for other papers by Barbara Coco in
Google Scholar
PubMed
Search for other papers by Eleonora Molinaro in
Google Scholar
PubMed
Search for other papers by Rossella Elisei in
Google Scholar
PubMed
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.
Search for other papers by Chantal A Lebbink in
Google Scholar
PubMed
Search for other papers by Thera P Links in
Google Scholar
PubMed
Search for other papers by Agnieszka Czarniecka in
Google Scholar
PubMed
Search for other papers by Renuka P Dias in
Google Scholar
PubMed
Search for other papers by Rossella Elisei in
Google Scholar
PubMed
Search for other papers by Louise Izatt in
Google Scholar
PubMed
Search for other papers by Heiko Krude in
Google Scholar
PubMed
Search for other papers by Kerstin Lorenz in
Google Scholar
PubMed
Search for other papers by Markus Luster in
Google Scholar
PubMed
Search for other papers by Kate Newbold in
Google Scholar
PubMed
Search for other papers by Arnoldo Piccardo in
Google Scholar
PubMed
Search for other papers by Manuel Sobrinho-Simões in
Google Scholar
PubMed
Search for other papers by Toru Takano in
Google Scholar
PubMed
Search for other papers by A S Paul van Trotsenburg in
Google Scholar
PubMed
Search for other papers by Frederik A Verburg in
Google Scholar
PubMed
Search for other papers by Hanneke M van Santen in
Google Scholar
PubMed
At present, no European recommendations for the management of pediatric thyroid nodules and differentiated thyroid carcinoma (DTC) exist. Differences in clinical, molecular, and pathological characteristics between pediatric and adult DTC emphasize the need for specific recommendations for the pediatric population. An expert panel was instituted by the executive committee of the European Thyroid Association including an international community of experts from a variety of disciplines including pediatric and adult endocrinology, pathology, endocrine surgery, nuclear medicine, clinical genetics, and oncology. The 2015 American Thyroid Association Pediatric Guideline was used as framework for the present guideline. Areas of discordance were identified, and clinical questions were formulated. The expert panel members discussed the evidence and formulated recommendations based on the latest evidence and expert opinion. Children with a thyroid nodule or DTC require expert care in an experienced center. The present guideline provides guidance for healthcare professionals to make well-considered decisions together with patients and parents regarding diagnosis, treatment, and follow-up of pediatric thyroid nodules and DTC.
