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Background: The aim of this study was to evaluate the effectiveness of sunitinib in patients with progressive radioiodine refractory (RAIR) thyroid cancer (TC). Materials and Methods: A multicentric retrospective analysis was performed of patients treated in six TUmeurs THYroïdiennes REFractaires participating centers. All patients with progressive RAIR TC who were treated with sunitinib outside a clinical trial between August 2007 and March 2015 were retrospectively and consecutively included. The primary endpoint was the overall response rate (ORR) and disease control rate ≥6 months based on RECIST criteria. Secondary endpoints included evaluation of overall survival (OS) and progression-free survival (PFS) from the first dose of sunitinib. Primary and secondary endpoints were also evaluated according to treatment setting: first or second line of tyrosine kinase inhibitor (TKI). Results: Fifty-seven patients (29 men; 50.8%), mean age 62.2 years (range 43-80 years) with progressive RAIR TC were included. Sunitinib was the first-line TKI treatment for 32 (56.1%) patients and the second-line TKI treatment for 25 (43.9%) patients. For all patients, according to RECIST criteria, ORR was 35.1% (20 patients) and disease control rate ≥6 months was 68.4% (39 patients). No complete response was observed. Six (10.5%) patients showed disease progression. When sunitinib was used as first-line TKI therapy, ORR was 46.9% (15/32 patients), and disease control rate ≥6 months was 75% (24/32 patients). When sunitinib was used as second-line TKI therapy, ORR was 20% (5/25 patients), and disease control rate ≥6 months was 60% (15/25 patients). The median OS and PFS were 21.0 (range 15-29) and 10.2 months (range 6-13), respectively, for all patients. With sunitinib as first-line TKI-therapy, median OS and PFS was 30.0 (range 19.0-53.0) and 15 (range 7.0-21.0) months, respectively. As second-line therapy, median OS and PFS were 13 (range 8.0-20.0) and 6 (range 5.0-11.0) months, respectively. Eleven (19.3%) patients experienced grade 3 toxicity, and four patients (7.0%) experienced grade 4 toxicity. Conclusion: The efficacy of sunitinib as first- and second-line TKI therapy in a large cohort of patients treated for progressive RAIR TC is herein reported. Further prospective studies are needed to evaluate the effectiveness of sunitinib in RAIR TC. [ABSTRACT FROM AUTHOR]

Background: A randomized phase III trial demonstrated that vandetanib treatment is effective in patients with metastatic medullary thyroid cancer (MTC), leading to regulatory approval, but its use may be associated with toxicities that require specific monitoring and management. The objective of the present study performed in France was to describe the toxicity profile and efficacy of vandetanib treatment when given outside any trial. Methods: Sixty-eight patients were treated with vandetanib in the frame of a temporary use authorization (ATU) in France from August 2010 to February 2012, when the drug was available on request for patients with locally advanced or metastatic MTC. Patients were registered by the French health authorities, and characteristics, treatment parameters, toxicity profile, and efficacy were retrospectively reviewed. Eight patients were excluded from the analysis because vandetanib treatment was not administered ( n=3), had been given in a trial before ATU ( n=3), or was given for a non-MTC cancer ( n=2). Results: Data from the 60 MTC patients were analyzed. Mean age was 58 years (range 11-83 years), 39 patients were male, and six had hereditary MTC. Fifty-six (93%) had metastatic disease in the mediastinum (82%), bones (65%), liver (53%), or lung (53%), and four had only locally advanced disease. At the time of study evaluation, with a median follow-up of 20 months and a median duration of treatment of 9.7 months (range 0.3-36 months), 15 patients were continuing vandetanib treatment (range 18-36 months). Median progression-free survival was 16.1 months. Twenty-five patients discontinued treatment for disease progression (range 0.3-29 months). Best tumor response was a complete response in one patient, a partial response in 12 (20%), stable disease in 33 (55%), and progression in seven patients (12%). All patients had at least one adverse event (AE) during treatment. The main AEs were skin toxicity, diarrhea, and asthenia. Sixteen patients (27%) discontinued treatment for toxicity, and one patient died from vandetanib-induced cardiac toxicity. Conclusions: Vandetanib is an effective option for patients with advanced MTC. AEs should be monitored carefully and should be minimized by educating both patients and care providers and by applying symptomatic treatment and dose reduction. [ABSTRACT FROM AUTHOR]

Background: Spinal metastases (SMs) due to thyroid cancer (TC) are associated with significantly reduced quality of life. The goal of this study is to analyze the clinical manifestations, presentation, and treatments of TC SMs, and to describe specific features of SMs associated with different TC types. Patients and Methods: A retrospective analysis of 202 TC SM patients treated at Medstar Washington Hospital Center (37) and collected from the literature (165) was performed. Results: The mean age of patients with SMs was 56.9±14.7 years, and the female-to-male ratio was 2.1:1. Of all patients, 29% (28% of follicular thyroid cancer [FTC] and 37% of papillary thyroid cancer [PTC]) had SMs only. Twenty-nine percent of all patients and 54% of patients with single-site SMs had neither bone non-SMs nor solid organ metastases at the time of presentation. Thirty-five percent of patients had SMs as an initial presentation of TC. TC patients presenting with SMs had a lower rate of other bone and visceral involvement compared with patients whose SMs were diagnosed at the time of thyroid surgery or during follow-up ( p<0.05). SMs were more often the initial manifestation of FTC (41% vs. 24%), while PTC SMs were more commonly diagnosed after TC diagnosis (76% vs. 59%; p<0.05). PTC SMs were more frequently diagnosed as synchronous (63% vs. 36% in FTC) versus FTC SMs that developed as metachronous metastases (64% vs. 37% in PTC; p<0.01). All FTC SMs developed within 82 (0-372) months and all PTC SMs within 35 (0-144) months ( p<0.01). In FTC SMs as TC manifestation, solid organ metastases involvement was less common than in FTC SMs that were found after TC diagnosis (34% vs. 67%; p<0.01); multisite FTC SMs compared to solitary FTC SMs were associated with the development of other bone nonspinal metastases (82% vs. 30%; p<0.01) and solitary organ metastases (65% vs. 41%; p<0.01). These correlations were not observed in PTC SMs. FTC patients often had neural structure compression (myelopathy/radiculopathy; 72% vs. 36% in PTC), while PTC patients frequently were asymptomatic (38% vs. 5% in FTC; p<0.01). FTC SMs more commonly were 131I-avid ( p<0.01). FTC patients required surgery more frequently (72% vs. 55% in PTC; p<0.05). Conclusions: Our study reveals that a significant part of TC SMs patients have solitary spinal involvement at the time of presentation and may be considered for aggressive treatment with the intention to improve quality of life and survival. FTC SMs and PTC SMs appear to have distinct presentations, behavior, and treatment modalities, and should be categorized separately for treatment and follow-up planning. [ABSTRACT FROM AUTHOR]

Background: Distant metastases from differentiated thyroid carcinoma occur in up to 20% of cases and represent the most frequent cause of thyroid cancer-related death. Metastatic disease to the spine has the potential to cause severe morbidity, including pain, neurological deficit, and paraplegia. Summary: We present a case series of eight consecutive patients with symptomatic spinal metastases due to thyroid carcinoma treated by our multidisciplinary team consisting of spinal surgeons, oncologists, and radiologists, with management of each case determined by our surgical algorithm. Four patients underwent surgical decompression and stabilization for spinal metastases causing instability, spinal cord compression, neurological deficit, or intractable pain. Three patients underwent vertebroplasty for focal mechanical pain due to osteolytic metastases in the absence of significant spinal cord compression or spinal instability; one of these patients required subsequent surgical decompression for spinal cord compression. One patient was nonoperatively treated. All patients underwent total thyroidectomy for the primary cancer and adjuvant radioiodine-131 treatment. The only patient with poorly differentiated thyroid cancer, which was refractory to radioiodine-131 died at 6 months after vertebroplasty procedures for symptomatic spinal metastases. One patient with medullary thyroid carcinoma died at 18 months after vertebroplasty. All remaining six patients who had well-differentiated papillary or follicular thyroid carcinoma were alive at an average of 50 months (range: 17-96 months) after diagnosis and treatment of symptomatic spinal metastases and were ambulant, independent, and able to perform activities of daily living and had no significant pain or neurologic symptoms. Conclusion: The potential for long-term survival of several years following development of spinal metastases should be considered during the counseling and decision-making process for patients with thyroid cancer. [ABSTRACT FROM AUTHOR]