scholarly journals The Next Generation of Orthotopic Thyroid Cancer Models: Immunocompetent Orthotopic Mouse Models of BRAFV600E-Positive Papillary and Anaplastic Thyroid Carcinoma

Thyroid ◽  
2014 ◽  
Vol 24 (4) ◽  
pp. 705-714 ◽  
Author(s):  
Pierre Vanden Borre ◽  
David G. McFadden ◽  
Viswanath Gunda ◽  
Peter M. Sadow ◽  
Shohreh Varmeh ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Thyroid Carcinoma ◽  
Mouse Models ◽  
Anaplastic Thyroid Carcinoma ◽  
Next Generation ◽  
Cancer Models

scholarly journals Thyroid Carcinoma with Pituitary Metastases: 2 Case Reports and Literature Review

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Weiying Lim ◽  
Dawn Shaoting Lim ◽  
Chiaw Ling Chng ◽  
Adoree Yiying Lim
Keyword(s):  
Thyroid Cancer ◽  
Thyroid Carcinoma ◽  
Radioiodine Therapy ◽  
Follicular Thyroid Carcinoma ◽  
Case Reports ◽  
Anaplastic Thyroid Cancer ◽  
Anaplastic Thyroid Carcinoma ◽  
Pituitary Metastases ◽  
History Of ◽  
Loss Of Appetite

We present 2 patients with pituitary metastases from thyroid carcinoma—the first from anaplastic thyroid carcinoma and the second from follicular thyroid carcinoma. The first patient, a 50-year-old lady, presented with 2-week history of hoarseness of voice, dysphagia, dyspnoea, and neck swelling. Imaging revealed metastatic thyroid cancer to lymph nodes and bone. Histology from surgery confirmed anaplastic thyroid cancer. She was found to have pituitary metastases postoperatively when she presented with nonvertiginous dizziness. She subsequently underwent radiotherapy and radioiodine treatment but passed away from complications. The second patient, a 65-year-old lady, presented with loss of appetite and weight with increased goitre size and dyspnoea. Surgery was performed in view of compressive symptoms and histology confirmed follicular thyroid carcinoma. Imaging revealed metastases to bone, lung, and pituitary. She also had panhypopituitarism with hyperprolactinemia and diabetes insipidus. She received radioiodine therapy but eventually passed away from complications.

scholarly journals Virotherapy as a Potential Therapeutic Approach for the Treatment of Aggressive Thyroid Cancer

Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1532 ◽  
Author(s):  
Malfitano ◽  
Somma ◽  
Prevete ◽  
Portella
Keyword(s):  
Thyroid Carcinoma ◽  
Therapeutic Potential ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Differentiated Thyroid Carcinoma ◽  
Anaplastic Thyroid Carcinoma ◽  
Oncolytic Viruses ◽  
Cancer Models ◽  
Poorly Differentiated ◽  
Immunosuppressive Microenvironment

Virotherapy is a novel cancer treatment based on oncolytic viruses (OVs), which selectively infect and lyse cancer cells, without harming normal cells or tissues. Several viruses, either naturally occurring or developed through genetic engineering, are currently under investigation in clinical studies. Emerging reports suggesting the immune-stimulatory property of OVs against tumor cells further support the clinical use of OVs for the treatment of lesions lacking effective therapies. Poorly differentiated thyroid carcinoma (PDTC) and anaplastic thyroid carcinoma (ATC), have a poor prognosis and limited treatment options. Therefore, several groups investigated the therapeutic potential of OVs in PDTC/ATC models producing experimental data sustaining the potential clinical efficacy of OVs in these cancer models. Moreover, the presence of an immunosuppressive microenvironment further supports the potential use of OVs in ATC. In this review, we present the results of the studies evaluating the efficacy of OVs alone or in combination with other treatment options. In particular, their potential therapeutic combination with multiple kinases inhibitors (MKIs) or immune checkpoint inhibitors are discussed.

scholarly journals Complete Remission of Anaplastic Thyroid Carcinoma after Concomitant Treatment with Docetaxel and Radiotherapy

2015 ◽  
Vol 2015 ◽  
pp. 1-4 ◽  
Author(s):  
Ichiro Abe ◽  
Satoko Karasaki ◽  
Yayoi Matsuda ◽  
Shohei Sakamoto ◽  
Torahiko Nakashima ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Survival Rate ◽  
Mortality Rate ◽  
Complete Remission ◽  
Thyroid Carcinoma ◽  
Therapeutic Potential ◽  
Anaplastic Thyroid Carcinoma ◽  
High Dose ◽  
Concomitant Treatment ◽  
Very High

Anaplastic thyroid carcinoma (ATC) although rare is the most lethal form of thyroid cancer. The mortality rate for ATC is very high, with a median survival time of only 5 months; the survival rate at 1 year after diagnosis is <20%. Management of ATC is extremely difficult and rife with uncertainties. Herein, we describe a 75-year-old woman who presented with ATC and was successfully treated using concomitant treatment with docetaxel and high-dose radiotherapy. This case appears to be the first to have been reported in the literature involving complete remission of ATC confirmed by autopsy, suggesting the therapeutic potential of this combination.

scholarly journals Anaplastic Transformation of Papillary Thyroid Cancer in the Retroperitoneum

2015 ◽  
Vol 2015 ◽  
pp. 1-4 ◽  
Author(s):  
James P. Solomon ◽  
Fang Wen ◽  
Lily J. Jih
Keyword(s):  
Thyroid Cancer ◽  
Thyroid Carcinoma ◽  
Rare Case ◽  
Case Reports ◽  
Anaplastic Thyroid Carcinoma ◽  
Papillary Thyroid ◽  
Cervical Lymph Nodes ◽  
Anaplastic Transformation ◽  
Metastatic Sites ◽  
Aggressive Variant

Anaplastic thyroid carcinoma is an aggressive variant of thyroid cancer that in most cases arises from anaplastic transformation of terminally differentiated thyroid carcinomas. This process usually occurs in the thyroid or cervical lymph nodes. Anaplastic transformation in distant metastatic sites is exceedingly rare, only previously documented in a few case reports. We report a rare case of anaplastic transformation of papillary thyroid carcinoma within a large retroperitoneal metastasis in a 64-year-old male 30 years after the initial diagnosis.

scholarly journals The Differences in Distant Metastatic Patterns and Their Corresponding Survival Between Thyroid Cancer Subtypes

2021 ◽  
Author(s):  
Huy Gia Vuong ◽  
Minh-Khang Le ◽  
Lewis Hassell ◽  
Tetsuo Kondo ◽  
Kennichi Kakudo
Keyword(s):  
Thyroid Cancer ◽  
Thyroid Carcinoma ◽  
Significant Risk ◽  
Differentiated Thyroid Carcinoma ◽  
Anaplastic Thyroid Carcinoma ◽  
Tumor Diameter ◽  
Large Tumor ◽  
Thyroid Cancers ◽  
Cancer Subtypes ◽  
Metastatic Patterns

Abstract Introduction: Distant metastasis (DM) at presentation is one of the important prognostic factors in thyroid cancers. Dissemination patterns of different thyroid cancer subtypes are still controversial. This study aimed to systematically elucidate the metastatic patterns and their corresponding survival of each thyroid cancer subtype at time of diagnosis. Methods: We accessed the Surveillance, Epidemiology, and End Results (SEER) database from 2010-2018 to search for primary thyroid cancers with DM at presentation (M1). Results: We included 2,787 M1 thyroid cancers for statistical analyses and the incidence of DM at presentation was 2.4%. Lung was the most common metastatic site for anaplastic thyroid carcinoma (ATC), poorly-differentiated thyroid carcinoma (PDTC), papillary thyroid carcinoma (PTC), and oncocytic (Hurthle) cell carcinoma (HCC) whereas bone is the favorable disseminated site of follicular thyroid carcinoma (FTC) and medullary thyroid carcinoma (MTC). The risk of liver metastasis was highest in MTC while metastases to the brain were uncommon among thyroid cancer subtypes. Among M1 thyroid cancers, ATC showed the worst outcome while PTC and FTC exhibited a superior survival. Patients with multi-organ metastases had the worst survival whereas bone metastases were associated with a favorable outcome (p < 0.001). We identified significant risk factors associated with multi-organ metastases including non-Caucasian race, large tumor diameter, ATC/FTC/MTC histology, and unifocality. Conclusion: There are significant differences in DM patterns of thyroid cancer subtypes and their corresponding survival. These clinical data could be useful for clinicians to better evaluate risk stratification and predict patient outcomes.

scholarly journals FOXM1 is a molecular determinant of the mitogenic and invasive phenotype of anaplastic thyroid carcinoma

2012 ◽  
Vol 19 (5) ◽  
pp. 695-710 ◽  
Author(s):  
Roberto Bellelli ◽  
Maria Domenica Castellone ◽  
Ginesa Garcia-Rostan ◽  
Clara Ugolini ◽  
Carmelo Nucera ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Thyroid Cancer ◽  
Thyroid Carcinoma ◽  
Cancer Progression ◽  
Target Genes ◽  
Cyclin B1 ◽  
Anaplastic Thyroid Carcinoma ◽  
Loss Of Function ◽  
Thyroid Carcinomas ◽  
Forkhead Box

Anaplastic thyroid carcinoma (ATC) is a very aggressive thyroid cancer. forkhead box protein M1 (FOXM1) is a member of the forkhead box family of transcription factors involved in control of cell proliferation, chromosomal stability, angiogenesis, and invasion. Here, we show that FOXM1 is significantly increased in ATCs compared with normal thyroid, well-differentiated thyroid carcinomas (papillary and/or follicular), and poorly differentiated thyroid carcinomas (P=0.000002). Upregulation of FOXM1 levels in ATC cells was mechanistically linked to loss-of-function of p53 and to the hyperactivation of the phosphatidylinositol-3-kinase/AKT/FOXO3a pathway. Knockdown of FOXM1 by RNA interference inhibited cell proliferation by arresting cells in G2/M and reduced cell invasion and motility. This phenotype was associated with decreased expression of FOXM1 target genes, like cyclin B1 (CCNB1), polo-like kinase 1 (PLK1), Aurora B (AURKB), S-phase kinase-associated protein 2 (SKP2), and plasminogen activator, urokinase: uPA (PLAU). Pharmacological inhibition of FOXM1 in an orthotopic mouse model of ATC reduced tumor burden and metastasization. All together, these findings suggest that FOXM1 represents an important player in thyroid cancer progression to the anaplastic phenotype and a potential therapeutic target for this fatal cancer.

204 The role of immune checkpoint inhibitor as a single agent or combination therapy in advanced thyroid cancer

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A219-A220
Author(s):  
Ju Young Lee ◽  
Inae Park ◽  
Myungwoo Nam ◽  
Christmann Low ◽  
Eugene Kim ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Combination Therapy ◽  
Thyroid Carcinoma ◽  
Clinical Oncology ◽  
Differentiated Thyroid Cancer ◽  
Kinase Inhibitor ◽  
Anaplastic Thyroid Cancer ◽  
Anaplastic Thyroid Carcinoma ◽  
Search Terms

BackgroundThere is a high unmet need for effective systemic treatment for patients with metastatic radioactive iodine refractory (RAI-R) differentiated thyroid cancer (DTC) and anaplastic thyroid cancer (ATC). Immunotherapy may be used as an alternative option for those without targetable mutations or have become resistant to targeted therapy. Here we review the clinical trials and retrospective studies and discuss the potential role of immune checkpoint inhibitors (ICIs) in advanced thyroid cancer.MethodsThe details of pertinent clinical trials were obtained from clinicaltrials.gov (NIH) using search terms including ‘thyroid cancer’ and ‘immunologic.’ The NCT numbers and search terms were used to search for published results on databases such as PubMed, American Association of Cancer Research, and American Society of Clinical Oncology. The efficacy outcome measures were determined using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.ResultsIn RAI-R DTC, responses to three different regimens have been reported: pembrolizumab, nivolumab plus ipilimumab, and pembrolizumab plus lenvatinib. No CR was reported, and the overall response rates (ORRs) varied from 9% (pembrolizumab monotherapy and nivolumab plus ipilimumab) to 64% (pembrolizumab plus lenvatinib) (figure 1a).1–4 In ATC, four studies have reported favorable outcomes in the context of dabrafenib and trametinib.5 The efficacy of spartalizumab, a PD1-inhibitor, was evaluated in a phase I/II trial, rendering an ORR of 19%, with 3 CRs (7%) and 5 PRs (12%) [6]. The study of nivolumab plus ipilimumab reported an ORR of 30% in ATC, with a near CR and two without clear evidence of disease at 13 and 26 months.2 A trial that tested the combination of atezolizumab, vemurafenib, and cobimetinib in BRAFV600E-mutated patients reported an ORR of 59%.7 A retrospective study reported an ORR of 60% after adding pembrolizumab at the time of progression on lenvatinib8 (figure 1b). There are 25 ongoing trials evaluating the efficacy of ICIs in different types of thyroid cancer. Three trials are testing pembrolizumab as monotherapy, three trials are assessing ICI combination therapy, and six trials are testing the efficacy of various ICI and tyrosine kinase inhibitor (TKI) combinations (figure 2).Abstract 204 Figure 1Comparison of responses in different regimens*The study population consisted only of BRAFV600E-positive patients**Retrospective studyAbbreviations: CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease; Uneval; unevaluable; PEM, pembrolizumab; IPI, ipilimumab; NIVO, nivolumab; LENV, lenvatinib; ATEZO, atezolizumab; VEM, vemurafenib; COBI, cobimetinib; DAB, dabrafenib; TRAME, trametinib.Abstract 204 Figure 2comparison of responses in different regimensA. Number of checkpoint inhibition trials for various thyroid cancer histologies. B. Landscape of combination checkpoint inhibition agents.Abbreviations: DTC, differentiated thyroid cancer; ATC, anaplastic thyroid cancer, MTC, medullary thyroid cancer; NIVO, nivolumab; IPI, ipilimumab; LENV, lenvatinib; ATEZO, atezolizumab; VEM, vemurafenib; COBI, cobimetinib, DAB, dabrafenib; TRAME, trametinib; PEM, pembrolizumab; DOXY, doxycycline; SBRT: Stereotactic radiation therapy.ConclusionsThe recent trials and a retrospective study have reported favorable outcomes in ATC, suggesting ICIs have a potential role in treating patients with ATC. In particular, dual ICIs or combination of TKI and ICI can be developed as treatment options for ATC. Further large scale randomized prospective studies are required to establish ICIs as standard of care.ReferencesMehnert JM, et al. Pembrolizumab for advanced papillary or follicular thyroid cancer: preliminary results from the phase 1b KEYNOTE-028 study. Journal of Clinical Oncology 2016; 34: 6091–6091.Lorch JH, et al. A phase II study of nivolumab (N) plus ipilimumab (I) in radioidine refractory differentiated thyroid cancer (RAIR DTC) with exploratory cohorts in anaplastic (ATC) and medullary thyroid cancer (MTC). Journal of Clinical Oncology38, no. 15_suppl (May 20, 2020) 6513–6513.Haugen B, et al. Lenvatinib plus pembrolizumab combination therapy in patients with radioiodine-refractory (RAIR), progressive differentiated thyroid cancer (DTC): Results of a multicenter phase II international thyroid oncology group trial. Journal of Clinical Oncology38, no. 15_suppl (May 20, 2020) 6512–6512.Schlumberger M, et al. Lenvatinib versus placebo in radioiodine-refractory thyroid cancer. N Engl J Med 2015; 372:621–30.Subbiah V, et al. Dabrafenib and Trametinib Treatment in Patients With Locally Advanced or Metastatic BRAF V600-Mutant Anaplastic Thyroid Cancer. Journal of Clinical Oncology 2018; 36:7–13.Capdevila J, et al. PD-1 Blockade in anaplastic thyroid carcinoma. Journal of Clinical Oncology38, no. 23 (August 10, 2020) 2620–2627.Cabanillas ME, et al. Atezolizumab combinations with targeted therapy for anaplastic thyroid carcinoma (ATC). Journal of Clinical Oncology 2020;38(15).Iyer PC, et al. Salvage pembrolizumab added to kinase inhibitor therapy for the treatment of anaplastic thyroid carcinoma. J Immunother Cancer 2018;6:68.

scholarly journals Current and Future Perspectives in Thyroid Carcinoma Treatment

2013 ◽  
Vol 09 (02) ◽  
pp. 171 ◽  
Author(s):  
José Manuel Gómez-Sáez ◽  
Keyword(s):  
Thyroid Cancer ◽  
Thyroid Carcinoma ◽  
Surgical Resection ◽  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
Clinical Problem ◽  
Needle Aspiration ◽  
Differentiated Thyroid Carcinoma ◽  
Anaplastic Thyroid Carcinoma ◽  
Adjuvant Chemoradiotherapy

Thyroid nodules are a common clinical problem and evaluation with neck and thyroid ultrasound and fine-needle aspiration biopsy are the most accurate methods for evaluating and identifying those that require surgical resection. The surgical treatment of differentiated thyroid carcinoma is the most common and recommended approach. Postoperative131I remnant ablation is used to eliminate the postsurgical thyroid remnant and may facilitate the early detection of recurrence. The conclusion of two important recent studies is that the use of recombinant human thyrotropin and low131I dose, 30 mCi, for postoperative ablation may be sufficient for the management of low-risk thyroid cancer. Recently, multitargeted kinase inhibitors have emerged as promising treatments for metastatic differentiated thyroid cancers based on mutation detection in samples from thyroid cancer. Motesanib, sorafenib, vandetanib, sunitinib, lenvatinib, imatinib, and cabozantinib are multikinase inhibitors that have the ability of inhibiting the rearranged during transection (RET) and vascular endothelial growth factor receptor (VEGFR), and other kinases, and have been used in advanced differentiated thyroid carcinoma. By contrast, axitinib and pazopanib seem to act only as anti-angiogenic agents. Anaplastic thyroid carcinoma is often advanced and metastatic at diagnosis. Patients with localized disease not amenable to surgical resection can be treated with adjuvant chemoradiotherapy.

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