scholarly journals Treatment of advanced thyroid cancer with targeted therapies: ten years of experience

2016 ◽  
Vol 23 (4) ◽  
pp. R185-R205 ◽  
Author(s):  
David Viola ◽  
Laura Valerio ◽  
Eleonora Molinaro ◽  
Laura Agate ◽  
Valeria Bottici ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Targeted Therapies ◽  
Kinase Inhibitors ◽  
Survival Rates ◽  
Current Status ◽  
Thyroid Cancers ◽  
Poorly Differentiated ◽  
Advanced Thyroid Cancer ◽  
Well Differentiated ◽  
Differentiated Thyroid Cancers

AbstractThyroid cancer is rare, but it is the most frequent endocrine malignancy. Its prognosis is generally favorable, especially in cases of well-differentiated thyroid cancers (DTCs), such as papillary and follicular cancers, which have survival rates of approximately 95% at 40 years. However, 15–20% of cases became radioiodine refractory (RAI-R), and until now, no other treatments have been effective. The same problems are found in cases of poorly differentiated (PDTC) and anaplastic (ATC) thyroid cancers and in at least 30% of medullary thyroid cancer (MTC) cases, which are very aggressive and not sensitive to radioiodine. Tyrosine kinase inhibitors (TKIs) represent a new approach to the treatment of advanced cases of RAI-R DTC, MTC, PDTC, and, possibly, ATC. In the past 10 years, several TKIs have been tested for the treatment of advanced, progressive, and RAI-R thyroid tumors, and some of them have been recently approved for use in clinical practice: sorafenib and lenvatinib for DTC and PDTC and vandetanib and cabozantinib for MTC. The objective of this review is to present the current status of the treatment of advanced thyroid cancer with the use of innovative targeted therapies by describing both the benefits and the limits of their use based on the experiences reported so far. A comprehensive analysis and description of the molecular basis of these therapies, as well as new therapeutic perspectives, are reported. Some practical suggestions are given for both the choice of patients to be treated and their management, with particular regard to the potential side effects.

scholarly journals Prognostic and Therapeutic Role of Angiogenic Microenvironment in Thyroid Cancer

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2775
Author(s):  
Assunta Melaccio ◽  
Lucia Ilaria Sgaramella ◽  
Alessandro Pasculli ◽  
Giovanna Di Meo ◽  
Angela Gurrado ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Kinase Inhibitors ◽  
Cell Cycle Control ◽  
Current Status ◽  
Thyroid Cancers ◽  
Angiogenic Switch ◽  
Poorly Differentiated ◽  
Differentiated Thyroid Cancers ◽  
Disease Understanding

Thyroid cancer is the most common endocrine malignancy, with a typically favorable prognosis following standard treatments, such as surgical resection and radioiodine therapy. A subset of thyroid cancers progress to refractory/metastatic disease. Understanding how the tumor microenvironment is transformed into an angiogenic microenvironment has a role of primary importance in the aggressive behavior of these neoplasms. During tumor growth and progression, angiogenesis represents a deregulated biological process, and the angiogenic switch, characterized by the formation of new vessels, induces tumor cell proliferation, local invasion, and hematogenous metastases. This evidence has propelled the scientific community’s effort to study a number of molecular pathways (proliferation, cell cycle control, and angiogenic processes), identifying mediators that may represent viable targets for new anticancer treatments. Herein, we sought to review angiogenesis in thyroid cancer and the potential role of proangiogenic cytokines for risk stratification of patients. We also present the current status of treatment of advanced differentiated, medullary, and poorly differentiated thyroid cancers with multiple tyrosine kinase inhibitors, based on the rationale of angiogenesis as a potential therapeutic target.

scholarly journals Thyroid Cancers: From Surgery to Current and Future Systemic Therapies through Their Molecular Identities

2021 ◽  
Vol 22 (6) ◽  
pp. 3117
Author(s):  
Loredana Lorusso ◽  
Virginia Cappagli ◽  
Laura Valerio ◽  
Carlotta Giani ◽  
David Viola ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Kinase Inhibitors ◽  
Therapeutic Option ◽  
Progression Free Survival ◽  
Thyroid Cancers ◽  
Poorly Differentiated ◽  
Differentiated Thyroid Cancers ◽  
Approved Drugs ◽  
New Generation ◽  
Systemic Therapies

Differentiated thyroid cancers (DTC) are commonly and successfully treated with total thyroidectomy plus/minus radioiodine therapy (RAI). Medullary thyroid cancer (MTC) is only treated with surgery but only intrathyroidal tumors are cured. The worst prognosis is for anaplastic (ATC) and poorly differentiated thyroid cancer (PDTC). Whenever a local or metastatic advanced disease is present, other treatments are required, varying from local to systemic therapies. In the last decade, the efficacy of the targeted therapies and, in particular, tyrosine kinase inhibitors (TKIs) has been demonstrated. They can prolong the disease progression-free survival and represent the most important therapeutic option for the treatment of advanced and progressive thyroid cancer. Currently, lenvatinib and sorafenib are the approved drugs for the treatment of RAI-refractory DTC and PDTC while advanced MTC can be treated with either cabozantinib or vandetanib. Dabrafenib plus trametinib is the only approved treatment by FDA for BRAFV600E mutated ATC. A new generation of TKIs, specifically for single altered oncogenes, is under evaluation in phase 2 and 3 clinical trials. The aim of this review was to provide an overview of the current and future treatments of thyroid cancer with regards to the advanced and progressive cases that require systemic therapies that are becoming more and more targeted on the molecular identity of the tumor.

scholarly journals What's New in Molecular Targeted Therapies for Thyroid Cancer?

2021 ◽  
Vol 37 (2) ◽  
pp. 1-9
Author(s):  
Seonyoung Min ◽  
Hyunseok Kang
Keyword(s):  
Thyroid Cancer ◽  
Targeted Therapies ◽  
Radioactive Iodine ◽  
Checkpoint Inhibitors ◽  
Braf V600e Mutation ◽  
Braf V600e ◽  
Thyroid Cancers ◽  
Ret Mutation ◽  
Poorly Differentiated ◽  
Differentiated Thyroid Cancers

Thyroid cancer refers to various cancers arising from thyroid gland. Differentiated thyroid cancers (DTCs) include papillary, follicular, and Hurthle cell carcinomas and represent cancers retain normal thyroid functions such as iodine uptake. Radioactive iodine (RAI) is generally used for upfront treatment of metastatic DTCs, but RAI refractory DTCs remain to be clinical challenges. Sorafenib and lenvatinib were approved for the treatment of RAI refractory DTCs and more recently, genomics-based targeted therapies have been developed for NTRK and RET gene fusion-positive DTCs. Poorly differentiated and anaplastic thyroid cancers (ATCs) are extremely challenging diseases with aggressive courses. BRAF/MEK inhibition has been proven to be highly effective in BRAF V600E mutation-positive ATCs and immune checkpoint inhibitors have shown promising activities. Medullary thyroid cancers, which arise from parafollicular cells of thyroid, represent a unique subset of thyroid cancer and mainly driven by RET mutation. In addition to vandetanib and cabozantinib, highly specific RET inhibitors such as selpercatinib and pralsetinib have demonstrated impressive activity and are in clinical use.

scholarly journals Immune responses in the thyroid cancer microenvironment: making immunotherapy a possible mission

2017 ◽  
Vol 24 (12) ◽  
pp. T311-T329 ◽  
Author(s):  
Robert C Mould ◽  
Jacob P van Vloten ◽  
Amanda W K AuYeung ◽  
Khalil Karimi ◽  
Byram W Bridle
Keyword(s):  
Thyroid Cancer ◽  
Immune System ◽  
Treatment Options ◽  
Survival Rates ◽  
Standard Of Care ◽  
Cancer Microenvironment ◽  
Current Standard ◽  
Thyroid Cancers ◽  
Hormonal Modulation ◽  
Differentiated Thyroid Cancers

The incidence of thyroid cancers has been steadily increasing worldwide over the past few decades. Although five-year survival rates for differentiated thyroid cancers are upwards of 90%, clinical outcomes for patients with undifferentiated, recurrent and/or metastatic disease are often dismal despite conventional interventions. As such, there is a demand for novel treatment options. Cancer immunotherapy represents the ultimate form of personalized medicine by leveraging the specificity and potency of a patient’s immune system to kill their tumor. The thyroid cancer microenvironment is rich in immunological cells, making it a reasonable candidate for immunotherapy. This review maps out the immunological features of thyroid cancers and how these can be modulated. There are surprising immunological consequences of conventional therapies that demand attention. Also, hormonal modulation of the immune system is highlighted as a unique and confounding feature of thyroid cancers. A variety of cutting-edge immune-based therapies are discussed, with an emphasis placed on how these can be integrated with the current standard of care. Several high priority areas in need of research are also highlighted.

scholarly journals Unusual Presentation of Differentiated Thyroid Cancer Metastasis

2017 ◽  
Vol 22 (02) ◽  
pp. 167-170 ◽  
Author(s):  
Haissan Iftikhar ◽  
Mubasher Ikram ◽  
Adnan Muhammad ◽  
Karim Nathani
Keyword(s):  
Thyroid Cancer ◽  
Distant Metastasis ◽  
Differentiated Thyroid Cancer ◽  
Cancer Metastasis ◽  
Treatment Protocol ◽  
Neck Of Femur ◽  
Thyroid Cancers ◽  
Well Differentiated ◽  
Differentiated Thyroid Cancers ◽  
Histopathology Exam

Introduction The rates of thyroid cancers are on a rise, especially well-differentiated thyroid cancers. This could be partly due to newer diagnostic modalities, like high-resolution ultrasound, that can pick up smaller lesions. Differentiated thyroid cancers with distant metastases are not common, and even rarer is the initial presentation with complaints not related to the neck. Objectives The objective of this series was to study and report the unusual cases of patients with differentiated thyroid cancer with distant metastasis. There is a lack of data in the literature on these cases, and due to the rarity of such metastases, no definite treatment protocol has been defined. Methods A retrospective chart review of 1,200 cases of thyroid surgeries was performed. A total of 10 cases of well-differentiated thyroid cancer on the final histopathology exam that had initially presented with usual complaints to departments other than the Otolaryngology Department were identified. Results A total of 6 patients had papillary carcinoma, whereas 4 patients had follicular carcinoma on final the histopathology exam. Two patients presented with iliac crest lesions, 2 with vertebral lesions one each with parapharyngeal mass, supraclavicular mass, labia majora swelling and bleeding, lung, rib and neck of femur lesion. Conclusion There are still no specific guidelines on how to address these patients with differentiated thyroid cancer with distant metastasis (except for the cases of bone and lung lesions) and on which treatment should be offered in case of recurrence. More studies on the subject are required.

Thyroid cancer

2018 ◽  
Vol 11 (4) ◽  
pp. 212-217
Author(s):  
Jonathan Mills ◽  
William Dalleywater
Keyword(s):  
Thyroid Cancer ◽  
Mortality Rate ◽  
Poor Prognosis ◽  
Survival Rates ◽  
Thyroid Neoplasms ◽  
Thyroid Cells ◽  
Endocrine Differentiation ◽  
Poorly Differentiated ◽  
Well Differentiated ◽  
The Uk

Thyroid neoplasms represent the most-common endocrine tumour and constitute an extremely varied spectrum of disease. At the most severe end, they may have a very poor prognosis. Malignant thyroid tumours constitute around 1% of cancers and cancer-specific deaths in the UK, with just under 3000 new diagnoses each year and around 350 deaths annually in the UK alone. Although the incidence has doubled over the last 20 years, the mortality rate among men has not changed, although survival rates have improved in women. Thyroid cancer originates from follicular or parafollicular thyroid cells that can give rise to cancer that is well-differentiated to poorly differentiated. Most tumours retain endocrine differentiation, however, and may cause problematic symptoms from aberrant hormone levels.

scholarly journals Foundation One Genomic Interrogation of Thyroid Cancers in Patients With Metastatic Disease Requiring Systemic Therapy

2020 ◽  
Vol 105 (7) ◽  
pp. e2346-e2357 ◽  
Author(s):  
Nicole M Iñiguez-Ariza ◽  
Sina Jasim ◽  
Mabel M Ryder ◽  
Ashish V Chintakuntlawar ◽  
John C Morris ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Outcome Measures ◽  
Systemic Therapy ◽  
Radioactive Iodine ◽  
Patient Characteristics ◽  
Genomic Alterations ◽  
Epithelial Tumor ◽  
Thyroid Cancers ◽  
Poorly Differentiated ◽  
Differentiated Thyroid Cancers

Abstract Context Clinical applications of genomic assessment of thyroid cancers are rapidly evolving. Objectives, Design, and Setting We studied tumor samples from patients with imminently threatening and rare thyroid cancers to identify genomic alterations that might correlate with outcomes and/or be productively therapeutically targetable. Patient Context Progressive and metastatic, and/or rare, thyroid cancers were studied, 2012 to 2016, at Mayo Clinic sites. Intervention The intervention was Foundation One tumor interrogation. Main Outcome Measures Main outcome measures included genomic alterations, patient characteristics, and overall survival. Results Samples from 55 patients were evaluated: 20 anaplastic thyroid cancers (ATCs) (36%), 25 radioactive iodine–refractory differentiated thyroid cancers (DTCs)/poorly differentiated thyroid cancers (PDTCs) (45%; 14 papillary thyroid cancer [PTCs], 6 PDTCs, 5 Hürthle cell cancers), 8 medullary thyroid cancers (MTCs) (15%), and 2 others (a spindle epithelial tumor with thymus-like differentiation, and a primary thyroid sarcoma). Overall, 72% of DTCs, 79% of ATCs, and 75% of MTCs were deemed to have potentially productively targetable alterations. The most commonly encountered mutation was of TERT promoter (56% of DTCs, 68% of ATCs)—but this is not presently targetable. Targetable BRAFV600E mutations were found in 40% of DTCs/PDTCs (83% of PTCs) and 32% of ATCs; of MTCs, 75% had targetable RET mutations, and 25% HRAS mutations. Of patient tumors with nonmutated BRAFV600E, 53% of DTC/PDTCs and 69% of ATCs had other potentially productively targetable mutations. Genomic alterations in our series of poor prognosis metastatic DTC/PDTCs also closely resembled those seen in ATC. Conclusions Whereas genomic interrogation of favorable prognosis thyroid cancer seems ill advised, potentially productively targetable mutations were demonstrated in the majority of tumors from patients with metastatic thyroid cancers requiring systemic therapy, suggesting a rationale for the selective application of this technology.

scholarly journals MON-502 Clinical-Pathological and Molecular Prognostic Markers in Aggressive and Poorly Differentiated Thyroid Cancers; A Tertiary-Center Experience

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Suhaib Radi ◽  
Sabin Filimon ◽  
Michael Tamilia
Keyword(s):  
Thyroid Cancer ◽  
Vascular Invasion ◽  
Prognostic Markers ◽  
Recurrent Disease ◽  
Primary Therapy ◽  
Tumor Involvement ◽  
Poorly Differentiated ◽  
Well Differentiated ◽  
Differentiated Thyroid Cancers

Abstract Background: Aggressive variants of papillary thyroid cancer (AV-PTC) and poorly differentiated thyroid cancers (PDTC) are 2 malignancies that lie in between the well-differentiated and the undifferentiated anaplastic cancers. While management of those well-differentiated cancers is established in the literature, that of AV-PTC and PDTC is less clear as they behave different to their more benign counterparts. The aim of this study is to describe the clinico-pathologic characteristics and genotypic background of AV-PTC and PDTC and to assess their prognostic value. Methods: The charts of all patients with thyroid cancer in our center for the last 10 years were retrospectively reviewed. Those with AV-PTC and PDTC were selected and included in the analysis. Clinical presentation, pathologic characteristics, molecular markers, specific treatments and clinical outcomes were compared among groups. Results: Out of 3244 thyroid cancer charts reviewed, 87 patients met the criteria for AV-PTC (n=45) and PDTC (n=42). Mean age at diagnosis was 48.1 years (SD 17.8), with female predominance (64.4% vs 35.6%). Median duration of follow up was 3 years (0.1-30). Out of the 75 patients with follow up for more than a year, 42.7% had either persistent disease or recurrence (52.6% in AV-PTC and 32.4% in PDTC) and 4.1% died. Presence of vascular invasion was associated with higher rates of persistent or recurrent disease (74.1% in positive vascular invasion vs 20.5% in negative vascular invasion, p < 0.001). Recurrence rate was 0% in patients with Ki67 < 10% and 40% in those >= 10%. There was no difference in terms of recurrence based on presence of BRAF mutation (33% in BRAF+ & 29% in BRAF-, p=1), or percentage of aggressive/poorly differentiated tumor involvement (48% in > 30% involvement vs 28% in < 30%, p = 0.132). Discussion and conclusion: The prevalence of AV-PTC and PDTC in this cohort was low at 1.3% each, and the rate of patients with persistent or recurrent disease at 1 year after primary therapy was also similar to that reported (42.7%). The mortality rates, however, in our study is surprisingly lower than that expected elsewhere (4.1%), most likely attributed to a shorter follow up period. Patients with absent vascular invasion were less likely to have persistent or recurrent disease. Those with lower Ki67 (<10%) also had lower relapse rate, although, the p value was > 0.05. It is worth mentioning that even though there were higher rates of recurrence among those with > 30% tumor involvement, it did not reach statistical significance, supporting recent studies stating that even tumor involvement of > 10% can have adverse outcomes. In conclusion, AV-PTC and PDTC are relatively rare but aggressive tumors. Possible prognostic markers that can be used to guide therapy and monitoring include: vascular invasion, extra-thyroidal extension, response to primary therapy and the proliferative index Ki67.

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