Anaplastic Thyroid Cancer

2019 ◽  
Author(s):  
Geeta Lal
Keyword(s):  
Thyroid Cancer ◽  
Kinase Inhibitors ◽  
Braf Inhibitor ◽  
Anaplastic Thyroid Cancer ◽  
Mek Inhibitor ◽  
Braf V600e ◽  
Multidisciplinary Teams ◽  
Neoadjuvant Radiotherapy ◽  
Current State ◽  
Targeted Treatments

Anaplastic thyroid cancer (ATC) is a rare thyroid malignancy with a nearly uniform poor prognosis. Most patients present with advanced disease, and optimal management requires rapid diagnosis, staging, and involvement of multidisciplinary teams. Treatment may include surgery in patients with resectable disease and adjuvant or neoadjuvant radiotherapy and chemotherapy. Improved understanding of molecular pathogenesis has allowed the assessment of tyrosine kinase inhibitors and other targeted treatments in these patients.  The FDA recently approved the combination of dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor) for the treatment of BRAF V600E mutation positive, unresectable or metastatic ATC. This review summarizes the current state-of-the-art concepts in the management of patients with ATC. This review contains 3 figures, 2 tables, and 25 references. Key words: anaplastic thyroid cancer, goals of care discussion, management, surgery, radiotherapy, chemotherapy novel therapies, NCCN and ATA guidelines

Anaplastic Thyroid Cancer

2019 ◽  
Author(s):  
Geeta Lal
Keyword(s):  
Thyroid Cancer ◽  
Kinase Inhibitors ◽  
Braf Inhibitor ◽  
Anaplastic Thyroid Cancer ◽  
Mek Inhibitor ◽  
Braf V600e ◽  
Multidisciplinary Teams ◽  
Neoadjuvant Radiotherapy ◽  
Current State ◽  
Targeted Treatments

Anaplastic thyroid cancer (ATC) is a rare thyroid malignancy with a nearly uniform poor prognosis. Most patients present with advanced disease, and optimal management requires rapid diagnosis, staging, and involvement of multidisciplinary teams. Treatment may include surgery in patients with resectable disease and adjuvant or neoadjuvant radiotherapy and chemotherapy. Improved understanding of molecular pathogenesis has allowed the assessment of tyrosine kinase inhibitors and other targeted treatments in these patients.  The FDA recently approved the combination of dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor) for the treatment of BRAF V600E mutation positive, unresectable or metastatic ATC. This review summarizes the current state-of-the-art concepts in the management of patients with ATC. This review contains 3 figures, 2 tables, and 25 references. Key words: anaplastic thyroid cancer, goals of care discussion, management, surgery, radiotherapy, chemotherapy novel therapies, NCCN and ATA guidelines

scholarly journals Salutary Response to Targeted Therapy in Anaplastic Thyroid Cancer

2019 ◽  
Vol 7 ◽  
pp. 232470961989094 ◽  
Author(s):  
Sasan Fazeli ◽  
Edina Paal ◽  
Jessica H. Maxwell ◽  
Kenneth D. Burman ◽  
Eric S. Nylen ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Targeted Therapy ◽  
Side Effects ◽  
Combination Therapy ◽  
Braf Inhibitor ◽  
Anaplastic Thyroid Cancer ◽  
Mek Inhibitor ◽  
Braf V600e ◽  
Aggressive Tumor ◽  
Well Differentiated

Context. Anaplastic thyroid cancer (ATC) is an aggressive tumor with a median survival of 3 to 9 months, a 1-year survival of less than 10% and without definitive therapies. Recently, in BRAF V600E mutated ATCs, new targeted therapy using a combination of a BRAF inhibitor, dabrafenib (Dab), with a mitogen-activated extracellular protein kinase (MEK) inhibitor, trametinib (Tram), has shown significant promise. Case Description. We report a case of aggressive ATC with 5 sequence mutations: BRAF V600E (mutation fraction [MF] 34%), TERT E441del (MF 37%), RET N579K (MF 55%), EZH2 D154E (MF 60%), and CDK4 S259L (MF 48%). The patient had a dramatic response to the Dab/Tram combination with near complete resolution of his lung, bone, hepatic, and splenic lesions soon after starting therapy. Unfortunately, intolerable side effects (grade 2-3) on this regimen required tapering and discontinuation of the treatment. He had a quick resurgence of disease after stopping the combination therapy. The patient died approximately 3 months after discontinuing Dab/Tram. Autopsy revealed an atrophic thyroid gland with microscopic subcapsular focus of well-differentiated papillary thyroid carcinoma. There was extensive lymphatic spread of the tumor throughout bilateral lungs with fibrosis. No other metastatic site was identified. Conclusion. We report a unique case of ATC with 2 new mutations of EZH2 D154E and CDK S529L. This case exemplifies the significant promise Dab/Tram therapy holds, the potential side effects that limit their use, and autopsy findings status post use of this combination therapy.

Efficacy of dabrafenib (D) and trametinib (T) in patients (pts) with BRAF V600E–mutated anaplastic thyroid cancer (ATC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 6023-6023 ◽  
Author(s):  
Vivek Subbiah ◽  
Robert J. Kreitman ◽  
Zev A. Wainberg ◽  
Jae Yong Cho ◽  
Jan H.M. Schellens ◽  
...  
Keyword(s):  
Metastatic Cancer ◽  
Treatment Options ◽  
Braf Inhibitor ◽  
Progression Free Survival ◽  
Credible Interval ◽  
Anaplastic Thyroid Cancer ◽  
Mek Inhibitor ◽  
Braf V600e ◽  
Open Label ◽  
Dismal Prognosis

6023 Background: ATC is a rare, aggressive malignancy with a dismal prognosis. Median overall survival (OS) is < 6 mo. Combined BRAF and MEK inhibition is efficacious in BRAF V600–mutated melanoma and lung cancer. One-fourth of ATCs harbor activating BRAF V600E mutations; thus, D (BRAF inhibitor) + T (MEK inhibitor) was evaluated as a treatment for pts with BRAF V600E–mutated ATC. Methods: In this phase 2, open-label trial (NCT02034110), pts with BRAF V600E mutations in 9 rare tumor types, including ATC, received continuous D (150 mg BID) + T (2 mg QD) until unacceptable toxicity, disease progression, or death. Eligible pts had advanced or metastatic cancer with no standard-of-care treatment options. The primary endpoint was investigator-assessed overall response rate (ORR). Secondary endpoints included duration of response (DOR), progression-free survival (PFS), OS, and safety. We report data from the ATC cohort. Results: 16 pts with BRAF V600E–mutated ATC had evaluable data with a median follow-up time of 47 wk (range 4-120 wk). BRAF V600E mutations were centrally confirmed in 15/16 pts. Median age was 72 y; all 16 pts had undergone prior tumor radiation and/or surgery and 6/16 pts (38%) had received ≥1 prior line of systemic therapy. Investigator-assessed confirmed ORR was 69% (11/16; 95% CI, 41%-89%), with 7/11 responses ongoing at the time of data cut. The Bayesian estimate of ORR was 69% (95% credible interval, 47%-87%) with a 100% probability that this ORR exceeded the 15% historical RR. Median DOR, PFS, and OS were not estimable due to insufficient progression and death events. Kaplan-Meier estimates of DOR, PFS, and OS at 12 mo were 90%, 79%, and 80%, respectively. The safety population comprised 100 pts enrolled in 7/9 histologies. Among all pts, 92% had an AE. Common AEs of any grade for all histologies were fatigue (38%), pyrexia (37%), and nausea (35%). In the ATC cohort, the most common grade 3/4 events were hyponatremia (19%), pneumonia (13%), and anemia (13%). Conclusions: D+T combination therapy significantly improved outcomes in ATC with a favorable safety profile. This regimen represents a clinically meaningful therapeutic advance for pts with advanced/metastatic BRAF V600–mutated ATC. Clinical trial information: NCT02034110.

scholarly journals Updates on the Management of Thyroid Cancer

2020 ◽  
Vol 52 (08) ◽  
pp. 562-577 ◽  
Author(s):  
Katherine A. Araque ◽  
Sriram Gubbi ◽  
Joanna Klubo-Gwiezdzinska
Keyword(s):  
Thyroid Cancer ◽  
Kinase Inhibitors ◽  
Treatment Options ◽  
Anaplastic Thyroid Cancer ◽  
Braf V600e ◽  
Treatment Modalities ◽  
American Thyroid Association ◽  
Novel Treatment ◽  
High Risk Disease ◽  
Diagnostic Modalities

AbstractThe diagnostic modalities, stratification tools, and treatment options for patients with thyroid cancer have rapidly evolved since the development of the American Thyroid Association (ATA) guidelines in 2015. This review compiles newer concepts in diagnosis, stratification tools and treatment options for patients with differentiated thyroid cancer (DTC), medullary thyroid carcinoma (MTC) and anaplastic thyroid cancer (ATC). Newer developments apply precision medicine in thyroid cancer patients to avoid over-treatment in low risk disease and under-treatment in high risk disease. Among novel patient-tailored therapies are selective RET inhibitors that have shown efficacy in the treatment of MTC with limited systemic toxicity compared with non-specific tyrosine kinase inhibitors. The combination of BRAF and MEK inhibitors have revolutionized management of BRAF V600E mutant ATC. Several immunotherapeutic agents are being actively investigated in the treatment of all forms of thyroid cancer. In this review, we describe the recent advances in the diagnosis and management of DTC, MTC, and ATC, with an emphasis on novel treatment modalities.

scholarly journals Evolution of anaplastic thyroid cancer management: perspectives in the era of precision oncology

2021 ◽  
Vol 12 ◽  
pp. 204201882110546
Author(s):  
Sarimar Agosto Salgado
Keyword(s):  
Thyroid Cancer ◽  
Kinase Inhibitors ◽  
Anaplastic Thyroid Cancer ◽  
Mek Inhibitor ◽  
Molecular Testing ◽  
Precision Oncology ◽  
Cancer Management ◽  
First Line Therapy ◽  
Poor Outcomes ◽  
Personalized Cancer

Anaplastic thyroid cancer is a rare aggressive malignancy resulting in poor outcomes, including significant morbidity and mortality. Historically, the overall survival of patients with anaplastic thyroid cancer has been less than 12 months. Multidisciplinary approaches combining surgery, radiation, and chemotherapy have been implemented to control this ominous disease. The evolution in science and technology has promoted deeper knowledge in the genetic pathways and mechanisms driving advance thyroid cancer. Furthermore, understanding molecular pathways resulted in the application of antineoplastic agents used in other tumors to thyroid cancer and the development of new highly selective drugs. A major landmark in anaplastic thyroid cancer management history was recently reached with the approval of BRAF and MEK inhibitor combination, specifically dabrafenib and trametinib for BRAF-mutated anaplastic thyroid cancer; this treatment has improved survival and outcomes in this population. Similarly, newer kinase inhibitors and immunotherapy are further shifting advanced thyroid cancer management to consider as first-line therapy inhibiting actionable oncogenic alterations. Therefore, newer treatment paradigms are incorporating molecular testing to provide personalized cancer care in anaplastic thyroid cancer. In this review, the principal aim is to provide an overview of the available international data on tyrosine kinase inhibitors and immunotherapy in the management of anaplastic thyroid cancer.

scholarly journals A case report of anaplastic thyroid cancer and papillary thyroid cancer lymph node metastasis: An unusual presentation as an invasive hypopharyngeal mass

2021 ◽  
Author(s):  
Veena Vishwanath ◽  
Nichola Gaunt ◽  
Durgesh Rana ◽  
Dominic St Leger ◽  
Michael Dykes ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Lymph Node ◽  
Papillary Thyroid Cancer ◽  
Cancer Metastasis ◽  
Braf Inhibitor ◽  
Anaplastic Thyroid Cancer ◽  
Unusual Presentation ◽  
Braf V600e ◽  
Papillary Thyroid ◽  
Dismal Prognosis

Anaplastic thyroid carcinoma is a rare undifferentiated tumour of the thyroid follicular epithelium. It almost always develops from a pre-existing well-differentiated thyroid cancer with a co-existent thyroid malignancy varying from 5-17% . The co-existence of papillary thyroid cancer (PTC) with anaplastic thyroid cancer is a rare occurrence in metastases outside the primary thyroid lesion. Traditionally, this has been regarded as an aggressive form of cancer associated with a dismal prognosis. Recently the focus has shifted to the development of novel therapies based on the availability of comprehensive genomic profiling platforms (CGP) with a rapid turn-around to identify molecular aberrations in tumours which acts as potential therapeutic targets. In the United Kingdom, we report the case of a 60-year old woman with an unusual presentation of (metastatic) ATC and concomitant papillary thyroid cancer metastasis within a contralateral lymph node. This was initially perceived as a left pyriform fossa mass involving and compressing her left hemi-larynx on clinical and radiological examination. Following the identification of BRAF V600E mutation on CGP, she was started on targeted therapy with the BRAF inhibitor dabrafenib and the MEK inhibitor trametinib and demonstrated excellent clinical and radiological response following 7 months of treatment. She has subsequently undergone total thyroidectomy alongside with bilateral neck dissection, and is due to start radio-active iodine treatment to reduce the risk of recurrence of disease.

scholarly journals Updated efficacy and safety data of dabrafenib (D) and trametinib (T) in patients (pts) with BRAF V600E–mutated anaplastic thyroid cancer (ATC)

2018 ◽  
Vol 29 ◽  
pp. viii645-viii646 ◽  
Author(s):  
B. Keam ◽  
R.J. Kreitman ◽  
Z.A. Wainberg ◽  
M.E. Cabanillas ◽  
D.C. Cho ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Safety Data ◽  
Anaplastic Thyroid Cancer ◽  
Braf V600e ◽  
Efficacy And Safety
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