scholarly journals Pembrolizumab in a Patient with Treatment-Naïve Unresectable BRAF-Mutation Negative Anaplastic Thyroid Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-5
Author(s):  
Fadi Nabhan ◽  
Elizabeth Kander ◽  
Rulong Shen ◽  
Amit Agrawal ◽  
Vineeth Sukrithan ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Standard Of Care ◽  
Distant Metastases ◽  
Anaplastic Thyroid Cancer ◽  
Needle Aspiration ◽  
Neck Mass ◽  
Braf V600e ◽  
Durable Response ◽  
Treatment Naïve ◽  
Immune Check Point Inhibitor

Immune check point inhibitor (ICI) therapy can be a potentially effective salvage treatment for anaplastic thyroid cancer (ATC) with progression despite standard of care therapies. We report a case of unresectable treatment-naïve ATC showing a dramatic and durable response to first-line pembrolizumab therapy. A 69-year-old male presented with a large, right-sided neck mass associated with compressive symptoms. A neck ultrasound showed a large, right-sided, and highly suspicious thyroid nodule. A fine needle aspiration (FNA) biopsy revealed tumor cells consistent with ATC that were positive for PD-L1, with an expression score of >95% and negative for the BRAF V600E mutation. Imaging studies were negative for distant metastases. The disease was declared surgically inoperable, and the patient declined chemotherapy/radiation therapy (XRT), but agreed to ICI therapy with intravenous pembrolizumab 200 mg every three weeks. The patient has received 25 doses of pembrolizumab to date, with rapid resolution of symptoms and a significant reduction in tumor size. He remains alive without disease progression 18 months since initial diagnosis.

Molecular Diagnostics of Thyroid Tumors

2011 ◽  
Vol 135 (5) ◽  
pp. 569-577 ◽  
Author(s):  
Yuri E. Nikiforov
Keyword(s):  
Thyroid Cancer ◽  
Molecular Markers ◽  
Fine Needle Aspiration ◽  
Thyroid Nodules ◽  
Needle Aspiration ◽  
Genetic Alterations ◽  
Braf V600e ◽  
Fine Needle ◽  
Molecular Alterations ◽  
Diagnostic Use

Abstract Context.—Thyroid cancer is the most common type of endocrine malignancy and its incidence is steadily increasing. Papillary carcinoma and follicular carcinoma are the most common types of thyroid cancer and represent those tumor types for which use of molecular markers for diagnosis and prognostication is of high clinical significance. Objective.—To review the most common molecular alterations in thyroid cancer and their diagnostic and prognostic utility. Data Sources.—PubMed (US National Library of Medicine)–available review articles, peer-reviewed original articles, and experience of the author. Conclusions.—The most common molecular alterations in thyroid cancer include BRAF and RAS point mutations and RET/PTC and PAX8/PPARγ rearrangements. These nonoverlapping genetic alterations are found in more than 70% of papillary and follicular thyroid carcinomas. These molecular alterations can be detected in surgically resected samples and fine-needle aspiration samples from thyroid nodules and can be of significant diagnostic use. The diagnostic role of BRAF mutations has been studied most extensively, and recent studies also demonstrated a significant diagnostic utility of RAS, RET/PTC, and PAX8/PPARγ mutations, particularly in thyroid fine-needle aspiration samples with indeterminate cytology. In addition to the diagnostic use, BRAF V600E mutation can also be used for tumor prognostication, as this mutation is associated with higher rate of tumor recurrence and tumor-related mortality. The use of these and other emerging molecular markers is expected to improve significantly the accuracy of cancer diagnosis in thyroid nodules and allow more individualized surgical and postsurgical management of patients with thyroid cancer.

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

scholarly journals Antineoplastic Effect of Lenvatinib and Vandetanib in Primary Anaplastic Thyroid Cancer Cells Obtained From Biopsy or Fine Needle Aspiration

2018 ◽  
Vol 9 ◽  
Author(s):  
Silvia Martina Ferrari ◽  
Concettina La Motta ◽  
Giusy Elia ◽  
Francesca Ragusa ◽  
Ilaria Ruffilli ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Cancer Cells ◽  
Fine Needle Aspiration ◽  
Anaplastic Thyroid Cancer ◽  
Needle Aspiration ◽  
Fine Needle ◽  
Antineoplastic Effect ◽  
Thyroid Cancer Cells

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.

scholarly journals Adrenal metastasis as the initial diagnosis of synchronous papillary and follicular thyroid cancer

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Xin He ◽  
Scott A. Soleimanpour ◽  
Gregory A. Clines
Keyword(s):  
Thyroid Cancer ◽  
Thyroid Nodules ◽  
Follicular Thyroid Carcinoma ◽  
Distant Metastases ◽  
Needle Aspiration ◽  
Left Lobe ◽  
Adrenal Metastasis ◽  
Bethesda Classification ◽  
The Right

Abstract Background Differentiated thyroid cancer uncommonly presents with distant metastases. Adrenal metastasis from differentiated thyroid cancer presenting as the initial finding is even less common. Case Presentation A 71-year-old male was incidentally found on chest CT to have bilateral thyroid nodules, which were confirmed on ultrasound. Fine needle aspiration of the dominant right 3.3 cm nodule contained histologic features most consistent with Bethesda classification III, and repeat fine needle aspiration revealed pathology consistent with Bethesda classification II. Follow-up thyroid ultrasound showed 1% increase and 14% increase in nodule volume at one and two years, respectively, compared to baseline. Prior to the second annual thyroid ultrasound, the patient was incidentally found to have a 4.1 cm heterogeneously enhancing mass in the right adrenal gland on CT of the abdomen and pelvis. Biochemical evaluation was unremarkable with the exception of morning cortisol of 3.2 µg/dL after dexamethasone suppression. The patient then underwent laparoscopic right adrenal gland excision, which revealed metastatic follicular thyroid carcinoma. Total thyroidectomy was then performed, with pathology showing a 4.8 cm well-differentiated follicular thyroid carcinoma of the right lobe, a 0.5 cm noninvasive follicular thyroid neoplasm with papillary-like nuclear features of the left lobe, and a 0.1 cm papillary microcarcinoma of the left lobe. Thyrotropin-stimulated whole body scan showed normal physiologic uptake of the remnant thyroid tissue without evidence of other iodine avid disease. The patient then received radioactive iodine. At follow-up 14 months after total thyroidectomy, he remains free of recurrent disease. Conclusion Despite following the recommended protocol for evaluation and surveillance of thyroid nodules, thyroid cancer can be challenging to diagnose, and may not be diagnosed until distant metastases are identified.

scholarly journals A Case of Thyroid Papillary Carcinoma: Remarkable Decrease in Multiple Lung Metastases within 40 Years after a Single Administration of Radioiodine without Thyroidectomy and with Later Anaplastic Transformation

2017 ◽  
Vol 10 (3) ◽  
pp. 928-937 ◽  
Author(s):  
Chio Okuyama ◽  
Mitsuhiro Kimura ◽  
Minori Oda ◽  
Naohiro Kodani ◽  
Norihiro Aibe ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Total Thyroidectomy ◽  
Pulmonary Metastases ◽  
Lung Metastases ◽  
Distant Metastases ◽  
Anaplastic Thyroid Cancer ◽  
Anaplastic Carcinoma ◽  
High Rate ◽  
Childhood And Adolescence ◽  
Anaplastic Transformation

Differentiated thyroid carcinoma is an uncommon malignancy of childhood and adolescence that is unique because it has an overall favorable prognosis despite its relatively high rate of nodal and distant metastases. Total thyroidectomy and positive 131I therapy are recommended for cases with pulmonary metastases. In contrast, anaplastic thyroid cancer is one of the most aggressive malignancies that have an unfavorable and miserable prognosis. We report a case with an impressively long history. The patient had multiple pulmonary metastases that had been diagnosed by 131I administration when he was 14 years old, about 45 years before he underwent thyroidectomy. He had been kept unaware of his disease by his family and received no treatment for most of his life. Pulmonary nodules were noted at several medical checkups and showed a remarkable decrease in size during the untreated 44-year period after the 131I administration. At age 58, his thyroid cancer was first detected and total thyroidectomy was performed, with subsequent radioiodine therapy for pulmonary metastases. Unfortunately, anaplastic carcinoma developed and he died of disseminated tumors later.

scholarly journals Age as a Prognostic Factor in Anaplastic Thyroid Cancer

2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Vladan Zivaljevic ◽  
Katarina Tausanovic ◽  
Ivan Paunovic ◽  
Aleksandar Diklic ◽  
Nevena Kalezic ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Thyroid Cancer ◽  
Prognostic Factor ◽  
Cox Regression ◽  
Postoperative Radiotherapy ◽  
Distant Metastases ◽  
Anaplastic Thyroid Cancer ◽  
Multivariate Regression Analysis ◽  
Rank Test ◽  
Cox Regression Analysis

Background.Anaplastic thyroid cancer (ATC) is one of the tumors with the shortest survival in human medicine.Aim.The aim was to determine the importance of age in survival of patients with ATC.Material and Methods. We analyzed the data on 150 patients diagnosed with ATC in the period from 1995 to 2006. The Kaplan-Meier method and log-rank test were used to determine overall survival. Prognostic factors were identified by univariate and multivariate Cox regression analysis.Results.The youngest patient was 35 years old and the oldest was 89 years old. According to univariate regression analysis, age was significantly associated with longer survival in patients with ATC. In multivariate regression analysis, patients age, presence of longstanding goiter, whether surgical treatment is carried out or not, type of surgery, tumor multicentricity, presence of distant metastases, histologically proven preexistent papillary carcinoma, radioiodine therapy, and postoperative radiotherapy were included. According to multivariate analysis, besides surgery (P=0.000, OR = 0.43, 95% CI = 0.29–0.63), only patients age (P=0.023, OR = 0.68, 95% CI = 0.49–0.95) was independent prognostic factor of favorable survival in patients with ATC.Conclusion. Age is a factor that was independently associated with survival time in ATC. Anaplastic thyroid cancer has the best prognosis in patients younger than 50 years.

scholarly journals MON-491 TRK-Fusion Thyroid Cancer: A Clinical Overview in a Large Population at a Single Cancer Center

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Sasan Fazeli ◽  
Ramona Dadu ◽  
Steven G Waguespack ◽  
Steven I Sherman ◽  
Naifa Lamki Busaidy ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Systemic Therapy ◽  
Large Population ◽  
Laboratory Data ◽  
Distant Metastases ◽  
Braf V600e ◽  
Driver Mutations ◽  
Cancer Center ◽  
Entire Cohort ◽  
And Behavior

Abstract Introduction: Most thyroid cancers (TC) are due to mutually exclusive somatic driver mutations. NTRK fusions are rare oncogenic drivers in papillary TC (PTC), poorly differentiated TC (PDTC) and anaplastic TC (ATC), estimated to be in 2.3% of all TC. However, the clinical presentation and behavior of TRK-fusion TC remains largely unknown. Methods / Case Presentation: Using institutional databases, we identified all TC patients (pts) with an NTRK fusion reported on somatic testing performed by a CLIA-certified laboratory. Data from the medical records were collected. The objective of this study was to investigate the clinical and pathological features of TC pts whose tumors harbored an NTRK fusion. Results / Discussion: We identified 36 TC pts with somatic NTRK fusions. Fusion testing was generally done in pts with advanced or radioactive iodine refractory (RAI-R) disease. Median age at diagnosis was 27.4 years (range 4–75 years), 21 (58%) were female and 16 (44%) were pediatric. 28/36 (78%) pts had PTC, 2/36 (5%) PDTC and 6/36 (17%) ATC. There were a total of 12 (33%) NTRK1, 24 (67%) NTRK3, and no NTRK2 fusions. In ATC and PDTC pts NTRK3 was the most common NTRK fusion 7/8 (87%). In PTC pts, 11 (39%) had NTRK1 and 17 (61%) had NTRK3. In the adult pts NTRK3 was more common 17/20 (85%) (Odds Ratio 7.2, P=0.013), however, in pediatric pts rate of NTRK1 and NTRK3 were similar. One pt had additional mutations along with the NTRK fusion, an ATC pt with multiple mutations including BRAF V600E. Of the 30 PTC/PDTC pts, 23 (77%) had distant metastases (mets). 14 (38%) pts had distant mets at diagnosis and 11 (69%) pediatric pts had distant mets. Lung 21 (70%) and bone 9 (30%) were the most common distant mets sites. In the PTC pts with distant mets, 9 (41%) had RAI-avid and 11 (50%) had RAI-R disease. In the entire cohort of 36 pts, 17 (53%) were on a systemic therapy of whom 11 pts were PTC. NTRK directed was the most common systemic therapy 16 (94%). All PTC pts were alive with a median time from diagnosis of 46 months (Interquartile 1–3: 25–118 months). Four ATC and one PDTC pts had died at the time of the analysis. Conclusions: In this study we confirmed that NTRK fusions occur primarily in PTC but also in less differentiated tumors. Most were young pts but NTRK fusions were identified in tumors from adults as old as 75 years. NTRK1 and NTRK3 were the most common NTRK fusions with NTRK3 being more common in adults. In thyrocyte-derived TC pts, NTRK fusions are mutually exclusive genetic events that occur in pts of all ages and varying histologies. Given the availability of NTRK targeted therapy, consideration should be given to testing for NTRK fusions in advanced thyroid cancer pts, especially those in whom prior genetic testing did not identify an oncogenic driver.

Sign in / Sign up

Export Citation Format

Share Document