Genetic profile of advanced thyroid cancers in relation to distant metastasis

Major clinical challenges exist with differentiated thyroid cancers with distant metastases or rare but aggressive types, such as poorly differentiated thyroid carcinomas and anaplastic thyroid carcinomas. The precise characterization of the mutational profile in these advanced thyroid cancers is crucial. Samples were collected from primary tumors and distant metastases of 64 patients with distant metastases from differentiated thyroid cancer, poorly differentiated thyroid carcinoma, or anaplastic thyroid carcinoma. Targeted next-generation sequencing was performed with 50 known thyroid-cancer-related genes. Of the 82 tissues, 63 were from primary tumors and 19 from distant metastases. The most prevalent mutation observed from the primary tumors was TERT promoter mutation (56%), followed by BRAF (41%) and RAS (24%) mutations. TP3 was altered by 11%. Mutations in histone methyltransferases, SWI/SNF subunit–related genes, and PI3K/AKT/mTOR pathway-related genes were present in 42%, 12%, and 22%, respectively. When the mutational status was analyzed in 15 matched pairs of thyroid tumors and their matched distant metastases and one pair of distant metastases with two distinct sites, the concordance was high. A similar frequency of mutations in TERT promoter (58%) and BRAF (42%) as well as histone methyltransferases (37%), SWI/SNF subunits (10%), and PI3K/AKT/mTOR pathway (26%) were noted. The same main, early and late mutations were practically always present in individual primary tumor–metastasis pairs. Enrichment of TERT promoter, BRAF, and RAS mutations were detected in highly advanced thyroid cancers with distant metastasis. The genetic profiles of primary thyroid tumors and their corresponding distant metastases showed a high concordance.

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Thyroid Carcinoma in Hot Nodules: Review of the Literature

World Journal of Endocrine Surgery ◽

10.5005/jp-journals-10002-1126 ◽

2013 ◽

Vol 5 (2) ◽

pp. 50-54 ◽

Cited By ~ 2

Author(s):

Pouya Iranmanesh ◽

Marc Pusztaszeri ◽

John Robert ◽

Patrick Meyer ◽

Boris Schiltz ◽

...

Keyword(s):

Thyroid Cancer ◽

Thyroid Carcinoma ◽

Clinical Case ◽

Survival Rates ◽

Review Of The Literature ◽

Abnormal Finding ◽

Thyroid Cancers ◽

Thyroid Carcinomas ◽

Medical Databases ◽

The Past

ABSTRACT Thyroid hot nodules are virtually always considered benign. Rare cases of hot thyroid carcinoma exist. We briefly described a clinical case and performed a review of the literature. We performed an extensive research on medical databases, such as PubMed and compiled all published cases matching preset criteria defining true hot thyroid carcinomas as well as guidelines regarding their management. We analyzed 103 articles published over the past 50 years. We selected 16 articles, including 45 cases matching our criteria. The majority were follicular carcinomas. Papillary carcinomas were infrequently found in this setting. Recommended management and survival rates were similar to classical cold thyroid cancer. Although hot nodules should continue to be considered benign most of the time, rare cases of hot thyroid cancers exist and clinicians should not hesitate to ask for additional tests if they encounter any abnormal finding. This form of thyroid cancer can reasonably be managed the same way as the cold thyroid cancers. How to cite this article Iranmanesh P, Pusztaszeri M, Robert J, Meyer P, Schiltz B, Sadowski SM, Goumaz MO, Triponez F. Thyroid Carcinoma in Hot Nodules: Review of the Literature. World J Endoc Surg 2013;5(2):50-54.

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SUN-490 Mass Cord Compression: Metastasis of Insular Thyroid Cancer

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.232 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Dina Jaber ◽

Bianca Vazques ◽

Gary Nagamoto ◽

Mohamad Hosam Horani

Keyword(s):

Thyroid Cancer ◽

Thyroid Carcinoma ◽

Chest Wall ◽

Distant Metastasis ◽

Tumor Resection ◽

Complex Form ◽

Lower Extremity Weakness ◽

Poorly Differentiated Carcinoma ◽

Patient Reported ◽

Poorly Differentiated

Abstract Intro: Insular thyroid cancer is a rare and complex form of thyroid cancer, often referred to as poorly differentiated carcinoma. The exact incidence of insular thyroid cancers is difficult to assess due to controversial classification of this thyroid cancer over the years. It is termed poorly differentiated as it falls between the well-differentiated and undifferentiated carcinomas both morphologically and biologically[1]. Case: A 41 year old Hispanic female, with a history of prolactinoma and hyperparathyroidism, presented to the hospital with 10 days of progressive lower extremity weakness and paresthesias from T4 downwards, inability to bear weight, and no bowel movement for 12 days. MRI revealed a large thoracic soft tissue mass (7x4x4cm) centered in the posterior and medial aspect of the chest wall at T4-T5 with involvement of the spinal cord and vertebral bodies. She was also found to have a right sided thyroid mass (4.5x5x4 cm) with tracheal deviation- HerThyoid function test, were normal Intact PTH was 261, Thyroglobulin over 300, and Thyroid Antibodies were negative. Patient underwent T3-T6 laminectomy, T2-T7 fusion, and T4-T5 tumor resection, which was subtotal due to vascularity. Second procedure included a right thoracotomy, chest wall resection of ribs 4 and 5 with full resection of paraspinal mass, total thyroidectomy, parathyroidectomy with central cervical lymphadenectomy. Pathology results of paraspinal mass showed insular thyroid carcinoma. Post operatively, the patient reported improvement of sensation and strength in lower extremities. Genetic testing for MEN syndrome was negative. Discussion: Insular thyroid carcinoma, also referred to as poorly differentiated carcinoma is a rare form of thyroid cancer. Insular carcinoma was characterized by to include the following complex histologic features, “formation of solid clusters (insulae) of tumor cells containing a variable number of small follicles; variable but consistently present mitotic activity, capsular and blood vessel invasion; and frequent necrotic foci, sometimes leading to formation of peritheliomatous patterns”[1]. The cells originate from follicular epithelium and possess the potential to concentrate radioiodine[2]. Unlike anaplastic carcinoma of the thyroid, p53 and p21 staining was negative in insular carcinomas[3]. Thyroglobulin staining is generally positive[4]. Distant metastasis occurs in about 31% of patients with insular thyroid carcinoma[5]. In cases of distant metastasis, treatment with thyroidectomy and radioiodine therapy were shown to independently improve survival[5]. The Constellation of Insular thyroid cancer, hyperparathyroidism and Prolactinoma, has not been reported before. References: [1]. Am J Surg Pathol. 1984;8:655- [2] J of Nuc Med 32(7), 1358 [3] Ann of Surg vol. 231,3 (2000): 329 [4] JCEM 99. 1167–9. 10.1210/jc.2014 [5] Cancer. 2012 Jul;118(13) 3260

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Solitary Liver Metastasis from Follicular Variant Papillary Thyroid Carcinoma: A Case Report

Bangladesh Journal of Nuclear Medicine ◽

10.3329/bjnm.v22i2.51768 ◽

2021 ◽

Vol 22 (2) ◽

pp. 146-149

Author(s):

Rahima Perveen ◽

Jasmin Ferdous ◽

Sharmin Quddus ◽

Tapati Mandal

Keyword(s):

Thyroid Cancer ◽

Papillary Thyroid Carcinoma ◽

Thyroid Carcinoma ◽

Distant Metastases ◽

Differentiated Thyroid Carcinoma ◽

Papillary Thyroid ◽

Follicular Variant ◽

Thyroid Carcinomas ◽

Visceral Metastases ◽

Solitary Liver

Papillary and follicular thyroid carcinomas, together known as differentiated thyroid carcinomas (DTC), are among the most curable of cancers. Distant metastases are rare events at the onset of DTC. Sites of metastases from follicular thyroid cancer (FTC) are usually osseous, and those from papillary thyroid cancer (PTC) metastasize to regional nodal basins and the lungs. Visceral metastases are rare, but the involvement of multiple sites has been reported so far. Liver metastases from differentiated thyroid carcinoma (LMDTC) are rare.We present the case of a patient with follicular variant of papillary thyroid carcinoma (FVPTC) unusually involving the liver. Bangladesh J. Nuclear Med. 22(2): 146-149, Jul 2019

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Loss of ZNF677 Expression Is an Independent Predictor for Distant Metastasis in Middle Eastern Papillary Thyroid Carcinoma Patients

International Journal of Molecular Sciences ◽

10.3390/ijms22157833 ◽

2021 ◽

Vol 22 (15) ◽

pp. 7833

Author(s):

Abdul K. Siraj ◽

Pratheesh Kumar Poyil ◽

Sandeep Kumar Parvathareddy ◽

Khadija Alobaisi ◽

Saeeda O. Ahmed ◽

...

Keyword(s):

Thyroid Cancer ◽

Papillary Thyroid Carcinoma ◽

Thyroid Carcinoma ◽

Distant Metastasis ◽

Zinc Finger Protein ◽

Independent Predictor ◽

Middle Eastern ◽

Distant Metastases ◽

Papillary Thyroid ◽

Finger Protein

Thyroid cancer incidence has increased in recent decades. Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. Approximately 30% of PTC patients develop recurrence or distant metastasis and tend to have poor prognosis. Therefore, the identification of targetable biomarkers in this subset of patients is of great importance. Accumulating evidence indicates that zinc finger protein 677 (ZNF677), which belongs to the zinc finger protein family, is an important effector during the progression of multiple malignancies. However, its role in Middle Eastern PTC patients has not been fully illustrated. Here, we uncovered the molecular mechanism and the clinical impact of ZNF677 expression in a large cohort of more than 1200 Middle Eastern PTC and 15 metastatic tissues. We demonstrated that ZNF677 is frequently downregulated in primary PTC (13.6%, 168/1235) and showed that complete loss of expression of ZNF677 is significantly associated with aggressive clinico-pathological markers such as extrathyroidal extension (p = 0.0008) and distant metastases (p < 0.0001). We also found a significantly higher incidence of ZNF677 loss in primary tumors with distant metastases (33.3%; p < 0.0001) as well as in distant metastatic tissues (46.7%; p = 0.0002) compared to the overall cohort (13.6%). More importantly, PTC with loss of ZNF677 expression showed significantly lower metastasis-free survival (p = 0.0090). Interestingly, on multivariate logistic regression analysis, ZNF677 loss was an independent predictor of distant metastasis in PTC (Odds ratio = 2.60, 95% Confidence interval = 1.20–5.62, p = 0.0155). In addition, we found a significant association between ZNF677 loss and phospho-AKT expression (p < 0.0001). Our functional molecular results suggest that ZNF677 acts as a tumor suppressor, mediating its effect by inhibiting AKT phosphorylation. Taken together, our results highlight the pivotal role played by ZNF677 during carcinogenesis and metastasis formation in Middle Eastern PTC patients.

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TERT, BRAF, and NRAS in Primary Thyroid Cancer and Metastatic Disease

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2016-2785 ◽

2017 ◽

Vol 102 (6) ◽

pp. 1898-1907 ◽

Cited By ~ 46

Author(s):

Miguel Melo ◽

Adriana Gaspar da Rocha ◽

Rui Batista ◽

João Vinagre ◽

Maria João Martins ◽

...

Keyword(s):

Thyroid Cancer ◽

Primary Tumor ◽

Low Frequency ◽

Distant Metastases ◽

Braf Mutations ◽

Tissue Samples ◽

Primary Tumors ◽

Thyroid Carcinomas ◽

Cancer Metastases ◽

Node Metastases

Abstract Context Little is known about the frequency of key mutations in thyroid cancer metastases and its relationship with the primary tumor genotype. Objectives To evaluate the frequency of TERT promoter (TERTp), BRAF, and NRAS mutations in metastatic thyroid carcinomas, analyzing primary thyroid tumors, lymph node metastases (LNMs), and distant metastases. Design and Patients Mutation analysis was performed in 437 tissue samples from 204 patients, mainly with papillary thyroid carcinomas (PTCs; n = 180), including 196 LNMs and 56 distant metastases. All the distant metastases included corresponded to radioiodine-refractory metastatic tissue. Results We found the following mutation frequency in primary PTCs, LNMs, and distant metastases, respectively: TERTp: 12.9%, 10.5%, and 52.4%; BRAF: 44.6%, 41.7%, and 23.8%; and NRAS: 1.2%, 1.3%, and 14.3%. There was a significant concordance between the primary tumor genotype and the corresponding LNM for all the genes, in particular BRAF-mutated PTC. The overall concordance between primary tumors and respective distant metastases was low. In the group of patients with PTCs, we found a high frequency of TERTp mutations and a low frequency of BRAF mutations in distant metastases, in comparison with the paired primary tumors. When present in distant metastases, BRAF mutations frequently coexisted with TERTp mutations. Conclusions When the genotype of primary tumors is compared with the genotype of LNMs, the concordance is high for all the genes studied. On the other hand, distant metastases show an enrichment in TERTp mutations and a decrease in BRAF mutations. TERTp mutations may play a role in distant metastases.

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Incidental Poorly Differentiated Thyroid Cancer in Trauma Patient

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.1821 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A892-A892

Author(s):

Alberto Javier Grana Santini ◽

Milliette Alvarado ◽

Loida Alejandra Gonzalez-Rodriguez ◽

Margarita Ramirez ◽

Nydia Ivette Burgos Ortega ◽

...

Keyword(s):

Lymph Node ◽

Thyroid Carcinoma ◽

Distant Metastases ◽

Whole Body ◽

Thyroid Lobe ◽

Thyroid Carcinomas ◽

Level 3 ◽

Poorly Differentiated ◽

Left Thyroid Lobe

Abstract Poorly differentiated carcinomas tend to arise de novo or transform from differentiated thyroid carcinomas. Females, middle-aged and elderly adults are most commonly affected. Patients present with an enlarging thyroid mass which is often locally advanced at presentation. This is a case of 30-year-old male patient admitted after burn injury who presented with neck enlarging mass. He had no family history of thyroid CA, no radiation exposure and normal thyroid function tests. Neck CT imaging found with heterogeneous enhancing mass arising from the left thyroid lobe. Thyroid ultrasound consistent with a large left thyroid lobe lesion described as a complex solid component measures at least 5.2 cm long x 4.0 cm AP by 5.0 cm transverse with coarse scattered echogenic foci, and smaller bright echoes with comet-tail artifacts. Fine needle biopsy was non-diagnostic or unsatisfactory. Second FNA with Atypia of undetermined significance. Left hemithyroidectomy performed consistent with a 5cm Poorly differentiated thyroid carcinoma arising in a preexisting papillary thyroid carcinoma with extensive necrosis, pT3aNx, TTF1 +, PAX 8 +, CK7 +. Right thyroid was negative for malignancy. A Therapeutic dose of 135.7 mCi of 131-iodine was given. Subsequent whole body scan with focal findings in the thyroid bed region is consistent with residual functional thyroid tissue. Follow up with normal thyroglobulin levels and negative thyroglobulin antibodies. Neck ultrasound without abnormal tissue or nodules seen at either thyroid bed. Follow up with 18-F-FDG PET/CT scan abnormal study with avid lymph node in the right side of the neck, Level 3. FNA lymph node, cervical right level 3, 1.1cm, ultrasound guided biopsy negative for metastatic carcinoma. Poorly differentiated thyroid carcinomas present as large thyroid masses. The tumor spreads by local invasion into perithyroidal tissues and by distant metastases. Poorly differentiated carcinoma is supported by immunohistochemical staining for Tg, TTF1, and paired box protein Pax 8 (PAX8). There is no standardized treatment for PDTC to date. If possible, a total thyroidectomy including lymph node dissection should be performed to improve survival rates. Due to the higher rate of ETE, positive margins, neck disease, and distant metastases, adjuvant treatment should be considered. Some experts recommended considering adjuvant RAI in all PDTC patients, giving the potential benefit and lack of morbidity. However, despite the capability of RAI uptake in a high percentage of PDTC, no significant impact on survival has been reported. It is important to recognize prognosis of PDTC is distinctly less favorable than that of PTC or FTC. Several factors have been identified to affect patient prognosis such as extensive tumor necrosis, >45 year of age, tumor size (>5 cm), extrathyroidal extension and distant metastases are unfavorable prognostic factors.

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Pre-operative serum TSH levels: A risk factor for advanced metastatic differentiated thyroid carcinoma

Pakistan Journal of Medical Sciences ◽

10.12669/pjms.35.5.704 ◽

2019 ◽

Vol 35 (5) ◽

Author(s):

Sumera Batool ◽

Muhammad Shakir Afridi ◽

Adeel Akbar Khoja ◽

Najmul Islam

Keyword(s):

Risk Factor ◽

Thyroid Cancer ◽

Lymph Node ◽

Thyroid Carcinoma ◽

Distant Metastasis ◽

Differentiated Thyroid Carcinoma ◽

Thyroid Cancers ◽

Multifocal Disease ◽

Serum Tsh ◽

Tsh Levels

Background and Objective: As the thyroid cancer incidence is increasing, the search for its risk factor is becoming more important. Serum thyroid stimulating hormone (TSH) levels being a growth factor for normal thyroid tissue, is also considered as growth promotor of cancer cells. In our study we aimed for pre-operative serum TSH levels of Differentiated thyroid cancers (DTC) done before their first surgery and determined its association with advanced disease in terms of stage, multifocal disease, lymph node involvement and distant metastasis. Methods: We have conducted a retrospective review of thyroid cancers from 1st January 2008 to 31st December 2017. Out of 281, 142 cases were included according to inclusion criteria. We noted the demographic details of participants, their histopathological diagnosis and serum TSH levels done before first surgery from the medical records. We calculated the stage of tumor through modified American Joint Committee (AJCC) staging system. Results: Out of 147 participants, 89.4% had papillary carcinoma or its variants whereas 10.6% reported follicular carcinoma. The mean pre-op TSH level of the patients included was 2.04 ± 1.79. In addition to the descriptive analysis, the univariate regression analysis revealed that the association of serum TSH levels was found to be statistically insignificant with advanced stage of thyroid cancer, multifocal disease, lymph node metastasis and distant metastasis respectively. Conclusion: The serum TSH levels before surgery was not associated with poor prognosis of differentiated thyroid cancer with respect to higher staging, multifocal disease, lymphatic or distant metastasis. doi: https://doi.org/10.12669/pjms.35.5.704 How to cite this:Batool S, Afridi MS, Khoja A, Islam N. Pre-operative serum TSH levels: A risk factor for advanced metastatic differentiated thyroid carcinoma. Pak J Med Sci. 2019;35(5):---------. doi: https://doi.org/10.12669/pjms.35.5.704 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MON-452 Poorly Differentiated Thyroid Carcinoma Metastatic to the Adrenal Gland

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.1260 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Priyanka Mathias ◽

Anjali Manavalan ◽

Sandra Aleksic ◽

Noah Bloomgarden ◽

Ulrich Schubart

Keyword(s):

Thyroid Cancer ◽

Adrenal Gland ◽

Thyroid Carcinoma ◽

Distant Metastasis ◽

Differentiated Thyroid Carcinoma ◽

Whole Body ◽

Poorly Differentiated Thyroid Carcinoma ◽

Poorly Differentiated ◽

The Right ◽

Post Therapy

Abstract Background: Poorly differentiated thyroid carcinoma (PDTC) constitutes 1-15% of all thyroid cancers.1 Invasive adrenal metastases secondary to PTDC are exceedingly rare. Clinical Case: A 64-year-old woman with a non-toxic multinodular goiter presented with right upper quadrant abdominal pain and distension for three months. CT imaging revealed a 13.5 cm right suprarenal retroperitoneal mass invading the liver and inferior vena cava (IVC), concerning for adrenocortical carcinoma. She underwent resection of the mass with en block right adrenalectomy, partial hepatectomy, and IVC resection. Pathology demonstrated metastatic thyroid cancer with necrosis of the adrenal gland and IVC. Immunohistochemical staining was positive for PAX8, TTF1, and thyroglobulin (Tg). Completion thyroidectomy revealed an encapsulated 2 cm focus of PDTC with Hurthle cell phenotype in the right thyroid lobe. The mitotic activity was 5/10 per HPF. There were focal areas of tumor necrosis, 3 foci of capsular invasion, and extensive angioinvasion. Surgical margins were free of tumor invasion. Eight resected lymph nodes were negative for malignancy (Stage T1bN0M1; AJCC 8, Stage IVb). Genetic testing was positive for somatic mutations of NRAS, TERT, PTEN, and GNAS with broad copy number loss on chromosome 22q conferring aggressive tumor behavior.3 MRI of the brain and spine ruled out additional metastases. A radioactive iodine (RAI) whole-body scan (WBS) showed residual uptake of 7.6% in the right thyroid bed and a focus of increased uptake at the right sternoclavicular joint. A therapeutic dose of 206 mCi of I-131 was administered. A post-therapy WBS demonstrated focal activity in the right thyroid bed, distal right clavicle, and lower lung lobes. Chest CT and MRI of the right shoulder revealed no structural evidence of metastases corresponding to radiotracer uptake. The stimulated Tg level prior to RAI was 323 ng/mL with a TSH of 66 uU/mL (0.4-4.6 uU/mL). Tg antibodies were undetectable. She was maintained on 150 mcg of levothyroxine with the goal of TSH suppression. Tg levels declined to 4.8 ng/mL at three months, and to 0.3 ng/mL eight months post-RAI. Discussion: PDTC is an aggressive thyroid cancer subtype with distant metastasis reported in 36-85% of cases.2 Distant metastasis is predictive of poorer outcomes, with patients three times more likely to die from the disease than those without metastatic disease.1 Adrenal metastasis of thyroid cancer is rare, and unlike in our patient, usually asymptomatic and frequently detected on a post-therapy scan. Despite a dramatic response to therapy, given the poorly differentiated features of the primary tumor, a whole-body PET-CT is warranted to evaluate for RAI refractory disease. References: 1. Ibrahimpasic T et al. J Clin Endocrinol Metab. 2014;99(4):1245-52. 2. Sanders EM Jr et al. World J Surg. 2007;31(5):934-45. 3. Cheng DT et al. J Mol Diagn. 2015;17(3):251-64.

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Comprehensive screening for PD-L1 expression in thyroid cancer

Endocrine Related Cancer ◽

10.1530/erc-16-0421 ◽

2017 ◽

Vol 24 (2) ◽

pp. 97-106 ◽

Cited By ~ 41

Author(s):

Soomin Ahn ◽

Tae Hyuk Kim ◽

Sun Wook Kim ◽

Chang Seok Ki ◽

Hye Won Jang ◽

...

Keyword(s):

Thyroid Cancer ◽

Thyroid Carcinoma ◽

Disease Progression ◽

Large Scale ◽

Anaplastic Thyroid Carcinoma ◽

Papillary Thyroid ◽

Thyroid Cancers ◽

Thyroid Carcinomas ◽

Oncogenic Mutation ◽

Potential Biomarker

PD-L1 expression is being considered a potential biomarker for response of anti-PD-1 or anti-PD-L1 agents in various tumors. The reported frequency of PD-L1 positivity varies in thyroid carcinomas, and multiple factors may contribute to the variability in PD-L1 positivity. We evaluated the PD-L1 expression in various thyroid cancers on a large scale. A total of 407 primary thyroid cancers with a median 13.7-year of follow-up were included. We evaluated the frequency of PD-L1 expression using a rabbit monoclonal antibody (clone SP142). In addition, we analyzed the relationships between PD-L1 expression and clinicopathologic factors, includingTERTpromoter, BRAFstatus and disease progression. Tumoral PD-L1 was expressed in 6.1% of papillary thyroid carcinomas, 7.6% of follicular thyroid carcinomas and 22.2% of anaplastic thyroid carcinomas. The distribution of PD-L1 positivity was different according to cancer histology types (P < 0.001). All PD-L1-positive cases of follicular thyroid carcinoma and anaplastic thyroid carcinoma showed strong intensity. The proportions of positivity in PD-L1 positive anaplastic thyroid carcinomas were more than 80%. PD-L1 in immune cells was positive in 28.5% of papillary thyroid carcinoma, 9.1% of follicular thyroid carcinomas and 11.1% of anaplastic thyroid carcinomas. There was no significant association between clinicopathologic variables, disease progression, oncogenic mutation and PD-L1 expression. PD-L1 was highly expressed in a subset of patients with advanced thyroid cancer, such as follicular and anaplastic thyroid carcinoma. Identification of PD-L1 expression may have direct therapeutic relevance to patients with refractory thyroid cancer.

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

International Journal of Molecular Sciences ◽

10.3390/ijms22063117 ◽

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.

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