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Cancers
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Advances in Thyroid Cancer
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Advances in Thyroid Cancer

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Clinical Research of Cancer".

Deadline for manuscript submissions: closed (15 April 2023) | Viewed by 29622

Special Issue Editors

Prof. Dr. Stefania Masone

E-Mail Website
Guest Editor
Department of Clinical Medicine and Surgery, University of Naples "Federico II", 80131 Naples, Italy
Interests: endocrine surgery; thyroid surgery; breast surgery; bariatric surgery; minimally invasive surgery
Dr. Nunzio Velotti

E-Mail Website
Guest Editor
Department of Advanced Biomedical Sciences, University of Naples “Federico II”, 80131 Naples, Italy
Interests: endocrine surgery; breast surgery; bariatric surgery; thyroid surgery; minimally invasive surgery

Special Issue Information

Dear Colleagues, 

The incidence of thyroid cancers has seen a significant increase in the world in the last decades, with a great impact on public health. At same time, advances in thyroid cancer management have resulted in substantial changes in the perspectives of patients affected by this pathology.

The scientific community is constantly involved in updating guidelines and characterizing new therapeutic strategies, with an important reflection on clinical practice.

With respect to this point of view, the significance of the topic and the social repercussions it demonstrates have moved our interest towards this Special Issue with the aim of providing the reader with an overview of new approaches to thyroid cancer.

Prof. Dr. Stefania Masone
Dr. Nunzio Velotti
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • thyroid cancer
  • radiotherapy
  • thyroid Surgery
  • minimally invasive surgery
  • cytopathology
  • endocrinology

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Published Papers (10 papers)

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Research

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13 pages, 2085 KiB  
Article
Oxidative Stress Correlates with More Aggressive Features in Thyroid Cancer
by Marina Muzza, Gabriele Pogliaghi, Carla Colombo, Erika Carbone, Valentina Cirello, Sonia Palazzo, Francesco Frattini, Davide Gentilini, Giacomo Gazzano, Luca Persani and Laura Fugazzola
Cancers 2022, 14(23), 5857; https://doi.org/10.3390/cancers14235857 - 28 Nov 2022
Cited by 16 | Viewed by 1921
Abstract
Oxidative stress (OS) can have an impact in the pathogenesis and in the progression of thyroid cancer. We investigated the levels of reactive oxygen species (ROS) in 50 malignant and benign thyroid lesions and 41 normal tissues, and correlated them with the thyroid [...] Read more.
Oxidative stress (OS) can have an impact in the pathogenesis and in the progression of thyroid cancer. We investigated the levels of reactive oxygen species (ROS) in 50 malignant and benign thyroid lesions and 41 normal tissues, and correlated them with the thyroid differentiation score-TDS and the clinico-pathologic features. NOX4 expression, GPx activity and the genetic pattern of tumors were evaluated. In malignant and benign lesions, ROS generation and NOX4 protein expression were higher than in normal tissues. Follicular (FTCs) and anaplastic/poorly differentiated cancers had increased OS relative to papillary tumors (PTCs). Moreover, OS in FTCs was higher than in follicular adenomas. Mutated PTCs showed increased OS compared with non-mutated PTCs. In malignant tumors, OS was inversely correlated with TDS, and directly correlated with tumor stage and ATA risk. GPx activity was increased in tumors compared with normal tissues, and inversely correlated to OS. In conclusion, our data indicate that thyroid tumors are exposed to higher OS compared with normal tissues, while showing a compensative increased GPx activity. OS correlates with tumor aggressiveness and mutations in the MEK-ERK pathway in PTC. The inverse correlation between OS and TDS suggests that ROS may repress genes involved in thyroid differentiation. Full article
(This article belongs to the Special Issue Advances in Thyroid Cancer)
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15 pages, 1786 KiB  
Article
Combined Shear Wave Elastography and EU TIRADS in Differentiating Malignant and Benign Thyroid Nodules
by Nonhlanhla Chambara, Xina Lo, Tom Chi Man Chow, Carol Man Sze Lai, Shirley Yuk Wah Liu and Michael Ying
Cancers 2022, 14(22), 5521; https://doi.org/10.3390/cancers14225521 - 10 Nov 2022
Cited by 9 | Viewed by 1934
Abstract
Although multimodal ultrasound approaches have been suggested to potentially improve the diagnosis of thyroid cancer; the diagnostic utility of the combination of SWE and malignancy-risk stratification systems remains vague due to the lack of standardized criteria. The purpose of the study was to [...] Read more.
Although multimodal ultrasound approaches have been suggested to potentially improve the diagnosis of thyroid cancer; the diagnostic utility of the combination of SWE and malignancy-risk stratification systems remains vague due to the lack of standardized criteria. The purpose of the study was to assess the diagnostic value of the combination of grey scale ultrasound assessment using EU TIRADS and shear wave elastography. 121 patients (126 nodules–81 benign; 45 malignant) underwent grey scale ultrasound and SWE imaging of nodules between 0.5 cm and 5 cm prior to biopsy and/or surgery. Nodules were analyzed based on size stratifications: <1 cm (n = 43); 1–2 cm (n = 52) and >2 cm (n = 31) and equivocal cytology status (n = 52), and diagnostic performance assessments were conducted. The combination of EU TIRADS with SWE using the SD parameter; maintained a high sensitivity and significantly improved the specificity of sole EU TIRADS for nodules 1–2 cm (SEN: 72.2% vs. 88.9%, p > 0.05; SPEC: 76.5% vs. 55.9%, p < 0.01) and >2 cm (SEN: 71.4% vs. 85.7%, p > 0.05; SPEC: 95.8% vs. 62.5%, p < 0.01). For cytologically-equivocal nodules; the combination with the SWE minimum parameter resulted in a significant reduction in sensitivity with increased specificity (SEN: 60% vs. 80%; SPEC: 83.4% vs. 37.8%; all p < 0.05). SWE in combination with EU TIRADS is diagnostically efficient in discriminating nodules > 1 cm but is not ideal for discriminating cytologically-equivocal nodules. Full article
(This article belongs to the Special Issue Advances in Thyroid Cancer)
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20 pages, 327 KiB  
Article
Optimization of the Management of Category III Thyroid Nodules Using Repeat FNA and TIRADS
by Dorota Słowińska-Klencka, Mariusz Klencki, Joanna Duda-Szymańska and Bożena Popowicz
Cancers 2022, 14(18), 4489; https://doi.org/10.3390/cancers14184489 - 16 Sep 2022
Cited by 4 | Viewed by 1608
Abstract
The aim of the study was to examine the benefits of the joint use of repeat FNA (rFNA) and EU-TIRADS in category III nodules in relation to the kind of atypia: nuclear vs. architectural (denoted by AUS and FLUS respectively). The study included [...] Read more.
The aim of the study was to examine the benefits of the joint use of repeat FNA (rFNA) and EU-TIRADS in category III nodules in relation to the kind of atypia: nuclear vs. architectural (denoted by AUS and FLUS respectively). The study included 127 AUS and 1739 FLUS nodules with a known category of EU-TIRADS. Repeat FNA was performed in 82 AUS and 934 FLUS nodules of which 57 and 515 were excised, respectively. AUS nodules had higher malignancy risk than FLUS nodules. EU-TIRADS showed higher accuracy for AUS nodules, the opposite to rFNA, that had higher accuracy for FLUS nodules. The combined criterion for AUS nodules (at least rFNA-V or EU-TIRADS-4) maximized sensitivity (92.3%) with acceptable specificity (70.0%); OR: 28.0. In the case of FLUS nodules, the combined criterion (rFNA-V or EU-TIRADS-5) maximized specificity (95.2%) with 57.7% sensitivity and a low percentage (13.9%) of positive nodules, OR: 27.0. In both types of nodules, the low risk category in EU-TIRADS and benign result of rFNA excluded cancer. Concluding, category III nodules with and without nuclear atypia differ in their risk of malignancy and, consequently, diagnostic criteria adopted for the evaluation of these nodules with rFNA and EU-TIRADS should be specific to AUS and FLUS nodules. Full article
(This article belongs to the Special Issue Advances in Thyroid Cancer)
23 pages, 1283 KiB  
Article
Thyroid Disease Prediction Using Selective Features and Machine Learning Techniques
by Rajasekhar Chaganti, Furqan Rustam, Isabel De La Torre Díez, Juan Luis Vidal Mazón, Carmen Lili Rodríguez and Imran Ashraf
Cancers 2022, 14(16), 3914; https://doi.org/10.3390/cancers14163914 - 13 Aug 2022
Cited by 38 | Viewed by 5605
Abstract
Thyroid disease prediction has emerged as an important task recently. Despite existing approaches for its diagnosis, often the target is binary classification, the used datasets are small-sized and results are not validated either. Predominantly, existing approaches focus on model optimization and the feature [...] Read more.
Thyroid disease prediction has emerged as an important task recently. Despite existing approaches for its diagnosis, often the target is binary classification, the used datasets are small-sized and results are not validated either. Predominantly, existing approaches focus on model optimization and the feature engineering part is less investigated. To overcome these limitations, this study presents an approach that investigates feature engineering for machine learning and deep learning models. Forward feature selection, backward feature elimination, bidirectional feature elimination, and machine learning-based feature selection using extra tree classifiers are adopted. The proposed approach can predict Hashimoto’s thyroiditis (primary hypothyroid), binding protein (increased binding protein), autoimmune thyroiditis (compensated hypothyroid), and non-thyroidal syndrome (NTIS) (concurrent non-thyroidal illness). Extensive experiments show that the extra tree classifier-based selected feature yields the best results with 0.99 accuracy and an F1 score when used with the random forest classifier. Results suggest that the machine learning models are a better choice for thyroid disease detection regarding the provided accuracy and the computational complexity. K-fold cross-validation and performance comparison with existing studies corroborate the superior performance of the proposed approach. Full article
(This article belongs to the Special Issue Advances in Thyroid Cancer)
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15 pages, 423 KiB  
Article
Treatment of RET-Positive Advanced Medullary Thyroid Cancer with Multi-Tyrosine Kinase Inhibitors—A Retrospective Multi-Center Registry Analysis
by Viktoria Florentine Koehler, Pia Adam, Carmina Teresa Fuss, Linmiao Jiang, Elke Berg, Karin Frank-Raue, Friedhelm Raue, Eva Hoster, Thomas Knösel, Hans-Ulrich Schildhaus, Thomas Negele, Udo Siebolts, Kerstin Lorenz, Stephanie Allelein, Matthias Schott, Christine Spitzweg and Matthias Kroiss
Cancers 2022, 14(14), 3405; https://doi.org/10.3390/cancers14143405 - 13 Jul 2022
Cited by 7 | Viewed by 2565
Abstract
Background: RET (rearranged during transfection) variants are the most prevalent oncogenic events in medullary thyroid cancer (MTC). In advanced disease, multi-tyrosine kinase inhibitors (MKIs) cabozantinib and vandetanib are the approved standard treatment irrespective of RET status. The actual outcome of patients with RET [...] Read more.
Background: RET (rearranged during transfection) variants are the most prevalent oncogenic events in medullary thyroid cancer (MTC). In advanced disease, multi-tyrosine kinase inhibitors (MKIs) cabozantinib and vandetanib are the approved standard treatment irrespective of RET status. The actual outcome of patients with RET-positive MTC treated with MKIs is ill described. Methods: We here retrospectively determined the RET oncogene variant status with a targeted DNA Custom Panel in a prospectively collected cohort of 48 patients with advanced MTC treated with vandetanib and/or cabozantinib at four German referral centers. Progression-free survival (PFS) and overall survival (OS) probabilities were estimated using the Kaplan-Meier method. Results: In total, 44/48 (92%) patients had germline or somatic RET variants. The M918T variant was found in 29/44 (66%) cases. In total, 2/32 (6%) patients with a somatic RET variant had further somatic variants, while in 1/32 (3%) patient with a germline RET variant, additional variants were found. Only 1/48 (2%) patient had a pathogenic HRAS variant, and no variants were found in 3 cases. In first-line treatment, the median OS was 53 (95% CI (95% confidence interval), 32–NR (not reached); n = 36), and the median PFS was 21 months (12–39; n = 33) in RET-positive MTC patients. In second-line treatment, the median OS was 18 (13–79; n = 22), and the median PFS was 3.5 months (2–14; n = 22) in RET-positive cases. Conclusions: RET variants were highly prevalent in patients with advanced MTC. The treatment results in RET-positive cases were similar to those reported in unselected cohorts. Full article
(This article belongs to the Special Issue Advances in Thyroid Cancer)
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12 pages, 896 KiB  
Article
A Multicenter Randomized Phase II Study of Single Agent Efficacy and Optimal Combination Sequence of Everolimus and Pasireotide LAR in Advanced Thyroid Cancer
by Julie E. Bauman, Zhengjia Chen, Chao Zhang, James P. Ohr, Robert L. Ferris, Gerald M. McGorisk, Stephen Brandt, Sumathi Srivatsa, Amy Y. Chen, Conor E. Steuer, Dong M. Shin, Nabil F. Saba, Fadlo R. Khuri and Taofeek K. Owonikoko
Cancers 2022, 14(11), 2639; https://doi.org/10.3390/cancers14112639 - 26 May 2022
Cited by 4 | Viewed by 3698
Abstract
Purpose: Aberrant mTOR pathway and somatostatin receptor signaling are implicated in thyroid cancer and offer potential therapeutic targets. We assessed the clinical efficacy of everolimus and Pasireotide long-acting release (LAR) in radioiodine-refractory differentiated thyroid cancer (DTC) and medullary thyroid cancer (MTC). Patients and [...] Read more.
Purpose: Aberrant mTOR pathway and somatostatin receptor signaling are implicated in thyroid cancer and offer potential therapeutic targets. We assessed the clinical efficacy of everolimus and Pasireotide long-acting release (LAR) in radioiodine-refractory differentiated thyroid cancer (DTC) and medullary thyroid cancer (MTC). Patients and methods: Adults with progressive MTC and DTC untreated or treated with no more than one systemic agent were eligible. The trial was designed to establish the most promising regimen and the optimal combination sequence. Patients were randomized to start treatment with single agent everolimus (10 mg QD; Arm A), pasireotide-LAR (60 mg intramuscular injection, Q4 weeks; Arm B), or the combination (Arm C). At initial progression (PFS1), patients on Arm A or B switched to the combination and continued until progression (PFS2). Efficacy was measured by RECIST criteria. Results: Study enrolled 42 patients: median age 65 years; female 17 (40.5%); White 31 (73.8%), African American 6 (14.3%), others 5 (11.9); DTC 32 (76.2%); MTC 10 (23.8%). There was no objective response by RECIST criteria across the three arms. Median and 1-year PFS1 rates were 8.3, 1.8, 8.1 months and 49.9%, 36.4%, 25.0% for Arms A, B, C, respectively. Median and 1-year PFS2 rates were 26.3, 17.5, 8.1 months and 78.4%, 70.0%, 25% for Arms A, B, C, respectively. The most frequent adverse events were anemia, stomatitis, fatigue, hyperglycemia, and hypercholesterolemia. Conclusions: The combination of everolimus and pasireotide-LAR showed promising efficacy over single agent. The delayed combination of everolimus and pasireotide-LAR following progression on single agent everolimus appeared intriguing as a combination strategy. Full article
(This article belongs to the Special Issue Advances in Thyroid Cancer)
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14 pages, 560 KiB  
Article
Epidemiological, Clinical, Ultrasonographic and Cytological Characteristics of Thyroid Nodules in an Afro-Caribbean Population: A Series of 420 Patients
by Elodie Rano, Lucien Lin, Vincent Molinie, Caroline Sulpicy, Marie-Josée Dorival, Kinan Drak Alsibai, Mathieu Nacher, Moustafa Drame and Nadia Sabbah
Cancers 2022, 14(10), 2365; https://doi.org/10.3390/cancers14102365 - 11 May 2022
Viewed by 1466
Abstract
The incidence of thyroid cancer is increasing worldwide. The aim of this study is to describe the epidemiological, clinical and ultrasound characteristics of malignancy in thyroid nodules and to evaluate the predictive value of the Bethesda system for thyroid cytology in the diagnosis [...] Read more.
The incidence of thyroid cancer is increasing worldwide. The aim of this study is to describe the epidemiological, clinical and ultrasound characteristics of malignancy in thyroid nodules and to evaluate the predictive value of the Bethesda system for thyroid cytology in the diagnosis of malignancy in an Afro-Caribbean population. We conducted a retrospective study in Martinique involving 420 patients with a diagnosis of thyroid nodules between 2011 and 2014. Of the 192/420 (45.7%) patients operated on for thyroid nodules, 9% had thyroid cancer. All patients with thyroid cancer were obese women with a mean age of 50 years. The final histological examination revealed papillary microcarcinomas in 61% of cases and papillary carcinomas in 39% of cases. Thyroid cytology alone had a low sensitivity (22.2%) and positive predictive value (15.4%) for the diagnosis of malignancy, with a good specificity (91.1%) and negative predictive value (94.2%). None of the standard ultrasound criteria of malignancy were significantly predictive of cancer, but hypoechogenicity and central vascularity were frequently found in malignant nodules. These epidemiological, clinical and ultrasound results could increase awareness and guide practitioners in their diagnostic approach and management of thyroid nodules in an Afro-Caribbean population. Bethesda system-based cytology revealed lower sensitivity in analyzing the risk of malignancy in this population. The high prevalence of papillary microcarcinomas may explain the inconclusive ultrasound and cytological results. Full article
(This article belongs to the Special Issue Advances in Thyroid Cancer)
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Review

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14 pages, 998 KiB  
Review
Thyroid Cancer and Fibroblasts
by Angelica Avagliano, Giuseppe Fiume, Claudio Bellevicine, Giancarlo Troncone, Alessandro Venuta, Vittoria Acampora, Sabrina De Lella, Maria Rosaria Ruocco, Stefania Masone, Nunzio Velotti, Pietro Carotenuto, Massimo Mallardo, Carmen Caiazza, Stefania Montagnani and Alessandro Arcucci
Cancers 2022, 14(17), 4172; https://doi.org/10.3390/cancers14174172 - 29 Aug 2022
Cited by 7 | Viewed by 2461
Abstract
Thyroid cancer is the most common type of endocrine cancer, and its prevalence continue to rise. Non-metastatic thyroid cancer patients are successfully treated. However, looking for new therapeutic strategies is of great importance for metastatic thyroid cancers that still lead to death. With [...] Read more.
Thyroid cancer is the most common type of endocrine cancer, and its prevalence continue to rise. Non-metastatic thyroid cancer patients are successfully treated. However, looking for new therapeutic strategies is of great importance for metastatic thyroid cancers that still lead to death. With respect to this, the tumor microenvironment (TME), which plays a key role in tumor progression, should be considered as a new promising therapeutic target to hamper thyroid cancer progression. Indeed, thyroid tumors consist of cancer cells and a heterogeneous and ever-changing niche, represented by the TME, which contributes to establishing most of the features of cancer cells. The TME consists of extracellular matrix (ECM) molecules, soluble factors, metabolites, blood and lymphatic tumor vessels and several stromal cell types that, by interacting with each other and with tumor cells, affect TME remodeling, cancer growth and progression. Among the thyroid TME components, cancer-associated fibroblasts (CAFs) have gained more attention in the last years. Indeed, recent important evidence showed that thyroid CAFs strongly sustain thyroid cancer growth and progression by producing soluble factors and ECM proteins, which, in turn, deeply affect thyroid cancer cell behavior and aggressiveness. Hence, in this article, we describe the thyroid TME, focusing on the desmoplastic stromal reaction, which is a powerful indicator of thyroid cancer progression and an invasive growth pattern. In addition, we discuss the origins and features of the thyroid CAFs, their influence on thyroid cancer growth and progression, their role in remodeling the ECM and their immune-modulating functions. We finally debate therapeutic perspectives targeting CAFs. Full article
(This article belongs to the Special Issue Advances in Thyroid Cancer)
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24 pages, 414 KiB  
Review
Update on the Diagnosis and Management of Medullary Thyroid Cancer: What Has Changed in Recent Years?
by Krzysztof Kaliszewski, Maksymilian Ludwig, Bartłomiej Ludwig, Agnieszka Mikuła, Maria Greniuk and Jerzy Rudnicki
Cancers 2022, 14(15), 3643; https://doi.org/10.3390/cancers14153643 - 27 Jul 2022
Cited by 17 | Viewed by 4434
Abstract
Medullary thyroid carcinoma (MTC) is a neoplasm originating from parafollicular C cells. MTC is a rare disease, but its prognosis is less favorable than that of well-differentiated thyroid cancers. To improve the prognosis of patients with MTC, early diagnosis and prompt therapeutic management [...] Read more.
Medullary thyroid carcinoma (MTC) is a neoplasm originating from parafollicular C cells. MTC is a rare disease, but its prognosis is less favorable than that of well-differentiated thyroid cancers. To improve the prognosis of patients with MTC, early diagnosis and prompt therapeutic management are crucial. In the following paper, recent advances in laboratory and imaging diagnostics and also pharmacological and surgical therapies of MTC are discussed. Currently, a thriving direction of development for laboratory diagnostics is immunohistochemistry. The primary imaging modality in the diagnosis of MTC is the ultrasound, but opportunities for development are seen primarily in nuclear medicine techniques. Surgical management is the primary method of treating MTCs. There are numerous publications concerning the stratification of particular lymph node compartments for removal. With the introduction of more effective methods of intraoperative parathyroid identification, the complication rate of surgical treatment may be reduced. The currently used pharmacotherapy is characterized by high toxicity. Moreover, the main limitation of current pharmacotherapy is the development of drug resistance. Currently, there is ongoing research on the use of tyrosine kinase inhibitors (TKIs), highly specific RET inhibitors, radiotherapy and immunotherapy. These new therapies may improve the prognosis of patients with MTCs. Full article
(This article belongs to the Special Issue Advances in Thyroid Cancer)
22 pages, 1213 KiB  
Review
Looking at Thyroid Cancer from the Tumor-Suppressor Genes Point of View
by Sadegh Rajabi, Catherine Alix-Panabières, Arshia Sharbatdar Alaei, Raziyeh Abooshahab, Heewa Shakib and Mohammad Reza Ashrafi
Cancers 2022, 14(10), 2461; https://doi.org/10.3390/cancers14102461 - 17 May 2022
Viewed by 2935
Abstract
Thyroid cancer is the most frequent endocrine malignancy and accounts for approximately 1% of all diagnosed cancers. A variety of mechanisms are involved in the transformation of a normal tissue into a malignant one. Loss of tumor-suppressor gene (TSG) function is one of [...] Read more.
Thyroid cancer is the most frequent endocrine malignancy and accounts for approximately 1% of all diagnosed cancers. A variety of mechanisms are involved in the transformation of a normal tissue into a malignant one. Loss of tumor-suppressor gene (TSG) function is one of these mechanisms. The normal functions of TSGs include cell proliferation and differentiation control, genomic integrity maintenance, DNA damage repair, and signaling pathway regulation. TSGs are generally classified into three subclasses: (i) gatekeepers that encode proteins involved in cell cycle and apoptosis control; (ii) caretakers that produce proteins implicated in the genomic stability maintenance; and (iii) landscapers that, when mutated, create a suitable environment for malignant cell growth. Several possible mechanisms have been implicated in TSG inactivation. Reviewing the various TSG alteration types detected in thyroid cancers may help researchers to better understand the TSG defects implicated in the development/progression of this cancer type and to find potential targets for prognostic, predictive, diagnostic, and therapeutic purposes. Hence, the main purposes of this review article are to describe the various TSG inactivation mechanisms and alterations in human thyroid cancer, and the current therapeutic options for targeting TSGs in thyroid cancer. Full article
(This article belongs to the Special Issue Advances in Thyroid Cancer)
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