Advances in the Diagnosis and Treatment of Thyroid Carcinoma

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Causes, Screening and Diagnosis".

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 51371

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Special Issue Editors

Department of Surgical Sciences, University of Cagliari, Cagliari, Italy
Interests: endocrine surgery, thyroid, parathyroid, mini-invasive surgery
Special Issues, Collections and Topics in MDPI journals
Evang. Krankenhaus Essen-Mitte, Akademisches Lehrkrankenhaus der Universität Duisburg-Essen, Essen, Germany
Interests: thyroid, parathyroid, adrenal glands

Special Issue Information

Dear Colleagues,

In the last 40 years, the incidence of thyroid carcinoma has considerably increased, making it the most common endocrine malignancy. Even if, in most cases, the initial treatment is curative, a certain number of patients experience a poor course of the disease, with local or distant recurrence, and require further medical or surgical treatment, which considerably worsens their quality of life.

Indeed, thyroid cancer represents a heterogeneous disease, comprising different molecular and histological subtypes with distinct clinical behavior and prognosis.

In the last two decades, a great effort has been made to improve its diagnosis and surgical outcomes. Molecular biomarkers have been studied and introduced in clinical practice, and new pathological and clinical classifications have been proposed to take into account tumor behavior and risk of disease recurrence. At the same time, new devices and surgical approaches have been developed to improve radicality and reduce surgical trauma, including mini-invasive and remote access surgery, intraoperative monitoring of recurrent laryngeal nerve, and use of indocyanine green fluorescence to identify parathyroid glands.

Nevertheless, many issues remain a matter of debate, regarding, for example, the indication and extent of lymphectomy of the central compartment, the treatment of microcarcinoma, the therapeutic options for poorly differentiated and anaplastic carcinomas, and the indications and strategies in cases of recurrent disease.

This Special Issue of Cancers aims to present the latest research on the diagnosis and therapy of thyroid cancer.

Relevant topics include, but are not limited to:

  1. Thyroid cancer proteomics and metabolomics
  2. Advances in cytopathology and role of molecular markers in preoperative evaluation of thyroid nodules
  3. Treatment of microcarcinoma: surgical approach vs active surveillance
  4. Medullary thyroid carcinoma
  5. Intraoperative Nerve Monitoring (IONM) and experience with two-stage thyroidectomy
  6. Adequacy of lobo-isthmectomy in low and intermediate risk thyroid carcinoma
  7. Indications to prophylactic central compartment lymph node dissection
  8. Usefulness of indocyanine green fluorescence in preventing hypoparathyroidism
  9. The influence of lymph node metastasis on prognosis
  10. Predictive factors of structural recurrent disease
  11. Treatment of poorly differentiated and anaplastic thyroid carcinoma
  12. Therapeutic options for radioiodine-resistant thyroid cancer
  13. Indications and treatment of recurrent disease
  14. Remote access thyroidectomy

Dr. Fabio Medas
Dr. Pier Francesco Alesina
Guest Editors

Manuscript Submission Information

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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 carcinoma, molecular markers, lymph node metastasis, prophylactic central compartment lymph node dissection, radical neck dissection, intraoperative nerve monitoring, recurrent disease, mini-invasive thyroidectomy

Published Papers (18 papers)

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Research

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11 pages, 993 KiB  
Article
CONUT Score: A New Tool for Predicting Prognosis in Patients with Advanced Thyroid Cancer Treated with TKI
by Cristina Dalmiglio, Lucia Brilli, Michele Campanile, Cristina Ciuoli, Alessandra Cartocci and Maria Grazia Castagna
Cancers 2022, 14(3), 724; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14030724 - 30 Jan 2022
Cited by 11 | Viewed by 2473
Abstract
(1) Background: The Controlling Nutritional Status (CONUT) score is an immuno-nutritional screening tool based on serum albumin, total cholesterol, and lymphocyte count. The aim of the study was to assess the CONUT score as a potential prognostic factor of response to therapy in [...] Read more.
(1) Background: The Controlling Nutritional Status (CONUT) score is an immuno-nutritional screening tool based on serum albumin, total cholesterol, and lymphocyte count. The aim of the study was to assess the CONUT score as a potential prognostic factor of response to therapy in patients with advanced thyroid cancer treated with tyrosine kinase inhibitors (TKIs). (2) Methods: We retrospectively evaluated 42 metastatic thyroid cancer patients (54.8% female). The median age at the time of TKI treatment was 69 years. Histological diagnosis was differentiated thyroid cancer in 66.7%, poorly differentiated thyroid cancer in 21.4%, and medullary thyroid cancer in 11.9% of patients. CONUT score was assessed before starting TKI therapy. (3) Results: Progression-free survival (PFS) and overall survival (OS) were significantly influenced by baseline CONUT score. The best CONUT cut-off able to predict the response to treatment was 3. Both PFS and OS were better in patients with CONUT score <3 than in those with CONUT score ≥3 (p < 0.0001). CONUT score was the only independent prognostic factor associated with PFS (p = 0.021) and OS (p = 0.007). (4) Conclusions: CONUT score represents a relatively new screening tool, easily applicable in clinical practice and potentially useful in predicting prognosis in thyroid cancer patients treated with TKIs. Full article
(This article belongs to the Special Issue Advances in the Diagnosis and Treatment of Thyroid Carcinoma)
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9 pages, 1297 KiB  
Article
Optimal Surgical Extent in Patients with Unilateral Multifocal Papillary Thyroid Carcinoma
by Joohyun Woo and Hyungju Kwon
Cancers 2022, 14(2), 432; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14020432 - 15 Jan 2022
Cited by 3 | Viewed by 2319
Abstract
Multifocality increases the risk of recurrence in patients with papillary thyroid carcinoma (PTC); however, it is unclear whether multifocality justifies more extensive or aggressive surgical treatment. Here, we evaluated the effect of the operative extent on the recurrence-free survival (RFS) of patients with [...] Read more.
Multifocality increases the risk of recurrence in patients with papillary thyroid carcinoma (PTC); however, it is unclear whether multifocality justifies more extensive or aggressive surgical treatment. Here, we evaluated the effect of the operative extent on the recurrence-free survival (RFS) of patients with multifocal PTC. Between 2010 and 2019, 718 patients with unilateral multifocal PTC were enrolled; 115 patients (16.0%) underwent ipsilateral thyroid lobectomy, and 606 patients (84.0%) underwent total thyroidectomy. With a mean follow up of 5.2 years, RFS was comparable between the total thyroidectomy and lobectomy groups (p = 0.647) after adjusting for potential confounders. Multivariable Cox regression analysis also demonstrated that the operative extent was not an independent predictor of recurrence (HR 1.686, 95% CI: 0.321–8.852). Subgroup analyses further indicated that both total thyroidectomy and thyroid lobectomy resulted in comparable RFS for multifocal PTC patients with other high-risk factors, including tumor size > 1 cm (p = 0.711), lymph node metastasis (p = 0.536), and intermediate ATA risk of recurrence (p = 0.682). In conclusion, thyroid lobectomy was not associated with the risk of recurrence in patients with multifocal PTCs. Multifocality in PTC may not always require aggressive surgery. Full article
(This article belongs to the Special Issue Advances in the Diagnosis and Treatment of Thyroid Carcinoma)
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9 pages, 831 KiB  
Article
Use of Diagnostic Criteria from ACR and EU-TIRADS Systems to Improve the Performance of Cytology in Thyroid Nodule Triage
by Davide Seminati, Giulia Capitoli, Davide Leni, Davide Fior, Francesco Vacirca, Camillo Di Bella, Stefania Galimberti, Vincenzo L’Imperio and Fabio Pagni
Cancers 2021, 13(21), 5439; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13215439 - 29 Oct 2021
Cited by 15 | Viewed by 1994
Abstract
Objective: The American College of Radiology (ACR) and the European Thyroid Association (EU) have proposed two scoring systems for thyroid nodule classification. Here, we compared the ability of the two systems in triaging thyroid nodules for fine-needle aspiration (FNA) and tested the putative [...] Read more.
Objective: The American College of Radiology (ACR) and the European Thyroid Association (EU) have proposed two scoring systems for thyroid nodule classification. Here, we compared the ability of the two systems in triaging thyroid nodules for fine-needle aspiration (FNA) and tested the putative role of an approach that combines ultrasound features and cytology for the detection of malignant nodules. Design and Methods: The scores obtained with the ACR and EU Thyroid Imaging Reporting and Data Systems (TIRADS) from a prospective series of 480 thyroid nodules acquired from 435 subjects were compared to assess their performances in FNA triaging on the final cytological diagnosis. The US features that showed the highest contribution in discriminating benign nodules from malignancies were combined with cytology to improve its diagnostic performance. Results: FNA was recommended on 46.5% and 51.9% of the nodules using the ACR and EU-TIRADS scores, respectively. The ACR system demonstrated a higher specificity as compared to the EU-TIRADS (59.0% vs. 52.4%, p = 0.0012) in predicting ≥ TIR3A/III (SIAPEC/Bethesda) nodules. Moreover, specific radiological features (i.e., echogenic foci and margins), combined with the cytological classes improved the specificity (97.5% vs. 91%, p < 0.0001) and positive predictive values (77.5% vs. 50.7%, p < 0.0001) compared to cytology alone, especially in the setting of indeterminate nodules (TIR3A/III and TIR3B/IV), maintaining an excellent sensitivity and negative predictive value. Conclusions: The ACR-TIRADS system showed a higher specificity compared to the EU-TIRADS in triaging thyroid nodules. The use of specific radiological features improved the diagnostic ability of cytology. Full article
(This article belongs to the Special Issue Advances in the Diagnosis and Treatment of Thyroid Carcinoma)
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14 pages, 1827 KiB  
Article
Head-to-Head Comparison of Neck 18F-FDG PET/MR and PET/CT in the Diagnosis of Differentiated Thyroid Carcinoma Patients after Comprehensive Treatment
by Yangmeihui Song, Fang Liu, Weiwei Ruan, Fan Hu, Muhsin H. Younis, Zairong Gao, Jie Ming, Tao Huang, Weibo Cai and Xiaoli Lan
Cancers 2021, 13(14), 3436; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13143436 - 09 Jul 2021
Cited by 6 | Viewed by 2435
Abstract
We explored the clinical value of 18F-FDG PET/MR in a head-to-head comparison with PET/CT in loco-regional recurrent and metastatic cervical lymph nodes of differentiated thyroid carcinoma (DTC) patients after comprehensive treatment. 18F-FDG PET/CT and neck PET/MR scans that were performed in [...] Read more.
We explored the clinical value of 18F-FDG PET/MR in a head-to-head comparison with PET/CT in loco-regional recurrent and metastatic cervical lymph nodes of differentiated thyroid carcinoma (DTC) patients after comprehensive treatment. 18F-FDG PET/CT and neck PET/MR scans that were performed in DTC patients with suspected recurrence or cervical lymph node metastasis after comprehensive treatment were retrospectively analyzed. Detection rates, diagnostic efficacy, image conspicuity, and measured parameters were compared between 18F-FDG PET/CT and PET/MR. The gold standard was histopathological diagnosis or clinical and imaging follow-up results for more than 6 months. Among the 37 patients enrolled, no suspicious signs of tumor were found in 10 patients, 24 patients had lymph node metastasis, and 3 patients had both recurrence and lymph node metastases. A total of 130 lesions were analyzed, including 3 malignant and 6 benign thyroid nodules, as well as 74 malignant and 47 benign cervical lymph nodes. Compared with PET/CT, PET/MR presented better detection rates (91.5% vs. 80.8%), image conspicuity (2.74 ± 0.60 vs. 1.9 ± 0.50, p < 0.001, especially in complex level II), and sensitivity (80.5% vs. 61.0%). SUVmax differed in benign and malignant lymph nodes in both imaging modalities (p < 0.05). For the same lesion, the SUVmax, SUVmean, and diameters measured by PET/MR and PET/CT were consistent and had significant correlation. In conclusion, compared with 18F-FDG PET/CT, PET/MR was more accurate in determining recurrent and metastatic lesions, both from a patient-based and from a lesion-based perspective. Adding local PET/MR after whole-body PET/CT may be recommended to provide more precise diagnostic information and scope of surgical resection without additional ionizing radiation. Further scaling-up prospective studies and economic benefit analysis are expected. Full article
(This article belongs to the Special Issue Advances in the Diagnosis and Treatment of Thyroid Carcinoma)
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13 pages, 1346 KiB  
Article
Diagnostic Value of Galectin-3 in Distinguishing Invasive Encapsulated Carcinoma from Noninvasive Follicular Thyroid Neoplasms with Papillary-Like Nuclear Features (NIFTP)
by Guodong Fu, Olena Polyakova, Ronald S. Chazen, Jeremy L. Freeman and Ian J. Witterick
Cancers 2021, 13(12), 2988; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13122988 - 15 Jun 2021
Cited by 5 | Viewed by 2516
Abstract
Background: non-invasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP), which is considered as low-risk cancer, should be distinguished from the malignant invasive encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC). Improved discrimination of NIFTPs from invasive EFVPTCs using a molecular biomarker [...] Read more.
Background: non-invasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP), which is considered as low-risk cancer, should be distinguished from the malignant invasive encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC). Improved discrimination of NIFTPs from invasive EFVPTCs using a molecular biomarker test could provide useful insights into pre- and post-surgical management of the indeterminate thyroid nodule. Galectin-3 (Gal-3), a β-galactosyl-binding molecule in the lectin group, is involved in different biological functions in well differentiated thyroid carcinomas. The aim of this study was to determine whether Gal-3 expression as a diagnostic marker could distinguish indolent NIFTP from invasive EFVPTC on tissue specimens from surgical thyroid nodules. Methods: immunohistochemical (IHC) analysis of cytoplasmic and nuclear Gal-3 expression was performed in formalin-fixed paraffin-embedded (FFPE) surgical tissues in four specific diagnostic subgroups- benign nodules, NIFTPs, EFVPTCs and lymphocytic/Hashimoto’s thyroiditis (LTs). Results: cytoplasmic Gal-3 expression (mean ± SD) was significantly increased in invasive EFVPTCs (4.80 ± 1.60) compared to NIFTPs (2.75 ± 1.58, p < 0.001) and benign neoplasms (2.09 ± 1.19, p < 0.001) with no significant difference between NIFTPs and benign lesions (p = 0.064). The presence of LT enhanced cytoplasmic Gal-3 expression (3.80 ± 1.32) compared to NIFTPs (p = 0.016) and benign nodules (p < 0.001). Nuclear Gal-3 expression in invasive EFVPTCs (1.84 ± 1.30) was significantly higher than in NIFTPs (1.00 ± 0.72, p = 0.001), but similar to benign nodules (1.44 ± 1.77, p = 0.215), thereby obviating its potential clinical application. Conclusions: our observations have indicated that increased cytoplasmic Gal-3 expression shows diagnostic potential in distinguishing NIFTP among encapsulated follicular variant nodules thereby serving as a possible ancillary test to H&E histopathological diagnostic criteria when LT interference is absent, to assist in the detection of the invasive EFVPTC among such nodules. Full article
(This article belongs to the Special Issue Advances in the Diagnosis and Treatment of Thyroid Carcinoma)
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13 pages, 1080 KiB  
Article
18F-FDG-PET/CT in Patients with Advanced, Radioiodine Refractory Thyroid Cancer Treated with Lenvatinib
by Freba Ahmaddy, Caroline Burgard, Leonie Beyer, Viktoria Florentine Koehler, Peter Bartenstein, Matthias P. Fabritius, Thomas Geyer, Vera Wenter, Harun Ilhan, Christine Spitzweg and Andrei Todica
Cancers 2021, 13(2), 317; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13020317 - 16 Jan 2021
Cited by 14 | Viewed by 2220
Abstract
Background: The tyrosine kinase inhibitor (TKI) Lenvatinib represents one of the most effective therapeutic options in patients with advanced radioiodine refractory differentiated thyroid carcinoma (DTC). We aimed to assess the role of 2-deoxy-2-[18F] fluoro-D-glucose positron-emission-tomography/computed-tomography (18F-FDG-PET/CT) in the monitoring [...] Read more.
Background: The tyrosine kinase inhibitor (TKI) Lenvatinib represents one of the most effective therapeutic options in patients with advanced radioiodine refractory differentiated thyroid carcinoma (DTC). We aimed to assess the role of 2-deoxy-2-[18F] fluoro-D-glucose positron-emission-tomography/computed-tomography (18F-FDG-PET/CT) in the monitoring of functional tumor response compared to morphological response. Methods: In 22 patients, a modified Positron Emission Tomography Response Criteria In Solid Tumors (mPERCIST) evaluation before treatment with Lenvatinib and at 3 and 6 month follow up was performed. Further PET-parameters and morphologic tumor response using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 were assessed and their prediction of progression-free survival (PFS) and disease-specific survival (DSS) was evaluated. Results: Most patients were rated stable in morphological evaluation and progressive using a metabolic response. All patients who responded to therapy through RECIST showed a decline in nearly all Positron Emission Tomography (PET)-parameters. For both time-points, non-responders according to mPERCIST showed significantly lower median PFS and DSS, whereas according to RECIST, only DSS was significantly lower. Conclusion: Tumor response assessment by 18F-FDG-PET outperforms morphological response assessment by CT in patients with advanced radioiodine refractory DTC treated with Lenvatinib, which seems to be correlated with clinical outcomes. Full article
(This article belongs to the Special Issue Advances in the Diagnosis and Treatment of Thyroid Carcinoma)
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13 pages, 1393 KiB  
Article
Evaluation of Clinicopathological and Molecular Parameters on Disease Recurrence of Papillary Thyroid Cancer Patient: A Retrospective Observational Study
by Salvatore Sorrenti, Giovanni Carbotta, Filippo Maria Di Matteo, Antonio Catania, Daniele Pironi, Francesco Tartaglia, Danilo Tarroni, Federica Gagliardi, Domenico Tripodi, Mikiko Watanabe, Stefania Mariani, Eleonora D’Armiento, Poupak Fallahi, Alessandro Sindoni, Corrado De Vito, Alessandro Antonelli, Salvatore Ulisse and Enke Baldini
Cancers 2020, 12(12), 3637; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers12123637 - 04 Dec 2020
Cited by 18 | Viewed by 1714
Abstract
The American Joint Committee on Cancer has revised the Tumor-Node-Metastasis (TNM) staging system for papillary thyroid cancer (PTC) patients. We examined the impact of this new classification (TNM-8) on patient stratification and estimated the prognostic value of clinicopathological features for the disease-free interval [...] Read more.
The American Joint Committee on Cancer has revised the Tumor-Node-Metastasis (TNM) staging system for papillary thyroid cancer (PTC) patients. We examined the impact of this new classification (TNM-8) on patient stratification and estimated the prognostic value of clinicopathological features for the disease-free interval (DFI) in a cohort of 1148 PTC patients. Kaplan–Meier analyses showed that all clinicopathological parameters analyzed, except age and multifocality, were associated significantly with DFI. Cox regression identified tall cell PTC variant and stage as independent risk factors for DFI. When the stage was replaced with age, tumor size, and lymph node (LN) metastases in the set of covariates, the lateral LN metastases stood out as the strongest independent predictor of DFI, followed by tall cell variant and age. A noteworthy result emerging from these analyzes is that regression models had lower Akaike and Bayesian information criterions if variables were categorized based on the TNM-7. In addition, we examined data from a different PTC patient cohort, acquired from The Cancer Genome Atlas database, to verify whether the DFI prediction could be enhanced by further clinicopathological and molecular parameters. However, none of these was found to be a significant predictor of DFI in the Cox model. Full article
(This article belongs to the Special Issue Advances in the Diagnosis and Treatment of Thyroid Carcinoma)
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11 pages, 472 KiB  
Article
Effects of the Minimal Extrathyroidal Extension on Early Response Rates after (Adjuvant) Initial Radioactive Iodine Therapy in PTC Patients
by Freba Ahmaddy, Vera Wenter, Harun Ilhan, Daniel Wacker, Marcus Unterrainer, Thomas Knösel, Peter Bartenstein, Christine Spitzweg, Sebastian Lehner and Andrei Todica
Cancers 2020, 12(11), 3357; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers12113357 - 13 Nov 2020
Cited by 8 | Viewed by 1763
Abstract
Background: Extrathyroidal extension of differentiated thyroid cancer is a poor outcome factor but seems to be less significant in minimal extrathyroidal extension (mETE). However, the impact of mETE on response rate after (adjuvant) initial radioactive iodine (RAI) therapy remains unclear. We therefore compared [...] Read more.
Background: Extrathyroidal extension of differentiated thyroid cancer is a poor outcome factor but seems to be less significant in minimal extrathyroidal extension (mETE). However, the impact of mETE on response rate after (adjuvant) initial radioactive iodine (RAI) therapy remains unclear. We therefore compared response rates of patients with classical and follicular variants of papillary thyroid cancer (PTC) according to the updated eighth tumor-node-metastasis (TNM) classification to a control group. Methods: 455 patients with T3 (primary tumor > 4 cm) PTC according to the seventh classification who underwent total thyroidectomy followed by RAI therapy were screened. Patients formerly classified as T3 PTC solely due to mETE were reclassified into patients with T1 (primary tumor ≤ 2 cm) or T2 (primary tumor > 2 cm but ≤ 4 cm) +mETE and compared to a control group of T1/T2 −mETE PTC patients. Results: 138/455 patients were reclassified as T1/2 +mETE and compared to 317/455 T1/T2 −mETE control patients. At initial presentation, +mETE patients showed significantly higher rates of cervical lymph node metastases (p-value 0.001). Response rates were comparable in both groups (p-value n.s.). N1a/N1b-stage (Hazard ratio, HR 0.716; 95% CI 0.536–0.956, p-value 0.024) was identified as an independent prognostic factor for lower response rates. Conclusion: Response rates after RAI therapy were comparable in PTC patients irrespective of mETE but with higher rates of lymph node metastases. Full article
(This article belongs to the Special Issue Advances in the Diagnosis and Treatment of Thyroid Carcinoma)
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12 pages, 598 KiB  
Article
Results and Clinical Interpretation of Germline RET Analysis in a Series of Patients with Medullary Thyroid Carcinoma: The Challenge of the Variants of Uncertain Significance
by Giovanni Innella, Cesare Rossi, Maria Romagnoli, Andrea Repaci, Davide Bianchi, Maria Elena Cantarini, Davide Martorana, Lea Godino, Andrea Pession, Antonio Percesepe, Uberto Pagotto and Daniela Turchetti
Cancers 2020, 12(11), 3268; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers12113268 - 05 Nov 2020
Cited by 5 | Viewed by 2521
Abstract
Germline RET variants are responsible for approximately 25% of medullary thyroid carcinoma (MTC) cases. Identification of RET variant carriers allows for the adoption of preventative measures which are dependent on the risk associated with the specific alteration. From 2002 to 2020, at our [...] Read more.
Germline RET variants are responsible for approximately 25% of medullary thyroid carcinoma (MTC) cases. Identification of RET variant carriers allows for the adoption of preventative measures which are dependent on the risk associated with the specific alteration. From 2002 to 2020, at our cancer genetics clinic, RET genetic testing was performed in 163 subjects (102 complete gene analyses and 61 targeted analyses), 72 of whom presented with MTC. A germline RET variant was identified in 31.9% of patients affected by MTC (93.8% of those having positive family history and 14.3% of clinically sporadic cases). Subsequent target testing in relatives allowed us to identify 22 asymptomatic carriers, who could undertake appropriate screening. Overall, patients with germline RET variants differed significantly from those who tested negative by family history (p < 0.001) and mean age at MTC diagnosis (44.45 vs. 56.42 years; p = 0.010), but the difference was not significant when only carriers of moderate risk variants were considered (51.78 vs. 56.42 years; p = 0.281). Out of 12 different variants detected in 49 patients, five (41.7%) were of uncertain significance (VUS). For two of these, p.Ser904Phe and p.Asp631_Leu633delinsGlu, co-segregation and genotype/phenotype analysis, matched with data from the literature, provided evidence supporting their classification in the moderate and the highest/high risk class (with a MEN2B phenotype), respectively. Full article
(This article belongs to the Special Issue Advances in the Diagnosis and Treatment of Thyroid Carcinoma)
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12 pages, 860 KiB  
Article
Prophylactic Central Lymph Node Dissection Improves Disease-Free Survival in Patients with Intermediate and High Risk Differentiated Thyroid Carcinoma: A Retrospective Analysis on 399 Patients
by Fabio Medas, Gian Luigi Canu, Federico Cappellacci, Giacomo Anedda, Giovanni Conzo, Enrico Erdas and Pietro Giorgio Calò
Cancers 2020, 12(6), 1658; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers12061658 - 23 Jun 2020
Cited by 30 | Viewed by 3094
Abstract
The role of prophylactic central lymph node dissection (pCLND) in the treatment of differentiated thyroid cancer (DTC) is controversial and still a matter of debate. The primary outcome of our study was to assess whether pCLND is effective in reducing the incidence of [...] Read more.
The role of prophylactic central lymph node dissection (pCLND) in the treatment of differentiated thyroid cancer (DTC) is controversial and still a matter of debate. The primary outcome of our study was to assess whether pCLND is effective in reducing the incidence of recurrent disease, and the secondary goal was to estimate the incidence of postoperative complications in patients who underwent pCLND and to evaluate the prognostic value of occult node metastases. In this retrospective study, we included patients with preoperative diagnosis of DTC and clinically uninvolved lymph nodes (cN0). The patients were divided into two groups, depending on the surgical approach: total thyroidectomy alone (TT group) or total thyroidectomy and pCLND (pCLND group). Three hundred and ninety-nine patients were included in this study, 320 (80.2%) in the TT group and 79 (19.8%) in the pCLND group. There were no significant differences in morbidity among the two groups. Histopathological evaluation demonstrated a similar distribution of aggressive features, especially regarding multicentricity, extrathyroidal extension, and angioinvasivity between the two groups. Occult lymph node metastases were found in 20 (25.3%) patients in the pCLND group. Prophylactic CLND was effective in improving disease-free survival in patients with intermediate and high risk of disease recurrence (p = 0.0392); occult lymph node metastases resulted as a significant negative prognostic factor (p < 0.001). Full article
(This article belongs to the Special Issue Advances in the Diagnosis and Treatment of Thyroid Carcinoma)
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Review

Jump to: Research

12 pages, 720 KiB  
Review
Current Management of Bone Metastases from Differentiated Thyroid Cancer
by Satoshi Kato, Satoru Demura, Kazuya Shinmura, Noriaki Yokogawa, Takaki Shimizu and Hiroyuki Tsuchiya
Cancers 2021, 13(17), 4429; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13174429 - 02 Sep 2021
Cited by 16 | Viewed by 3696
Abstract
After the lung, the skeleton is the second most common site of distant metastases in differentiated thyroid carcinoma (DTC). Patients with osteolytic bone metastases (BMs) from thyroid carcinoma often have significantly reduced performance status and quality of life. Recent advancements in cancer therapy [...] Read more.
After the lung, the skeleton is the second most common site of distant metastases in differentiated thyroid carcinoma (DTC). Patients with osteolytic bone metastases (BMs) from thyroid carcinoma often have significantly reduced performance status and quality of life. Recent advancements in cancer therapy have improved overall survival in multiple cancer subtypes, including thyroid cancer. Therefore, long-term local control of thyroid BMs is desired, especially in patients with a single metastasis or oligometastases. Here, we reviewed the current management options for DTC-BMs and especially focused on local treatments for long-term local tumor control from an orthopedic tumor surgeon’s point of view. Metastasectomy and stereotactic radiosurgery can be performed either alone or in combination with radioiodine therapy and kinase inhibitors to cure skeletal lesions in selected patients. Percutaneous procedures have been developed in recent years, and they can also have a curative role in small BMs. Recent advancements in local therapies have the potential to provide not only long-term local tumor control but also a better prognosis. Full article
(This article belongs to the Special Issue Advances in the Diagnosis and Treatment of Thyroid Carcinoma)
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16 pages, 844 KiB  
Review
PRKAR1A and Thyroid Tumors
by Georgia Pitsava, Constantine A. Stratakis and Fabio R. Faucz
Cancers 2021, 13(15), 3834; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13153834 - 30 Jul 2021
Cited by 10 | Viewed by 3184
Abstract
Thyroid cancer is the most common type of endocrine malignancy and the incidence is rapidly increasing. Follicular (FTC) and papillary thyroid (PTC) carcinomas comprise the well-differentiated subtype and they are the two most common thyroid carcinomas. Multiple molecular genetic and epigenetic alterations have [...] Read more.
Thyroid cancer is the most common type of endocrine malignancy and the incidence is rapidly increasing. Follicular (FTC) and papillary thyroid (PTC) carcinomas comprise the well-differentiated subtype and they are the two most common thyroid carcinomas. Multiple molecular genetic and epigenetic alterations have been identified in various types of thyroid tumors over the years. Point mutations in BRAF, RAS as well as RET/PTC and PAX8/PPARγ chromosomal rearrangements are common. Thyroid cancer, including both FTC and PTC, has been observed in patients with Carney Complex (CNC), a syndrome that is inherited in an autosomal dominant manner and predisposes to various tumors. CNC is caused by inactivating mutations in the tumor-suppressor gene encoding the cyclic AMP (cAMP)-dependent protein kinase A (PKA) type 1α regulatory subunit (PRKAR1A) mapped in chromosome 17 (17q22–24). Growth of the thyroid is driven by the TSH/cAMP/PKA signaling pathway and it has been shown in mouse models that PKA activation through genetic ablation of the regulatory subunit Prkar1a can cause FTC. In this review, we provide an overview of the molecular mechanisms contributing to thyroid tumorigenesis associated with inactivation of the RRKAR1A gene. Full article
(This article belongs to the Special Issue Advances in the Diagnosis and Treatment of Thyroid Carcinoma)
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24 pages, 1143 KiB  
Review
Fluorescence Image-Guided Surgery for Thyroid Cancer: Utility for Preventing Hypoparathyroidism
by Marco Stefano Demarchi, Barbara Seeliger, Jean-Christophe Lifante, Pier Francesco Alesina and Frédéric Triponez
Cancers 2021, 13(15), 3792; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13153792 - 28 Jul 2021
Cited by 24 | Viewed by 3032
Abstract
Background: Hypoparathyroidism is one of the most frequent complications of thyroid surgery, especially when associated with lymph node dissection in cases of thyroid cancer. Fluorescence-guided surgery is an emerging tool that appears to help reduce the rate of this complication. The present review [...] Read more.
Background: Hypoparathyroidism is one of the most frequent complications of thyroid surgery, especially when associated with lymph node dissection in cases of thyroid cancer. Fluorescence-guided surgery is an emerging tool that appears to help reduce the rate of this complication. The present review aims to highlight the utility of fluorescence imaging in preserving parathyroid glands during thyroid cancer surgery. Methods: We performed a systematic review of the literature according to PRISMA guidelines to identify published studies on fluorescence-guided thyroid surgery with a particular focus on thyroid cancer. Articles were selected and analyzed per indication and type of surgery, autofluorescence or exogenous dye usage, and outcomes. The Methodological Index for Non-Randomized Studies (MINORS) was used to assess the methodological quality of the included articles. Results: Twenty-five studies met the inclusion criteria, with three studies exclusively assessing patients with thyroid cancer. The remaining studies assessed mixed cohorts with thyroid cancer and other thyroid or parathyroid diseases. The majority of the papers support the potential benefit of fluorescence imaging in preserving parathyroid glands in thyroid surgery. Conclusions: Fluorescence-guided surgery is useful in the prevention of post-thyroidectomy hypoparathyroidism via enhanced early identification, visualization, and preservation of the parathyroid glands. These aspects are notably beneficial in cases of associated lymphadenectomy for thyroid cancer. Full article
(This article belongs to the Special Issue Advances in the Diagnosis and Treatment of Thyroid Carcinoma)
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18 pages, 3328 KiB  
Review
Poorly Differentiated and Anaplastic Thyroid Cancer: Insights into Genomics, Microenvironment and New Drugs
by Alessandro Prete, Antonio Matrone, Carla Gambale, Liborio Torregrossa, Elisa Minaldi, Cristina Romei, Raffaele Ciampi, Eleonora Molinaro and Rossella Elisei
Cancers 2021, 13(13), 3200; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13133200 - 26 Jun 2021
Cited by 18 | Viewed by 4990
Abstract
PDTC and ATC present median overall survival of 6 years and 6 months, respectively. In spite of their rarity, patients with PDTC and ATC represent a significant clinical problem, because of their poor survival and the substantial inefficacy of classical therapies. We reviewed [...] Read more.
PDTC and ATC present median overall survival of 6 years and 6 months, respectively. In spite of their rarity, patients with PDTC and ATC represent a significant clinical problem, because of their poor survival and the substantial inefficacy of classical therapies. We reviewed the newest findings about genetic features of PDTC and ATC, from mutations occurring in DNA to alterations in RNA. Therefore, we describe their tumor microenvironments (both immune and not-immune) and the interactions between tumor and neighboring cells. Finally, we recapitulate how this upcoming evidence are changing the treatment of PDTC and ATC. Full article
(This article belongs to the Special Issue Advances in the Diagnosis and Treatment of Thyroid Carcinoma)
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28 pages, 5987 KiB  
Review
Next-Generation Molecular Imaging of Thyroid Cancer
by Yuchen Jin, Beibei Liu, Muhsin H. Younis, Gang Huang, Jianjun Liu, Weibo Cai and Weijun Wei
Cancers 2021, 13(13), 3188; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13133188 - 25 Jun 2021
Cited by 6 | Viewed by 3733
Abstract
An essential aspect of thyroid cancer (TC) management is personalized and precision medicine. Functional imaging of TC with radioiodine and [18F]FDG has been frequently used in disease evaluation for several decades now. Recently, advances in molecular imaging have led to the [...] Read more.
An essential aspect of thyroid cancer (TC) management is personalized and precision medicine. Functional imaging of TC with radioiodine and [18F]FDG has been frequently used in disease evaluation for several decades now. Recently, advances in molecular imaging have led to the development of novel tracers based on aptamer, peptide, antibody, nanobody, antibody fragment, and nanoparticle platforms. The emerging targets—including HER2, CD54, SHP2, CD33, and more—are promising targets for clinical translation soon. The significance of these tracers may be realized by outlining the way they support the management of TC. The provided examples focus on where preclinical investigations can be translated. Furthermore, advances in the molecular imaging of TC may inspire the development of novel therapeutic or theranostic tracers. In this review, we summarize TC-targeting probes which include transporter-based and immuno-based imaging moieties. We summarize the most recent evidence in this field and outline how these emerging strategies may potentially optimize clinical practice. Full article
(This article belongs to the Special Issue Advances in the Diagnosis and Treatment of Thyroid Carcinoma)
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19 pages, 715 KiB  
Review
Prognostic and Therapeutic Role of Angiogenic Microenvironment in Thyroid Cancer
by Assunta Melaccio, Lucia Ilaria Sgaramella, Alessandro Pasculli, Giovanna Di Meo, Angela Gurrado, Francesco Paolo Prete, Angelo Vacca, Roberto Ria and Mario Testini
Cancers 2021, 13(11), 2775; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13112775 - 03 Jun 2021
Cited by 11 | Viewed by 2536
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Advances in the Diagnosis and Treatment of Thyroid Carcinoma)
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19 pages, 960 KiB  
Review
Radiomics in Differentiated Thyroid Cancer and Nodules: Explorations, Application, and Limitations
by Yuan Cao, Xiao Zhong, Wei Diao, Jingshi Mu, Yue Cheng and Zhiyun Jia
Cancers 2021, 13(10), 2436; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13102436 - 18 May 2021
Cited by 19 | Viewed by 2956
Abstract
Radiomics is an emerging technique that allows the quantitative extraction of high-throughput features from single or multiple medical images, which cannot be observed directly with the naked eye, and then applies to machine learning approaches to construct classification or prediction models. This method [...] Read more.
Radiomics is an emerging technique that allows the quantitative extraction of high-throughput features from single or multiple medical images, which cannot be observed directly with the naked eye, and then applies to machine learning approaches to construct classification or prediction models. This method makes it possible to evaluate tumor status and to differentiate malignant from benign tumors or nodules in a more objective manner. To date, the classification and prediction value of radiomics in DTC patients have been inconsistent. Herein, we summarize the available literature on the classification and prediction performance of radiomics-based DTC in various imaging techniques. More specifically, we reviewed the recent literature to discuss the capacity of radiomics to predict lymph node (LN) metastasis, distant metastasis, tumor extrathyroidal extension, disease-free survival, and B-Raf proto-oncogene serine/threonine kinase (BRAF) mutation and differentiate malignant from benign nodules. This review discusses the application and limitations of the radiomics process, and explores its ability to improve clinical decision-making with the hope of emphasizing its utility for DTC patients. Full article
(This article belongs to the Special Issue Advances in the Diagnosis and Treatment of Thyroid Carcinoma)
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14 pages, 299 KiB  
Review
Differentiated Thyroid Cancer: A Health Economic Review
by Klaas Van Den Heede, Neil S. Tolley, Aimee N. Di Marco and Fausto F. Palazzo
Cancers 2021, 13(9), 2253; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13092253 - 07 May 2021
Cited by 15 | Viewed by 2082
Abstract
The incidence of differentiated thyroid cancer (DTC) is rising, mainly because of an increased detection of asymptomatic thyroid nodularity revealed by the liberal use of thyroid ultrasound. This review aims to reflect on the health economic considerations associated with the increasing diagnosis and [...] Read more.
The incidence of differentiated thyroid cancer (DTC) is rising, mainly because of an increased detection of asymptomatic thyroid nodularity revealed by the liberal use of thyroid ultrasound. This review aims to reflect on the health economic considerations associated with the increasing diagnosis and treatment of DTC. Overdiagnosis and the resulting overtreatment have led to more surgical procedures, increasing health care and patients’ costs, and a large pool of community-dwelling thyroid cancer follow-up patients. Additionally, the cost of thyroid surgery seems to increase year on year even when inflation is taken into account. The increased healthcare costs and spending have placed significant pressure to identify potential factors associated with these increased costs. Some truly ground-breaking work in health economics has been undertaken, but more cost-effectiveness studies and micro-cost analyses are required to evaluate expenses and guide future solutions. Full article
(This article belongs to the Special Issue Advances in the Diagnosis and Treatment of Thyroid Carcinoma)
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