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JCM
Special Issues
New Strategies in the Treatment of Thyroid Carcinoma
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New Strategies in the Treatment of Thyroid Carcinoma

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Oncology".

Deadline for manuscript submissions: closed (15 February 2024) | Viewed by 5791

Special Issue Editor

Prof. Dr. Seza Ali Gulec

E-Mail Website
Guest Editor
1. HCA Florida, Aventura Hospital, Miami, FL, USA
2. Miami Cancer Research Center, Miami, FL, USA
3. Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA
Interests: thyroid and parathyroid diseases; molecular imaging; radionuclide therapy; dosimetry

Special Issue Information

Dear Colleagues,

The new millennium has marked the beginning of individualized therapeutic approaches in cancer treatments. Cancer is not a single disease. Cancer initiation and progression involve multiple mechanisms and pathways. The identification of the critical steps and molecules in the process allows for the devising of disease- and patient-specific (individualized) treatment protocols. This concept is known as “Theranostics”. Theranostics is an innovative phrase combining the terms diagnosis and therapy. It is best defined as the direct linking of diagnostic information to therapeutic interventions. The goal in the development of patient-specific cancer treatments in this new paradigm is identifying diagnostic tools with theranostics value that can influence a particular therapeutic intervention, determine their theranostics power, and develop as well as implement clinical protocols with high theranostics performance.

The new paradigm in the management of thyroid cancer involves molecular and nuclear theranostics. Under this umbrella, we place a number of small molecules for targeted therapy, slight differences in modes of action producing substantial differences in therapeutic impact. The molecular theranostics concept not only directly influences RAI theranostics, but also initial and subsequent surgical interventions. RAI is the epitome of theranostics; however, the theranostics power of RAI is substantially depressed due to the genetic and epigenetic aberrations in cancer cells involving the expressions and functions of specific molecules.

This Special Issue of the JCM will review the evolving role of molecular therapies in the context of theranostics value in thyroid cancer. Special emphasis will be given to MAPK pathway modulation as a novel therapeutic strategy, the new techniques and approaches in RAI treatment, and, in lieu of molecular innovations, the changes in surgical treatment philosophy.

Prof. Dr. Seza Ali Gulec
Guest Editor

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 short 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. Journal of Clinical Medicine 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 2600 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
  • thyroidectomy
  • radioactive iodine (RAI)
  • theranostics
  • molecular theranostics
  • RAI theranostics

Published Papers (7 papers)

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Research

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10 pages, 1164 KiB  
Article
An Artificial Intelligence System for Optimizing Radioactive Iodine Therapy Dosimetry
by Michalis F. Georgiou, Joshua A. Nielsen, Rommel Chiriboga and Russ A. Kuker
J. Clin. Med. 2024, 13(1), 117; https://doi.org/10.3390/jcm13010117 - 25 Dec 2023
Cited by 1 | Viewed by 1083
Abstract
Thyroid cancer, specifically differentiated thyroid carcinoma (DTC), is one of the most prevalent endocrine malignancies worldwide. Radioactive iodine therapy (RAIT) using I-131 has been a standard-of-care approach for DTC due to its ability to ablate remnant thyroid disease following surgery, thus reducing the [...] Read more.
Thyroid cancer, specifically differentiated thyroid carcinoma (DTC), is one of the most prevalent endocrine malignancies worldwide. Radioactive iodine therapy (RAIT) using I-131 has been a standard-of-care approach for DTC due to its ability to ablate remnant thyroid disease following surgery, thus reducing the risk of recurrence. It is also used for the treatment of iodine-avid metastases. RAIT dosimetry can be employed to determine the optimal treatment dose of I-131 to effectively treat cancer cells while safeguarding against undesirable radiation effects such as bone marrow toxicity or radiation pneumonitis. Conventional dosimetry protocols for RAIT, however, are complex and time-consuming, involving multiple days of imaging and blood sampling. This study explores the use of Artificial Intelligence (AI) in simplifying and optimizing RAIT. A retrospective analysis was conducted on 83 adult patients with DTC who underwent RAIT dosimetry at our institution between 1996 and 2023. The conventional MIRD-based dosimetry protocol involved imaging and blood sampling at 4, 24, 48, 72, and 96 h post-administration of a tracer activity of I-131. An AI system based on a deep-learning neural network was developed to predict the maximum permissible activity (MPA) for RAIT using only the data obtained from the initial 4, 24, and 48 h time points. The AI system predicted the MPA values with high accuracy, showing no significant difference compared to the results obtained from conventional MIRD-based analysis utilizing a paired t-test (p = 0.351, 95% CI). The developed AI system offers the potential to streamline the dosimetry process, reducing the number of imaging and blood sampling sessions while also optimizing resource allocation. Additionally, the AI approach can uncover underlying relationships in data that were previously unknown. Our findings suggest that AI-based dosimetry may be a promising method for patient-specific treatment planning in differentiated thyroid carcinoma, representing a step towards applying precision medicine for thyroid cancer. Further validation and implementation studies are warranted to assess the clinical applicability of the AI system. Full article
(This article belongs to the Special Issue New Strategies in the Treatment of Thyroid Carcinoma)
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9 pages, 761 KiB  
Communication
Substance P and Neurokinin-1 Receptor System in Thyroid Cancer: Potential Targets for New Molecular Therapies
by Inmaculada Isorna, Miguel Ángel González-Moles, Miguel Muñoz and Francisco Esteban
J. Clin. Med. 2023, 12(19), 6409; https://doi.org/10.3390/jcm12196409 - 9 Oct 2023
Viewed by 1020
Abstract
In recent years, numerous approaches have been developed to comprehend the molecular alterations underlying thyroid cancer (TC) oncogenesis and explore novel therapeutic strategies for TC. It is now well established that the neurokinin-1 receptor (NK-1R) is overexpressed in cancer cells and that NK-1R [...] Read more.
In recent years, numerous approaches have been developed to comprehend the molecular alterations underlying thyroid cancer (TC) oncogenesis and explore novel therapeutic strategies for TC. It is now well established that the neurokinin-1 receptor (NK-1R) is overexpressed in cancer cells and that NK-1R is essential for the viability of cancer cells. The binding of substance P (SP) to NK-1R in neoplastic cells plays a pivotal role in cancer progression by promoting neoplastic cell growth, protecting tumor cells from apoptosis, triggering invasion and metastasis through the enhanced migration of cancer cells, and stimulating endothelial cell proliferation for tumor angiogenesis. Remarkably, all types of human TC (papillary, follicular, medullary, anaplastic), as well as metastatic lesions, exhibit the overexpression of SP and NK-1R compared to the normal thyroid gland. TC cells synthesize and release SP, which exerts its multiple functions through autocrine, paracrine, intracrine, and neuroendocrine processes, including the regulation of tumor burden. Consequently, the secretion of SP from TC results in increased SP levels in plasma, which are significantly higher in TC patients compared to controls. Additionally, NK-1R antagonists have demonstrated a dose-dependent antitumor action. They impair cancer cell proliferation on one side and induce apoptosis of tumor cells on the other side. Furthermore, it has been demonstrated that NK-1R antagonists inhibit neoplastic cell migration, thereby impairing both invasiveness and metastatic abilities, as well as angiogenesis. Given the consistent overexpression of NK-1R in all types of TC, targeting this receptor represents a promising therapeutic approach for TC. Therefore, NK-1R antagonists, such as the drug aprepitant, may represent novel drugs for TC treatment. Full article
(This article belongs to the Special Issue New Strategies in the Treatment of Thyroid Carcinoma)
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Review

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16 pages, 323 KiB  
Review
Diagnostic, Theranostic and Prognostic Value of Thyroglobulin in Thyroid Cancer
by Luca Giovanella, Federica D’Aurizio, Petra Petranović Ovčariček and Rainer Görges
J. Clin. Med. 2024, 13(9), 2463; https://doi.org/10.3390/jcm13092463 - 23 Apr 2024
Viewed by 701
Abstract
Thyroglobulin (Tg) is an iodinated glycoprotein, which is normally stored in the follicular colloid of the thyroid, being a substrate for thyroid hormone production. Since it is produced by well-differentiated thyroid cells, it is considered a reliable tumor marker for patients with differentiated [...] Read more.
Thyroglobulin (Tg) is an iodinated glycoprotein, which is normally stored in the follicular colloid of the thyroid, being a substrate for thyroid hormone production. Since it is produced by well-differentiated thyroid cells, it is considered a reliable tumor marker for patients with differentiated thyroid carcinoma (DTC) during their follow-up after total thyroidectomy and radioiodine ablation. It is used to monitor residual disease and to detect recurrent disease. After total thyroid ablation, unstimulated highly sensitive Tg measurements are sufficiently accurate to avoid exogenous or endogenous thyrotropin (TSH) stimulation and provide accurate diagnostic and prognostic information in the great majority of DTC patients. Adopting sophisticated statistical analysis, i.e., decision tree models, the use of Tg before radioiodine theranostic administration was demonstrated to be useful in refining conventional, pathology-based risk stratification and providing personalized adjuvant or therapeutic radioiodine administrations. The follow-up of DTC patients aims to promptly identify patients with residual or recurrent disease following primary treatment. Our review paper covers the diagnostic, theranostic and prognostic value of thyroglobulin in DTC patients. Full article
(This article belongs to the Special Issue New Strategies in the Treatment of Thyroid Carcinoma)
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12 pages, 277 KiB  
Review
Recurrent Laryngeal Nerve Intraoperative Neuromonitoring Indications in Non-Thyroid and Non-Parathyroid Surgery
by Aina Brunet, Aleix Rovira, Miquel Quer, Alvaro Sanabria, Orlando Guntinas-Lichius, Mark Zafereo, Dana M. Hartl, Andrés Coca-Pelaz, Ashok R. Shaha, Jean-Paul Marie, Vincent Vander Poorten, Cesare Piazza, Luiz P. Kowalski, Gregory W. Randolph, Jatin P. Shah, Alessandra Rinaldo and Ricard Simo
J. Clin. Med. 2024, 13(8), 2221; https://doi.org/10.3390/jcm13082221 - 11 Apr 2024
Viewed by 481
Abstract
Introperative nerve monitoring (IONM) of the recurrent laryngeal nerve (RLN) is a well-established technique to aid in thyroid/parathyroid surgery. However, there is little evidence to support its use in non-thyroid or non-parathyroid surgery. The aim of this paper was to review the current [...] Read more.
Introperative nerve monitoring (IONM) of the recurrent laryngeal nerve (RLN) is a well-established technique to aid in thyroid/parathyroid surgery. However, there is little evidence to support its use in non-thyroid or non-parathyroid surgery. The aim of this paper was to review the current evidence regarding the use of IONM in non-thyroid/non-parathyroid surgery in the head and neck and thorax. A literature search was performed from their inception up to January 2024, including the term “recurrent laryngeal nerve monitoring”. IONM in non-thyroid/non-parathyroid surgery has mainly been previously described in oesophageal surgery and in tracheal resections. However, there is little published evidence on the role of IONM with other resections in the vicinity of the RLN. Current evidence is low-level for the use of RLN IONM in non-thyroid/non-parathyroid surgery. However, clinicians should consider its use in surgery for pathologies where the RLN is exposed and could be injured. Full article
(This article belongs to the Special Issue New Strategies in the Treatment of Thyroid Carcinoma)
13 pages, 3265 KiB  
Review
Pre-Treatment and Post-Treatment I-131 Imaging in Differentiated Thyroid Carcinoma
by Jasna Mihailović
J. Clin. Med. 2024, 13(7), 1984; https://doi.org/10.3390/jcm13071984 - 29 Mar 2024
Viewed by 556
Abstract
Radioiodine imaging in initial perioperative settings, after the total thyroidectomy, includes pre-treatment and post-treatment radioiodine imaging. While the benefit of post-treatment whole-body imaging (PT-WBI) is well established, the role of diagnostic whole-body imaging (dx WBI), prior to radioiodine (I-131) ablative or therapeutic doses, [...] Read more.
Radioiodine imaging in initial perioperative settings, after the total thyroidectomy, includes pre-treatment and post-treatment radioiodine imaging. While the benefit of post-treatment whole-body imaging (PT-WBI) is well established, the role of diagnostic whole-body imaging (dx WBI), prior to radioiodine (I-131) ablative or therapeutic doses, is controversial. Dx WBI has been abandoned in most nuclear medicine centers long ago. Planar low-dose dxWBI provides the volume of postoperative thyroid remnants, but it cannot detect occult metastatic foci in the neck. The modern integrated multimodality, i.e., SPECT/CT imaging, provides three dimensional images and accurate anatomic/metabolic data. This hybrid technology offers better spatial resolution but not better sensitivity. Dx WBI has low theranostic power because of the radioiodine indifference and low detection sensitivity for small-volume nodal disease in the neck. Since dx WBI cannot clarify the paratracheal cervical uptake, thyroid remnants may be easily misinterpreted as nodal disease, leading to a false N upstaging (from N0 stage to N1 stage) in DTC patients. Post-ablation I-131 imaging has a significant role in the initial staging of radioiodine-avid DTC and in the identification of non-radioiodine avid tumors. Additionally, SPECT/CT in the post-treatment setting provides more accurate initial TNM staging and better risk stratification of DTC patients. Post-treatment I-131 imaging is obligatory and must be performed in all DTC patients who receive radioiodine treatment. Full article
(This article belongs to the Special Issue New Strategies in the Treatment of Thyroid Carcinoma)
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15 pages, 2700 KiB  
Review
Techniques for Thyroidectomy and Functional Neck Dissection
by Orhan Agcaoglu, Serkan Sucu, Safa Toprak and Serdar Tezelman
J. Clin. Med. 2024, 13(7), 1914; https://doi.org/10.3390/jcm13071914 - 26 Mar 2024
Viewed by 686
Abstract
Thyroidectomy is a commonly performed surgery for thyroid cancer, Graves’ disease, and thyroid nodules. With the increasing incidence of thyroid cancer, understanding the anatomy and surgical techniques is crucial to ensure successful outcomes and minimize complications. This review discusses the anatomical considerations of [...] Read more.
Thyroidectomy is a commonly performed surgery for thyroid cancer, Graves’ disease, and thyroid nodules. With the increasing incidence of thyroid cancer, understanding the anatomy and surgical techniques is crucial to ensure successful outcomes and minimize complications. This review discusses the anatomical considerations of the thyroid and neck, including lymphatic drainage and the structures at risk during thyroidectomy. Emphasis is placed on the significance of cautious dissection to preserve critical structures, such as the parathyroid glands and recurrent laryngeal nerve. Neck dissection is also explored, particularly in cases of lymph node metastasis, in which its proper execution is essential for better survival rates. Additionally, this review evaluates various thyroidectomy techniques, including minimally invasive approaches, highlighting their potential benefits and limitations. Continuous surgical knowledge and expertise updates are necessary to ensure the best results for patients undergoing thyroidectomy. Full article
(This article belongs to the Special Issue New Strategies in the Treatment of Thyroid Carcinoma)
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10 pages, 207 KiB  
Review
Current State of Molecular Cytology in Thyroid Nodules: Platforms and Their Diagnostic and Theranostic Utility
by Zeina C. Hannoush, Roberto Ruiz-Cordero, Mark Jara and Atil Y. Kargi
J. Clin. Med. 2024, 13(6), 1759; https://doi.org/10.3390/jcm13061759 - 19 Mar 2024
Cited by 1 | Viewed by 750
Abstract
The high prevalence of thyroid nodules and increased availability of neck ultrasound have led to an increased incidence of diagnostic thyroid fine needle aspirations, with approximately 20% yielding indeterminate results. The recent availability of molecular tests has helped guide the clinical management of [...] Read more.
The high prevalence of thyroid nodules and increased availability of neck ultrasound have led to an increased incidence of diagnostic thyroid fine needle aspirations, with approximately 20% yielding indeterminate results. The recent availability of molecular tests has helped guide the clinical management of these cases. This paper aims to review and compare three main commercially available molecular cytology platforms in the U.S.—Afirma GSC, Thyroseq GC, and ThyGeNEXT + ThyraMIR. Sequential improvements of the Afirma GSC and Thyroseq GC tests have increased positive and negative predictive values, sensitivity, and specificity. Comparative studies revealed similar diagnostic performance between these tests, with considerations for factors such as cost and processing time. Thyroseq GC provides detailed genomic information and specific management recommendations. ThyGeNEXT + ThyraMIR, though less studied, presents promising results, particularly in miRNA analysis for weak driver mutations. Challenges in interpreting results include variations in reporting and the evolving nature of testing platforms. Questions persist regarding cost-effectiveness and the utility of ultrasound characteristics in selecting candidates for molecular testing. While molecular testing has primarily served diagnostic purposes, advancements in understanding genetic alterations now offer therapeutic implications. FDA-approved options target specific genetic alterations, signaling a promising future for tailored treatments. Full article
(This article belongs to the Special Issue New Strategies in the Treatment of Thyroid Carcinoma)
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