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Thyroid Cancer: Diagnosis, Prognosis and Treatment

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

Deadline for manuscript submissions: closed (15 January 2024) | Viewed by 11021

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Prof. Dr. Luca Giovanella

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1. Clinic for Nuclear Medicine and Molecular Imaging, Imaging Institute of Southern Switzerland, Ente Ospedaliero Cantonale, 6500 Bellinzona, Switzerland
2. Clinic for Nuclear Medicine and Intedisciplinary Thyroid Centre, University Hospital of Zurich, 8091 Zurich, Switzerland
Interests: nuclear medicine; molecular imaging; theranostics; thyroid diseases; endocrine tumors; radiomics; predictive imaging; molecular biomarkers; integrated diagnostics
Special Issues, Collections and Topics in MDPI journals

Dr. Petra Petranović Ovčariček

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Department of Oncology and Nuclear Medicine, University Hospital Center Sestre Milosrdnice, Zagreb, Croatia
Interests: thyroid diseases; nuclear medicine; molecular imaging; theranostics; endocrine tumors
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Thyroid cancer is the most common malignancy of the endocrine system, representing approximately 4% of all new cancer cases. The prognosis and treatment of thyroid cancer depend on the tumor type and its stage at the time of diagnosis. Early diagnosis and appropriate treatment can improve prognosis and reduce mortality. The well-established treatments (surgery and radioiodine) and new options (molecular targeting drugs) for patients with aggressive thyroid cancers have kept the mortality rate from this malignancy low, despite the increase in its incidence. This Special Issue will highlight the role of different diagnostic procedures (i.e., ultrasound, molecular imaging, laboratory, cytology, and molecular cytology), therapeutic approaches (i.e., surgery, theranostics, hormone therapy, non-invasive procedures, radiotherapy, molecular targeting drugs, redifferentiating agents), and prognostic markers in personalized thyroid cancer treatment.

Prof. Dr. Luca Giovanella
Dr. Petra Petranović Ovčariček
Guest Editors

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Keywords

thyroid cancer
ultrasound
molecular imaging
fine-needle aspiration cytology
thyroidectomy
radioactive iodine
radioiodine-refractory thyroid cancer
tyrosine kinase inhibitors

Published Papers (9 papers)

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Research

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0 pages, 1052 KiB

Open AccessArticle

Relationship between the Expression of CHK2 and p53 in Tumor Tissue and the Course of Papillary Thyroid Cancer in Patients with CHEK2 Germline Mutations

by Danuta Gąsior-Perczak, Artur Kowalik, Janusz Kopczyński, Paweł Macek, Kornelia Niemyska, Agnieszka Walczyk, Krzysztof Gruszczyński, Monika Siołek, Tomasz Dróżdż, Marcin Kosowski, Iwona Pałyga, Piotr Przybycień, Olga Wabik, Stanisław Góźdź and Aldona Kowalska

Cancers 2024, 16(4), 815; https://doi.org/10.3390/cancers16040815 - 17 Feb 2024

Viewed by 825

Abstract

The aim of this study was to determine whether the expression of CHK2 and p53 in tumor tissue in carriers of germline CHEK2 mutations can serve as a prognostic marker for PTC, and whether CHEK2 and TP53 copy numbers correlates with the course of PTC disease. This study included 156 PTC patients previously tested for the presence of CHEK2. Clinicopathological features, treatment response, disease outcome, and germline mutation status of the CHEK2 gene were assessed with respect to CHK2 and p53 expression, and CHEK2 and TP53 gene copy statuses. In patients with and without a germline mutation in CHEK2 and with higher CHK2 expression, the chances of an excellent treatment response and no evidence of disease were lower than in patients without or with lower CHK2 expression. TP53 deletion was associated with angioinvasion. In patients with a truncating mutation, the chance of a CHEK2 deletion was higher than in patients with WT CHEK2 alone or those with WT CHEK2 and with the missense I157T mutation. Higher CHK2 expression was associated with poorer treatment responses and disease outcomes. Higher CHK2 expression and positive p53 together with a TP53 deletion could be a prognostic marker of unfavorable disease outcomes in patients with germline truncating mutations in CHEK2. Full article

(This article belongs to the Special Issue Thyroid Cancer: Diagnosis, Prognosis and Treatment)

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17 pages, 3085 KiB

Open AccessArticle

Differentiating Benign from Malignant Thyroid Tumors by Kinase Activity Profiling and Dabrafenib BRAF V600E Targeting

by Riet Hilhorst, Adrienne van den Berg, Piet Boender, Tom van Wezel, Tim Kievits, Rik de Wijn, Rob Ruijtenbeek, Willem E. Corver and Hans Morreau

Cancers 2023, 15(18), 4477; https://doi.org/10.3390/cancers15184477 - 8 Sep 2023

Cited by 1 | Viewed by 1234

Abstract

Differentiated non-medullary thyroid cancer (NMTC) can be effectively treated by surgery followed by radioactive iodide therapy. However, a small subset of patients shows recurrence due to a loss of iodide transport, a phenotype frequently associated with BRAF V600E mutations. In theory, this should enable the use of existing targeted therapies specifically designed for BRAF V600E mutations. However, in practice, generic or specific drugs aimed at molecular targets identified by next generation sequencing (NGS) are not always beneficial. Detailed kinase profiling may provide additional information to help improve therapy success rates. In this study, we therefore investigated whether serine/threonine kinase (STK) activity profiling can accurately classify benign thyroid lesions and NMTC. We also determined whether dabrafenib (BRAF V600E-specific inhibitor), as well as sorafenib and regorafenib (RAF inhibitors), can differentiate BRAF V600E from non-BRAF V600E thyroid tumors. Using 21 benign and 34 malignant frozen thyroid tumor samples, we analyzed serine/threonine kinase activity using PamChip^®peptide microarrays. An STK kinase activity classifier successfully differentiated malignant (26/34; 76%) from benign tumors (16/21; 76%). Of the kinases analyzed, PKC (theta) and PKD1 in particular, showed differential activity in benign and malignant tumors, while oncocytic neoplasia or Graves’ disease contributed to erroneous classifications. Ex vivo BRAF V600E-specific dabrafenib kinase inhibition identified 6/92 analyzed peptides, capable of differentiating BRAF V600E-mutant from non-BRAF V600E papillary thyroid cancers (PTCs), an effect not seen with the generic inhibitors sorafenib and regorafenib. In conclusion, STK activity profiling differentiates benign from malignant thyroid tumors and generates unbiased hypotheses regarding differentially active kinases. This approach can serve as a model to select novel kinase inhibitors based on tissue analysis of recurrent thyroid and other cancers. Full article

(This article belongs to the Special Issue Thyroid Cancer: Diagnosis, Prognosis and Treatment)

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14 pages, 3621 KiB

Open AccessArticle

Portrait of the Inflammatory Response to Radioiodine Therapy in Female Patients with Differentiated Thyroid Cancer with/without Type 2 Diabetes Mellitus

by Adina Elena Stanciu, Anca Hurduc, Marcel Marian Stanciu, Mirela Gherghe, Dan Cristian Gheorghe, Virgiliu Mihail Prunoiu and Adina Zamfir-Chiru-Anton

Cancers 2023, 15(15), 3793; https://doi.org/10.3390/cancers15153793 - 26 Jul 2023

Viewed by 991

Abstract

No clinical studies have investigated the effect of radioiodine (¹³¹I)-targeted therapy on the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) as inflammatory response markers in patients with differentiated thyroid cancer (DTC) associated with type 2 diabetes mellitus (T2DM) and obesity. This study aimed to assess the relationship between blood radioactivity, body mass index (BMI), and peripheral blood cells three days after ¹³¹I intake in 56 female patients without T2DM (DTC/−T2DM) vs. 24 female patients with T2DM (DTC/+T2DM). Blood radioactivity, measured three days after ¹³¹I intake, was significantly lower in the DTC/+T2DM than in the DTC/−T2DM patients (0.7 mCi vs. 1.5 mCi, p < 0.001). The relationship between blood radioactivity and BMI (r = 0.83, p < 0.001), blood radioactivity and NLR (r = 0.53, p = 0.008), and BMI and NLR (r = 0.58, p = 0.003) indicates a possible connection between the bloodstream ¹³¹I uptake and T2DM-specific chronic inflammation. In patients without T2DM, ¹³¹I therapy has immunosuppressive effects, leading to increased NLR (19.6%, p = 0.009) and PLR (39.1%, p = 0.002). On the contrary, in the chronic inflammation context of T2DM, ¹³¹I therapy amplifies immune metabolism, leading to a drop in NLR (10%, p = 0.032) and PLR (13.4%, p = 0.021). Our results show that, in DTC/+T2DM, the bidirectional crosstalk between neutrophils and obesity may limit ¹³¹I uptake in the bloodstream. Considering the immune response to ¹³¹I therapy, the two groups of patients can be seen as a synchronous portrait of two sides. The explanation could lie in the different radiosensitivity of T and B lymphocytes, with T lymphocytes being predominant in patients with DTC/−T2DM and, most likely, B lymphocytes being predominant in T2DM. Full article

(This article belongs to the Special Issue Thyroid Cancer: Diagnosis, Prognosis and Treatment)

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11 pages, 651 KiB

Open AccessArticle

Clinical Implication of Bilateral and Unilateral Multifocality in Papillary Thyroid Carcinoma: A Propensity Score-Matched Study

by Youngmin Kim, Solji An, Joonseon Park, Ja Seong Bae, Jeong Soo Kim and Kwangsoon Kim

Cancers 2023, 15(14), 3596; https://doi.org/10.3390/cancers15143596 - 13 Jul 2023

Viewed by 1020

Abstract

Papillary thyroid cancer (PTC) is commonly characterized by multifocality, which is associated with aggressive features and a less favorable prognosis. The current study aimed to compare the clinicopathologic characteristics and long-term oncological outcomes of bilateral and unilateral multifocal PTC. The medical records of 1745 patients with multifocal PTC who underwent thyroid surgery at Seoul St. Mary’s Hospital were retrospectively reviewed. The clinicopathological characteristics and recurrence rates were compared based on cancer laterality. Further, 357 patients who underwent total thyroidectomy were matched to investigate the recurrence risk and disease-free survival (DFS). Before propensity score matching (PSM), there was no significant difference in the recurrence rate between the bilateral and unilateral multifocal PTC groups. Cancer laterality was not a predictor of DFS based on the Cox regression analyses. However, after PSM, unilateral multifocality was associated with a significantly high risk of recurrence. Similarly, unilateral multifocality was associated with a significantly poor DFS based on the Kaplan–Meier analysis. Compared with bilateral PTC, unilateral multifocal PTC was associated with a poor DFS. A comprehensive preoperative examination should be performed to detect multifocality before the initial surgical intervention for optimal treatment. Postoperative short-term follow-up is recommended for unilateral multifocal PTC for recurrence surveillance. Full article

(This article belongs to the Special Issue Thyroid Cancer: Diagnosis, Prognosis and Treatment)

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9 pages, 1775 KiB

Open AccessArticle

Radioiodine-131 Therapy Used for Differentiated Thyroid Cancer Can Impair Titanium Dental Implants: An In Vitro Analysis

by Doina Piciu, Simion Bran, Marioara Moldovan, Simona Varvara, Andra Piciu, Stanca Cuc, Cristina Moisescu-Goia, Elena Barbus, Alexandru Mester and Florin Onisor

Cancers 2023, 15(9), 2558; https://doi.org/10.3390/cancers15092558 - 29 Apr 2023

Viewed by 1170

Abstract

Background: The aim was to assess, in vitro, the effects of radioiodine-131 (I-131) on the structure of titanium implants. Material and Methods: A total of 28 titanium implants were divided into 7 groups (n = 4) and irradiated at 0, 6, 12, 24, 48, 192 and 384 hours. At the end of the experiment, each sample was investigated via scanning electron microscopy (SEM) and electrochemical measures. Results: The control sample revealed a smooth and compact surface. The small micro-sized porosity is slightly visible at the macroscopic level, but the precise details cannot be observed. A mild exposure to the radioactive solution for 6 to 24 h showed a good preservation of the macro-structural aspects such as thread details and surface quality. Significant changes occurred after 48 h of exposure. It was noticed that the open-circuit potential (OCP) value of the non-irradiated implants move toward more noble potentials during the first 40 min of exposure to the artificial saliva and then stabilizes at a constant value of −143 mV. A displacement of the OCP values toward more negative values was observed for all irradiated implants; these potential shifts are decreasing, as the irradiation period of the tested implants increased. Conclusion: After exposure to I-131, the structure of titanium implants is well preserved up to 12 h. The eroded particles start to appear in the microstructural details after 24 h of exposure and their numbers progressively increase up to 384 h after exposure. Full article

(This article belongs to the Special Issue Thyroid Cancer: Diagnosis, Prognosis and Treatment)

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14 pages, 1066 KiB

Open AccessArticle

Thyroglobulin Value Predict Iodine-123 Imaging Result in Differentiated Thyroid Cancer Patients

by Alfredo Campennì, Rosaria Maddalena Ruggeri, Massimiliano Siracusa, Davide Romano, Giulia Giacoppo, Ludovica Crocè, Helena Rosarno, Simona Russo, Davide Cardile, Francesca Capoccetti, Angela Alibrandi, Sergio Baldari and Luca Giovanella

Cancers 2023, 15(8), 2242; https://doi.org/10.3390/cancers15082242 - 11 Apr 2023

Cited by 1 | Viewed by 1446

Abstract

Background: In differentiated thyroid cancer (DTC) patients, the response to initial treatments is evaluated 6–12 months after radioiodine therapy (RIT) according to the 2015 American Thyroid Association (2015 ATA) criteria. In selected patients, diagnostic 131-radioiodine whole-body scintigraphy (Dx-WBS) is recommended. We evaluated the diagnostic performance of ¹²³I-Dx-WBS-SPECT/CT imaging in detecting incomplete structural responses in the early follow-up of DTC patients and, additionally, derived optimized basal-Tg value as a yardstick for scintigraphic imaging. Methods: We reviewed the records of 124 low or intermediate-risk DTC patients with negative anti-thyroglobulin antibody. All patients had undergone (near)-total-thyroidectomy followed by RIT. The response to initial treatments was evaluated 6–12 months after RIT. Results: According to the 2015 ATA criteria, 87, 19 and 18 DTC patients were classified to have excellent response (ER), indeterminate/incomplete biochemical response (BIndR/BIR) or structural incomplete response (SIR), respectively. Among patients with less than ER, 18 had a positive ¹²³I-Dx-WBS-SPECT/CT. Metastatic disease at ¹²³I-Dx-WBS-SPECT/CT mainly involved lymph nodes within the central compartment, and corresponding neck ultrasound examinations were negative. The ROC curve analysis was performed to define the best basal-Tg cut-off (i.e., 0.39 ng/mL; AUC = 0.852) able to discriminate patients with and without positive ¹²³I-Dx-WBS-SPECT/CT, respectively. The overall sensitivity, specificity, accuracy, PPV and NPV were 77.8%, 89.6%, 87.9%, 56.0% and 95.9%, respectively. Basal-Tg cut-off was an independent risk factor for having a positive ¹²³I-Dx-WBS-SPECT/CT. Conclusion: ¹²³I-Dx-WBS-SPECT/CT identified lymph node metastases in 14/37 patients with less than ER and a negative neck ultrasound, thus modifying the management of such patients. The diagnostic performance of ¹²³I-Dx-WBS-SPECT/CT significantly increased in patients with basal-Tg values ≥ 0.39 ng/mL. Full article

(This article belongs to the Special Issue Thyroid Cancer: Diagnosis, Prognosis and Treatment)

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Review

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12 pages, 1689 KiB

Open AccessReview

Theranostic Risk Stratification for Thyroid Cancer in the Genomic Paradigm

by Seza A. Gulec and Evander Meneses

Cancers 2024, 16(8), 1585; https://doi.org/10.3390/cancers16081585 - 20 Apr 2024

Viewed by 512

Abstract

Theranostics define diagnostic evaluations directing patient-specific therapeutic decisions. Molecular theranostics involves genomic, transcriptomic, proteomic, metabolomic and finally phenonic definitions thyroid cancer differentiation. It is the functional differentiation that determines the sensitivity and accuracy of RAI imaging as well as the effectiveness of RAI treatment. Total thyroidectomy is performed to empower an anticipated RAI treatment. A preoperative determination of the genomic and transcriptomic profile of the tumor is a strong predictor of response to therapeutic interventions. This article discusses the oncopathophysiologic basis of the theranostic risk stratification approach. Full article

(This article belongs to the Special Issue Thyroid Cancer: Diagnosis, Prognosis and Treatment)

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12 pages, 248 KiB

Open AccessReview

Advances in the Development of Positron Emission Tomography Tracers for Improved Detection of Differentiated Thyroid Cancer

by Hannelore Iris Coerts, Bart de Keizer and Frederik Anton Verburg

Cancers 2024, 16(7), 1401; https://doi.org/10.3390/cancers16071401 - 2 Apr 2024

Viewed by 804

Abstract

Thyroid cancer poses a significant challenge in clinical management, necessitating precise diagnostic tools and treatment strategies for optimal patient outcomes. This review explores the evolving field of radiotracers in the diagnosis and management of thyroid cancer, focusing on prostate-specific membrane antigen (PSMA)-based radiotracers, fibroblast activation protein inhibitor (FAPI)-based radiotracers, Arg-Gly-Asp (RGD)-based radiotracers, and ¹⁸F-tetrafluoroborate (¹⁸F-TFB). PSMA-based radiotracers, initially developed for prostate cancer imaging, have shown promise in detecting thyroid cancer lesions; however, their detection rate is lower than ¹⁸F-FDG PET/CT. FAPI-based radiotracers, targeting fibroblast activation protein highly expressed in tumors, offer potential in the detection of lymph nodes and radioiodine-resistant metastases. RGD-based radiotracers, binding to integrin αvβ3 found on tumor cells and angiogenic blood vessels, demonstrate diagnostic accuracy in detecting radioiodine-resistant thyroid cancer metastases. ¹⁸F-TFB emerges as a promising PET tracer for imaging of lymph node metastases and recurrent DTC, offering advantages over traditional methods. Overall, these radiotracers show promise in enhancing diagnostic accuracy, patient stratification, and treatment selection in differentiated thyroid cancer, warranting further research and clinical validation. Given the promising staging capabilities of 18F-TFB and the efficacy of FAP-targeting tracers in advanced, potentially dedifferentiated cases, continued investigation in these domains is justified. Full article

(This article belongs to the Special Issue Thyroid Cancer: Diagnosis, Prognosis and Treatment)

26 pages, 6348 KiB

Open AccessReview

Integrated Diagnostics of Thyroid Nodules

by Luca Giovanella, Alfredo Campennì, Murat Tuncel and Petra Petranović Ovčariček

Cancers 2024, 16(2), 311; https://doi.org/10.3390/cancers16020311 - 11 Jan 2024

Viewed by 1700

Abstract

Thyroid nodules are common findings, particularly in iodine-deficient regions. Our paper aims to revise different diagnostic tools available in clinical thyroidology and propose their rational integration. We will elaborate on the pros and cons of thyroid ultrasound (US) and its scoring systems, thyroid scintigraphy, fine-needle aspiration cytology (FNAC), molecular imaging, and artificial intelligence (AI). Ultrasonographic scoring systems can help differentiate between benign and malignant nodules. Depending on the constellation or number of suspicious ultrasound features, a FNAC is recommended. However, hyperfunctioning thyroid nodules are presumed to exclude malignancy with a very high negative predictive value (NPV). Particularly in regions where iodine supply is low, most hyperfunctioning thyroid nodules are seen in patients with normal thyroid-stimulating hormone (TSH) levels. Thyroid scintigraphy is essential for the detection of these nodules. Among non-toxic thyroid nodules, a careful application of US risk stratification systems is pivotal to exclude inappropriate FNAC and guide the procedure on suspicious ones. However, almost one-third of cytology examinations are rendered as indeterminate, requiring “diagnostic surgery” to provide a definitive diagnosis. ^99mTc-methoxy-isobutyl-isonitrile ([^99mTc]Tc-MIBI) and [¹⁸F]fluoro-deoxy-glucose ([¹⁸F]FDG) molecular imaging can spare those patients from unnecessary surgeries. The clinical value of AI in the evaluation of thyroid nodules needs to be determined. Full article

(This article belongs to the Special Issue Thyroid Cancer: Diagnosis, Prognosis and Treatment)

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