Differentiated Thyroid Cancer Research Articles

Ultrasound-guided approach to surgery for nodal recurrence following lateral neck dissection for differentiated thyroid carcinoma. A single institution experience.

Total thyroidectomy (TT) and central neck dissection (CND) had a significant effect on the reduction of local recurrence compared with TT alone. Lateral Neck Dissection (LND) was performed in all the cases with therapeutic intent. The suspicion of nodal recurrence is provided by the appearance of one or more enlarged nodes in the central and/or laterocervical compartment during the follow up period. From January 2018 to November 2023, 16 patients at the University General Surgery unit of the Polyclinic of Foggia underwent reoperation due to nodal recurrence after previously undergoing total thyroidectomy with central and lateral cervical dissection. All surgical interventions were approached with intraoperative ultrasound performed by the operating surgeon. In all cases, ultrasound identification of the suspicious lymph node led to histological confirmation of malignancy. In only two cases it was necessary to carry out an extemporaneous intraoperative histological examination. No complications were recorded during the operations. Surgical reintervention in patients with nodal recurrence is challenging and requires an assessment by members of the interdisciplinary team. The ideal method should be economically convenient, easy to practice, with a quick learning curve, easily reproducible, and safe for patients. Intraoperative, ultrasound-guided, is a safe and effective technique. It facilitates tumor localization and removal, especially in patients requiring re-operative neck surgery.

Update on lacrimal apparatus dysfunction associated with differentiated thyroid cancer after I-131 therapy.

The most prevalent lacrimal apparatus dysfunctions associated with differentiated thyroid cancer(DTC) after I-131 therapy are dry eye and nasolacrimal duct obstruction(NLDO), leading to ocular discomfort and lower quality of life for patients. It is crucial to diagnose and manage lacrimal apparatus dysfunction associated with I-131 therapy for DTC. Therefore, this review aims to comprehensively summarize and analyze the advances in mechanisms and therapeutic options underlying lacrimal apparatus dysfunction induced by I-131 therapy for DTC. A comprehensive search of CNKI, PubMed, and Wed of Science was performed from the database to December of 2023. Key search terms were "Thyroid cancer", "I-131", "Complications", "Dry eye", "Epiphora", "Tear", "Nasolacrimal duct" and "NLDO". The research indicates that I-131 therapy for DTC causes damage to the lacrimal glands and nasolacrimal duct system, resulting in symptoms such as dry eye, epiphora, and mucoid secretions. Moreover, recent research has focused on exploring relevant risk factors of the condition and experimental and clinical treatments. However, there is some controversy regarding the mechanisms involved, whether it is due to the passive flow of I-131 in tears, active uptake of I-131 by the sodium-iodide symporter (NIS) in the lacrimal sac and nasolacrimal duct, or secondary metabolic and hormonal disturbances caused by I-131. It is crucial for early detection and preventive measures by ophthalmologists and the need for further studies to elucidate the mechanisms underlying the disease.

Clinical Significance of Diffuse Hepatic Uptake on Post-Therapeutic 131I- Whole Body Scan in Differentiated Thyroid Cancer

Clinical Significance of Diffuse Hepatic Uptake on Post-Therapeutic 131I- Whole Body Scan in Differentiated Thyroid Cancer

Pregnancy Outcome and Health Status of The Offsprings of Differentiated Thyroid Cancer Patients Who Accidentally Conceived within two years of Radioiodine Therapy

Pregnancy Outcome and Health Status of The Offsprings of Differentiated Thyroid Cancer Patients Who Accidentally Conceived within two years of Radioiodine Therapy

Molecular Perspectives in Radioactive Iodine Theranostics: Current Redifferentiation Protocols for Mis-Differentiated Thyroid Cancer.

Thyroid cancer molecular oncogenesis involves functional dedifferentiation. The initiating genomic alterations primarily affect the MAPK pathway signal transduction and generate an enhanced ERK output, which in turn results in suppression of the expression of transcription of the molecules of iodine metabolomics. The clinical end result of these molecular alterations is an attenuation in theranostic power of radioactive iodine (RAI). The utilization of RAI in systemic therapy of metastatic disease requires restoration of the functional differentiation. This concept has been accomplished by modulation of MAPK signaling. Objective responses have been demonstrated in metastatic disease settings. RAI-refractoriness in "differentiated thyroid cancers" remains a clinical problem despite optimized RAI administration protocols. Functional mis-differentiation and associated RAI-indifference are the underlying primary obstacles. MAPK pathway modulation offers a potential for reversal of RAI-indifference and combat refractoriness. This review presents the latest clinical experience and protocols for the redifferentiation of radioiodine-refractory mis-differentiated thyroid cancer, providing a comprehensive overview of the current protocols and intervention strategies used by leading institutions. Timing and techniques of imaging, thyrotropin (TSH) stimulation methods, and redifferentiation agents are presented. The efficacy and limitations of various approaches are discussed, providing an overview of the advantages and disadvantages associated with each of the protocols.

Enhancing Predictive Accuracy for Differentiated Thyroid Cancer (DTC) Recurrence Through Advanced Data Mining Techniques

Enhancing Predictive Accuracy for Differentiated Thyroid Cancer (DTC) Recurrence Through Advanced Data Mining Techniques

Thyroid carcinomas: the role of systemic therapies in internal medicine

The molecular pathogenesis of thyroid carcinoma is well studied and of importance for the treatment of advanced stages. Differentiated, poorly differentiated and anaplastic carcinomas originate in the follicular cells, while medullary carcinomas derive from the C‑cells. The prognosis of differentiated thyroid carcinoma is generally very favourable after surgery and radioiodine therapy. Where tumours progress and lose the ability to enrich iodine, curative treatment is usually not possible. Astrategy of watchful waiting is often appropriate. Activating mutations in BRAF or gene fusions of RET and NTRK provide opportunities for targeted therapies. These may be applied with the aim of restoring iodine uptake (redifferentiation). In the absence of molecular therapy targets, multityrosine kinase inhibitors (MKI) are the therapy of choice. If anaplastic thyroid carcinoma is suspected, rapid diagnostic workup including molecular pathology is warranted. Surgery where possible and radiochemotherapy are essential components of therapy. In the presence of aBRAF mutation, inhibition of BRAF and MEK is effective, even if it is not approved in Germany. Where molecular targets are lacking, combination therapy with the MKI lenvatinib and immune checkpoint inhibition is highly effective. Mutations in RET are present in the vast majority of cases of medullary thyroid carcinoma. In aggressive advanced disease, selective RET inhibition has recently been approved as first-line therapy and often leads to an objective response and long-lasting disease stabilisation. In summary, thyroid carcinomas are among the tumour entities for which molecularly targeted therapies can be used most frequently. The involvement of specialised centres is advisable.

Initial versus Staged Thyroidectomy for Differentiated Thyroid Cancer: A Retrospective Multi-Dimensional Cohort Analysis of Effectiveness and Safety.

The optimal surgical approach for differentiated thyroid cancer remains controversial, with debate regarding the comparative risks of upfront total thyroidectomy versus staged completion thyroidectomy following the initial lobectomy. This study aimed to assess the complication rates associated with these two strategies and identify the optimal timing for completion thyroidectomy using a multi-dimensional analysis of four cohorts: an institutional series (n = 148), the National Surgical Quality Improvement Program (NSQIP) database (n = 39,992), the TriNetX repository (n > 30,000), and a pooled literature review (10 studies, n = 6015). Institutional data revealed higher overall complication rates with total thyroidectomy (18.3%) compared to completion thyroidectomy (6.8%), primarily due to increased temporary hypocalcemia (10% vs. 0%, p = 0.004). The NSQIP analysis demonstrated that total thyroidectomy was associated with a 72% increased risk of transient hypocalcemia (p < 0.001) and a 25% increased risk of permanent hypocalcemia (p < 0.001). TriNetX data confirmed these findings and identified obesity and concurrent neck dissection as risk factors for complications. A meta-analysis showed that total thyroidectomy increased the rates of transient (RR = 1.63) and permanent (RR = 1.23) hypocalcemia (p < 0.001). Institutional and TriNetX data suggested that performing completion thyroidectomy between 1 and 6 months after the initial lobectomy minimized permanent complication rates compared to delays beyond 6 months. In conclusion, for differentiated thyroid cancer, total thyroidectomy is associated with higher risks of transient and permanent hypocalcemia compared to staged completion thyroidectomy. However, performing completion thyroidectomy within 1-6 months of the initial lobectomy may mitigate the risk of permanent complications. These findings can inform personalized surgical decision-making for patients with differentiated thyroid cancer.

The Long Journey towards Personalized Targeted Therapy in Poorly Differentiated Thyroid Carcinoma (PDTC): A Case Report and Systematic Review.

Poorly differentiated thyroid carcinoma (PDTC) has an intermediate prognosis between indolent well-differentiated thyroid carcinoma (TC) and anaplastic carcinoma. Herein, we present a case report with a PDTC component, along with a systematic review of the literature. We report a case of a 45-year-old man diagnosed with a PDTC component, along with hobnail and tall-cell variant features positive for BRAFV600E mutation, after a total thyroidectomy and neck dissection. Radioactive iodine (RAI)-131 therapy was applied, but an early recurrence led to complementary surgeries. The anti-Tg rise, the presence of new lymph nodes, and the negative whole-bodyradioiodine scan were suggestive of a radioiodine-resistant tumor. Lenvatinib, sorafenib, dabrafenib/trametinib, cabozantinib and radiotherapy were all administered, controlling the tumor for a period of time before the patient ultimately died post-COVID infection. Systematic Review: We searched PubMed, Scopus, and WebofScience to identify studies reporting clinicopathological characteristics, molecular marker expression, and management of non-anaplastic TC with any proportion of PDTC in adult patients. Of the 2007 records retrieved, 82were included in our review (PROSPERO-ID545847). Our case, together with the systematic review, imply that a combination of molecular-targetedtreatments may be safe and effective in patients with RAI-resistantBRAF-mutated advanced PDTC when surgery has failed to control tumor progression.

Poorly Differentiated Thyroid Cancer—Still a Clinical Dilemma: A Case Study

Poorly Differentiated Thyroid Cancer—Still a Clinical Dilemma: A Case Study

Lobectomy in patients with differentiated thyroid cancer: experience of a Chilean tertiary center.

Thyroid lobectomy (TL) is an appropriate treatment for up to 4 cm intrathyroidal differentiated thyroid cancer (DTC). There is scarce data regarding TL outside first-world centers. Our aim is to report a cohort of patients with DTC treated with TL in Chile. We included DTC patients treated with TL, followed for at least 6 months, characterized their clinicopathological features and classified their risk of recurrence and response to treatment. Eighty-two patients followed for a median of 2.3 years (0.5-7.0). Seventy-three (89%) patients had papillary, 8 (9.8%) follicular and 1 (1.2%) high-grade DTC. The risk of recurrence was low in 56 (68.3%) and intermediate in 26 (31.7%). Eight (9.8%) patients required early completion thyroidectomy and radioiodine. At last follow-up, 52 (70.3%) had excellent, 19 (25.7%) had indeterminate, and 1 (1.4%) had structural incomplete response. In a developing country, TL is an adequate option for appropriately selected DTC patients.

Risk of Lymphoma and Leukemia in Thyroid Cancer Patients: A Retrospective Cohort Study in Germany.

Thyroid cancer is the ninth most common cancer worldwide. While differentiated thyroid cancer (DTC) has a high survival rate, concerns arise regarding optimal treatment strategies and potential long-term risks, including second primary malignancies (SPMs), associated with therapies such as radioiodine (RAI). The aim of the present study was to investigate the association between thyroid cancer and the incidence of subsequent lymphoma and leukemia in Germany. This retrospective cohort study used the IQVIA TM Disease Analyzer database and included adults with a first documented diagnosis of thyroid cancer between January 2005 and December 2021 as well as propensity score matched individuals without thyroid cancer in 1284 general practices. Univariate Cox regression models were performed to examine the association between thyroid cancer and the incidence of subsequent lymphoma and leukemia. A total of 4232 thyroid cancer patients (mean age: 54.2 years; 73.6% female) and 21 160 controls (mean age: 54.2 years; 72.6% female) were available for analyses. Thyroid cancer was significantly associated with a higher lymphoma incidence (HR: 3.35, 95% CI: 2.04-5.52), especially in men (HR: 5.37) and those aged 61-70 years. Leukemia incidence was not significantly associated with thyroid cancer (HR: 1.79, 95% CI: 0.91-3.53), although associations were notable in younger age groups. Thyroid cancer is positively associated with a risk of subsequent lymphoma, highlighting the need for vigilant surveillance and tailored treatment strategies. While the association with leukemia is less pronounced, close surveillance remains critical, especially in younger patients.

Development and validation of a lung metastases-predicting nomogram for intermediate- to high-risk differentiated thyroid carcinomapatients.

Aim: This research aimed to construct a clinical model for forecasting the likelihood of lung metastases in differentiated thyroid carcinoma (DTC) with intermediate- to high-risk.Methods: In this study, 375 DTC patients at intermediate to high risk were included. They were randomly divided into a training set (70%) and a validation set (30%). A nomogram was created using the training group and then validated in the validation set using calibration, decision curve analysis (DCA) and receiver operating characteristic (ROC) curve.Results: The calibration curves demonstrated excellent consistency between the predicted and the actual probability. ROC analysis showed that the area under the curve in the training cohort was 0.865 and 0.845 in the validation cohort. Also, the DCA curve indicated that this nomogram had good clinical utility.Conclusion: A user-friendly nomogram was constructed to predict the lung metastases probability with a high net benefit.

Polymorphism Pro64His within galectin-3 has functional consequences at proteome level in thyroid cells.

The single nucleotide polymorphism (SNP) rs4644 at codon 64 of galectin-3 (gal-3, gene name: LGALS3), specifying the variant proline (P64) to histidine (H64), is known to affect the protein's functions and has been associated with the risk of several types of cancer, including differentiated thyroid carcinoma (DTC). To deepen our understanding of the biological effects of this SNP, we analyzed the proteome of two isogenic cell lines (NC-P64 vs. NA-H64) derived from the immortalized non-malignant thyrocyte cell line Nthy-Ori, generated through the CRISPR-Cas9 technique to differ by rs4644 genotype. We compared the proteome of these cells to detect differentially expressed proteins and studied their proteome in relation to their transcriptome. Firstly, we found, consistently with previous studies, that gal-3-H64 could be detected as a monomer, homodimer, and heterodimer composed of one cleaved and one uncleaved monomer, whereas gal-3-P64 could be found only as a monomer or uncleaved homodimer. Moreover, results indicate that rs4644 influences the expression of several proteins, predominantly upregulated in NA-H64 cells. Overall, the differential protein expression could be attributed to the altered mRNA expression, suggesting that rs4644 shapes the function of gal-3 as a transcriptional co-regulator. However, this SNP also appeared to affect post-transcriptional regulatory mechanisms for proteins whose expression was oppositely regulated compared to mRNA expression. It is conceivable that the rs4644-dependent activities of gal-3 could be ascribed to the different modalities of self-dimerization. Our study provided further evidence that rs4644 could affect the gal-3 functions through several routes, which could be at the base of differential susceptibility to diseases, as reported in case-control association studies.

Automatic prediction of non-iodine-avid status in lung metastases for radioactive I131 treatment in differentiated thyroid cancer patients.

The growing incidence of differentiated thyroid cancer (DTC) have been linked to insulin resistance and metabolic syndrome. The imperative need for developing effective diagnostic imaging tools to predict the non-iodine-avid status of lung metastasis (LMs) in differentiated thyroid cancer (DTC) patients is underscored to prevent unnecessary radioactive iodine treatment (RAI). Primary cohort consisted 1962 pretreated LMs of 496 consecutive DTC patients with pretreated initially diagnosed LMs who underwent chest CT and subsequent post-treatment radioiodine SPECT. After automatic lesion segmentation by SE V-Net, SE Net deep learning was trained to predict non-iodine-avid status of LMs. External validation cohort contained 123 pretreated LMs of 24 consecutive patients from other two hospitals. Stepwise validation was further performed according to the nodule's largest diameter. The SE-Net deep learning network yielded area under the receiver operating characteristic curve (AUC) values of 0.879 (95% confidence interval: 0.852-0.906) and 0.713 (95% confidence interval: 0.613-0.813) for internal and external validation. With the LM diameter decreasing from ≥10mm to ≤4mm, the AUCs remained relatively stable, for smallest nodules (≤4mm), the model yielded an AUC of 0.783. Decision curve analysis showed that most patients benefited using deep learning to decide radioactive I131 treatment. This study presents a noninvasive, less radioactive and fully automatic approach that can facilitate suitable DTC patient selection for RAI therapy of LMs. Further prospective multicenter studies with larger study cohorts and related metabolic factors should address the possibility of comprehensive clinical transformation.

Differentiated thyroid cancer: long-term follow-up and management options for persistent/recurrent disease

Differentiated thyroid cancer: long-term follow-up and management options for persistent/recurrent disease

Genotoxic effects of ablative treatment with I-131 determined through the analysis of dicentric chromosomes in peripheral blood lymphocytes. Can it influence the clinical management of patients with differentiated thyroid carcinoma?

Study including 61 differentiated thyroid cancer (DTC) patients who received ablative doses of I-131 after total thyroidectomy. Biodosimetry was performed by dicentric chromosomes analysis before and after treatment, determining dicentric yield and blood absorbed dose. An increased yield of dicentrics after treatment was demonstrated. With an average administered activity of 4.32 ± 0.879 GBq, the absorbed dose in bone marrow was 0.28 Gy (0.25–0.30 95% CI). These data were compared with the administered I-131 activity and body mass index. Increased genotoxic effects were observed, with a slightly higher dicentric yield rising along I-131 activity. No correlation was found between administered activity and BMI. No significant risk of myelotoxicity due to dose regimens of I-131 intended for ablative purposes in “de novo” treated patients was found among the ranges of activities used in clinical practice. Biodosimetric data was included in patients’ Clinical History, which translates into a more detailed dosimetric report. With this information, physicians can take a more patient-specific approach. Personalized administration would be of special consideration in the event of re-treatments, be it due to recurrent disease or I-131 refractory DTC patients.

B7-H3 and ICAM-1 are potentially therapeutic targets for thyroid carcinoma

Although most differentiated thyroid carcinoma has a clinically favorable prognosis, some of specific types of thyroid cancer (such as anaplastic thyroid carcinoma and advanced papillary thyroid carcinoma) show fatal outcomes and require novel treatments. Immunotherapy is a promising avenue for the treatment of advanced thyroid carcinoma. B7-H3 (B7 homolog 3 protein) and ICAM-1 (intercellular adhesion molecule 1), as two important immune checkpoints (ICPs), is becoming hopeful target spots for immunotherapy. A growing amount of evidence has suggested that B7-H3 and ICAM-1 are upregulated in papillary thyroid carcinoma. However, their expression level in specific types of thyroid cancer remains largely unclear. In the present study, we explored the expression level of B7-H3 and ICAM-1 in different types of thyroid carcinoma. In the groups of the TCGA cohort, both B7-H3 and ICAM-1 mRNA were highly expressed in thyroid carcinoma. Furthermore, the patients with Stage2, 61-80y, Follicular thyroid papillary carcinoma and N0 had lower B7-H3 and ICAM-1 mRNA expression. In the groups of our cohort, PTCs and ATCs showed frequently moderate to strong expression of B7-H3 and ICAM-1 protein expression. The significant relevance of B7-H3 staining score with ICAM-1 staining score was observed in TCGA database and our cohort, which might open avenues for the combination therapy in advanced thyroid cancer.

Frequency of Distant Metastasis of Differentiated Thyroid Carcinoma- A Descriptive Analysis

Introduction: The presence of distant metastases is one of the important predictive factors of poor outcomes in patients with thyroid carcinoma. It is rarely observed at early presentation of differentiated thyroid carcinoma (DTC). This study aimed to analyze the frequency of distant metastasis in differentiated carcinoma of the thyroid. Methods: This cross-sectional observational study was conducted at the Department of Otolaryngology, Rajshahi Medical College Hospital, Rajshahi, and Department of Otolaryngology Bangabandhu Sheikh Mujib Medical University (BSMMU), from July 2011 to Jun 2012. A total of 40 patients were selected as study subjects by simple random sampling technique. A descriptive analysis of data was carried out by using a statistical package for social science (SPSS) 22.0 for Windows. Result: In this study, a majority (35, 87.5%) of the patients suffered from papillary carcinoma, followed by (5,12.5%) follicular carcinoma. Considering the distant metastasis, 2 (5.71%) patients had metastasis to the lung among the patients with papillary carcinoma (n=35). 1 patient had lung metastasis and another 1 patient had bony metastasis among the follicular carcinoma patients. In terms of distant metastasis, 50% of the patients had distant metastasis from each papillary and follicular carcinoma. Conclusion: This study concludes that metastasis in differentiated thyroid carcinoma is not uncommon. Distant metastasis is more common in follicular thyroid carcinoma than papillary carcinoma. Lung and bone metastasis are common regarding the site of metastasis.

A strategy for estimating radiation dose to the blood in outpatient settings in differentiated thyroid cancer therapy with 131I-NaI.

Although standard operational procedures for pre-therapeutic dosimetry already exist for the determination of the maximum safe activity to treat differentiated thyroid cancer patients, empiric activity administration of 131I is still the most frequent way of treatment. In this way, the absorbed dose to the blood/bone marrow remains unknown. In this work, we present a strategy to estimate radiation dose to the blood in an outpatient setting. A mobile application was developed, which together with an off-the-shelf compact semiconductor radiation detector allows the determination of whole-body time-integrated activity coefficients. The methodology was tested in a cohort of 79 differentiated cancer patients who received therapeutic 131I activities. Post-therapeutic whole-body time-integrated activity coefficients were compared against pre-therapeutic estimates in a subset of 13 patients. The 95% limits of agreement between pre whole-body and post whole-body time integrated activity coefficients were [-14.4; 6.6] h when considering outliers and [-6.2; 3.6] h without outliers. A high dispersion in blood dose coefficients was found, with a four-fold difference between the highest and lower values. Blood doses were significantly higher for patients treated with dosimetrically guided activities than for empirical activities (median dose=118vs. 49cGy, respectively). Blood dose coefficients were significantly lower for patients prepared with recombinant human thyroid stimulating hormone (rhTSH) than for patients prepared with thyroid hormone withdrawal. A low correlation between blood dose and administered activity was found in empirically treated patients (R2=0.26). We successfully implemented a post-therapeutic internal dosimetry methodology for differentiated thyroid cancer therapy with 131I, which allows to estimate dose to the blood from outpatient measurements with mobile devices. The proposed methodology avoids the need of daily visits to the nuclear medicine department, thus reducing the burden for the patient and for the staff.