Iodine Therapy Research Articles

Prevalence and Analysis of Risk Factors for RAI-Refractory Thyroid Cancer Patients: A 5-Year Retrospective Analysis from a Single Institution in Indonesia

Background: Radioactive iodine (RAI) therapy is a cornerstone in the management of differentiated thyroid cancer (DTC). However, a subset of patients develops RAI-refractory disease, characterized by the inability to concentrate radioiodine, leading to limited treatment options and a poorer prognosis. This study aimed to investigate the prevalence and identify potential risk factors associated with RAI-refractory DTC in an Indonesian population. Methods: A retrospective analysis was conducted on patients diagnosed with DTC and treated with RAI at a single tertiary care center in Indonesia between 2019 and 2023. Data on demographics, clinical characteristics, tumor features, and treatment outcomes were collected. RAI-refractoriness was defined as the absence of iodine uptake on diagnostic whole-body scans after cumulative RAI activity of 600 mCi or more. Bivariate and multivariate analyses were performed to identify risk factors for RAI-refractoriness. Results: A total of 194 patients with DTC were included in the study. The prevalence of RAI-refractoriness was 90%. The median age at diagnosis was 55 years (range 18-82), and 72% were female. Papillary thyroid carcinoma was the most common histological subtype (92%). In bivariate analysis, older age at diagnosis (p=0.02), male gender (p=0.04), and the presence of distant metastases at diagnosis (p<0.001) were significantly associated with RAI-refractoriness. In multivariate analysis, only the presence of distant metastases remained an independent predictor of RAI-refractoriness (odds ratio 3.8, 95% confidence interval 1.5-9.2, p=0.003). Conclusion: RAI-refractoriness is a significant clinical challenge in the management of DTC, with a high prevalence observed in this Indonesian cohort. The presence of distant metastases at diagnosis emerged as a strong predictor of RAI-refractoriness. Further research is needed to elucidate the underlying mechanisms of RAI-refractoriness and develop novel therapeutic strategies for this patient population.

Radioactive iodine ablation therapy reduces the risk of recurrent disease in pediatric differentiated thyroid carcinoma

BackgroundWhile radioactive iodine (RAI) therapy in older adults with differentiated thyroid carcinoma (DTC) reduces recurrence, data in pediatrics remain limited. We conducted a meta-analysis to quantify outcomes and recurrence risk with RAI versus thyroidectomy alone in the pediatric population. MethodsSystematic literature review identified 34 retrospective studies including 2913 DTC patients under age 22 years (published 2005–2023). Meta-analysis calculated pooled rates of disease persistence and recurrence. Relative risk ratios compared odds of recurrence with RAI versus no RAI. ResultsPatients had mean age 14.7 years (95 % CI, 14.2–15.2) and were 75.9 % female (95 % CI, 73.8–78.1 %). Majority (90.2 %) received RAI. Pooled persistence rate was 30.3 % (95 % CI, 21.7–39.5 %); higher with RAI (31.5 %; 95 % CI, 22.4–41.3 %) than no RAI (4.5 %; 95 % CI, 0.0–18.7 %) (OR 3.28; 95 % CI,1.82–5.91; p < 0.001). Recurrence rate was 8.97 % (95 % CI, 4.78–14.3 %). Those with RAI had 53.1 % lower recurrence risk versus no RAI (RR 0.47; 95 % CI, 0.27–0.82; p = 0.007). Median follow-up was 7.2 years (95 % CI, 5.8–8.5 years), with no association between follow-up duration and recurrence (r = −0.053; p = 0.80). ConclusionsRAI therapy as an adjunct to thyroidectomy is associated with a significantly lower risk of long-term recurrence in pediatric DTC. These findings advocate for the use of RAI in preventing recurrence among high-risk pediatric patients with DTC.

Treatment Patterns and Preferences for Graves' Disease in Korea: Insights from a Nationwide Cohort Study.

Treatment patterns and preferences for patients with Graves' disease (GD) vary across countries. In this study, we assessed the initial therapies and subsequent treatment modalities employed for GD in real-world clinical practice in Korea. We analyzed 452,001 patients with GD from 2004 to 2020, obtained from the Korean National Health Insurance Service database. Initial treatments included antithyroid drug (ATD) therapy (98% of cases), thyroidectomy (1.3%), and radioactive iodine (RAI) therapy (0.7%). The rates of initial treatment failure were 58.5% for ATDs, 21.3% for RAI, and 2.1% for thyroidectomy. Even among cases of ATD treatment failure or recurrence, the rates of RAI therapy remained low. Regarding initial treatment, the 5-year remission rate was 46.8% among patients administered ATDs versus 91.0% among recipients of RAI therapy; at 10 years, these rates were 59.2% and 94.0%, respectively. Our findings highlight a marked disparity in the use of RAI therapy in Korea compared to Western countries. Further research is required to understand the reasons for these differences in treatment patterns.

Radioactive iodine therapy for thyroid cancer coexisting with Hashimoto's thyroiditis: a systematic review and meta-analysis.

To investigate the clinical character of differentiated thyroid cancer (DTC) coexisting with Hashimoto's thyroiditis (HT) and provide state-of-art evidence for personalized radioactive iodine-131 therapy (RAIT) for patients coexisting with HT. From January 2000 to January 2023, PubMed, Embase, and Web of Science databases were searched for relevant original articles that published in English on the RAIT efficacy for DTC with HT. RevMan 5.4 and Stata 17.0 were used for data analysis. Eleven studies involving 16605 DTC patients (3321 with HT) were included. HT was more frequent in female (OR: 2.90, 95% confidence interval [CI]: 1.77-4.76, P < .00001). The size of tumour (MD: -0.20, 95% CI: -0.30 to -0.11), extrathyroidal extension rate (OR: 0.77, 95% CI: 0.67-0.90), and metastasis rate (OR: 0.18, 95% CI: 0.08-0.41) were less in HT, but tumour, node, metastasis (TNM) stage had no significant difference among HT and non-HT group. Disease-free survival (DFS) rate (OR: 1.96, 95% CI: 1.57-2.44, P < .00001), 5-year DFS (OR: 1.73, 95% CI: 1.04-2.89, P = .04), and 10-year DFS (OR: 1.56, 95% CI: 1.17-2.09, P = .003) were higher in HT group. The recurrent (OR: 0.62, 95% CI: 0.45-0.83, P = .002), RAIT dosage (MD = -38.71, 95% CI: -60.86 to -16.56, P = .0006), and treatment (MD: -0.13, 95% CI: -0.22 to -0.03, P = .008) were less in HT group. DTC coexisting with HT was associated with less invasion. DFS of HT group was higher than non-HT group after RAIT. Low-dose treatment did not impair the efficacy of RAIT in DTC with HT. Hashimoto's thyroiditis is a risk for DTC, but it minimalizes the progression of cancer and enhance the efficacy of RAIT, which should be considered in personalizing RAIT.

Reducing anxiety and enhancing satisfaction in thyroid patients with DietLens application during radioactive iodine therapy: A quasi-experimental study

Hyperthyroidism and thyroid cancer significantly impact health, and often require Radioactive Iodine (RAI) therapy. Anxiety is common in patients undergoing RAI, particularly related to dietary compliance. This study aimed to assess the effectiveness of the mobile health application, DietLens in reducing anxiety and increasing satisfaction in patients preparing for RAI therapy, focusing on low-iodine diet (LID). A quasi-experimental study was conducted in a Singapore tertiary hospital outpatient department from March 13, 2019 to March 27, 2020, involving patients scheduled for their first RAI treatment. Participants were divided into a control group receiving standard care and an intervention group using DietLens alongside standard care. Anxiety levels were assessed using the Zung Self-Rating Anxiety Scale, and satisfaction levels were measured through self-reported questionnaires. In the study, 56 participants were initially divided into control (n = 28) and intervention (n = 28) groups. After accounting for dropouts, 50 participants finished the study, with each group comprising 25 individuals. Anxiety levels were similar between groups pre-intervention. Post-intervention, the intervention group displayed a significant decrease in anxiety levels compared to the control group (independent t-test: t (48) = 2.50, p = 0.02). The multivariate linear regression analysis indicated that being in the intervention group was significantly associated with a decrease in post-intervention anxiety score (β = −4.03, 95 % CI: −7.33 to −0.72, p = 0.02). Fisher's Exact Test revealed a borderline significant difference in satisfaction with educational materials and the overall treatment process, with 100 % of the intervention group expressing satisfaction compared to 80 % in the control group, resulting in a p-value of 0.052 in both instances. DietLens was effective in reducing anxiety and enhancing satisfaction related to RAI therapy preparation, particularly in managing a LID, highlighting a beneficial role for digital interventions in healthcare settings.

The impact of Hashimoto's thyroiditis on the clinical outcome of papillary thyroid cancer after radioactive iodine therapy: a propensity score matching study.

The potential association between Hashimoto's thyroiditis (HT) and papillary thyroid carcinoma (PTC) has been studied from different perspectives for many years. This study was aimed to evaluate the impact of HT on the clinical outcomes of PTC patients after radioactive iodine (RAI) therapy. We conducted a retrospective study on consecutive patients with PTC who underwent RAI therapy from April 2017 to May 2020. The diagnosis of HT was based on pathological examination, and patients were divided into the HT and non-HT group. Distributions of age, gender, ultrasound features, papillary variants, extrathyroidal extension, and other histopathological characteristics were observed. Propensity score matching (PSM) was used to compare the clinical features and outcomes between the two groups at 1 and 3-year follow-up. In total, 782 patients with PTC were enrolled (570 women, 212 men). HT was presented in 130 (16.6%) patients, and was associated with younger age, smaller primary tumors, less extrathyroidal extension, and less lymph node metastasis at presentation. On review of the images, only calcification and blood flow distribution were significantly different among the US features (P < 0.05). At the end of follow-up (three years), the responses to RAI therapy were significantly different between the two groups (ER: 76.9% vs 64.9%; IDR:11.5% vs 17.2%; BIR: 4.6% vs 10.7%; SIR: 6.9% vs 7.2%, P = 0.03). Patients with HT had less frequently evidence of disease (11.6% vs 17.9%). When compared with the matched groups, 123 pairs of patients were successfully matched, PTC patients with HT were found to have a better response to RAI therapy. PTC patients with HT had less aggressive characteristics at presentation. Importantly, the presence of HT not only had a significant association with the outcome, but was also protective from the risk of recurrence.

The effects of iodine 131 treatment on chromosomal and oxidative DNA damage in papillary thyroid carcinoma

Papillary thyroid carcinoma (PTC) is a common endocrine cancer with a good prognosis. Radioactive iodine is thought to be useful for individuals who have had a total or almost total thyroidectomy, but its effects are still controversial. The effects of radioactive iodine-131 (I-131) treatment on oxidative and chromosomal damage in PTC patients were examined in this study, which was carried out with 16 patients newly diagnosed with PTC and 20 healthy control subjects with similar age and gender. Blood samples were taken from patients with PTC at five sampling times (before total thyroidectomy, after total thyroidectomy, and seven days, six months, and one year after treatment) and from control subjects. The cytokinesis block micronucleus cytome (CBMN-cyt) assay parameters in peripheral blood lymphocytes of patients with PTC and controls were evaluated and plasma 8-hydroxydeoxyguanosine (8-OHdG) levels were measured. Furthermore, genome instability and oxidative DNA damage in peripheral blood lymphocytes and plasma of patients with PTC were evaluated before total thyroidectomy (n=16), after total thyroidectomy (before I-131 treatment) (n=16), seven days (n=10), six months (n=5), and one year after treatment (n=5). The numbers of CBMN-cyt assay parameters (micronucleus; MN and nucleoplasmic bridges; NPB) and 8-OHdG levels in patients with PTC were determined to be significantly higher than in those of the control subjects and these values significantly decreased after total thyroidectomy (before I-131 treatment). While the number of MN, apoptotic, and necrotic cells increased after I-131 treatment, it significantly decreased after six months and one year after treatment. The results achieved in this study suggest that I-131 treatment may pose a threat to cells and that radioactive iodine therapy should be avoided (if possible) for patients with PTC after total thyroidectomy.

Predictors of response to Radioactive Iodine Therapy in Intermediate and high risk patients with papillary thyroid carcinoma

BackgroundRadioactive iodine (RAI) therapy is the standard treatment approach after total thyroidectomy in patients with papillary thyroid carcinoma (PTC). We aimed to identify predictive factors of response to the treatment in intermediate and high-risk patients with PTC. In addition, the impact of multiple RAI treatments was explored.MethodsIn a 3-year retrospective study, data from intermediate and high-risk patients with PTC who received RAI therapy following total thyroidectomy, were analyzed by the end of year-one and year-three. Demographic data, tumor size, capsular/vascular invasion, extrathyroidal extension, local or distant metastasis, initial dose and cumulative dose of RAI, serum thyroglobulin(Tg), antithyroglobulin antibody(TgAb), and imaging findings were investigated. Patients with an excellent response to a single dose of RAI treatment, after three years of follow-up were classified as the “Responder group”. Excellent response was defined as stimulated serum Tg less than 1 ng/ml, or unstimulated serum Tg less than 0.2 ng/ml in TgAb-negative patients with negative imaging scans.Results333 patient records with a complete data set were analyzed in this study. After three years of initial treatment, 271 patients were non-responders (NR) and 62 were responders (R). At baseline, the median pre-ablation serum Tg level was 5.7 ng/ml in the NR group, and 1.25 ng/ml in the R group (P < 0.001). TSH-Stimulated serum Tg greater than 15.7 ng/ml, was associated with response failure even after multiple RAI therapy, AUC: 0.717(0.660–0.774), sensitivity: 52.5%, specificity: 89.47%, P < 0.001. On the other hand, multiple RAI therapy was associated with excellent response in 16.2% of the patients. The chance of ER was decreased by 74% if initial post-operation ultrasound imaging confirmed the presence of locoregional involvement, OR 0.26, (95% CI: 0.12–0.55), P < 0.001.ConclusionStimulated serum Tg and locoregional involvement after total thyroidectomy are predictive factors of non-response to RAI therapy in intermediate and high-risk patients with PTC. In addition, a minority of patients achieve excellent response after multiple RAI therapy.

Paraplegic Patient with Metastatic Papillary Thyroid Cancer: A Multidisciplinary Approach to Radioactive Iodine Therapy Safety and Efficacy Strategy.

High-activity radioactive iodine (RAI) therapy for metastatic thyroid cancer (TC) requires isolation to minimize radiation exposure to third parties, thus posing challenges for patients needing hands-on care. There are limited data on the approach to high-activity RAI treatment in paraplegic patients. We report a state-of-the-art multidisciplinary approach to the management of bedbound patients, covering necessary radiation safety measures that lead to radiation exposure levels as low as reasonably achievable. Given the limited literature resources on standardized approaches, we provide a practical example of the safe and successful treatment of a woman with BRAFV600E-mutant tall-cell-variant papillary TC and pulmonary metastases, who underwent dabrafenib redifferentiation before RAI therapy. The patient was 69 y old and had become paraplegic because of a motor-vehicle accident. Since caring for a paraplegic patient with neurogenic bowel and bladder dysfunction poses radiation safety challenges, a multidisciplinary team comprising endocrinologists, nuclear medicine physicians, radiation safety specialists, and the nursing department developed a radiation mitigation strategy to ensure patient and staff safety during RAI therapy. The proposed standardized approach includes thorough monitoring of radiation levels in the workplace, providing additional protective equipment for workers who handle radioactive materials or are in direct patient contact, and implementing strict guidelines for safely disposing of radioactive waste such as urine collected in lead-lined containers. This approach requires enhanced training, role preparation, and practice; use of physical therapy equipment to increase the exposure distance; and estimation of the safe exposure time for caregivers based on dosimetry. The effective and safe treatment of metastatic TC in paraplegic patients can be successfully implemented with a comprehensive radiation mitigation strategy and thorough surveying of personnel for contamination.

Systemic therapy for differentiated thyroid cancer with distant metastasis

Background: Thyroid cancer is a slow-growing tumor with excellent oncological outcomes. However, few patients with unexpectedly severe outcomes are usually ignored.Current Concepts: Radioactive iodine therapy is the mainstay treatment for differentiated thyroid cancer with distant metastasis. The refractoriness to radioactive iodine therapy has been overcome by the emergence of targeted agents. First, multikinase inhibitors (sorafenib and lenvatinib) targeting the growth factor pathway were developed and approved as anticancer agents for patients with advanced differentiated thyroid cancer, regardless of their genetic features. With progress in sequencing techniques, the genetic backgrounds of tumors have unveiled new targets, including rearrangements during transformation and tropomyosin receptor kinase. Special attention should be paid to the national health insurance coverage of systemic therapeutics and genetic studies.Discussion and Conclusion: New drugs were introduced to treat previously untreatable advanced thyroid cancers. However, the cost of these drugs has increased with new developments, and only first-line drugs for thyroid cancer are still covered by insurance. These medical advances will remain an illusion for clinics and patients if improvements in healthcare policies do not accompany them.

Current Advances in Radioactive Iodine-Refractory Differentiated Thyroid Cancer.

Differentiated thyroid cancer (DTC) patients have an outstanding overall long-term survival rate, and certain subsets of DTC patients have a very high likelihood of disease recurrence. Radioactive iodine (RAI) therapy is a cornerstone in DTC management, but cancer cells can eventually develop resistance to RAI. Radioactive iodine-refractory DTC (RAIR-DTC) is a condition defined by ATA 2015 guidelines when DTC cannot concentrate RAI ab initio or loses RAI uptake ability after the initial therapy. The RAIR condition implies that RAI cannot reveal new met-astatic foci, so RAIR-DTC metabolic imaging needs new tracers. 18F-FDG PET/CT has been widely used and has demonstrated prognostic value, but 18F-FDG DTC avidity may remain low. Fibroblast activation protein inhibitors (FA-Pi)s, prostatic-specific membrane antigen (PSMA), and somatostatin receptor (SSTR) tracers have been proposed as theragnostic agents in experimental settings and Arg-Gly-Asp (RGD) peptides in the diagnostic trial field. Multi-targeted tyrosine kinase inhibitors are relatively new drugs approved in RAIR-DTC therapy. Despite the promising targeted setting, they relate to frequent adverse-event onset. Sorafenib and trametinib have been included in re-differentiation protocols aimed at re-inducing RAI accumulation in DTC cells. Results appear promising, but not excellent. RAIR-DTC remains a challenging nosological entity. There are still controversies on RAIR-DTC definition and post-RAI therapy evaluation, with post-therapy whole-body scan (PT-WBS) the only validated criterion of response. The recent introduction of multiple diagnostic and therapeutic agents obliges physicians to pursue a multidisciplinary approach aiming to correct drug introduction and timing choice.

Central lymph node ratio is an important recurrence prognostic factor for pediatric differentiated thyroid cancer.

The current risk stratification methods for Pediatric Differentiated Thyroid Carcinoma (DTC) are deemed inadequate due to the high recurrence rates observed in this demographic. This study investigates alternative clinicopathological factors, specifically the Central Lymph Node Ratio (CLNR), for improved risk stratification in pediatric DTC. A retrospective review of 100 pediatric DTC patients, aged 19 or younger, treated between December 2012 and January 2021 at the First Affiliated Hospital of Guangxi Medical University was conducted. Clinicopathological variables were extracted, and univariate logistic regression identified factors correlated with recurrence. Kaplan-Meier (KM) survival analysis and subsequent statistical tests were used to assess the significance of these factors. The CLNR, with a cutoff value of 77.78%, emerged as a significant predictor of recurrence. Patients with a CLNR above this threshold had a 5.467 times higher risk of recurrence. The high CLNR group showed a higher proportion of male patients, clinically lymph node positivity (cN1), and extrathyroidal extension (ETE) compared to the low-risk group (p<0.05). CLNR is a valuable predictor for recurrence in pediatric DTC and aids in stratifying patients based on Recurrence-Free Survival (RFS). For patients with a high CLNR, aggressive iodine-131 therapy, stringent TSH suppression, and proactive postoperative surveillance are recommended to mitigate recurrence risk and facilitate timely detection of recurrent lesions.

Distant lymph node metastasis in differentiated thyroid cancer: A population-based cohort study

BackgroundCervical lymph node metastasis (LNM) is the most common clinical event in patients with differentiated thyroid cancer (DTC). However, the incidence, pattern, treatment, and prognosis of distant LNM are yet to be reported. MethodsDTC patients with distant LNM were identified from the Surveillance, Epidemiology, and End Results (SEER) database between 2016 and 2020. Multivariate models and propensity score matching (PSM) were used to account for the effects of covariates. The Kaplan-Meier method was used to evaluate the overall survival (OS) and cancer-specific survival (CSS). A nomogram was established to predict the probability of distant LNM in DTC patients, with calibration and Receiver Operating Characteristic (ROC) curves utilized to validate the nomogram's accuracy. ResultsOf the 42,339 DTC patients screened, 100 (0.24 %) patients presented with distant LNM. Risk factors including age, sex, T stage, N stage, bone metastasis, brain metastasis, and lung metastasis were included in the nomogram to predict the probability of distant LNM. The calibration curve of the nomogram was close to the ideal diagonal line and the area under the curve (AUC) of the ROC curve is 0.953. Distant LNM showed a worse prognosis after adjusting for confounders compared with non-distant LNM (P < 0.05). Remarkably, radioactive iodine (RAI) therapy did not improve the OS and CSS in DTC patients with distant LNM in the overall or PSM cohort. ConclusionsDistant LNM presents as a comparatively rare but grave condition with a substantial negative impact on prognosis in patients with DTC. Identified risk factors of distant LNM are older age, male, advanced T stage and N stage, bone metastasis, brain metastasis, and lung metastasis. Remarkably, the current RAI therapy does not appear to significantly improve the survival outcome of DTC patients with distant LNM.

Pediatric thyroid cancer in Saudi Arabia: a literature review of current trends in management and outcomes.

Pediatric thyroid cancer is on the rise, especially among adolescents. It is more aggressive than adult thyroid cancer and often presents with advanced features. This review aims to examine the current trends in the management and outcomes of pediatric thyroid cancer in Saudi Arabia. A comprehensive literature search was conducted to identify relevant studies on pediatric thyroid cancer in Saudi Arabia. PubMed and Google Scholar were searched from inception until December 2023. Extracted information included study identifiers, patient demographics, clinicopathological features, treatment modalities, complications, surveillance practices, recurrence patterns, and survival outcomes. The literature search identified ten eligible studies on pediatric thyroid cancer in Saudi Arabia. Pediatric thyroid cancer in Saudi Arabia often presents with advanced features, including higher rates of lymph nodes and distant metastases at diagnosis compared to adults. Fine-needle aspiration remains accurate, correlating well with final histopathology. Treatment primarily involves surgery, with total thyroidectomy being common, followed by radioactive iodine therapy for high-risk patients or those with positive iodine uptake. Survival rates exceed 95%, indicating a generally favorable prognosis. Recurrence rates can reach up to 30% in some studies, particularly with larger tumors or distant metastases. Hypocalcemia and recurrent laryngeal nerve injury are common postoperative complications, highlighting the need for experienced surgeons and meticulous technique. Genetic alterations in pediatric thyroid cancer are being investigated, but their impact on prognosis and treatment response is unclear. Limited data on management and outcomes in other regions of Saudi Arabia calls for multicenter studies to address healthcare disparities. Pediatric thyroid cancer in Saudi Arabia has unique characteristics compared to its adult counterpart, mandating specialized management approaches. More research is needed on early detection, risk stratification, personalized treatment, and addressing regional disparities to improve outcomes for this vulnerable population.

A Mathematical Model for Differentiated Thyroid Cancer with Combination Therapy

Objectives: Differentiated thyroid cancer (DTC) is usually treated with surgery and radioactive iodine therapy. However, in advanced stages, molecular changes can lead to a progressive loss of sensitivity to iodine, making the cancer resistant to radioactive iodine treatment (known as radioactive iodine-refractory, or RAIR). For cases of RAIR-DTC, alternative treatments such as tyrosine kinase inhibitors and immunotherapy are explored. To better understand the dynamics of these alternative treatments, a new mathematical model has been developed. In this model, Sorafenib represents the tyrosine kinase inhibitor, while Pembrolizumab is the immunotherapy agent under investigation. Methods: Two mathematical models were developed based on systems of ordinary differential equations to study differentiated thyroid cancer treated with (1) Sorafenib alone and (2) a combination of a Sorafenib and Pembrolizumab. The first model included three variables: drug concentration of Sorafenib, number of cancer cells, and number of immune cells with fourteen parameters. The second model additionally incorporated the concentration of the Pembrolizumab. Parameter values were estimated through simulations utilizing the fmincon optimization technique in MATLAB. Local asymptotic stability analysis was performed to investigate the models' behavior around equilibrium points. Moreover, the Lyapunov method was employed to establish global asymptotic stability of the models. Findings: The findings revealed insights into the dynamics of treating RAIR-DTC patients with tyrosine kinase inhibitors and immunotherapy. The stability analysis contributed to the understanding of the system's behavior under different conditions, offering valuable information for clinical application. Numerical simulations were then performed using Simbiology in MATLAB to simulate the treatment dynamics over time. Novelty: This research contributes to the field by presenting a novel mathematical model that integrates tyrosine kinase inhibitors and immunotherapy for the treatment of RAIR-DTC. The comprehensive analysis of equation stability enhances the reliability of the model, while the numerical simulations provide a practical and visual tool for assessing the potential outcomes of the proposed therapeutic strategy. This study offers a valuable framework for further exploration and refinement of treatment approaches for patients with challenging DTC cases. Keywords: Mathematical modeling, Routh Hurwitz Criteria, Jacobian, Differentiated thyroid Cancer, Stability Analysis

Impact of the COVID-19 Pandemic on Thyroid Cancer Surgery.

The COVID-19 pandemic caused major disruptions to healthcare services in 2020, delaying cancer diagnosis and treatment. While early-stage thyroid cancer often progresses slowly, it is crucial to determine whether treatment delays associated with the pandemic have impacted the clinical presentation and management of advanced-stage thyroid cancer. The purpose of our study was to determine the impact of the early COVID-19 pandemic on thyroid cancer presentation and treatment times. Utilizing the National Cancer Database, chi-squared tests and regression analyses were performed to compare patient demographic and clinical characteristics over time for 56,011 patients diagnosed with primary thyroid cancer who were treated at the Commission on Cancer-accredited sites in 2019 and 2020. We found that thyroid cancer diagnoses decreased between 2019 and 2020, with the biggest drop among patients with cT1 disease relative to other T stages. We also found that patients diagnosed with thyroid cancer in 2020 had similar treatment times to patients diagnosed in 2019, as measured by both the time between diagnosis and start of treatment and the time between surgery and start of radioactive iodine therapy. Overall, our study suggests that resources during the pandemic were allocated to patients with advanced thyroid disease, despite a decrease in diagnoses.

Could effective iodine-131 half-life be extended by lithium carbonate in Graves' disease patients: Results from a retrospective analysis.

The effective iodine-131 (I-131) half-life (EHL) plays an important role in the evaluation of radioactive iodine therapy for Graves' disease (GD) patients. It has been observed that the EHL of GD patients varies after taking lithium carbonate. The purpose of this study is to investigate whether EHL can be extended and to identify the predictive factors associated with this outcome. The clinical data of 225 GD patients were retrospectively reviewed. Patients were divided into two groups based on whether the ΔEHL was ≥ 0.5 days. EHL tested after lithium carbonate was defined as Li-EHL. In the univariate analysis, age, sex, thyrotropin receptor antibody (TRAb), thyroglobulin antibody (TgAb), thyroid peroxidase antibody (TPOAb), and baseline-EHL exhibited significant differences between the two groups (P < 0.05). Cutoff values of age and baseline-EHL to predict significant EHL extension were 40.5 years and 4.85 days, respectively, as determined by receiver operating characteristic (ROC) curve analysis. Multiple linear regression analysis further revealed that the regression equation, which included age, sex, baseline-EHL, and the FT3, free triiodothyronine (FT4)/free thyroxine(FT3) ratio, was statistically significant (P < 0.05). Li-EHL positively correlated with baseline-EHL and the FT4/FT3 ratio, but negatively correlated with age. Li-EHL was also increased in female individuals. In conclusion, age, sex, baseline-EHL and the FT4/FT3 ratio were associated with Li-EHL in GD patients.

Serum metabolome analysis in hyperthyroid cats before and after radioactive iodine therapy.

Hyperthyroidism is the most common feline endocrinopathy. In hyperthyroid humans, untargeted metabolomic analysis identified persistent metabolic derangements despite achieving a euthyroid state. Therefore, we sought to define the metabolome of hyperthyroid cats and identify ongoing metabolic changes after treatment. We prospectively compared privately-owned hyperthyroid cats (n = 7) admitted for radioactive iodine (I-131) treatment and euthyroid privately-owned control (CON) cats (n = 12). Serum samples were collected before (T0), 1-month (T1), and three months after (T3) I-131 therapy for untargeted metabolomic analysis by MS/MS. Hyperthyroid cats (T0) had a distinct metabolic signature with 277 significantly different metabolites than controls (70 increased, 207 decreased). After treatment, 66 (T1 vs. CON) and 64 (T3 vs. CON) metabolite differences persisted. Clustering and data reduction analysis revealed separate clustering of hyperthyroid (T0) and CON cats with intermediate phenotypes after treatment (T1 & T3). Mevalonate/mevalonolactone and creatine phosphate were candidate biomarkers with excellent discrimination between hyperthyroid and healthy cats. We found several metabolic derangements (e.g., decreased carnitine and α-tocopherol) do not entirely resolve after achieving a euthyroid state after treating hyperthyroid cats with I-131. Further investigation is warranted to determine diagnostic and therapeutic implications for candidate biomarkers and persistent metabolic abnormalities.

Analysis of delayed initial radioactive iodine therapy and clinical outcomes in papillary thyroid cancer: a two-center retrospective study.

It remains unclear whether the time interval between total thyroidectomy and radioactive iodine (RAI) therapy influences clinical outcomes in papillary thyroid carcinoma (PTC). This study aims to evaluate the impact of the timing to initiate RAI therapy on the response in PTC patients. We retrospectively included 405 patients who underwent total thyroidectomy and subsequent RAI therapy at two tertiary hospitals in southwest China. Patients were categorized into two groups based on the interval between thyroidectomy and initial RAI therapy, that is, an early group (interval ≤90 days, n = 317) and a delayed group (interval >90 days, n = 88). Responses to RAI therapy were classified as excellent, indeterminate, biochemical incomplete, or structural incomplete. Univariate and multivariate analyses were conducted to identify factors associated with a nonexcellent response. Excellent responses were observed in 77.3% of the early group and 83.0% of the delayed group ( P = 0.252). No significant impact of RAI therapy timing was also observed across all American Thyroid Association risk classification categories. These findings persisted when patients were analyzed separately according to RAI dose (intermediate-dose group: 3.7 GBq [ n = 332]; high-activity group: ≥5.5 GBq [ n = 73]), further subdivided by the timing of RAI therapy. Multivariate analysis identified lymph node dissection, RAI dose, and stimulated thyroglobulin as independent risk factors for excellent response ( P < 0.05). The timing of initial RAI therapy following surgery did not significantly affect outcomes in patients with PTC.

Increased risk for thyroid carcinoma in patients with Li-Fraumeni syndrome.

10612 Background: Patients with Li-Fraumeni syndrome (LFS) are predisposed to a 90% lifetime risk of cancer, thus undergoing extensive cancer surveillance. While thyroid cancer is not a core LFS-associated malignancy, increased incidence of thyroid carcinoma has been reported within the LFS tumor spectrum. In the general population, thyroid cancer incidence has soared mainly via incidental detection. We investigated the rate of thyroid carcinoma in relation to p53 mutational process and increased screening. Methods: A retrospective chart review was conducted for clinico-pathological features for adult carriers of confirmed germline TP53 variants at three tertiary cancer centers. Standardized incidence ratio (SIR) was calculated using age, sex, and year-specific expected incidence rates of thyroid cancer from Surveillance, Epidemiology, and End Results (SEER) 1975 – 2020 data. Results: Among 600 patients from 400 families with LFS, 39 (6.5%) patients from 36 (9%) families developed thyroid carcinoma at an average age of 42 years (median = 40, ranged from 23 to 70 years of age). The majority of LFS patients with thyroid carcinoma were female (N=30, 77%). Thyroid carcinoma was the presenting cancer diagnosis in 17 (44%) patients. Over 70% of thyroid carcinoma diagnoses (N=31) were detected incidentally either via LFS cancer screening (N=12, 39%) or via an imaging study unrelated to LFS screening (N=10, 32%). All 39 thyroid carcinomas were of follicular cell origin (non-medullary), most were multifocal (67% of N=32), and 30% had nodal metastasis (N=10 of 33). Of 35 tumors with histologic data, papillary carcinoma (papillary, follicular, and tall cell subtypes) was most common (N=29, 83%), followed by follicular carcinoma (N=4, 11%) and oncocytic carcinoma (N=2, 6%). LFS patients most often underwent a total thyroidectomy (N=27, 69%) compared to a hemithyroidectomy (N=10, 26%) or hemithyroidectomy with completion surgery within three months (N=2, 5%). Intermediate to high risk of recurrence based on tumor characteristics was noted in 17 patients (44%), warranting consideration of radioactive iodine (RAI) therapy, including tall cell subtype (N=3), oncocytic or follicular histology, incomplete resection (N=2), extrathyroidal extension (N = 6), and greater than five positive lymph nodes (N=6). Five (29%) of these 17 patients received RAI. The SIR for thyroid carcinoma in LFS compared to SEER was 13 (95% CI 9.2-17.8, p&lt;0.0001). The SIR was elevated for LFS patients diagnosed with thyroid carcinoma both prior to and after genetic testing (SIR 9.0, CI 5.3-14.2, p&lt;0.0001 and SIR 20, CI 12.2- 30.9, p&lt;0.0001, respectively). Conclusions: In this multi-institutional cohort, a 6-9% prevalence rate of thyroid carcinoma was observed in LFS patients and families, with &gt;70% of the tumors identified incidentally. The rate of thyroid carcinoma in LFS is significantly elevated over the general population.