Pediatric Differentiated Thyroid Cancer Research Articles

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.

Risk Factors for Lymph Node Metastases in Pediatric Differentiated Thyroid Cancer (DTC) - A Comprehensive Review

Risk Factors for Lymph Node Metastases in Pediatric Differentiated Thyroid Cancer (DTC) - A Comprehensive Review

Korean Thyroid Association Guidelines on the Management of Differentiated Thyroid Cancers; Part V. Pediatric Differentiated Thyroid Cancer 2024

Korean Thyroid Association Guidelines on the Management of Differentiated Thyroid Cancers; Part V. Pediatric Differentiated Thyroid Cancer 2024

Current approach to pediatric differentiated thyroid cancer.

Differentiated thyroid cancers (DTC) is a rare cancer in children and adolescents, having features of different clinical presentation, biological behavior, and treatment from adult population. Most of the patient management guidelines are based on literature on adult population and the literature on children and adolescents still limited. There are still unsettled issues regarding both patient management and the therapy. However, the current approach for treatment of DTC includes thyroidectomy, lymph node dissection in patients with nodal metastases and possible use of Iodine-131 radiotherapy. The incidence of DTC is low in pediatric population, and the characteristics of the disease vary among different age groups within this population. Therefore, the literature depends on small cohorts and heterogeneous retrospective studies. This paper aims to review the current literature and give an overview to the approach in the management of DTC in pediatric population. DTC in pediatric population, has an aggressive nature, however the patient's overall survival is excellent. A multidisciplinary approach in the management of pediatric DTC patients would yield fewer side effects and a better life quality.

Strategies for Management and Long-term Surveillance of Pediatric Differentiated Thyroid Cancer: Balancing Efficacy and Quality of Life

Pediatric differentiated thyroid cancer (DTC) presents unique challenges distinct from its adult counterparts, including higher rates of multifocality, regional lymph node involvement, and distant metastases. This article reviews the latest advancements and controversies in the surgical management, postoperative care, and long-term surveillance of pediatric DTC, emphasizing the importance of a tailored approach based on individual risk assessments. The evolving landscape of treatment strategies aims to balance the imperative of effective cancer control with the need to mitigate long-term adverse effects and ensure quality of life. The review also highlights the critical need for ongoing research and multidisciplinary collaboration to refine and optimize management protocols for this vulnerable population.

Predictive factors for lung metastasis in pediatric differentiated thyroid cancer: a clinical prediction study.

The objective of this study was to develop and evaluate the efficacy of a nomogram for predicting lung metastasis in pediatric differentiated thyroid cancer. The SEER database was utilized to collect a dataset consisting of 1,590 patients who were diagnosed between January 2000 and December 2019. This dataset was subsequently utilized for the purpose of constructing a predictive model. The model was constructed utilizing a multivariate logistic regression analysis, incorporating a combination of least absolute shrinkage feature selection and selection operator regression models. The differentiation and calibration of the model were assessed using the C-index, calibration plot, and ROC curve analysis, respectively. Internal validation was performed using a bootstrap validation technique. The results of the study revealed that the nomogram incorporated several predictive variables, namely age, T staging, and positive nodes. The C-index had an excellent calibration value of 0.911 (95 % confidence interval: 0.876-0.946), and a notable C-index value of 0.884 was achieved during interval validation. The area under the ROC curve was determined to be 0.890, indicating its practicality and usefulness in this context. This study has successfully developed a novel nomogram for predicting lung metastasis in children and adolescent patients diagnosed with thyroid cancer. Clinical decision-making can be enhanced by assessing clinicopathological variables that have a significant predictive value for the probability of lung metastasis in this particular population.

Absorbed dose coefficients for pediatric differentiated thyroid cancer patients undergoing radioiodine therapy

The escalating incidence of differentiated thyroid cancer (DTC) in pediatric patients and the resultant growing use of radioactive iodine (RAI) reinforce the need to evaluate radiation exposure to normal tissues and radiation-induced health risks in pediatric patients undergoing RAI therapy. In the current study, we calculated absorbed dose coefficients (i.e. absorbed dose per unit activity administered, mGy MBq−1) specific for pediatric patients with localized DTC undergoing RAI therapy following total thyroidectomy for use in epidemiological studies. We first modified previously-published biokinetic models for adult thyroid cancer patients to achieve a reasonable agreement with iodine biokinetics observed in pediatric patients or design principles addressed in the International Commission on Radiological Protection (ICRP) reference age-specific biokinetic models. We then combined the biokinetic models in conjunction with S values derived from ICRP reference pediatric voxel phantoms. The absorbed dose coefficients for pediatric patients were overall greater than those for adults with a ratio (pediatric/adult) up to 11.6 and rapidly decreased with increasing age. The sensitivity analysis showed that the renal clearance rate and S values may have the greatest impact on the absorbed dose coefficients with the rank correlation coefficients ranging from −0.53 to −0.82 (negative correlations) and from 0.51 to 0.80 (positive correlations), respectively. The results of the current study may be utilized in clinical or epidemiological studies to estimate organ-specific radiation absorbed doses and radiation-associated health risks among pediatric thyroid cancer patients.

Serum anti-Müllerian hormone is lower in patients with multiple radioiodine dose for treatment of pediatric thyroid cancer.

Treatment of patients with pediatric differentiated thyroid cancer (DTC) often involves radioiodine (RAI), which is associated with increased risks of short- and long-term adverse outcomes. The impact of RAI treatment on the female reproductive system remains uncertain. Anti-Müllerian hormone (AMH) is a marker of ovarian reserve and is related to fertility. The aim was to analyze the association between RAI and serum AMH level in women treated with RAI. We evaluated women with pediatric DTC treated with RAI at the age of ≤19 years. Serum AMH was measured. The study included 47 patients with a mean age of 25.1 years (12.4-50.8) at AMH measurement and follow-up of 11.8 ± 8.4 years. The mean RAI administered was 235 mCi (30-1150). Sixteen (34%) received multiple RAI doses (471 ± 215 mCi). Mean AMH level was 2.49 ng/mL (0.01-7.81); the level was 1.57 ng/mL (0.01-7.81) after multiple RAI doses and 2.99 ng/mL (0.01-6.63) after a single RAI dose (P = 0.01). Patients who received a cumulative RAI lower than 200 mCi had higher AMH levels (2.23 ng/mL, 0.39-7.81) than those who received more (1.0 ng/mL, 0.01-6.63; P = 0.02). In patients with similar cumulative RAI activities, administration of multiple RAI doses was significantly and independently associated with AMH level lower than the reference range for age (HR: 5.9, 1.55-52.2, P = 0.014) after age adjustments. Levels of AMH were lower after multiple RAI doses, especially after a cumulative RAI dose above 200 mCi. More studies are needed to clarify the impact of RAI on fertility considering its cumulative activity and treatment strategy.

Survival Trends in Pediatric Differentiated Thyroid Cancer: A Middle Eastern Perspective.

Pediatric Differentiated Thyroid Cancer (pedDTC) is a rare pediatric malignancy with an increasing incidence over time. To date, there is a paucity of literature specifically addressing pedDTC within the context of Middle Eastern ethnicity. This retrospective study aimed to assess the risk-stratifying factors for overall survival (OS) and event-free survival (EFS) in pediatric DTC patients from Iraq and Jordan. The medical records of 81 patients from two tertiary cancer institutes were retrieved. Kaplan-Meier analysis was employed to investigate OS and EFS, and the Cox proportional hazards model was employed to estimate hazard ratios. All patients underwent surgery and radioactive iodine therapy, with a median age of 14 and an interquartile range of 12-15. Lymph node involvement was observed in 55% of cases, while distant metastases were present in 13.5%. After a median follow-up period of 68 months, the 10-year survival rate was determined to be 94%, while the 10-year EFS rate was 58%. EFS was negatively impacted by cervical lymph node metastases and early age of diagnosis (p ≤ 0.01, each). Therefore, pediatrics with initial cervical lymph node metastases and those diagnosed before puberty tend to experience poorer EFS, which may justify the need for more aggressive management plans.

Chapter 11: Pediatric Differentiated Thyroid Cancers

ABSTRACT The document discusses pediatric differentiated thyroid cancer (DTC), focusing on papillary thyroid carcinoma (PTC), which is increasingly prevalent globally, including in India. Despite a more aggressive initial presentation in children, the long-term prognosis is generally positive. Key differences between pediatric and adult DTC are highlighted, such as a higher risk of malignancy in children with thyroid nodules and common RET/PTC gene rearrangements. There is a debate on the age cutoff for defining pediatric DTC, but the document suggests that 18 years is considered appropriate in the Indian context. Diagnostic methods, including ultrasonography-guided fine needle aspirate (FNA) and the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC), are emphasized. The importance of genomic analysis for indeterminate cytology is also proposed. Treatment approaches involve total thyroidectomy due to higher multifocality in children, with consideration of potential complications. Post-operative risk stratification, utilizing the TNM staging system, is seen as crucial and correlates with disease-free survival. Post-operative staging includes TSH-stimulated thyroglobulin (Tg) and anti-thyroglobulin antibody (ATg) levels, along with a diagnostic whole-body 131I scan to assess surgical completeness. Radioactive iodine therapy (RAI) is recommended for iodine-avid persistent/metastatic disease, with an empirical activity of 30 mCi for remnant ablation and adjustments based on age or weight. Regular follow-ups include monitoring TSH-suppressed Tg, Anti-Tg levels, and neck ultrasound. Dynamic risk stratification at 2 years refines risk based on treatment responses. Genetic considerations reveal prevalent RET fusion oncogene and less common BRAF mutations, which are associated with RAI refractoriness. In summary, the document provides a comprehensive understanding of pediatric DTC, emphasizing the need for tailored guidelines in the Indian context. It covers various aspects of diagnosis, surgery, and post-operative care, with a focus on age-appropriate management and ongoing research in this specialized field.

Pediatric thyroid cancer: Socioeconomic disparities and their impact on access to care

BackgroundFew studies have examined the disparities in access to care for pediatric thyroid cancers. We sought to clarify socioeconomic and patient factors that affect access to care for pediatric differentiated thyroid cancer and aggressive variants of papillary thyroid cancer. MethodsUsing the National Cancer Database, we performed a retrospective study on pediatric differentiated thyroid cancer and aggressive variants of papillary thyroid cancer (2004–2019). Patients were divided into three periods (2004–2008, 2009–2013, 2014–2019) to assess for trends. The χ2 analysis and Kruskal–Wallis test were used to test for independence of groupings for each socioeconomic and disease-related factor. ResultsIn all, 6,275 patients with pediatric differentiated thyroid cancer and 182 with aggressive variants of papillary thyroid cancer were analyzed. Differentiated thyroid cancer patients with Medicaid (median 18.0 miles) and those from lower-income households (median 21–30 miles) had to travel greater distances for care in recent years (2014–2019). Racial/ethnic disparities were evident; Black and Hispanic patients have higher odds of waiting >30 days for surgery (odds ratio 1.39, 1.49, P < .05, respectively) than White patients. Black patients with differentiated thyroid cancer had a higher risk of mortality compared with White and Hispanic patients (hazard ratio 4.31, 95% confidence interval: 1.95–9.51, P < .05). Nodal positivity was higher in Hispanic patients with differentiated thyroid cancer (60%, P < .05, White patients 51% and Black patients 36%). Socioeconomic factors did not significantly affect survival or nodal positivity in aggressive variants of papillary thyroid cancer. ConclusionThis study highlights disparities in access to care and survival outcomes in pediatric differentiated thyroid cancer and aggressive variants of papillary thyroid cancer. Race, income status, and type of insurance all play a role in these disparities. Understanding the complex etiologies and developing interventions to improve access and patient outcomes are crucial.

Predictive risk factors for distant metastasis in pediatric differentiated thyroid cancer from Saudi Arabia.

Despite their excellent prognosis, children and young adults (CAYA) with differentiated thyroid cancer (DTC) tend to have more frequent occurrence of distant metastasis (DM) compared to adult DTC. Data about DM in CAYA from Middle Eastern ethnicity is limited. Medical records of 170 patients with DTC ≤18 years were retrospectively reviewed. Clinico-pathological factors associated with lung metastasis in CAYA, their clinical presentation and outcome were analyzed. Rick factors related to distant metastasis-free survival (DMFS) for the whole cohort were evaluated. DM was observed in 27 patients and all were lung metastasis. Lung metastasis was significantly associated with younger age (≤15 years), extrathyroidal extension (ETE), multifocal tumors, bilaterality, presence of lymph node (LN) disease and high post-operative stimulated thyroglobulin (sTg). Highest negative predictive values were seen with low post-operative sTg (97.9%), absence of LN disease (93.8%), absence of ETE (92.2%) and age older than 15 years (92.9%). Post-therapy whole body scan (WBS) identified most of the lung metastasis (21 of 27; 77.8%). Upon evaluating patients response according to ATA guidelines, excellent response was seen in only one patient, while biochemical persistence and structural persistence were seen in 11.1% (3/27) and 77.8% (21/27), respectively. Elevated post-operative sTg (>10ng/ml) was the only risk factor found to be significantly associated with both biochemical persistence (with or without structural persistence (p = 0.0143)) and structural persistence (p = 0.0433). Cox regression analysis identified age and post-operative sTg as independent risk factors related to DMFS. Based on these two risk factors for DMFS, patients were divided into 3 groups: low risk (no risk factors), intermediate risk (1 risk factor) and high risk (both risk factors). 20-year DMFS rates in the low-, intermediate- and high-risk groups were 100.0%, 81.3% and 23.7% respectively (p < 0.0001). Higher suspicion for metastatic pediatric DTC should be considered in patients who are young, have LN disease, extrathyroidal extension and elevated post-operative sTg. Persistent disease, despite therapy, is very common and it appears to be related to post-operative sTg level. Hence, risk adaptive management is desirable in CAYA with DTC.

Global incidence and prevalence of differentiated thyroid cancer in childhood: systematic review and meta-analysis.

Differentiated thyroid cancer (DTC) is rare in childhood and adolescence although it represents the most frequent endocrine malignancy in this population. DTC includes both papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC). Most pediatric DTCs are PTCs, while FTCs are rare. To date, no systematic reviews on the global epidemiology of pediatric and adolescent DTC have been published. This systematic review and meta-analysis aims to estimate the overall incidence and prevalence of DTCs in patients aged 0-19 years. The systematic research was conducted from January 2000 to December 2021 through MEDLINE via PubMed, Cochrane Library, and Embase databases. Two separate meta-analyses were performed for PTC and FTC. After the selection phase, a total of 15 studies (3,332 screened) met the inclusion criteria and are reported in the present systematic review. Five studies were conducted in Europe, five in North America, two in South America, one in Asia, one reported data for 49 countries and territories across the five continents, and one from both the USA and Africa. Most of the studies (n = 14) reported data obtained from national registries, and only one provided information collected from hospital medical records. Beyond the actual trend over time, our study reported a pooled global incidence rate (IR) of PTC and FTC in the pediatric age of 0.46 (95% CI: 0.33-0.59) and 0.07 (95% CI: 0.02-0.12) per 100,000 person-years, respectively. The highest IRs were recorded among Caucasian girls, and the lowest in black or other races/ethnicities. Our data confirm that DTC in the pediatric population is a rare condition. The pooled IRs of the studies included in this meta-analysis are ~0.5 for PTC, which is the most common histological type when both genders and all age groups are considered. The implementation of a prospective international registry on pediatric DTC, as part of the wider European Registries for Rare Endocrine Conditions, has been recently proposed. In addition to providing relevant information on the clinical behavior of this rare disease, standardization of data collection will be pivotal to fill current gaps and allow an accurate estimation of the real incidence and risk factors of DTC.

Fusion Oncogenes in Patients With Locally Advanced or Distant Metastatic Differentiated Thyroid Cancer.

Fusion oncogenes are involved in the underlying pathology of advanced differentiated thyroid cancer (DTC), and even the cause of radioactive iodine (RAI)-refractoriness. We aimed to investigation between fusion oncogenes and clinicopathological characteristics involving a large-scale cohort of patients with advanced DTC. We collected 278 tumor samples from patients with locally advanced (N1b or T4) or distant metastatic DTC. Targeted next-generation sequencing with a 26-gene ThyroLead panel was performed on these samples. Fusion oncogenes accounted for 29.86% of the samples (72 rearrangement during transfection (RET) fusions, 7 neurotrophic tropomyosin receptor kinase (NTRK) fusions, 4 anaplastic lymphoma kinase (ALK) fusions) and occurred more frequently in pediatric patients than in their adult counterparts (P = .003, OR 2.411, 95% CI 1.329-4.311) in our cohort. DTCs with fusion oncogenes appeared to have a more advanced American Joint Committee on Cancer (AJCC)_N and AJCC_M stage (P = .0002, OR 15.47, 95% CI 2.54-160.9, and P = .016, OR 2.35, 95% CI 1.18-4.81) than those without. DTCs with fusion oncogenes were associated with pediatric radioactive iodine (RAI) refractoriness compared with those without fusion oncogenes (P = .017, OR 4.85, 95% CI 1.29-15.19). However, in adult DTCs, those with fusion oncogenes were less likely to be associated with RAI refractoriness than those without (P = .029, OR 0.50, 95% CI 0.27-0.95), owing to a high occurrence of the TERT mutation, which was the most prominent genetic risk factor for RAI refractoriness in multivariate logistic regression analysis (P < .001, OR 7.36, 95% CI 3.14-17.27). Fusion oncogenes were more prevalent in pediatric DTCs than in their adult counterparts and were associated with pediatric RAI refractoriness, while in adult DTCs, TERT mutation was the dominant genetic contributor to RAI refractoriness rather than fusion oncogenes.

Appropriateness of 14-year cutoff in pediatric differentiated thyroid cancer: Comparison of clinical characteristics and long-term outcomes in 14years and younger and 15-18years age groups.

Pediatric differentiated thyroid cancers (DTCs) differ in pathophysiology, presentation, and clinical outcomes from adult DTCs. However, the cutoff age for defining pediatric DTCs remains debatable, with the American Thyroid Association (ATA) and International Incidence of Childhood Cancer (IICC) report recommending different cutoffs of 18 and 14years, respectively. In this study, we investigated the appropriateness of 14-year cutoff by comparing the clinical characteristics and long-term outcomes in the 14years and younger and 15-18years age groups. Data of DTC patients, aged 18years and older, from 1981 to 2016, were sequentially extracted and compared between two age groups: ≤14 and 15-18years. Total of 176 pediatric DTC patients were included (age group ≤14years: n=75; age group 15-18years: n=101). None of the baseline clinical characteristics were significantly different between the two age groups. At 2-year follow-up, patients in the age group ≤14years had significantly higher incomplete response rate compared to those in the age group 15-18years (69% vs. 42%, respectively, p<.001). However, over a median follow-up of 10.6years (interquartile range: 7.7-15.5), the 5- and 10-year Disease-free survival (DFS) probabilities were not significantly different (p=.406). On multivariate analysis, incomplete response at 2-year follow-up was the sole independent predictor of poor DFS (hazard ratio: 5.85, 95% confidence interval: 1.69-20.23). Subdivision of pediatric DTCs into less than or equal to 14years and 15-18years age groups did not have any long-term predictive value. The cutoff of 18years as recommended by ATA is reasonable and should be uniformly followed to avoid inconsistencies and confusion.

Cytogenetic Damage Induced by Radioiodine Therapy: A Follow-Up Case Study.

The risk of toxicity attributable to radioiodine therapy (RIT) remains a subject of ongoing research, with a whole-body dose of 2 Gy proposed as a safe limit. This article evaluates the RIT-induced cytogenetic damage in two rare differentiated thyroid cancer (DTC) cases, including the first follow-up study of a pediatric DTC patient. Chromosome damage in the patient's peripheral blood lymphocytes (PBL) was examined using conventional metaphase assay, painting of chromosomes 2, 4, and 12 (FISH), and multiplex fluorescence in situ hybridization (mFISH). Patient 1 (female, 1.6 y.o.) received four RIT courses over 1.1 years. Patient 2 (female, 49 y.o.) received 12 courses over 6.4 years, the last two of which were examined. Blood samples were collected before and 3-4 days after the treatment. Chromosome aberrations (CA) analyzed by conventional and FISH methods were converted to a whole-body dose accounting for the dose rate effect. The mFISH method showed an increase in total aberrant cell frequency following each RIT course, while cells carrying unstable aberrations predominated in the yield. The proportion of cells containing stable CA associated with long-term cytogenetic risk remained mostly unchanged during follow-up for both patients. A one-time administration of RIT was safe, as the threshold of 2 Gy for the whole-body dose was not exceeded. The risk of side effects projected from RIT-attributable cytogenetic damage was low, suggesting a good long-term prognosis. In rare cases, such as the ones reviewed in this study, individual planning based on cytogenetic biodosimetry is strongly recommended.

Radioiodine Therapy in Pediatric Differentiated Thyroid Cancer: Dosimetry, Clinical Care, and Future Challenges.

Thyroid cancer is very rare in children. 131 I therapy after thyroidectomy is established in pediatric differentiated thyroid cancer (DTC). Pediatric DTC guideline is silent on the optimum amount of 131 I that could be safely and effectively administered to children who are more radiosensitive. Like adult DTC, children are also given 131 I therapy empirically based either on age or body weight. Pediatric DTC guideline recommends that patient-specific dosimetry is important in children. Still, due to the low incidence rate and the practical difficulties of dosimetry, it has neither been established nor adopted in routine practice. This review article aims to discuss current approaches of 131 I therapy in children and young adult patients with DTC and dosimetric data obtained by several investigators. Efforts are required to simplify dosimetric procedures and precise results, especially in determining lesion size. We prefer 3-dimensional dosimetry over planar dosimetry, where lesion size could be measured accurately. 124 I PET/CT-based dosimetry is expected to give accurate dosimetric results. The most challenging aspect is that no randomized controlled trials are available to compare the empiric 131 I therapy results versus dosimetry-based treatment outcomes in children and young adults. Suppose dosimetry-based 131 I therapy could be shown to have better outcomes, namely, successful ablation rate, better disease-free survival, and lesser treatment-emergent adverse events than empirical 131 I treatment. In that case, one can argue in favor of the former. Unfortunately, no convincing study is currently available. Thus, there is a need for a randomized control trial to settle this issue.

Late Breaking Abstracts

Late Breaking Abstracts

Progressive diastolic dysfunction in survivors of pediatric differentiated thyroid carcinoma.

Pediatric differentiated thyroid cancer (DTC) has an excellent prognosis but unknown late effects of treatment. The initial cardiac evaluation showed subclinical diastolic dysfunction in 20% of adult survivors. The objective of this follow-up study was to determine the clinical course of this finding. This multicenter study, conducted between 2018 and 2020, re-evaluated survivors after 5 years. The primary endpoint was echocardiographic diastolic cardiac function (depicted by the mean of the early diastolic septal and early diastolic lateral tissue velocity (e' mean)). Secondary endpoints were other echocardiographic parameters and plasma biomarkers. Follow-up evaluation was completed in 47 (71.2%) of 66 survivors who had completed their initial evaluation. Of these 47 survivors, 87.2% were women. The median age was 39.8 years (range: 18.8-60.3), and the median follow-up after the initial diagnosis was 23.4 years (range: 10.2-48.8). Between the first and second evaluation, the e' mean significantly decreased by 2.1 cm/s (s.d. 2.3 cm/s, P < 0.001). The median left ventricular ejection fraction did not significantly change (58.0% vs 59.0%, P= NS). In the best explanatory model of e' mean, multivariate linear regression analysis showed that BMI and age were significantly associated with e' mean (β coefficient: -0.169, 95% CI: -0.292; -0.047, P = 0.008 and β coefficient: -0.177, 95% CI: -0.240; -0.113, P < 0.001, respectively). In these relatively young survivors of pediatric DTC, diastolic function decreased significantly during 5-year follow-up and is possibly more pronounced than in normal aging. This finding requires further follow-up to assess clinical consequences.

Strategies for Radioiodine Treatment: What’s New

Simple SummaryRadioactive iodine treatment is the oldest targeted therapy for differentiated thyroid cancer. It can be used for normal thyroid remnant ablation (in order to increase the sensitivity and the specificity of the serum marker thyroglobulin), as an adjuvant treatment (in order to improve recurrence-free survival), or to treat radioiodine avid residual disease. Thanks to the use of sensible diagnostic tools, reliable prognostic classifications, and molecular profiling, the indication and modalities of radioiodine treatment are shifting from a one-size-fits-all to a tailored approach. This review provides insights into the most recent and high-quality evidence relating to radioactive iodine treatment.Radioiodine treatment (RAI) represents the most widespread and effective therapy for differentiated thyroid cancer (DTC). RAI goals encompass ablative (destruction of thyroid remnants, to enhance thyroglobulin predictive value), adjuvant (destruction of microscopic disease to reduce recurrences), and therapeutic (in case of macroscopic iodine avid lesions) purposes, but its use has evolved over time. Randomized trial results have enabled the refinement of RAI indications, moving from a standardized practice to a tailored approach. In most cases, low-risk patients may safely avoid RAI, but where necessary, a simplified protocol, based on lower iodine activities and human recombinant TSH preparation, proved to be just as effective, reducing overtreatment or useless impairment of quality of life. In pediatric DTC, RAI treatments may allow tumor healing even at the advanced stages. Finally, new challenges have arisen with the advancement in redifferentiation protocols, through which RAI still represents a leading therapy, even in former iodine refractory cases. RAI therapy is usually well-tolerated at low activities rates, but some concerns exist concerning higher cumulative doses and long-term outcomes. Despite these achievements, several issues still need to be addressed in terms of RAI indications and protocols, heading toward the RAI strategy of the future.