Differentiated Thyroid Cancer In Children Research Articles

8578 Papillary Thyroid Carcinoma in Autonomous Nodule with Low Risk Characteristics in Adolescent

Abstract Disclosure: A. Aponte Velez: None. M.M. Mangual Garcia: None. Thyroid nodules in children are uncommon but are known to carry a greater risk of malignancy than adult thyroid nodules. Additionally, differentiated thyroid cancer (DTC) in children is more commonly found with extrathyroidal extension and metastases which makes the approach and treatment similar but with important differences. The incidence of DTC in children is increasing, making a personalized evaluation of thyroid nodules in pediatric patients even more valuable. Guidelines recommend evaluation of nodules based on sonographic characteristics rather than size of nodule. However, not having worrisome sonographic characteristics may not be as reassuring as in adult patients. A 13 year old female patient presented with a palpable non tender right sided solid thyroid mass. She had no family history of thyroid cancer or history of irradiation. Thyroid function tests were remarkable for TSH:0.017 and positive thyroid stimulating immunoglobulin. Thyroid Ultrasound findings described heterogenous parenchyma with multiple discrete lesions on right thyroid lobe with a dominant solid isoechoic nodule at upper lobe measuring 2.1 x 3.5 x 1.9cm and a smaller nodule in lower lobe. Thyroid scan demonstrated a large functional hot nodule occupying most of right thyroid lobe with suppression of rest of thyroid parenchyma. Ultrasound guided FNA was performed of this lesion and results were negative for malignancy. Patient underwent total thyroidectomy with pathology report revealing right thyroid nodule encapsulated classical variant of papillary thyroid carcinoma. No lymph node metastases were identified. Non neoplastic thyroid parenchyma revealed chronic lymphocytic thyroiditis. Patient underwent radioiodine therapy with Whole Body Scan post radioiodine therapy demonstrating focal increased radionuclide localization at in region of neck consistent with functional thyroid tissue. There was no evidence of metastatic disease. In children, risk of malignancy is underestimated in ultrasonography and cytology. In this patient, papillary thyroid carcinoma was identified despite being stratified as having low risk of malignancy based on ultrasonography characteristics, hyperfunctioning nodule in scintigraphy study along with negative FNA results. Hyperfunctional nodules are usually reassuring for low risk of malignancy but rarely DTC can be found as in our patient. Guidelines agree that FNA is not recommended in functional nodules as surgical resection is the main therapy in children. However, surgery may be deferred if subclinical hyperthyroidism and low risk sonographic characteristics are present such as in our patient. If surgery had been deferred, based on low risk of malignancy, the risk of progression of disease would have been higher. Prognosis of DTC in children is good but the recurrence rate along with morbidity at such a young age may improve with more studies of DTC in children. Presentation: 6/2/2024

Association Between Radioactive Iodine Treatment for Pediatric and Young Adulthood Differentiated Thyroid Cancer and Risk of Second Primary Malignancies.

PURPOSESince the 1980s, both the incidence of differentiated thyroid cancer (DTC) and use of radioactive iodine (RAI) treatment increased markedly. RAI has been associated with an increased risk of leukemia, but risks of second solid malignancies remain unclear. We aimed to quantify risks of second malignancies associated with RAI treatment for DTC in children and young adults, who are more susceptible than older adults to the late effects of radiation.METHODSUsing nine US SEER cancer registries (1975-2017), we estimated relative risks (RRs) for solid and hematologic malignancies associated with RAI (yes v no or unknown) using Poisson regression among ≥ 5- and ≥ 2-year survivors of nonmetastatic DTC diagnosed before age 45 years, respectively.RESULTSAmong 27,050 ≥ 5-year survivors (median follow-up = 15 years), RAI treatment (45%) was associated with increased risk of solid malignancies (RR = 1.23; 95% CI, 1.11 to 1.37). Risks were increased for uterine cancer (RR = 1.55; 95% CI, 1.03 to 2.32) and nonsignificantly for cancers of the salivary gland (RR = 2.15; 95% CI, 0.91 to 5.08), stomach (RR = 1.61; 95% CI, 0.70 to 3.69), lung (RR = 1.42; 95% CI, 0.97 to 2.08), and female breast (RR = 1.18; 95% CI, 0.99 to 1.40). Risks of total solid and female breast cancer, the most common cancer type, were highest among ≥ 20-year DTC survivors (RRsolid = 1.47; 95% CI, 1.24 to 1.74; RRbreast = 1.46; 95% CI, 1.10 to 1.95). Among 32,171 ≥ 2-year survivors, RAI was associated with increased risk of hematologic malignancies (RR = 1.51; 95% CI, 1.08 to 2.01), including leukemia (RR = 1.92; 95% CI, 1.04 to 3.56). We estimated that 6% of solid and 14% of hematologic malignancies in pediatric and young adult DTC survivors may be attributable to RAI.CONCLUSIONIn addition to leukemia, RAI treatment for childhood and young-adulthood DTC was associated with increased risks of several solid cancers, particularly more than 20 years after exposure, supporting the need for long-term surveillance of these patients.

MON-LB83 The Initial Dose of 131I as a Potential Independent Predictor for Residual/Relapsed Disease in Pediatric Differentiated Thyroid Cancer

Introduction: In the guidelines for management of pediatric Differentiated Thyroid Cancer (DTC) 131I therapy is recommended for treatment of iodine-avid persistent locoregional disease that cannot be resected as well as iodine-avid distant metastases. To date, no consensus has been reached regarding the 131I dose for treatment of DTC in children. We report our institutional experience and highlight the initial dose of 131I as a potential independent predictor of residual/relapsed disease. Methods: We performed a retrospective analysis of all pediatric patients diagnosed with DTC between 2010 and 2018. The cohort included all patients up to 21 years of age, with minimal length of follow-up of 24 months. The risk stratification was done following the American Thyroid Association guidelines for pediatric DTC. We defined residual/relapsed disease as detectable thyroglobulin and positive anatomical lesions in imaging studies during the follow-up period. The log-rank test was used to evaluate disease-free survival. The P value was set at < 0.05. Results: Among 59 eligible patients, females were 69.5% (n=41) and males were 30.5% (n=18). The mean age at diagnosis was 16 years (9-21 years). All patients were alive at follow-up (median, 42 months; range 24 to 144 months). Fifty-eight patients had classic papillary thyroid cancer (PTC) and only 1 patient had follicular thyroid cancer. Among the patient with PTC, 39.6% (23/58) had follicular-variant PTC, 8.6% (5/52) had diffuse-sclerosing PTC and 17.2% (10/58) had other variants. Nineteen (32%), 30 (51%), and 10 (17%) had low-risk, intermediate-risk, and high-risk disease, respectively.Within the Low-risk group, 68% (13/19) received 131I. The mean initial dose was 60.9 mCi [26-150 mCi]. Eighty four percent (11/13) received ≤100 mCi and 27% (3/11) had residual/relapsed disease. Fifteen percent (2/13) received >100 mCi and none had residual/relapsed disease. Sixteen percent (1/6) of patients without 131I therapy had residual/relapsed disease. (P=0.48)Within the Intermediate-risk group, all 30 patients received 131I. The mean initial dose was 97.5 mCi [27.3-215 mCi]. Sixty percent (18/30) received ≤100 mCi and 38.8% (7/18) had residual/relapsed disease. Forty percent (12/30) received >100 mCi and 16.6 % (2/12) had residual/relapsed disease. (P=0.15)Within the High-risk group all 10 patients received 131I. The mean initial dose was 159.9 mCi [129.3-384 mCi]. Fifty percent (5/10) received ≤150 mCi and 60% (3/5) had residual/relapsed disease. Fifty percent (5/5) received >150 mCi and 20% (1/5) had residual/relapsed disease. (P=0.2) Conclusion: There are no statistical differences of disease-free rate between the initial dose of 131I among all risk categories. However, the use of more than 100 mCi in the intermediate-risk category and more than 150 mCi in the high-risk category may be recommended.

Pediatric Differentiated Thyroid Carcinoma Risk Factor For Analysis For Disease Free Survival

Abstract Context:The context of this study was epidemiology pediatric thyroid cancer in Bandung, Indonesia. Aims: The aim of this study is to evaluate clinical characteristics and outcome between children and young adult patients with differentiated thyroid cancer (DTC) treated in our hospital. Settings and Design:This was a cohort retrospective study. Materials and Methods: The medical records of 144 patients with DTC who underwent thyroid surgery followed by radioiodine and thyroid hormone suppression were retrospectively reviewed. Thyroid cancers were diagnosed between January 2007 and December 2010. Participants consisted of 43 patients who were younger than 21 years old and 101 young adult patients (older than 21 years old but younger or equal to 40 years). The clinical characteristics and outcomes were analyzed and compared, and then, recurrence-free survival was evaluated using Kaplan–Meier methods. Statistical Analysis Used: Software R 3.3.0 version for Windows was used in this study. Results: Female has higher tendency to have thyroid cancer than male (P = 0.006). Based on histopathology report, classic papillary thyroid cancer is the most common cancer type in children than young adult. However, there was no significant difference between two groups regarding thyroid cancer size and multifocality (P = 0.815 and P = 0.370). The risk of recurrent ratio of children to young adults is 3.88 (95% confidence interval [CI] 1.38; 10.91). A similar result trend has been shown for sex type, histopathology type, number of nodules, surgical technique, and metastasis parameters (adjusted hazard ratio = 7.91, 95% CI 2.11; 29.67). Conclusions: DTC in children shows more aggressive behavior compared to young adult patients.

Current management of pediatric thyroid disease and differentiated thyroid cancer.

In this article, we focus on the role of ultrasound and fine needle aspiration, management of benign nodules, extent of thyroid resection, management of regional lymph node disease, and risk stratification in staging for well differentiated thyroid cancer (DTC) in children. The recent guidelines by the American Thyroid Association focused specifically on the management of thyroid nodules and DTC in children and adolescents marks a change from previous versions, which extrapolated adult guidelines to the pediatric population. DTC in children has a distinct presentation and clinical behavior compared with adult disease. The overall excellent outcomes for pediatric patients have led to a risk stratification approach in their management (low, intermediate, and high-risk disease groupings), aiming to minimize the potential morbidity of treatment. In this review, we focus on pediatric thyroid disease, including recent studies and debates regarding the management of thyroid nodules and DTC.

Differentiated thyroid cancer in children: a series of 29 cases

To explore the best administration for the differentiated thyroid cancer in children under 14 years by reviewing of their clinical characteristics, treatment methods and results. Clinical data of 29 patients under 14 years with differentiated thyroid cancer in Xinhua Hospital, Shanghai Jiao Tong University School of Medicine between January 1998 and July 2014 were reviewed respectively. Neck mass was the chief complaint in 27 of 29 patients. Unilateral thyroid carcinoma was found in 16 cases, and bilateral in 13 cases. Solid tumor with multiple punctate calcification was observed in 21 cases (72.4%). Cervical lymph nodes enlargement was found in 24 cases (82.8%), and 15 cases (62.5%) were bilateral. Among 20 patients received primary thyroid surgery in our hospital, 18 cases presented with T2 or advanced diseases and 16 cases had cervical lymph nodes enlargement. The resection of unilateral lobe with isthmus was performed in 2 cases, and total thyroidectomy in 18 patients, including 1 case with partial trachea resection. Neck dissection was performed in 16 patients. Of 9 patients received primary thyroid surgery in other hospitals, 8 cases presented with cervical lymph node enlargement after surgery and 6 cases with pulmonary metastasis, of them 5 patients received neck dissection, 4 patients underwent resection of residual thyroid cancer plus neck dissection. Twenty-seven of all patients were treated postoperatively with 131I. All patients received follow-up, and the meaning follow-up time was 6 years and 10 months (0.5 years-16 years). No cases with death, local recurrence, and metastasis were observed in the follow-up period. Differentiated thyroid cancer is more invasive in children compared with adults. Comprehensive treatment including total thyroidectomy, neck dissection and postoperative 131I therapy may be a basic approach for the differentiated thyroid cancer in children.

Management Guidelines for Children with Thyroid Nodules and Differentiated Thyroid Cancer.

Previous guidelines for the management of thyroid nodules and cancers were geared toward adults. Compared with thyroid neoplasms in adults, however, those in the pediatric population exhibit differences in pathophysiology, clinical presentation, and long-term outcomes. Furthermore, therapy that may be recommended for an adult may not be appropriate for a child who is at low risk for death but at higher risk for long-term harm from overly aggressive treatment. For these reasons, unique guidelines for children and adolescents with thyroid tumors are needed. A task force commissioned by the American Thyroid Association (ATA) developed a series of clinically relevant questions pertaining to the management of children with thyroid nodules and differentiated thyroid cancer (DTC). Using an extensive literature search, primarily focused on studies that included subjects ≤18 years of age, the task force identified and reviewed relevant articles through April 2014. Recommendations were made based upon scientific evidence and expert opinion and were graded using a modified schema from the United States Preventive Services Task Force. These inaugural guidelines provide recommendations for the evaluation and management of thyroid nodules in children and adolescents, including the role and interpretation of ultrasound, fine-needle aspiration cytology, and the management of benign nodules. Recommendations for the evaluation, treatment, and follow-up of children and adolescents with DTC are outlined and include preoperative staging, surgical management, postoperative staging, the role of radioactive iodine therapy, and goals for thyrotropin suppression. Management algorithms are proposed and separate recommendations for papillary and follicular thyroid cancers are provided. In response to our charge as an independent task force appointed by the ATA, we developed recommendations based on scientific evidence and expert opinion for the management of thyroid nodules and DTC in children and adolescents. In our opinion, these represent the current optimal care for children and adolescents with these conditions.

Determinants of successful ablation and complete remission after total thyroidectomy and ¹³¹I therapy of paediatric differentiated thyroid cancer.

In adult differentiated thyroid cancer (DTC) patients, successful ablation and the number of (131)I therapies needed carry a prognostic significance. The goal was to assess the prognosis of DTC in children and adolescents treated in our centre in relation to the number of treatments needed and to establish the determinants of both complete remission (CR) and successful ablation. Seventy-six DTC patients <21 years of age at diagnosis were included. Recurrence and death rates, rates of CR (=negative stimulated thyroglobulin, negative neck ultrasound and negative (131)I whole-body scintigraphy) and successful ablation (=CR after initial (131)I therapy) were studied. No patients died of DTC. Seven patients were treated by surgery alone and did not show signs of recurrence during follow-up. Of the 69 patients also treated with (131)I therapy, 47 patients achieved CR, 25 of whom had successful ablation. In multivariate analysis, female gender and the absence of distant metastases were independent determinants of a higher CR rate. Female gender, lower T stage and higher (131)I activity (successful ablation, median activity 3.1 GBq, unsuccessful ablation 2.6 GBq) were determinants of a higher rate of successful ablation. After (131)I therapy no patient showed recurrence after reaching CR or disease progression if CR was not reached. In our paediatric DTC population prognosis is extremely good with no deaths or recurrences occurring regardless of the number of (131)I therapies needed or whether CR was reached. The determinants of CR and successful ablation can be used to optimize the chance of therapy success.

Initial Management and Follow-up of Differentiated Thyroid Cancer in Children

Children with differentiated thyroid cancer (DTC) often present with metastatic disease and have a high risk for recurrence, but rarely die of the disease. This article reviews DTC in children and discusses current approaches to their initial care and follow-up. These recommendations take into account the greater risk for recurrence and lower disease-specific mortality in these patients. Total thyroidectomy and central compartment lymph node dissection are appropriate for most children, but should be performed by a high-volume thyroid surgeon. Radioactive iodine (RAI) should generally be prescribed for those at very high risk for recurrence or known to have microscopic residual disease, and those with iodine-avid distant metastases. RAI should be considered in other patients only after carefully weighing the relative risks and benefits and the aggressiveness of the clinical presentation, because RAI may be associated with an increased risk for second malignancies and an increase in overall morbidity and mortality. All patients should be treated with thyroid hormone suppression, and follow-up should be lifelong. However, the degree of thyroid hormone suppression and frequency of disease surveillance usually decrease over time as patients are determined to be disease-free.

Current Understanding and Treatment of Differentiated Thyroid Cancer in Children—A Review

Differentiated thyroid cancer (DTC) often presents in children with regional lymph node metastasis accompanied by a high risk for recurrence. However, children rarely die from DTC, even those who present with distant metastatic disease. The most common presentation for DTC in children is a thyroid nodule, approximately one quarter of which are malignant. In this manuscript, we review the differential diagnosis, approach, and treatment for DTC in children with a special emphasis on future perspectives.

UICC‐2002 TNM classification is not suitable for differentiated thyroid cancer in children and adolescents

Recently the UICC-TNM classification for differentiated thyroid cancer (DTC) was changed neglecting the special circumstances for children affected by the disease. While the 1997 TNM classification grouped tumours </=1 cm as T1, the 2002 system changed this to a margin of </=2 cm. The consequences of this change were evaluated by analysing patients enrolled in the multicentre interdisciplinary therapy study of the German Society of Paediatric Oncology and Haematology (GPOH) on malignant endocrine tumours in children and adolescents, GPOH-MET 97. Between 1998 and 2005, 82 patients with histologically proven DTC entered the study. Patients classified according to UICC-TNM classification 1997 were reclassified according to the new classification (2002/2003) and vice versa by cross checking with original pathologist's reports. Twenty males and 62 females at a mean age of 12.5 years were evaluated. We observed a definite shift from patients formerly classified as T2 (1-4 cm) to category T1 (</=2 cm) according to the 2002 TNM classification. Among these patients a threefold increase of lymph node involvement and/or distant metastases could be demonstrated. The 2002 UICC-classification may have a disadvantage for children with tumours measuring between 1 and 2 cm, as those are now classified as T1. A high rate of lymph node involvement in this group reflects the risk of under-diagnosis and -treatment of this group. The current TNM classification for DTC in children should be changed taking the physiological and anatomical differences between children and adults into consideration.

Multivariate analysis of prognostic factors for differentiated thyroid carcinoma in children.

At most centres, the standard treatment for differentiated thyroid cancer (DTC) comprises total thyroidectomy, radioiodine treatment and thyroid-stimulating hormone (TSH) suppressive therapy. There is, however, considerable disagreement over the appropriate treatment for DTC in children. Some dispute the use of total thyroidectomy and/or question the routine application of iodine-131 therapy in children. The aim of this study was to perform a retrospective analysis of treatment results and prognostic factors for DTC in children treated at our centre. The study included 109 children with DTC (aged 6-17 years). The primary treatment comprised total thyroidectomy in 81 cases, radioiodine therapy in 85 cases and TSH suppressive therapy with L-thyroxine in all patients. Uni- and multivariate analysis of prognostic factors for disease-free survival was performed using the Cox regression method. The actuarial survival rate was 100%, and the 5- and 10-year actuarial disease-free survival rates were 80% and 61% respectively. Univariate analysis revealed that older age, total thyroidectomy and radioiodine treatment had a positive impact on disease-free survival whereas there were no statistical differences with regard to the child's sex, histological type of cancer or lymph node status. On multivariate analysis, radical surgery was estimated to be the most significant factor (P=0.007) for disease-free survival, while less than total thyroidectomy increased the relative risk of relapse by a factor of 10. Radioiodine treatment decreased the relative risk of relapse by a factor of 5, but with borderline significance (P=0.07). Permanent postoperative complications were observed in 17% of children: in 11 laryngeal palsy occurred, in six there was hypoparathyroidism, and one suffered from both. It is concluded that total thyroidectomy and radioiodine treatment significantly improve recurrence-free survival in children and should be routinely applied even in young children as the primary treatment of DTC.

Differentiated Thyroid Cancer in Children and Adolescents: The Importance of Adequate Surgery and Review of Literature

Within 25 years, 13 girls and 5 boys between the ages of 9 to 20 years were treated for differentiated thyroid cancer (DTC) at our institution. In 67% of the cases the diagnosis was made at an advanced stage indicated by cervical lymphnode metastases, two children showed metastases of the lung. Except for one girl, all patients underwent a total thyroidectomy with various forms of lymph node dissections. All were treated post-surgically with radio-iodine (131I) and all patients received levothyroxine in suppressive doses. The complication rate was low (laryngeal nerve injury in only 3 cases and no permanent hypoparathyroidism) and after a follow-up period of 26 years all patients are alive and without disease. In the case of DTC in children and adolescents, a total thyroidectomy with an appropriate lymph node dissection is the best surgical management. Besides the rather high incidence of local and distant recurrence, particularly in this age group, the detection and treatment of the metastases with radio-iodine are significantly facilitated by this surgical procedure. Additionally it allows the use of serum thyroglobulin as a reliable indicator of recurrence. To prevent high complication rates, surgical treatment should be performed in centers with skilled and experienced endocrine surgeons.

DIFFERENTIATED THYROID CANCER MAY HAVE GENETIC DETERMINANTS. 587

The etiology of differentiated thyroid cancer (DTC) is unknown, but there are several risk factors including female sex, exposure to ionizing radiation, and previous malignancy. Recent studies have suggested a role for altered oncogene expression [e.g. c-myc, ras, and papillary thyroid cancer gene (PTC)] in DTC. None has been abnormal in the majority of patients although PTC may be present in more aggressive tumors. To seek supporting evidence for the possible role of such genetic factors in pediatric patients with DTC, we reviewed 120 records of patients with DTC from the Department of Defense (DoD) Centralized Tumor Registry. All were diagnosed between 1953-1994 and ≤ 21 yr of age. Of these, 100 were papillary, 19 follicular, and 1 mixed papillary/follicular. Of note, 88.3% were Caucasian, 4.2% Black and 7.5% of other races. Although the exact racial distribution of all DoD pediatric patients is not known for this time period, we did compare this distribution to that of 18,832 representative DoD pediatric admissions for 1995. This was 69% Caucasian, 23% Black, and 8% other races and differed significantly from that of patients with DTC diagnosed in the 1990s (86.5% Caucasian; CI 73.6-93.9%, p<0.0005). When the data were stratified by decade of diagnosis, the incidence of DTC was greater in Caucasians from each decade. These differences support the hypothesis that there are genetic determinants in the etiology of DTC in children.