Radioiodine treatment in pediatric Graves' disease and thyroid carcinoma

Graves' disease (GD) is the most common cause of hyperthyroidism in pediatric patients. Most pediatric thyroid cancer is differentiated thyroid cancer (DTC). The two diseases can be treated using different methods, such as antithyroid drug, radioactive iodine (RAI), and surgery for GD and surgery and RAI for DTC. RAI can be used to treat pediatric GD and DTC. In the article, we reviewed the RAI application in pediatric GD and DTC.     

Evidence-based review of treatment and follow up of pediatric patients with differentiated thyroid carcinoma

Childhood onset differentiated thyroid cancer (DTC) is distinct from the adult-onset disease being more aggressive at the time of initial evaluation with a higher risk category for disease recurrence; however, it is ultimately less lethal. International groups have outlined consensus statements detailing follow up and management guidelines for adult DTC, but since disease progression and markers are significantly different in childhood DTC compared to adults, management protocols may differ. Unfortunately, there is no consensus regarding the means of follow up, timing and management strategy regarding pediatric DTC. We performed an evidence-based review of DTC in children targeted to address the following questions: What is the most appropriate initial treatment? What is the goal of thyroid hormone replacement management? What is the approach to follow-up of childhood DTC? and, How should tumor recurrence/persistence be assessed and treated? We conducted a literature search using PubMed, Cochrane databases, guidelines from various international groups, and studies pertaining to pediatric DTC management and outcome in order to answer these questions. We suggest a pre-set algorithm and approach for the management of children with DTC according to our review.     

Clinical course of pediatric and adolescent Graves' disease treated with radioactive iodine

The use of radioactive iodine (RAI) therapy in children and adolescents with Graves' disease is increasing; however, few data exist to guide dosing in this population. We aimed to determine the clinical course, failure rate and factors associated with failure of RAI for pediatric Graves' disease. A retrospective chart review from a tertiary care pediatric endocrinology clinic (1990-2003) identified 22 patients (12.7 +/- 4.0 years at diagnosis) with Graves' disease treated with RAI after initial pharmacological therapy. Patients received a calculated dose of RAI (0.1 mCi/g thyroid tissue, adjusted for 6-h radio-iodine uptake). Twenty-seven percent (95% CI 11-50%) remained hyperthyroid and required a second dose. If the first RAI was successful, the average time to hypothyroidism was 2.96 +/- 1.05 months. There were no statistically significant differences between those successfully treated with one dose and those requiring re-treatment. This high failure rate indicates a need to examine dosing of RAI in this age group.     

Imaging of pediatric thyroid tumors: A COG Diagnostic Imaging Committee/SPR Oncology Committee White Paper

Pediatric thyroid cancer is rare in children; however, incidence is increasing. Papillary thyroid cancer and follicular thyroid cancer are the most common subtypes, comprising about 90% and 10% of cases, respectively. This paper provides consensus imaging recommendations for evaluation of pediatric patients with thyroid cancer at diagnosis and during follow-up.     

Management of thyroid carcinoma in children and young adults

Thyroid cancers represent the largest group of pediatric carcinomas. Unlike other cancers of childhood, they have not been prospectively studied; instead adult data has been extrapolated to childhood and adolescent treatment. In this article we review the treatment of both well differentiated thyroid cancer (WDTC), as well as medullary thyroid cancer (MTC). The approach to both cancers relies on a low threshold of suspicion, and a willingness to biopsy suspicious lesions. Surgery remains the primary method of curing these patients, although radioactive iodine (RAI) may offer some benefit in WDTC for selected patients. For patients with MTC new medications, such as Vandetanib, may offer some adjuvant benefit following surgery. Lastly, suppression of thyroid stimulating hormone (TSH) may be one of the most beneficial treatments for WDTC.     

THYROID CANCER IN LEBANESE CHILDREN AND ADOLESCENTS: A 15-Year Experience at a Single Institution

Background and Aim: Thyroid carcinomas are rare in childhood and adolescence. Management of this entity remains controversial. The aim of this study is to review our experience with multidisciplinary management of papillary thyroid cancer in the pediatric population at a tertiary care specialized medical center in Lebanon. Procedure: The medical records of all patients with thyroid cancer younger than 20 years who presented to our center between January 1991 and January 2006 were reviewed. Results: Thirteen patients with papillary thyroid carcinoma (PTC) were identified. No patient had previous exposure to ionizing radiation. The mean age at diagnosis was 14.5 years. There were 8 females; all patients presented with a cervical mass. Ten patients underwent total thyroidectomy and three subtotal thyroidectomy. Eight patients (61.5%) had regional lymph node metastases, only one of whom (7.6%) had lung metastases. All received radioactive “131I” ablation postsurgical excision. Five (38.5%) had recurrences and needed multiple surgeries and/or “131I” ablation. At a median follow-up time of 8.3 years all patients are disease free. Conclusion: Pediatric thyroid cancer in Lebanon is a rare tumor that presents mainly as a primary malignancy. The main clinical presentation is a cervical mass with locoregional lymph nodes metastasis. The mainstay of therapy is total thyroidectomy with lymph node dissection when indicated and radioactive “131I” ablation. Despite recurrences the prognosis is excellent.     

Genetic predisposition and screening in pediatric cancer

Pediatricians are often the health care providers who first detect the signs and symptoms of childhood cancer. Although pediatric malignancies are rare diseases, early diagnosis is an important factor leading to high cure rates of many types of cancers including retinoblastomara, Wilms' tumor, hepatoblastoma, rhabdomyosarcoma. thyroid carcinoma, and other solid tumors. A number of familial cancer syndromes present with childhood cancers that can be recognized or diagnosed by pediatricians. The genetic origins of several syndromes have been elucidated. Genetic testing is not yet available for all of these inherited cancers. A frequently updated list of genetic tests is available at www.genetests.org. The ordering and interpreting of genetic tests, however, is often best done by trained genetic counselors. The pediatrician will play a vital on-going role in following the at-risk child. In many of syndromes discussed, the cost effectiveness of the tests as well as that of any potential intervention needs further study. The role of the subtle genetic polymorphisms in pediatric tumorigenesis. many more of which will undoubtedly be described in the coming years, has not yet been translated into defined needs for interventions. Perhaps in the future it will be possible to understand the additive effect of multiple genetic polymorphisms and to determine genetic profiles of high cancer risk. Until suitable interventions are established, however, the study of genetic variability and cancer will await practical significance. Undoubtedly other major important cancer genes are yet to be discovered and characterized. An additional challenge is the counseling and management of children and adults who have a strong family history of cancer yet who do not have a recognizable syndrome. The role of the primary pediatrician is to recognize the major cancer genetic syndromes, to make appropriate referrals for genetic counseling and testing when indicated, and to ensure that adequate screening tests are being done.     

Natural history of thyroid nodules in survivors of pediatric Hodgkin lymphoma

BACKGROUND: Survivors of Hodgkin lymphoma and other patients who receive neck irradiation are at increased risk of thyroid cancer. Ultrasonography provides an inexpensive and non-invasive method of thyroid screening, but the clinical significance of thyroid nodules detected by ultrasound screening is uncertain. PROCEDURE: We reviewed the demographics, clinical characteristics, method of detection, and outcome of patients who developed thyroid nodules after treatment for pediatric Hodgkin lymphoma at our institution. One radiologist reviewed all imaging studies. RESULTS: Sixty-seven children treated for Hodgkin lymphoma from 1962 to 2001 developed thyroid nodules. The study group represented 9,024 person-years of follow-up after the diagnosis of Hodgkin lymphoma and 581 person-years after diagnosis of a thyroid nodule. A median of 10.5 years (range, 0.2-24.8 years) elapsed between the diagnoses of Hodgkin lymphoma and thyroid nodule(s). All but one patient had received neck irradiation for Hodgkin lymphoma, with a median thyroid radiation dose of 35 Gy (range, 12-45 Gy). Thyroid nodules were found to be malignant in seven patients (10%), at a median of 16.2 years (range, 8.4-23.7 years) after diagnosis of Hodgkin lymphoma. Only one malignancy was found through screening ultrasonography. All patients with thyroid cancer remained disease-free at 0.4-16.2 years of follow-up. CONCLUSIONS: Thyroid nodules are common in Hodgkin lymphoma survivors treated with neck irradiation, but the majority of these lesions have an indolent clinical course and do not undergo malignant transformation. Only patients with a palpable mass or clinical symptoms need more extensive evaluation, including Doppler-flow ultrasonography and fine-needle aspiration.     

Conservative surgical approach for thyroid and lymph-node involvement in papillary thyroid carcinoma of childhood and adolescence

BACKGROUND: Prior to 1990s, papillary thyroid carcinomas (PTCs) in childhood/adolescence underwent a standard therapeutic approach (total thyroidectomy plus elective neck dissection, followed by radioactive iodine (RAI) ablation), with an overall survival of about 100%. The aim of this study is to outline the possibility of a conservative approach (hemithyroidectomy plus selective neck dissection of clinically involved nodes, followed by TSH-suppressive therapy) in a selected group of patients. PROCEDURE: From 1968 to 2001, 42 pediatric PTC patients were treated at our institution. Absence of distant metastases and a tumor clinically limited to one lobe were both present in 28 cases that underwent a radical (20 cases) or a conservative (8 cases) surgical approach at the thyroid level. At cervical node level, 10 patients underwent a radical and 32 a conservative surgical approach. Clinicopathologic features at onset, type of therapy (radical vs. conservative), post-operative complications, and outcome till May 31, 2004 were recorded. The impact of the type of surgery on outcome was evaluated. RESULTS: Overall and progression-free survival (PFS) curves were found to be independent of the type of therapy (radical vs. conservative) in subgroups of patients matched for extent of disease at onset. Post-operative complications occurred only with radical surgical approaches. CONCLUSIONS: Childhood and adolescence PTCs show a high rate of spread but an excellent outcome independent of the type of therapy (radical vs. conservative). Taking into account the marked responsiveness to TSH-suppression and the complications after radical therapy, in selected cases, a conservative approach should be considered, reserving more aggressive therapies in case of metastases or relapse.     

Assessment of pain and anxiety related to painful medical procedures in pediatric oncology

In this article we review the instruments most commonly used in clinical practice and research to assess the pain and anxiety experienced by children with cancer undergoing painful medical procedures. Issues such as the prevalence of pain in childhood cancer, the psychologic impact of medical procedures in children, and the efforts some institutions are making to implement pediatric pain assessment programs are also reviewed, bearing in mind that pain is a subjective and multidimensional experience. Behavioral measures, self-reports, multidimensional assessment tools and physiological measures are included, emphasizing the importance of self-reports, which are considered the gold standard in pediatric pain assessment. This literature review indicates the need for research and for the education of health care professionals in pediatric pain assessment. Finally, recommendations for pediatric pain assessment are suggested.     

Guidelines for pediatric cancer centers

Since the American Academy of Pediatrics published guidelines for pediatric cancer centers in 1986 and 1997, significant changes in the delivery of health care have prompted a review of the role of tertiary medical centers in the care of pediatric patients. The potential effect of these changes on the treatment and survival rates of children with cancer led to this revision. The intent of this statement is to delineate personnel and facilities that are essential to provide state-of-the-art care for children and adolescents with cancer. This statement emphasizes the importance of board-certified pediatric hematologists/oncologists, pediatric subspecialty consultants, and appropriately qualified pediatric medical subspecialists and pediatric surgical specialists overseeing the care of all pediatric and adolescent cancer patients and the need for facilities available only at a tertiary center as essential for the initial management and much of the follow-up for pediatric and adolescent cancer patients.     

Attitudes and practices of pediatric oncology providers regarding fertility issues

PURPOSE: Given the higher survival rates of childhood cancer, health care providers must be aware of the side effects of cancer therapies to educate patients and provide appropriate interventions to reduce cancer-related morbidity. To understand the current practices and attitudes in a pediatric hematology/oncology clinic, health care providers were surveyed regarding fertility issues pertinent to their patient care. PARTICIPANTS AND INSTRUMENTS: In this study, 93.8% (30/32) health care providers in one pediatric hematology/oncology department completed a 44-item survey assessing knowledge, current practices, obstacles to current practices, perceptions of patient differences, and improvements to future practice. RESULTS: The majority of health care providers were aware of the adverse effects of alkylating agents (90.7%) and of abdominal and pelvic radiation (100.0%) on fertility. However, only half were aware of gender differences in gonadotoxicity (50.0%) or knowledgeable of current research and technology in fertility preservation (53.3%). While only 34.6% of providers currently consulted with specialists, nearly all (92.8%) indicated a desire to do so in the future, but 64.3% indicated difficulties in finding proper facilities and specialists for their patients. Almost all (96.6%) agreed that providers and patient families need more information regarding the effects of cancer therapy on fertility. CONCLUSIONS: Surveyed pediatric oncology providers considered fertility to be an important issue for childhood cancer patients and desired more resources regarding effects on fertility and fertility preservation. Greater communication needs to be established between pediatric oncology providers and specialists in reproductive medicine and endocrinology to ensure adequate professional collaboration and patient referrals.     

小儿分化型甲状腺癌的外科治疗策略

目的 探讨小儿甲状腺癌的临床特点，选择恰当的外科治疗方法，减少合并症的发生。方法 回顾性分析1975年7月～1997年12月我院头颈外科治疗的15岁以下31例小儿分化型甲状腺癌的临床资料、根据病变范围程度，选择腺叶峡部切除，次全切除或近全切除，甲状腺全切除治疗甲状腺原发灶，颈淋巴结转移行根治性或改良根治性清扫术。颈淋巴结清扫术的范围包括Ⅱ，Ⅲ，Ⅳ，Ⅴ和Ⅵ区。远处转移行Ⅰ或甲状腺素治疗。结果 31例中乳头状癌25例，滤泡癌6例，术后随访5～27年，平均随访13年8个月，无死亡病例。局部复发2例，颈部复发1例，复发率为9．7％(3／31)。颈淋巴结转移率为74．2％(23／31)，甲状腺外浸润占58．1(18／31)。全甲状腺切除的合并症为42．9%(3／7)，腺叶及次全切除合并症为8．3％(2／24)。结论 小儿分化型甲状腺癌病程长，转移率高，甲状腺外浸润较成年人更常见，但预后较成人好。主张行腺叶及次全切除术或近全切除，癌在甲状腺外侵及的器官及神经应尽可能保留其功能的完整，少许残留癌可行Ⅰ或甲状腺素治疗。     

Thyroid disease in the pediatric patient: emphasizing imaging with sonography

Thyroid disease does occur in the pediatric patient, and imaging plays an important role in its evaluation. A review is presented of normal development of the thyroid gland, the technique and indications for thyroid sonography, and key imaging features of congenital thyroid disorders (ectopic or absent thyroid, infantile goiter, thyroglossal duct remnants), benign thyroid masses (follicular adenoma, degenerative nodules, colloid and thyroid cysts), malignant masses (follicular, papillary and medullary carcinoma) and diffuse thyroid disease (acute bacterial thyroiditis, Hashimoto's thyroiditis, Grave's disease).     

De novo malignances in pediatric organ transplant recipients

A study of 10813 types of cancer that occurred in 10151 organ transplant recipients showed that the pattern of malignancies that occurred in pediatric recipients was very different from the general pediatric population and from adult recipients. Tumors (527) occurred in 512 pediatric patients (aged 18 years or less), and 9639 adults developed 10286 neoplasms. Post-transplant lymphoproliferative disease (PTLD) was the predominant neoplasm in pediatric recipients and comprised 52% of all tumors compared with 15% in adult recipients. Eighty-four percent of PTLD in the former patients presented during childhood. There was a disproportionately high incidence among nonrenal allograft recipients compared with renal recipients (81% vs. 31% of all tumors). The second most common malignancy in pediatric patients was skin cancer (19% of tumors), but this was less frequent than in adult recipients, in whom it comprised 39% of neoplasms. Only 16 pediatric patients (16%) with skin cancers developed their tumors during childhood (6 had malignant melanomas), with an average time of appearance after transplantation of 126 months (range 5.5-292). Malignant melanomas were more common in pediatric than adult recipients (12% vs. 5% of skin cancers), as were lip cancers (23% vs. 12%). Spread to lymph nodes was also more common in pediatric than in adult recipients (9% vs. 6%). Sarcomas comprised 4% of tumors compared with 1% in adults. Carcinomas of the vulva and perineum also comprised 4% of tumors. Females outnumbered males in a ratio of 8.5:1. These tumors appeared beyond childhood at an average of 142 months (range 42-262 months) post-transplantation. Other cancers observed in recipients transplanted during childhood were thyroid carcinomas (15), Kaposi's sarcomas (15), carcinomas of the liver (13), leukemias (13), carcinomas of the cervix (10), brain tumors (7), renal carcinomas (7), ovarian carcinomas (5), and miscellaneous tumors (19). Of all 527 malignancies, 314 (60%) appeared during childhood and 213 (40%) manifested themselves between the ages of 19 and 40 years. By far the most common tumor diagnosed during childhood was PTLD, which comprised 230 of the 314 (73%) malignancies.     

Current approaches for risk stratification of infectious complications in pediatric oncology

Infections are serious complications of cytoreductive therapy in pediatric cancer patients presenting with febrile neutropenia. It is standard of care to initiate empirical intravenous broad-spectrum antibiotics until the fever and neutropenia resolve. However, it might be effective and safe to allow for early hospital discharge in certain subgroups of patients. Two strategies for risk stratification of pediatric cancer patients with regard to infectious complications are discussed in this review: (1) clinical risk parameters and laboratory measures to assist therapeutic management at presentation with fever in neutropenia, and (2) investigations of individual genetic susceptibility factors to tailor potential prophylactic approaches. Given the data available from a significant number of small studies, a large prospective non-inferiority trial is essential to assess low-risk clinical factors and additional laboratory or genetic markers for their predictive value.     

Development and field testing of protocols for the management of pediatric telephone calls: protocols for pediatric telephone calls.

Although telephone calls comprise almost one fourth of all childhood patient-physician contacts, the content of telephone care is not emphasized in most educational and service programs. In response to the need to improve management of telephone calls to our pediatric emergency room, we developed 28 protocols to deal with the 25 most common complaints presented by phone. This paper describes the content of these protocols, the training of the health assistants who administered them, and the measures we took to assure their safety and general utility in pediatric practice settings. The study demonstrates the feasibility of an organized system for telephone care based on protocols which include: (1) basic data to be collected for each chief complaint category; (2) a range of appropriate dispositions; and (3) advice for home management when the patient does not require an immediate medical visit. Potential uses of these protocols for medical and nursing education and for clinical service needs are discussed.     

In situ breast carcinoma after treatment during adolescence for thyroid cancer with radioiodine

We reviewed the courses of patients treated during childhood or adolescence for thyroid cancer to estimate the frequency of, and to identify possible risk factors for, the occurrence of second malignant tumors in this population. We identified all patients treated for thyroid cancer in a cohort of 1,406 pediatric cancer patients who were diagnosed prior to 20 years of age during the period January 1, 1960 through December 31, 1988 and who were treated at Roswell Park Cancer Institute. Twelve patients were treated for thyroid cancer, of whom nine were women. In situ breast carcinoma was diagnosed 25 and 26 years after diagnosis of thyroid cancer in two of four women treated with radioiodine. No new cancers were diagnosed in the five women treated with thyroidectomy only. Two of four women treated for thyroid cancer during adolescence with radioiodine, which is concentrated in the breast as well as other organs, developed in situ breast carcinoma. Review of a large cohort of adolescent female thyroid cancer patients treated with radioiodine is necessary to provide an accurate estimate of their risk of developing breast cancer. These patients must remain under medical surveillance throughout their lifetimes to facilitate prompt diagnosis of and early intervention for new conditions, such as the occurrence of breast cancer. © 1995 Wiley-Liss, Inc.     

Obesity in pediatric oncology

Today's obesity pandemic began in the United States, spread to Western Europe and other developed regions, and is emerging in developing countries. Its influences on outcomes of childhood cancer are unknown. A recent Children's Oncology Group symposium considered epidemiology of obesity, pharmacology of chemotherapy and outcomes in obese adults with cancer, excess mortality in obese pediatric patients with acute myeloid leukemia (AML), and complications in obese survivors. The salient points are summarized herein. Body mass index (BMI) is the accepted index of weight for height and age. In the US, obesity prevalence (BMI > 95th centile) is increasing in all pediatric age groups and accelerating fastest among black and Hispanic adolescents. Pharmacologic investigations are few and limited: half-life, volume of distribution, and clearance in obese patients vary between drugs. Obese adults with solid tumors generally experience less toxicity, suggesting underdosing. For patients undergoing bone marrow transplantation, obese adults generally experience greater toxicity. In pediatric acute myeloblastic leukemia, obese patients have greater treatment-related mortality (TRM), similar toxicity and relapse rates, and inferior survival compared with patients who are not obese. An excess of female survivors of childhood leukemia who received cranial irradiation are obese. Ongoing treatment effects of childhood cancer may predispose to a sedentary lifestyle. These findings call for measures to prevent obesity, retrospective and prospective studies of chemotherapy pharmacology of analyzed according to BMI and outcomes, additional studies of the obesity impact on outcomes in pediatric cancer, and promotion of a healthy lifestyle among survivors.     

Current status of palliative care in Israel: a pediatric oncologist's perspective

Pediatric cancer palliative care is characterized by diversity of care delivery models; effect of cancer on the family as the central focus of care and consideration of culture, spirituality, communication, and ethical standards. In Israel, children who are in palliative care are treated by the staff of the centers and about 70 to 80 % of the children are dying in the pediatric Hematology Oncology departments and units. Special efforts are also made in the pediatric departments in order to better treat adolescents in terminal phases. Palliative care education program in Israel was started several years ago together with adult palliative care specialists, the Israeli pediatric oncologists still witness many barriers for treatment amongst parents as well as in medical pediatric teams especially in pain management. During the last years, the Israeli pediatric palliative care teams improved the management of all symptoms in a dying child with special attention to existential, emotional and social demands of the child and the whole family. Education of the medical and nursing team is imperative, training in pharmacology and metabolism of antalgic drugs is also mandatory in order to better manage symptom control of the children at the end of life.