Referral patterns for patients with high-risk thyroid cancer.

OBJECTIVE: Knowledge of referral patterns for specialty cancer care is sparse. Information on both the need and reasons for referral of high-risk, well-differentiated thyroid cancer patients should provide a foundation for eliminating obstacles to appropriate patient referrals and improving patient care. METHODS: We surveyed 370 endocrinologists involved in thyroid cancer management. From information in a clinical vignette, respondents were asked to identify the reasons they would need to refer a high-risk patient to a more specialized facility for care. We performed multivariable analysis controlling for hospital and physician characteristics. RESULTS: Thirty-two percent of respondents reported never referring thyroid cancer patients to another facility. Of those that would refer a high-risk patient to another facility, the opportunity for a patient to enter a clinical trial was the most common reason reported (44%), followed by high-dose radioactive iodine (RAI) with or without dosimetry (33%), lateral neck dissection (24%), and external beam radiation (15%). In multivariable analysis, endocrinologists with a higher percentage of their practice devoted to thyroid cancer care were significantly less likely to refer patients to another facility (P = .003). CONCLUSION: The majority of endocrinologists treating thyroid cancer patients report referring a high-risk patient to another facility for some or all of their care. Knowledge of the patterns of physician referrals and the likelihood of need for referral are key to understanding discrepancies in referral rates and obstacles in the referral process.

Variation in the management of thyroid cancer.

CONTEXT: Little is known about practice patterns in thyroid cancer, a cancer that is increasing in incidence. OBJECTIVE: We sought to identify aspects of thyroid cancer management that have the greatest variation. DESIGN/SETTING/PARTICIPANTS: We surveyed 944 physicians involved in thyroid cancer care from 251 hospitals affiliated with the US National Cancer Database. Physicians were asked questions in the following four domains: thyroid surgery, radioactive iodine use, thyroid hormone replacement postsurgery, and long-term thyroid cancer management. We calculated the ratio of observed variation to hypothetical maximum variation under the assumed distribution of the response. Ratios closer to 1 indicate greater variation. RESULTS: We had a 66% response rate. We found variation in multiple aspects of thyroid cancer management, including the role of central lymph node dissections (variation, 0.99; 95% confidence interval [CI], 0.98-1.00), the role of pretreatment scans before radioactive iodine treatment (variation, 1.00; 95% CI, 0.98-1.00), and all aspects of long-term thyroid cancer management, including applications of ultrasound (variation, 0.97; 95% CI, 0.93-0.99) and radioactive iodine scans (variation, 0.99; 95% CI, 0.97-1.00). For the management of small thyroid cancers, variation exists in all domains, including optimal extent of surgery (variation, 0.91; 95% CI, 0.88-0.94) and the role of both radioactive iodine treatment (variation, 0.91; 95% CI, 0.89-0.93) and suppressive doses of thyroid hormone replacement (variation, 1.00; 95% CI, 0.99-1.00). CONCLUSION: We identified areas of variation in thyroid cancer management. To reduce the variation and improve the management of thyroid cancer, there is a need for more research and more research dissemination.

Factors that influence radioactive iodine use for thyroid cancer.

BACKGROUND: There is variation in the use of radioactive iodine (RAI) as treatment for well-differentiated thyroid cancer. The factors involved in physician decision-making for RAI remain unknown. METHODS: We surveyed physicians involved in postsurgical management of patients with thyroid cancer from 251 hospitals. Respondents were asked to rate the factors important in influencing whether a thyroid cancer patient receives RAI. Multivariable analyses controlling for physician age, gender, specialty, case volume, and whether they personally administer RAI, were performed to determine correlates of importance placed on patients' and physicians' worry about death from cancer and differences between low- versus higher-case-volume physicians. RESULTS: The survey response rate was 63% (534/853). Extent of disease, adequacy of surgical resection, patients' willingness to receive RAI, and patients' age were the factors physicians were most likely to report as quite or very important in influencing recommendations for RAI to patients with thyroid cancer. Interestingly, both physicians' and patients' worry about death from thyroid cancer were also important in determining RAI use. Physicians with less thyroid cancer cases per year were more likely than higher-volume physicians to report patients' (p<0.001) and physicians' worry about death (p=0.016) as quite or very important in decision-making. Other factors more likely to be of greater importance in determining RAI use for physicians with lower thyroid cancer patient volume versus higher include the accepted standard at the affiliated hospital (p=0.020), beliefs about RAI expressed by colleagues comanaging patients (p=0.003), and patient distance from the nearest facility administering RAI (p=0.012). CONCLUSION: In addition to the extent of disease and adequacy of surgical resection, physicians place importance on physician and patient worry about death from thyroid cancer when deciding whether to treat a patient with RAI. The factors important to physician decision-making differ based on physician thyroid-cancer case-volume, with worry about death being more influential for low-case-volume physicians. As the mortality from thyroid cancer is low, the importance placed on death in decision making may be unwarranted.

Theranostics: evolution of the radiopharmaceutical meta-iodobenzylguanidine in endocrine tumors.

Since 1981, meta-iodobenzylguanidine (MIBG), labeled with (131)I and later (123)I, has become a valuable agent in the diagnosis and therapy of a number of endocrine tumors. Initially, the agent located pheochromocytomas and paragangliomas (PGLs), both sporadic and familial, in multiple anatomic sites; surgeons were thereby guided to excisional therapies, which were previously difficult and sometimes impossible. The specificity in diagnosis has remained above 95%, but sensitivity has varied with the nature of the tumor: close to 90% for intra-adrenal pheochromocytomas but 70% or less for PGLs. For patients with neuroblastoma, carcinoid tumors, and medullary thyroid carcinoma, imaging with radiolabeled MIBG portrays important diagnostic evidence, but for these neoplasms, use has been primarily as an adjunct to therapy. Although diagnosis by radiolabeled MIBG has been supplemented and sometimes surpassed by newer scintigraphic agents, searches by this radiopharmaceutical remain indispensable for optimal care of some patients. The radiation imparted by concentrations of (131)I-MIBG in malignant pheochromocytomas, PGLs, carcinoid tumors, and medullary thyroid carcinoma has reduced tumor volumes and lessened excretions of symptom-inflicting hormones, but its value as a therapeutic agent is being fulfilled primarily in attacks on neuroblastomas, which are scourges of children. Much promise has been found in tumor disappearance and prolonged survival of treated patients. The experiences with therapeutic (131)I-MIBG have led to development of new tactics and strategies and to well-founded hopes for elimination of cancers. Radiolabeled MIBG is an exemplar of theranostics and remains a worthy agent for both diagnosis and therapy of endocrine tumors.

Three endocrine neoplasms: an unusual combination of pheochromocytoma, pituitary adenoma, and papillary thyroid carcinoma.

BACKGROUND: Three endocrine neoplasms-bilateral pheochromocytomas, somatotrophic pituitary adenoma inducing acromegaly, and papillary carcinoma of the thyroid-occurred concurrently in a patient. A genetic mutation was hypothesized. Possible previously described genetic mutations were explored. METHODS: Clinical assessments, laboratory data, images of tumors, histopathology, and immunohistochemistry of excised tissues documented the three neoplasms. Clinical assessment of the patient, family history, and a review of the literature sought a familial basis for the disorders. RESULTS: The methods confirmed the presence of three endocrine neoplasms. Each neoplasm was surgically excised and histologically verified. Surgical and (131)I treatments reduced the papillary carcinoma, but eventually this tumor progressed to a lethal degree. History, including that of nine siblings, uncovered no familial neoplasms. No similar case was found in the literature, but possible associations with germline mutations were considered. CONCLUSIONS: The concurrent development of pheochromocytomas, pituitary somatotrophic adenoma, and papillary thyroid carcinoma appears to be unique. Nevertheless, such tumors, particularly bilateral pheochromocytomas, strongly suggest a de novo germline mutation in a gene not previously associated with multiple endocrine neoplasia syndromes.

Radiation safety in the treatment of patients with thyroid diseases by radioiodine 131I : practice recommendations of the American Thyroid Association.

BACKGROUND: Radiation safety is an essential component in the treatment of patients with thyroid diseases by ¹³¹I. The American Thyroid Association created a task force to develop recommendations that would inform medical professionals about attainment of radiation safety for patients, family members, and the public. The task force was constituted so as to obtain advice, experience, and methods from relevant medical specialties and disciplines. METHODS: Reviews of Nuclear Regulatory Commission regulations and International Commission on Radiological Protection [corrected] recommendations formed the basic structure of the recommendations. Members of the task force contributed both ideas and methods that are used at their respective institutions to aid groups responsible for treatments and that instruct patients and caregivers in the attainment of radiation safety. There are insufficient data on long-term outcomes to create evidence-based guidelines. RESULTS: The information was used to compile delineations of radiation safety. Factors and situations that govern implementation of safety practices are cited and discussed. Examples of the development of tables to ascertain the number of hours or days (24-hour cycles) of radiation precaution appropriate for individual patients treated with ¹³¹I for hyperthyroidism and thyroid cancer have been provided. Reminders in the form of a checklist are presented to assist in assessing patients while taking into account individual circumstances that would bear on radiation safety. Information is presented to supplement the treating physician's advice to patients and caregivers on precautions to be adopted within and outside the home. CONCLUSION: Recommendations, complying with Nuclear Regulatory Commission regulations and consistent with guidelines promulgated by the National Council on Radiation Protection and Measurement (NCRP-155), can help physicians and patients maintain radiation safety after treatment with ¹³¹I of patients with thyroid diseases. Both treating physicians and patients must be informed if radiation safety, an integral part of therapy with ¹³¹I, is to be attained. Based on current regulations and understanding of radiation exposures, recommendations have been made to guide physicians and patients in safe practices after treatment with radioactive iodine.

Staging of differentiated thyroid carcinoma using diagnostic 131I SPECT/CT.

OBJECTIVE: The purpose of this study was to evaluate the feasibility of staging differentiated thyroid carcinoma (DTC) before initial radioiodine therapy using diagnostic radioiodine-131 ((131)I) scintigraphy with SPECT/CT and to determine the additional value of SPECT/CT. MATERIALS AND METHODS: Forty-eight patients (12 men and 36 women; age range, 17-82 years) with DTC underwent diagnostic (131)I planar imaging and SPECT/CT scintigraphy reinterpreted by two readers, one of whom was not blinded to patients' clinical details. Staging and scoring of carcinomas was done by use of TNM with three levels of sequential information: histopathologic analysis and chest radiograph data, planar images, and SPECT/CT data. Restaging based on the imaging findings was designated as "iTNM." RESULTS: Diagnostic (131)I scintigraphy allowed TNM staging of DTC before initial radioiodine therapy. Planar images detected previously unsuspected distant disease in four (50%) of eight patients with a score of M1. SPECT/CT changed the planar scan interpretation for 19 (40%) of 48 patients, detecting regional nodal metastases in four patients and clarifying equivocal focal neck uptake in 15 patients. Compared with histopathologic analysis and chest radiograph data, planar images and SPECT/CT changed the postsurgical DTC stage for 10 (21%) of 48 patients. SPECT/CT information changed the proposed (131)I therapeutic dose for 28 (58%) of 48 patients, on the basis of our department protocol. CONCLUSION: Diagnostic (131)I scintigraphy, planar images, and SPECT/CT complete the postsurgical staging of DTC. SPECT/CT reduces the number of equivocal diagnoses on planar imaging and improves the interpretation of (131)I scintigraphy. The consequent changes in TNM scores and staging should influence the (131)I dose prescribed at initial therapy.

A phase II study of imatinib in patients with advanced anaplastic thyroid cancer.

BACKGROUND: Currently, there is no standard treatment for metastatic anaplastic thyroid cancer (ATC). DNA microarray analysis has shown platelet-dervived growth factor receptor (PDGFR) overexpression in ATC relative to well-differentiated thyroid cancer. In p53-mutated/deficient ATC cell lines, cABL is overexpressed, and selective inhibition of cABL results in a cytostatic effect. Imatinib inhibits tyrosine kinase activity of Bcr-ABL and PDGF. We hypothesize that patients with ATC that over-expresses PDGF receptors or cABL will respond to imatinib. METHODS: Patients with histologically confirmed ATC who had measurable disease and whose disease expressed PDGF receptors by immunohistochemistry were eligible for study. Imatinib was administered at 400 mg orally twice daily without drug holiday. Response to treatment was assessed every 8 weeks. Patients with complete response, partial responses, or stable disease were treated until disease progression. The study was terminated early due to poor accrual. RESULTS: From February 2004 to May 2007, 11 patients were enrolled and were started on imatinib. At baseline, 4/11 had locoregional disease, 5/11 had distant metastases, and 2/11 had both. Nine of 11 had prior chemoradiation, and 7/11 had thyroidectomy. Eight of 11 were evaluable for response; 4 were excluded for lack of follow-up with radiologic evaluation. The overall response rates at 8 weeks were complete response 0/8, partial response 2/8, and stable disease 4/8. The median time to follow-up was 26 months (ranges 23-30 months). The rate of 6-month progression-free survival was 36% (95% confidence interval, 9%-65%). The rate of 6-month overall survival was 45% (95% confidence interval, 16%-70%). The most common grade 3 toxicity was edema in 25%; other grade 3 toxicities included fatigue and hyponatremia (12.5% each). There were no grade 4 toxicities or treatment related deaths. CONCLUSIONS: Imatinib appears to have activity in advanced ATC and is well tolerated. Due to difficulty of accruing patients with a rare malignancy at a single institution, further investigation of imatinib in ATC may be warranted in a multi-institutional setting.

Familial medullary thyroid carcinoma associated with cutaneous lichen amyloidosis.

BACKGROUND: This is a report of a patient with a novel genotype-phenotype relationship of a c804 mutation of the RET proto-oncogene manifesting as medullary thyroid carcinoma (MTC) and cutaneous lichen amyloidosis (CLA). SUMMARY: Clinical data were obtained for patient appearance and laboratory results. Analyzed were histopathology of the skin lesion and thyroid gland, genetic mutation, and family pedigree. Skin histology and histochemistry were consistent with CLA. Serum calcitonin levels were moderately elevated. Thyroid histology demonstrated a 4 mm focus of MTC. Measurements of serum parathormone, calcium, and plasma metanephrines were normal. DNA analysis demonstrated a mutation in codon 804 of the RET proto-oncogene resulting in a Valine to Methionine (V804M) substitution. Genetic testing in two siblings revealed the same mutation. CONCLUSIONS: This is the first description of a patient with CLA not associated with a mutation in codon 634. The patient is one of the few with a V804M mutation in whom the clinical expression did not fully conform to the definition of familial MTC.

Thyroid carcinoma metastasis to skull with infringement of brain: treatment with radioiodine.

BACKGROUND: Infringement by differentiated thyroid carcinoma on the brain is rare but, when suspected, the patient deserves special attention. A patient with an enlarging metastasis of thyroid carcinoma to the skull that was impinging on the brain illustrates diagnostic and therapeutic strategies applicable to the treatment of metastatic carcinoma. METHODS: A case study was performed. Computed tomography (CT) and magnetic resonance imaging (MRI) were done, serum thyroglobulin was measured, and tumor responses to thyroxine and (131)I treatments were monitored. Tumor dosimetry, enabled by scintigraphy with (131)I employing single photon emission tomography fused with CT (SPECT-CT), was performed. RESULTS: The metastasis was from a follicular variant of papillary thyroid carcinoma. During thyrotropin stimulation the tumor enlarged. The tumor decreased in volume after each of two (131)I therapies. Dosimetry indicated delivery of 1970 and 2870 cGy to the tumor and 35 and 42 cGy to the brain, respectively, in the two treatments. The patient has survived for more than 11 years since diagnosis. CONCLUSIONS: A metastasis from a follicular variant of papillary carcinoma increased in volume during hypothyroidism producing more infringement on the brain. Beyond the effects of thyroxine therapy, (131)I treatments induced recession of tumor volume. In patients with metastases that concentrate (131)I, dosimetry with SPECT-CT can predict absorbed doses of radiation to the tumor and to the adjacent organs and thus lay a basis for data-based decisions on (131)I therapies. Therapy may induce prolonged survival in patients with metastases infringing on the brain.

Diagnosis and management of hereditary paraganglioma syndrome due to the F933>X67 SDHD mutation.

BACKGROUND: The hereditary paraganglioma syndromes (PGLs) are autosomal dominant conditions with an increased risk for tumors of the sympathetic and parasympathetic neuroendocrine systems. The recognition of patients with hereditary PGL and identification of the responsible gene are important for the management of index patients and family members. METHODS: We present the clinical, radiological, biochemical, and family history findings of a 15-year-old boy patient with a glomus vagale versus glomus jugulare tumor. RESULTS: Evaluation of the family history and the patient's history led to the identification of a familial succinate dehydrogenase subunit D (SDHD) gene mutation (F933>X67), consistent with a diagnosis of hereditary PGL1. Although this family had all head and neck tumors, this SDHD mutation has previously been described in a family with primarily functional pheochromocytomas. CONCLUSIONS: This case report highlights the variable expressivity of a single mutation in SDHD, (F933>X67). Careful and comprehensive screening is warranted for individuals at risk.

First description of parathyroid disease in multiple endocrine neoplasia 2A syndrome.

Hyperparathyroidism and/or parathyroid hyperplasia, medullary thyroid carcinoma (MTC), and pheochromocytomas compose the hallmarks of the multiple endocrine neoplasia type 2A (MEN 2A) syndrome. Revisiting a report in 1939 of a patient with hyperparathyroidism and parathyroid hyperplasia led to a search for evidence of MEN 2A. From medical records and discussion with family members, longitudinal follow-up of the patient and her descendants was obtained. Molecular diagnostics were integrated in the care of subsequent generations. The literature on hyperparathyroidism and MEN 2A was reviewed. Children of the proband exhibited all components of MEN 2A and the RET mutation of 634 TGC>CGC. The pedigree was typical for this mutation. Papers on anthropologic studies demonstrate skeletal evidence of hyperparathyroidism in humans centuries ago. The initial report of the proband preceded the publications defining both MTC and MEN 2A. The values of in-depth family histories and genetic analyses are exemplified.

Radioiodine therapy and Graves' ophthalmopathy.

UNLABELLED: Appearances of and increases in Graves' ophthalmopathy (GO) have been reported after treatment of patients with hyperthyroidism with radioiodine. We sought to determine the rates of appearance or increase in manifestations of GO in American patients treated with radioiodine for hyperthyroidism. METHODS: The study population, which consisted of 76 patients (range, 10.6-72 y), included 61 women and individuals of diverse ethnicity. The patients were followed for 1 y after radioiodine treatment. The clinical activity score (CAS) included 10 items of ophthalmic change that were evaluated at 2 and 6 mo and at 1 y; appearance of a new item scored 1 point. We evaluated interactions of 6 covariates-prolonged hyperthyroidism, prolonged hypothyroidism, smoking, treatment with an antithyroid drug (ATD), and serum levels of thyroid-stimulating immunoglobulin (TSI) and of high free T3 (FT3)--with the numbers of patients with 2 or more CAS points and with exophthalmometer readings increased by at least 2 mm. In addition, patients completed a scored quality-of-life (QOL) questionnaire at baseline and at 1 y to assess eye symptoms. RESULTS: The mean CAS points for all patients at 2 mo was 0.63 and was not significantly different at 1 y. In 9 of 10 CAS items, there were few patients affected at 1 y and for the most part there were fewer patients affected than at baseline. However, exophthalmometer readings increased in 39% of patients by a mean of 2.6 mm. Individual patients frequently exhibited increases and decreases in item manifestations. Exophthalmometer readings decreased by 2 mm or less in 13%. Of the covariates, only hyperthyroidism prolonged by at least 2.5 mo was significantly associated with 2 or more CAS points at 1 y; no covariate was significantly associated with the development of increased exophthalmometer readings. Eye symptoms recorded in the QOL were insignificantly improved over the year; symptoms did not correlate with CAS points or with exophthalmometer readings. CONCLUSION: After radioiodine treatment, no substantial change was seen in manifestations of CAS items except for a modest increase in exophthalmometer readings in 39% of patients. Manifestations of CAS items frequently appeared and disappeared. Prolonged hyperthyroidism is best avoided. Ocular symptoms were insignificantly fewer at 1 y after radioiodine therapy. The observed changes do not warrant prophylactic treatment of patients with steroids.

Biochemical diagnosis and localization of pheochromocytoma: can we reach a consensus?

Pheochromocytomas can have a highly variable presentation, making diagnosis challenging. To think of the tumor represents the crucial initial step, but establishing the diagnosis requires biochemical evidence of excessive catecholamine production and imaging studies to localize the source. Currently, however, there exist no generally agreed upon guidelines based on which tests and testing algorithms should be used to confirm and locate or exclude a suspected pheochromocytoma. Choice of biochemical tests and imaging studies instead usually depends on institutional experience. At the First International Symposium on Pheochromocytoma (ISP2005), held in Bethesda in October 2005, a panel of experts and patient representatives discussed current problems and available options for tumor diagnosis and localization and formulated recommendations, which were subsequently agreed upon by those in attendance at the meeting. This article summarizes the discussion and recommendations derived from that session.

Current trends in functional imaging of pheochromocytomas and paragangliomas.

Most pheochromocytomas/paragangliomas should be evaluated with anatomical imaging (computed tomography or magnetic resonance imaging) followed by functional imaging (nuclear medicine modalities). Functional imaging assures that the tumor is indeed a pheochromocytoma/paraganglioma and enables more thorough localization, especially detecting as many lesions as possible (in particular for metastatic disease). Functional imaging for pheochromocytomas/paragangliomas, can use radiolabeled ligands specific for pathways of synthesis, metabolism, and inactivation of catecholamines or nonspecific ligands. In an overview of the available nuclear medicine modalities, we summarize the accumulated experience and recommend when functional imaging should be applied to patients with pheochromocytoma/paraganglioma.

Courses of malignant pheochromocytoma: implications for therapy.

Survival of patients with metastatic pheochromocytoma that have exceeded 30 years without therapy to reduce tumors have been reported. We reviewed the records of 38 patients with malignant pheochromocytoma who had received 131I-metaiodiobenzylguanidine (131I-MIBG) treatments between 1981 and 1996 to evaluate longevity. Survival from diagnosis to last follow-up exceeded 5 years in 21 of 38 (55%) and >or=10 years in 50%. In 17 of 21, the interval from diagnosis to 131I-MIBG therapy was greater than 5 years. Survival following 131I-MIBG was >or=5 years in 12 of 17 and >or=10 years in 7 of 17 patients despite continued evidence of excessive circulating catecholamines. Objective responses to 131I-MIBG therapy were seen in about 30% and were usually of a few years, duration, but one individual exhibited marked reductions in volume and function of tumors that have persisted for 21 years. No feature, including a remission of >5 years following surgical excision, was found to predict prolonged survival. In summary, many patients with malignant pheochromocytoma will follow a course extending over many years. The role of 131I-MIBG therapy in longevity is uncertain, but this radiopharmaceutical reduces evidence of tumors in some patients. Criteria for selecting patients who will benefit from treatment remain to be determined.

The so-called stunning of thyroid tissue.

UNLABELLED: When thyroid tissues exhibited concentrations of therapeutic (131)I that appeared to be less than that predicted by data from the preceding diagnostic (131)I, the phenomenon was called stunning. We hypothesized that stunning arose from the early effects of the therapeutic dose of (131)I and that the initial uptake of (131)I, observed within the first day, was not impaired by the diagnostic dose. METHODS: The hypothesis was tested by 2 types of studies. In each type, the fractional concentrations of (131)I in residual neck thyroid tissues of patients with papillary thyroid carcinoma were quantified. In the first study, fractional concentrations of diagnostic and therapeutic (131)I were measured at 2 d, a time when stunning has been observed, and expressed as ratios of radioactivity: therapeutic/diagnostic (Rx/Dx). Three different doses of diagnostic (131)I were prescribed to assess a dose response. In the second study, patients were prospectively recruited and tested to record disappearances of radioactivity from thyroid tissues. Diagnostic doses were 1.0 mCi (37 MBq) in all; therapeutic doses were 150 and 30 mCi (5,550 and 1,110 MBq), each to half of the patients. The disappearance curves were extrapolated to the period between 0 and 1 d, an interval when maximum uptake of ingested (131)I would be expected. The fractional concentrations of (131)I at 2 d and at 0-1 d were compared in terms of Rx/Dx ratios to assess changes at each time point. RESULTS: In the first study, after diagnostic doses of 2, 1, and 0.5 mCi (74, 37, and 18.5 MBq), mean 2-d Rx/Dx values in 24, 29, and 17 patients were 0.35, 0.50, and 0.46 (P = 0.087). Of all patients, 74% exhibited Rx/Dx <0.6. In the second study, 6 of 10 patients exhibited disappearance curves of (131)I in which Rx/Dx was <0.6 at 2 d; 5 of the 6 had Rx/Dx values >0.97 at the 0- to 1-d point. In 1 patient the Rx/Dx was 0.54 at 2 d and 0.66 at the earlier time point. The other 4 patients had disappearance curves in which Rx/Dx values were >1.0 throughout or were above 0.6 and did not greatly change. CONCLUSION: Two days after the administration of (131)I, the mean fractional concentration of radioactivity in thyroid tissues after a therapeutic dose is <60% of the diagnostic dose in most patients, but no correlation of Rx/Dx with the mCi in the diagnostic dose was seen. In 5 of 6 patients in whom the Rx/Dx at 2 d was <0.6, the maximum fractional concentrations of therapeutic and diagnostic (131)I (i.e., the tissue uptakes during the first day) were similar; this pattern was most apparent after therapies with 150 mCi. These results support the hypothesis that "stunning" of thyroid tissues, often observable by 2 d, is primarily the consequence of early destructive effects from therapeutic (131)I.

Radiation-induced osteosarcoma and papillary carcinoma of the thyroid.

PURPOSE: This article describes a patient with dual radiation-induced malignancies after treatment of neuroblastoma. MATERIALS AND METHODS: A 12-year-old boy with a history of neuroblastoma was treated with chemotherapy, I-131 MIBG, and radiotherapy at age 4. He was disease-free for 8 years, but then developed left shoulder pain resulting from osteosarcoma. A thyroid malignancy was discovered during the evaluation. RESULTS: The patient was treated with thyroidectomy and then chemotherapy according to a Children's Cancer Group Study protocol. CONCLUSION: Radiation-induced sarcoma should be suspected whenever a patient who has received radiation several years previously presents with pain or swelling in the irradiated area.