Radioiodine treatment of differentiated thyroid cancer related to guidelines and scientific literature. / Tratamiento del cáncer diferenciado de tiroides con radioyodo a la luz de las guías y de la literatura científica.

In differentiated thyroid cancer (DTC), radioiodine is administered to eliminate residual normal thyroid tissue after thyroidectomy (ablative treatment), to treat residual microscopic disease (adjuvant treatment), and to treat macroscopic or metastatic disease. Currently, treatment of DTC with 131I is still a matter of controversy due to the absence of prospective clinical trials assessing its benefit in terms of overall survival and recurrence-free interval. The current recommendations of the experts are based on observational retrospective data and on their interpretation of the literature. Pending the results of the prospective trials that are currently underway, the use of 131I seems to be justified not only in high-risk patients, but also in intermediate-risk and low-risk patients. The guidelines of The American and British Thyroid Association, European and American Societies of Nuclear Medicine, The European Consensus Group and the latest edition of National Comprehensive Cancer Network (NCCN) were considered in drawing up this continuing education document, we also undertook a review of the related scientific literature.

Cost-effectiveness of using recombinant human thyroid-stimulating hormone before radioiodine ablation for thyroid cancer treatment in Spanish hospitals. / Coste-efectividad de la utilización de la tirotropina recombinante humana previa a la ablación con radioyodo en el tratamiento del cáncer de tiroides en hospitales españoles.

OBJECTIVES: In thyroid cancer treatment, the thyroid-stimulating hormone (TSH) must be elevated before radioiodine ablation, either by exogenous (with recombinant human thyrotropin [rhTSH]) or endogenous stimulation by thyroid hormone withdrawal (THW). The use of rhTSH avoids hypothyroidism and favours the subsequent elimination of radioiodine, but involves the cost of the product. For this reason, a cost-effectiveness analysis was performed, taking into account all costs involved and the benefits associated with the use of this therapy. MATERIAL AND METHODS: Using a Markov modelling with two analysis arms (rhTSH and THW), stratified into high (100mCi/3700 MBq) and low (30mCi/1110 MBq) radioiodine doses, and using 17 weekly cycles, the incremental cost per quality-adjusted life-year (QALY) related to the use of rhTSH was determined. The clinical inputs included in the model were based on published studies and in a treatment survey conducted in Spain. RESULTS: Radioablation preparation with rhTSH is superior to THW, showing additional benefits (0.048 AVAC), as well as cost savings (-€614.16), with an incremental cost-effectiveness rate (ICER) of -€12,795/QALY. The univariate and multivariate sensitivity analyses showed the result to be robust. CONCLUSIONS: The use of rhTSH previous to radioablation in Spain has cost savings, as well as a series of health benefits for the patient, making it highly cost-effective.

The role of early 18F-FDG PET/CT in therapeutic management and ongoing risk stratification of high/intermediate-risk thyroid carcinoma.

Little is known about the role in ongoing risk stratification of fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) performed early after radioactive iodine (RAI) ablation in differentiated thyroid carcinoma (DTC). The aim of the study is to investigate whether 18F-FDG PET/CT performed early after RAI ablation is useful to detect disease and to influence therapy and ongoing risk stratification. Patients with high/intermediate risk of recurrent DTC were included. 18F-FDG PET/CT scan was performed within 6 months after RAI ablation. We confirmed results with other imaging techniques, pathology reports, or follow-up. We classified the patient response as excellent, acceptable, or incomplete. Modified Hicks criteria were used to evaluate clinical impact. We included 81 patients with high/intermediate risk of recurrent DTC. Forty-one (50.6%) had positive uptake in 18F-FDG PET/CT, with negative (131)I whole-body scan ((131)I WBS). Sensitivity, specificity, and diagnostic accuracy of 18F-FDG PET/CT were 92.5, 90.2, and 91.4%, respectively. 18F-FDG PET/CT results had an impact on therapy in 38.3% of patients. One year after initial therapy, 45.7% showed excellent response, 8.6% acceptable response, and 45.7% incomplete response. A statistically significant relationship was found between negative 18F-FDG PET/CT and excellent response (80 vs. 12.2%, p < 0.001; OR 52.8). 18F-FDG PET/CT scan performed early in surveillance of patients with high/intermediate-risk thyroid carcinoma provides important additional information not available with conventional follow-up methods and had a high impact on therapy. A negative 18F-FDG PET/CT predicts an excellent response to therapy in the new ongoing risk stratification.

[Treatment protocols and follow-up of differentiated thyroid carcinoma: results of a questionnaire sent to the Spanish Metabolic Therapy Units]. / Los protocolos de tratamiento y seguimiento del carcinoma diferenciado de tiroides: resultados de un cuestionario enviado a las Unidades de Terapia Metabólica españolas.

OBJECTIVE: To know the treatment and follow-up protocols of differentiated thyroid carcinoma patients in Spanish Metabolic Therapy Units, the clinical variability between them and the adaptation to the consensus guidelines. MATERIALS AND METHODS: Analysis of the results obtained from the questionnaire submitted by E-mail to the Spanish Society of Nuclear Medicine (SEMNIM) members on the treatment and follow-up of differentiated thyroid carcinoma patients. A descriptive study was made of the qualitative variables (frequency, percentage) and quantitative variables (mean, standard deviation). RESULTS: Twenty Radiometabolic Therapy Units responded to the questionnaire. In spite of the varied origin of the patients, the Units receive sufficient clinical information and have specialized surgeons. There is variability in the surgical protocols and indication for ablation in patients with intermediate and low risk of recurrence. The Units agree on the use of (131)I doses for ablation and therapy, but show great variability regarding the preparation protocols (previous (131)I-whole body scan or other imaging techniques, (131)I-whole body scan dose, diet and radioiodine contrast prohibition, total dose per patient). Nuclear Medicine physicians perceive radioiodine adverse effects and prevention methods are used. The post-ablation follow-up protocol differs between Units. CONCLUSIONS: Treatment and follow-up protocols of differentiated thyroid carcinoma patients in the Spanish Radiometabolic Therapy Units show variability in aspects such as surgery and ablation indications, patient preparation for radioiodine therapy and follow-up. Our clinical practice differs in several aspects from the recent consensus guideline recommendations.

Clinical and pathological factors related to 18F-FDG-PET positivity in the diagnosis of recurrence and/or metastasis in patients with differentiated thyroid cancer.

BACKGROUND: Objectives were to analyze the relationship between a positive (18)F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) result and clinical and tumor factors in patients treated for differentiated thyroid cancer (DTC) and under suspicion of recurrence or metastasis, and to determine the diagnostic validity of PET in DTC patients with elevated serum thyroglobulin (Tg) and negative (131)I whole-body scan ((131)I-WBS). METHODS: We studied 50 DTC patients with elevated serum Tg and negative WBS treated with total thyroidectomy and (131)I ablation. Thyroxin treatment was withdrawn and patients were on iodine-free diet before WBS. Tg, anti-Tg antibodies, and thyroid-stimulating hormone (TSH) were determined. Patients with negative WBS and elevated Tg underwent PET study 1 week later. PET findings were verified by pathology findings or other imaging techniques [computed tomography (CT), magnetic resonance imaging (MRI), ultrasound (US)] and/or 12-month follow-up. The relationship between PET findings and tumor (histological type, size, multifocality, thyroid capsular invasion, lymph-node and/or metastatic involvement) and clinical (age at diagnosis, sex, Tg, accumulated iodine dose, and recurrence time) variables was analyzed. RESULTS: PET was positive in 32/39 patients with confirmed disease (82% sensitivity) and negative in 7/11 of disease-free cases (64% specificity), a positive predictive value (PPV) of 89%. Tumor size (P < 0.05) and thyroid capsular invasion (P < 0.05) were significantly associated with positive PET study. The relationship of PET findings with Tg levels and age at diagnosis was close to significance. CONCLUSION: (18)F-FDG-PET study offers a high sensitivity and positive predictive value (PPV) in patients with negative WBS and Tg positive. The use of FDG-PET is strongly recommended in DTC patients with large tumors, thyroid capsule invasion or poor-prognosis variants.

Outcome of treating advanced neuroendocrine tumours with radiolabelled somatostatin analogues.

OBJECTIVES: To evaluate the initial response and outcomes (quality of life and presence of side effects) in patients with advanced neuroendocrine tumours (NET) after treatment with radiolabelled somatostatin analogues: (90)Y-DOTATyr3- octreotide ((90)Y-DOTATOC) and (177)Lu-DOTA-Tyr3- octreotate ((177)Lu-DOTATATE). MATERIAL AND METHODS: The study included 5 patients with advanced NET referred to European centres for treatment with (90)Y-DOTATOC and (177)Lu-DOTATATE after lack of response to conventional treatment. The mean age was 45.6 years (29-68 years). Response to therapy was assessed according to: (1) RECIST criteria, as complete response, partial response, stable disease or disease progression, (2) post-treatment survival time and (3) quality of life, using the Karnofsky performance index. RESULTS: All patients survived for >20 months after treatment; mean survival time was 28 months. At the time of writing, three of the patients are alive after 20, 26 and 37 months. Partial response was observed in one patient, stable disease in three and disease progression in the fifth patient. A good-to-excellent post-treatment quality of life was observed in all patients. CONCLUSION: Therapy with radiolabelled somatostatin analogues showed promising results in patients with advanced NET, with a partial response or disease stabilisation in four of the five patients, who have enjoyed an extended survival period and an improved quality of life.

Outcome of treating advanced neuroendocrine tumours with radiolabelled somatostatin analogues

OBJECTIVES: To evaluate the initial response and outcomes (quality of life and presence of side effects) in patients with advanced neuroendocrine tumours (NET) after treatment with radiolabelled somatostatin analogues: (90)Y-DOTATyr3- octreotide ((90)Y-DOTATOC) and (177)Lu-DOTA-Tyr3- octreotate ((177)Lu-DOTATATE). MATERIAL AND METHODS: The study included 5 patients with advanced NET referred to European centres for treatment with (90)Y-DOTATOC and (177)Lu-DOTATATE after lack of response to conventional treatment. The mean age was 45.6 years (29-68 years). Response to therapy was assessed according to: (1) RECIST criteria, as complete response, partial response, stable disease or disease progression, (2) post-treatment survival time and (3) quality of life, using the Karnofsky performance index. RESULTS: All patients survived for >20 months after treatment; mean survival time was 28 months. At the time of writing, three of the patients are alive after 20, 26 and 37 months. Partial response was observed in one patient, stable disease in three and disease progression in the fifth patient. A good-to-excellent post-treatment quality of life was observed in all patients. CONCLUSION: Therapy with radiolabelled somatostatin analogues showed promising results in patients with advanced NET, with a partial response or disease stabilisation in four of the five patients, who have enjoyed an extended survival period and an improved quality of life (AU)

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The role of somatostatin receptor scintigraphy in patients with pituitary adenoma or post-surgical recurrent tumours.

To assess the role of scintigraphy with 111In-DTPA-D-Phe-octreotide (111In-octreotide) in the diagnosis of pituitary adenomas and in the evaluation of post-surgical recurrent or residual tumours, we performed scintigraphy with 111In-DTPA-D-Phe-octreotide (SRS) in 35 patients: 14 patients with confirmed pituitary tumours and 15 with confirmed recurrent tumours. Clinical, biochemical and histological analyses, conventional images (CT/MRI), and follow-up assessments during a period of 1 year to 4 years were recorded in all patients. In the present study, scintigraphy with 111In-octreotide showed positive uptake in 10 out of 14 patients with confirmed pituitary tumour and in 13 out of 15 patients with confirmed recurrent tumour, with an overall sensitivity of 79%. SRS showed better results in growth hormone (GH)- and prolactin (PRL)-secreting tumours (7/8 patients correctly identified) than in other adenomas (3/9). SRS detected recurrence of adenocorticotrophic hormone (ACTH)-secreting tumours (4/5 patients correctly identified) and non-secreting tumours (5/7 patients correctly identified). 111In-octreotide scintigraphy, in combination with other imaging modalities, is useful in the diagnosis and follow-up of pituitary tumours. It allows scar tissue to be differentiated from tumour recurrence after surgical treatment and ensures better selection of patients who will benefit from medical treatment with somatostatin analogues.

[Scintigraphy with thallium chloride in a case of clear cell sarcoma of the tendons and aponeurosis]. / Gammagrafía con cloruro de talio en un caso de sarcoma de células claras de tendones y aponeurosis.

Clear cell sarcoma of the soft parts (CCSSP) is a rare and highly malignant tumor. This is a case report of a 31 years old woman who presented with a tumor in the internal face of left thigh. The tumor biopsy was suggestive of a possible malignant tumor of the peripheral nerve sheath (malignant schwannoma). Biochemical analyses, computed tomography and magnetic resonance were performed and reported a sarcoma of soft parts (CCSSP) without abnormal inguinal lymph nodes. With this diagnostic suspicion, the patient was sent to the Nuclear Medicine Service of our center where a 201Thallium scintigraphy study was performed. In this study, it showed the primary tumor together with a hot spot in the homolateral inguinal region, suggestive of the presence of a metastastic lymph node. This finding would change the surgical attitude in the patient, including inguinal lymphadenectomy. The post-surgical histological study confirmed a clear cell sarcoma of soft parts (CCSSP) with a metastatic inguinal lymph node.

Gammagrafía con cloruro de talio en un caso de sarcoma de células claras de tendones y aponeurosis / Scintigraphy with thallium chloride in a case of clear cell sarcoma of the soft parts

El sarcoma de células claras de tendones y aponeurosis (SCCTA) es un tumor poco frecuente y de elevada malignidad. Presentamos el caso de una mujer de 31 años que consulta por una tumoración a nivel de muslo izquierdo de un mes de evolución. Se le realiza biopsia de la lesión que se informa como posible tumor maligno de la vaina del nervio periférico (schwanoma maligno). Se le realizan exploraciones complementarias de rutina, TC y RMN, que son informadas como posible sarcoma de partes blandas sin que se informen metástasis ganglionares inguinales. Con esta sospecha diagnóstica, es remitida al Servicio de Medicina Nuclear de nuestro centro donde se le realiza estudio gammagráfico con 201Talio. En este estudio se evidencia la tumoración primaria junto a un foco hipercaptante a nivel de región inguinal homolateral, sugerente de la presencia de una adenopatía metastásica a ese nivel. Este hallazgo cambiaría la actitud quirúrgica en la paciente, incluyéndose entonces vaciamiento funcional inguinal homolateral. La anatomía patológica definitiva sobre la pieza quirúrgica fue informada como Sarcoma de células claras, confirmandose la naturaleza metastásica de la adenopatía inguinal (AU)

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Utility of fluorine-18-fluorodeoxyglucose positron emission tomography in differentiated thyroid carcinoma with negative radioiodine scans and elevated serum thyroglobulin levels.

BACKGROUND: This study aimed to determine the role of fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET) in the follow-up of patients who underwent total thyroidectomy and iodine-131 ((131)I) ablation therapy for differentiated thyroid cancer and presented increased thyroglobulin levels with negative (131)I and thallium-201 ((201)Tl) scans. METHODS: Two patients with follicular carcinoma and eight with papillary tumors underwent total thyroidectomy and (131)I therapy until the (131)I scan was negative. (131)I and (201)Tl scans were performed with negative results in all cases, while serum thyroglobulin measurements were all positive with negative thyroglobulin autoantibodies. One week after the (131)I scans, all the patients underwent FDG-PET whole-body scans. RESULTS: The FDG-PET scan detected in 4 patients, a single focal increase of FDG uptake in one lymph node metastasis (subsequently confirmed histologically); in 1 patient, multiple pathological focal uptakes in brain, neck, and chest; and in 1 patient, two mild focal uptakes in the mediastinum, close to the tracheal branch. In 2 other patients, pathological FDG uptakes in cervical spine and mediastinum were not confirmed by other imaging techniques, and in the 2 remaining patients the scan results were inconclusive. The sensitivity of FDG-PET whole-body scan for detecting metastatic thyroid cancer was 60%. CONCLUSIONS: This study indicates that the FDG-PET whole-body scan is a useful tool in the follow-up of patients with differentiated thyroid cancer, negative (131)I and (201)Tl scans and elevated serum thyroglobulin levels. The FDG-PET scan detects metastatic disease in 60% of patients with differentiated thyroid cancer, enabling surgical therapy to be performed on accessible lesions.

An alternative to the reference method for testing the radiochemical purity of 99Tcm-tetrofosmin.

The recommended method for controlling the radiochemical purity (RCP) of 99Tcm-labelled tetrofosmin is thin-layer chromatography (TLC) with silica gel as the stationary phase and acetone:dichloromethane (35:65, v/v) as the mobile phase. However, this test is time-consuming and uses a toxic substance. We propose an alternative method to control RCP, based on a solid-phase extraction method (SPE) using a Sep Pak C18 cartridge. We used both methods to analyse 35 samples and to determine the percentages of colloid, radiopharmaceutical and free 99Tcm-pertechnetate. Normal labelling processes were modified to obtain a wide range of values. The range of RCP values obtained was 63.4-96.5% (median = 93.8%) by the standard TLC method and 70.1-96.4% (median = 94.1%) by the SPE method. A significant difference was observed only for the percentage of free 99Tcm-pertechnetate (P < 0.05). The agreement between the two methods, using 90% RCP as the limit, gave a kappa index = +1 (P < 0.001), indicating total agreement between them. The proposed method is useful to control RCP because it yields results that are in good agreement with those of the standard method, and because it is safer and less time-consuming.

111In-pentetreotide scintigraphy is superior to 123I-MIBG scintigraphy in the diagnosis and location of chemodectoma.

Chemodectomas, or glomus tumours, are unusual head and neck paragangliomas. A non-invasive imaging technique, 123I-metaiodobenzylguanidine (123I-MIBG) scintigraphy, has long been used for the diagnosis of all types of paraganglioma. The aim of this study was to evaluate and compare classic 123I-MIBG scintigraphy with the more recent 111In-pentetreotide scintigraphy in the diagnosis and location of chemodectomas. We performed 123I-MIBG and 111In-pentetreotide scintigraphy in eight patients (7 females, 1 male) with histologically or radiologically confirmed chemodectomas (five carotid body and three jugulotympanic chemodectomas). 123I-MIBG uptake was visualized in four patients on planar views and SPET images (sensitivity 50%); uptake was low in three patients. Using 111In-pentetreotide scintigraphy, all chemodectomas in eight patients were visualized (sensitivity 100%) and 111In-pentetreotide uptake was high in all cases. In conclusion, our results indicate that 111In-pentetreotide scintigraphy is superior to 123I-MIBG scintigraphy in the diagnosis and location of chemodectomas. In-pentetreotide or 123I-MIBG uptake suggests a neuroendocrine origin, providing important functional information in the diagnosis of chemodectomas. Moreover, 111In-pentetreotide scintigraphy permits a good classification of patients with or without somatostatin receptors in the chemodectoma in the application of pharmacological therapy with somatostatin analogues to inoperable tumours. The main therapeutic action of cold somatostatin analogues is to inhibit hormonal hypersecretion in different neuroendocrine tumours. In chemodectomas, however, the most important effect of somatostatin analogues is to reduce tumour volume or inhibit growth progression.

Modulation of contractile proteins in embryonic and fetal chick cardiac cells by phorbol ester, gamma-interferon, 5-azacytidine and diacylglycerols.

We studied changes in the concentration of tropomyosin, actin, desmin and vimentin in cultured myocardiocytes from Hamburger and Hamilton's stages 29 and 39 chick embryos (HH29 and HH39) (1), treated with 12-o-tetradecanoyl-phorbol-13-acetate (TPA), 5-azacytidine (AZA), gamma interferon (INF) and diacylglycerols (DAG). In embryonic myocardiocytes at HH29, the first three agents modified the intracellular distribution of the thin filament proteins tropomyosin and actin, increasing their cytoplasmic concentration and decreasing their cytoskeletal concentration. The concentration of the intermediate filament proteins desmin and vimentin increased in both subcellular fractions after treatment with these drugs. In fetal myocardiocytes at HH39, total protein content decreased after treatment with these drugs. Cytoplasmic and cytoskeletal concentrations of actin and tropomyosin decreased to different degrees after treatment with TPA, AZA or DAG in HH39 myocardiocytes. TPA, AZA and DAG decreased desmin in the cytoplasmic and cytoskeletal fractions. These findings suggest that the drugs tested alter the normal protein composition in cultured myocardiocytes, and have different effects depending on the developmental stage in which the embryo is treated.

Circulating alpha-actin protein in acute myocardial infarction.

We used Western-blot analysis to investigate the possible presence in the bloodstream of the contractile protein alpha-actin in 70 patients diagnosed with acute myocardial infarction on the basis of clinical, electrocardiographic and laboratory (creatine kinase and lactate dehydrogenase) criteria. Circulating protein was identified with a monoclonal antibody specific for cardiac alpha-actin. Of the 70 control samples of blood, the immunoblot results were negative for alpha-actin in 98% of the cases. Of the 30 patients with skeletal muscle damage caused by surgery, 26 were negative for circulating alpha-actin. Of the 70 patients with acute myocardial infarction, circulating alpha-actin was found in 67 (95%) as a 43 kDa band in immunoblots; the highest circulating concentrations (0.0580 micrograms/microliters) were found in those with anterior acute myocardial infarction. Circulating alpha-actin was detected in samples taken between 1 and 180 h after the onset of pain, and showed a biphasic pattern of appearance. Our findings for serum alpha-actin, together with the relationship between serum concentrations of this protein and sex (p = 0.001), tobacco use (p = 0.007) and postepisode complications (p = 0.002), should make it possible to gain a deeper understanding of acute myocardial infarction as a clinical entity.

Changes in subcellular accumulation of contractile proteins in myocardiocyte cultures: effects of fibric acid derivatives.

We analyzed the influence of 6 and 24 h of treatment with the fibric acid derivatives bezafibrate (10 micrograms/ml), gemfibrozil (23 micrograms/ml), and fenofibrate (30 micrograms/ml) on alpha-actinin, troponin-T, and tropomyosin proteins in the cytoplasmic and cytoskeletal fractions of cultured chick myocardiocytes. The findings with sodium dodecyl sulfate-gel electrophoresis and immunoblotting showed that all three drugs modified cellular and subcellular protein levels in different ways: bezafibrate and fenofibrate produced the most significant alterations in both fractions, modifying alpha-actinin, troponin T, and tropomyosin compartmentalization in myocardiocytes, whereas gemfibrozil altered these proteins less notably. Given the role of these proteins in heart muscle contraction, fibric acid derivative-induced changes may be related with the secondary effects of these drugs on heart rhythmicity.