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1.
Int J Clin Oncol ; 23(4): 625-633, 2018 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-29492793

RESUMEN

BACKGROUND: Thyroid carcinoma is a very rare tumor in the pediatric age group, accounting for only 1.5-3% of childhood carcinomas in the United States and Europe. We aimed to identify the risk of a second malignancy among pediatric thyroid cancer survivors. METHODS: The cohort analysis consisted of pediatric cancer patients aged less than 20 years, diagnosed with a primary thyroid cancer, identified by site code ICD-0-3: C739, and reported to the SEER 9 database between 1973 and 2013. They were followed up until December 31, 2013; the end of the study period, or up to death if earlier. RESULTS: Out of 1769 patients diagnosed primarily with thyroid carcinoma, 42 patients had a total of 45 incidences of subsequent malignancies. The mean age of patients at the initial diagnosis of thyroid cancer was 16 years. Females (90.5%) had a significantly higher incidence of second malignancies (SM) than males (9.5%). The overall Standardized Incidence Ratio (SIR) of SM in the study patients was higher than expected (SIR = 1.48). Some specific sites showed significantly higher incidences: the salivary glands (SIR = 33.95), the gum and other parts of the mouth [excluding the lips, tongue, salivary glands and floor of the mouth] (SIR = 24.53)*** and the kidneys (SIR = 5.72). The overall risk of SM in patients who had received radioactive iodine was higher than expected (SIR = 4.41). The cumulative incidence of SM after treatment of thyroid cancer in children increases steadily over 40 years (11.92%). CONCLUSIONS: Race, gender, histological subtypes, and radioactive iodine are potentially significant prognostic factors for the development of SM among pediatric thyroid cancer survivors. Identification of underlying mechanisms that raise the risk of SM is important for both treatment and follow-up strategies.


Asunto(s)
Adenocarcinoma Folicular/radioterapia , Adenocarcinoma Papilar/radioterapia , Carcinoma Medular/radioterapia , Neoplasias Primarias Secundarias/epidemiología , Radioterapia , Sobrevivientes/estadística & datos numéricos , Neoplasias de la Tiroides/radioterapia , Adenocarcinoma Folicular/patología , Adenocarcinoma Papilar/patología , Adolescente , Adulto , Carcinoma Medular/patología , Niño , Preescolar , Estudios de Cohortes , Femenino , Humanos , Incidencia , Lactante , Masculino , Pronóstico , Factores de Riesgo , Programa de VERF , Tasa de Supervivencia , Neoplasias de la Tiroides/patología , Estados Unidos/epidemiología , Adulto Joven
2.
Curr Opin Oncol ; 26(1): 45-50, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24225415

RESUMEN

PURPOSE OF REVIEW: The role of external beam radiation therapy (EBRT) in the management of thyroid cancer is not clearly defined. In the absence of randomized studies, the review aims to identify any recent literature that helps define the role. RECENT FINDINGS: In differentiated thyroid cancer, single institutional studies report durable locoregional disease control in patients considered to be at high risk of local relapse after EBRT and recent guidelines are consistent in their recommendations. In medullary thyroid cancer, the evidence is more limited but again there is benefit in selected cases. In anaplastic thyroid cancer, multimodality therapy is superior to surgery alone in achieving local control and possibly survival but the benefit must be weighed against the toxicity. Newer radiation techniques may help reduce toxicity. SUMMARY: Although surgery is the main treatment for thyroid carcinoma, EBRT has a role in the adjuvant setting following surgery in high-risk patients and in unresectable cancer. Advances in the delivery of external beam radiotherapy, including intensity-modulated radiotherapy reduces toxicity.


Asunto(s)
Carcinoma/radioterapia , Radioterapia de Intensidad Modulada/métodos , Neoplasias de la Tiroides/radioterapia , Carcinoma Medular/radioterapia , Humanos , Dosis de Radiación , Radioterapia Adyuvante
3.
Eur J Nucl Med Mol Imaging ; 41(8): 1501-10, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24806110

RESUMEN

PURPOSE: PET is a powerful tool for assessing targeted therapy. Since (18)F-FDG shows a potential prognostic value in medullary thyroid carcinoma (MTC), this study evaluated (18)F-FDG PET alone and combined with morphological and biomarker evaluations as a surrogate marker of overall survival (OS) in patients with progressive metastatic MTC treated with pretargeted anti-CEA radioimmunotherapy (pRAIT) in a phase II clinical trial. METHODS: Patients underwent PET associated with morphological imaging (CT and MRI) and biomarker evaluations, before and 3 and 6 months, and then every 6 months, after pRAIT for 36 months. A combined evaluation was performed using anatomic, metabolic and biomarker methods. The prognostic value of the PET response was compared with demographic parameters at inclusion including age, sex, RET mutation, time from initial diagnosis, calcitonin and CEA concentrations and doubling times (DT), SUVmax, location of disease and bone marrow involvement, and with response using RECIST, biomarker concentration variation, impact on DT, and combined methods. RESULTS: Enrolled in the study were 25 men and 17 women with disease progression. The median OS from pRAIT was 3.7 years (0.2 to 6.5 years) and from MTC diagnosis 10.9 years (1.7 to 31.5 years). After pRAIT, PET/CT showed 1 patient with a complete response, 4 with a partial response and 24 with disease stabilization. The combined evaluation showed 20 responses. For OS from pRAIT, univariate analysis showed the prognostic value of biomarker DT (P = 0.011) and SUVmax (P = 0.038) calculated before pRAIT and impact on DT (P = 0.034), RECIST (P = 0.009), PET (P = 0.009), and combined response (P = 0.004) measured after pRAIT. PET had the highest predictive value with the lowest Akaike information criterion (AIC 74.26) as compared to RECIST (AIC 78.06), biomarker variation (AIC 81.94) and impact on DT (AIC 79.22). No benefit was obtained by combining the methods (AIC 78.75). This result was confirmed by the analysis of OS from MTC diagnosis. CONCLUSION: (18)F-FDG PET appeared as the most potent and simplest prognostic method to predict survival in patients with progressive MTC treated with pRAIT. Biomarker DT before pRAIT also appeared as an independent prognostic factor, but no benefit was found by adding morphological and biomarker evaluation to PET assessment.


Asunto(s)
Carcinoma Medular/diagnóstico por imagen , Fluorodesoxiglucosa F18 , Tomografía de Emisión de Positrones , Radioinmunoterapia , Radiofármacos , Neoplasias de la Tiroides/diagnóstico por imagen , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Medular/radioterapia , Carcinoma Medular/secundario , Carcinoma Neuroendocrino , Femenino , Humanos , Masculino , Persona de Mediana Edad , Imagen Multimodal , Valor Predictivo de las Pruebas , Neoplasias de la Tiroides/radioterapia , Neoplasias de la Tiroides/secundario , Tomografía Computarizada por Rayos X , Resultado del Tratamiento
4.
Vopr Onkol ; 59(6): 781-4, 2013.
Artículo en Ruso | MEDLINE | ID: mdl-24624792

RESUMEN

The paper analyzes the effectiveness of external beam radiation therapy of medullary thyroid cancer in 38 patients. The radiation therapy of the first phase combined therapy was performed in 9 (24 %) patients: after treatment, 5 patients had a partial response, 4--stabilization. The radiation therapy of the second phase combined therapy was performed in 27 (71%) patients: after treatment, 2 patients had a complete response (booster method), 5--partial response, 4--stabilization. External beam therapy has been performed in 2 (5 %) patients with palliative and symptomatic goals. Additionally has been estimated level of calcitonin in patients after combined treatment. The calcitonin level becomes normal without radiation therapy. Therefore, exposure for medullary thyroid carcinoma is questionable (exception for cases gain exposure to the rest of the tumor).


Asunto(s)
Carcinoma Medular/radioterapia , Cuidados Paliativos/métodos , Neoplasias de la Tiroides/radioterapia , Tiroidectomía , Adulto , Anciano , Calcitonina/sangre , Carcinoma Medular/sangre , Carcinoma Medular/cirugía , Carcinoma Neuroendocrino , Femenino , Humanos , Masculino , Persona de Mediana Edad , Radioterapia Adyuvante , Neoplasias de la Tiroides/sangre , Neoplasias de la Tiroides/cirugía , Tiroidectomía/métodos , Resultado del Tratamiento
5.
Ann Surg Oncol ; 17(6): 1490-8, 2010 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-20224861

RESUMEN

BACKGROUND: Surgery is the mainstay of treatment for medullary thyroid cancer (MTC), with long-term patient outcomes associated with adequacy of resection. This study benchmarked national practice patterns against 2009 American Thyroid Association (ATA) guidelines for MTC regarding use of thyroidectomy, lymphadenectomy, radioactive iodine (RAI), and external-beam radiotherapy (EBRT). METHODS: This is a cross-sectional, retrospective cohort study of MTC patients in the Surveillance, Epidemiology, and End Results Program database, 1973 to 2006. ATA recommendations 61 to 66 (extent of surgery), 85 (RAI), and 93 (EBRT) were analyzed. Outcome of interest was practice accordance with these recommendations. Predictors of accordance were determined and Kaplan-Meier survival analyses were performed. RESULTS: A total of 2033 patients with MTC were identified. Fifty-nine percent were women; 78% were white. Forty-one percent of patients did not receive appropriate surgical therapy (recommendations 61 to 63). Most patients with distant metastatic disease had less aggressive surgery and more EBRT (P < 0.001) (recommendations 64 to 66). Four percent of patients received inappropriate RAI (recommendation 85). Two hundred nine patients had gross incomplete resections, with 33% receiving postoperative EBRT (recommendation 93). Statistically significant predictors of receiving surgery discordant with ATA recommendations in multivariate analysis were patient age >65, female sex, earlier year of diagnosis (1988 to 1997), geographic region, intrathyroidal tumor extent, and tumor size of

Asunto(s)
Carcinoma Medular/cirugía , Adhesión a Directriz , Guías de Práctica Clínica como Asunto , Pautas de la Práctica en Medicina , Neoplasias de la Tiroides/cirugía , Tiroidectomía , Adulto , Anciano , Benchmarking , Carcinoma Medular/patología , Carcinoma Medular/radioterapia , Estudios Transversales , Femenino , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Escisión del Ganglio Linfático , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Radioterapia Adyuvante , Estudios Retrospectivos , Factores de Riesgo , Sociedades Médicas , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/radioterapia , Resultado del Tratamiento , Estados Unidos
6.
J Surg Oncol ; 102(2): 175-8, 2010 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-20648590

RESUMEN

BACKGROUND: Adjuvant radiation is rarely used to treat medullary thyroid carcinoma (MTC). We hypothesized that external beam radiation therapy (EBRT) would improve overall survival (OS) in MTC patients. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database identified patients who underwent total thyroidectomy and lymph nodes excision for MTC between 1988 and 2004. The Kaplan-Meier method was used for univariate comparisons of OS. Multivariate Cox proportional hazards models controlled for gender, age, lymph node status, tumor size, extent of disease, and EBRT. RESULTS: After 12 years, EBRT did not significantly improve OS (log rank, P < 0.14). In node-positive patients, univariate analysis demonstrated an OS benefit with EBRT (log rank, P < 0.05). In a multivariate model of node-positive patients, only increasing age (P < 0.001) and tumor size (P < 0.001) significantly influenced OS. CONCLUSIONS: The OS benefit attributed to EBRT in node-positive patients by univariate analysis could not be duplicated when controlling for known prognostic factors.


Asunto(s)
Carcinoma Medular/mortalidad , Carcinoma Medular/radioterapia , Radioterapia Adyuvante , Neoplasias de la Tiroides/mortalidad , Neoplasias de la Tiroides/radioterapia , Factores de Edad , Carcinoma Medular/patología , Carcinoma Medular/cirugía , Femenino , Humanos , Escisión del Ganglio Linfático , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Programa de VERF , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/cirugía , Tiroidectomía
7.
Head Neck ; 42(3): 401-416, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31755622

RESUMEN

BACKGROUND: The primary aim of this study was to evaluate the therapeutic efficacy and outcome of 177 Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) in somatostatin receptor-positive metastatic medullary thyroid carcinoma (MTC), including progression-free survival (PFS) and overall survival (OS), and also to determine the various prognostic variables. The secondary aim was toxicity assessment of PRRT in this group of patients. METHODS: A total of 43 somatostatin receptor-positive metastatic MTC patients, treated with 177 Lu-DOTATATE PRRT in a large tertiary care center, were included in this analysis. After receiving the therapy, post-treatment response evaluation was undertaken for symptomatic and biochemical responses (serum calcitonin) and imaging responses with 68 Ga-DOTATATE, 18 F-FDG PET-CT, CeCT (PERCIST and RECIST 1.1 criteria). Calcitonin doubling time (CtnDT) was calculated by the American Thyroid Association calculator. The adverse events were graded according to the NCI-CTCAE v5.0 criteria. The observed Kaplan-Meier curves for both PFS and OS since first PRRT were compared with CtnDT (more than 24 months vs less than 24 months) by log-rank (Mantel-Cox) test. The prognostic variables were investigated for their association with CtnDT and response to PRRT using Cox proportional-hazards model. RESULTS: The median OS was 26 months (95% CI 16.6-35.3 months) and the median PFS 24 months (95%.CI: 15.1-32.9 months). Following 177Lu-DOTATATE PRRT, the observed median PFS and OS was longer in patients who had CtnDT more than 24 months compared to those with CtnDT less than 24 months (median PFS not yet reached vs 10 months and median OS 60 months vs 20 months). Assessing from the time-point of first 177 Lu-DOTATATE PRRT cycle, the patients with CtnDT more than 24 months had a significantly longer PFS (P < .001) and OS (P < .001) compared to those with less than 24 months. Less than 5 lesions, FDG uptake in lesions (SUVmax of <5) and patients alive at the time of analysis were the significant variables for association with CtnDT (more than 24 months). Out of 43 patients, 26 were responders (61%) and 17 nonresponders (39%) based upon PERCIST criteria, and 27 were responders (62%) while 16 patients were nonresponders (38%) based upon RECIST 1.1 criteria. The univariate analysis showed significant association between responses to PRRT with following prognostic variables: (a) size of lesions (<2 cm) and (b) FDG uptake in lesions (SUVmax of <5). PRRT was well tolerated in all patients without any major grade 3 or 4 toxicity. CONCLUSION: The results demonstrated that, 177 Lu-DOTATATE is a potentially efficacious and safe therapeutic option in SSTR avid metastatic MTC patients.


Asunto(s)
Carcinoma Medular , Tumores Neuroendocrinos , Compuestos Organometálicos , Neoplasias de la Tiroides , Carcinoma Medular/diagnóstico por imagen , Carcinoma Medular/radioterapia , Humanos , Octreótido/uso terapéutico , Compuestos Organometálicos/uso terapéutico , Tomografía Computarizada por Tomografía de Emisión de Positrones , Pronóstico , Receptores de Somatostatina , Análisis de Supervivencia , Neoplasias de la Tiroides/diagnóstico por imagen , Neoplasias de la Tiroides/radioterapia
8.
J Clin Endocrinol Metab ; 94(1): 164-70, 2009 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-18854394

RESUMEN

CONTEXT: Aberrant histone deacetylase activity is seen in a variety of malignancies, and histone deacetylase inhibitors such as vorinostat have been shown to induce cell death and sensitize cells to cytotoxic chemotherapy in thyroid cancer cell lines. This phase II study was undertaken to assess objective response to vorinostat in patients with advanced thyroid cancer. EXPERIMENTAL DESIGN: A total of 19 patients with differentiated thyroid cancer (n = 16) and medullary thyroid cancer (n = 3) were enrolled in the study. Patients received oral vorinostat at a starting dose of 200 mg twice daily, with dose adjustments allowed as necessary for toxicity. Patients were treated for 2 wk, followed by 1 wk off therapy (3-wk cycle) until disease progression or study withdrawal. Responses were measured by Response Evaluation Criteria in Solid Tumors criteria and correlated with tumor markers. RESULTS: No patient achieved a partial or complete response. Median duration of therapy in patients with differentiated thyroid cancer was 17 wk, whereas in medullary thyroid cancer patients it was 25 wk. Reasons for termination included progression of disease by RECIST criteria (n = 7), clinical progression (n = 3), and adverse events (AEs) (n = 9). AEs were primarily grade 1-3; no clinical grade 4 or grade 5 events were observed. Clinical grade 3 AEs consisted of fatigue, dehydration, ataxia, pneumonia, bruises, and deep vein thrombosis. Severe thrombocytopenia was seen in seven patients (grade 3, n = 5; grade 4, n = 2) and was associated with minor bleeding or bruises. CONCLUSIONS: Vorinostat at this dose and schedule is not an effective treatment for advanced thyroid cancer.


Asunto(s)
Antineoplásicos/uso terapéutico , Inhibidores Enzimáticos/uso terapéutico , Inhibidores de Histona Desacetilasas , Ácidos Hidroxámicos/uso terapéutico , Radioisótopos de Yodo/uso terapéutico , Neoplasias de la Tiroides/tratamiento farmacológico , Adulto , Anciano , Calcitonina/sangre , Antígeno Carcinoembrionario/análisis , Carcinoma Medular/tratamiento farmacológico , Carcinoma Medular/patología , Carcinoma Medular/radioterapia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Tiroglobulina/sangre , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/radioterapia , Vorinostat
9.
Hell J Nucl Med ; 12(2): 161-4, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-19675872

RESUMEN

Medullary thyroid carcinoma (MTC) is rare derived from C cells of the thyroid gland and represents approximately 5% of all thyroid carcinomas. We report a case of a 74 years old male with MTC, diagnosed in 2002 and treated with total thyroidectomy and lymphadenectomy. A metastatic lesion was diagnosed on the right ventricle by indium-111-octreoscan, fluorine-18-fluorodeoxyglucose-positron emission tomography/computerized tomography, echocardiography, magnetic resonance imaging, high resolution computed tomography and was confirmed by histopathology. We present the results of treatment of this patient with yttrium-90-DOTA-tyr(3)-octreotide.


Asunto(s)
Carcinoma Medular/radioterapia , Carcinoma Medular/secundario , Neoplasias Cardíacas/radioterapia , Neoplasias Cardíacas/secundario , Ventrículos Cardíacos , Octreótido/análogos & derivados , Neoplasias de la Tiroides/radioterapia , Anciano , Humanos , Masculino , Octreótido/uso terapéutico , Radiofármacos/uso terapéutico , Resultado del Tratamiento
11.
Endocrine ; 65(3): 515-519, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31273680

RESUMEN

PURPOSE: Minimally invasive image-guided thermal ablation has been proposed as alternative to surgery for treatment of benign thyroid nodules and recurrent differentiated thyroid carcinoma. Here, we report for the first time the use of radiofrequency ablation (RFA) in a patient with non-metastatic medullary thyroid carcinoma (MTC) who did not undergo surgery due to high anesthesiological risk. METHODS AND RESULTS: A 64-year-old woman was referred to our institution for a routine endocrinological visit. No thyroid-related symptoms were present. She had a history of metabolic, cardiovascular and neurological diseases. On clinical examination, a nodular lesion of about 10 mm was palpable in the right thyroid lobe; ultrasonography (US) confirmed the presence of a 13 mm thyroid nodule in the lower pole of the right lobe, that was hypoechoic and with regular margins. Serum calcitonin (Ctn) level was significantly high (647 pg/mL). Fine-needle aspiration (FNA) of the thyroid nodule was negative for malignant cells, but the marked increase of Ctn level in the FNA wash-out fluid confirmed the diagnostic suspicion of MTC. Since patient refused surgery due to high anesthesiological risk, percutaneous US-guided RFA in single session was performed. At 6-months follow-up the serum Ctn level decreased from the initial value of 647 pg/mL, reaching near-normal range (15 pg/mL), and neck ultrasound showed a complete necrosis of the tumour. Afterward, serum Ctn slowly increased to 49 pg/mL at 15-month follow-up. The US performed at 6 and 12 months of follow-up revealed fibrotic tissue in place of the thyroid nodule, without evidence of cervical lymph-node metastases. CONCLUSIONS: This clinical case suggests that RFA may be effective and safe for treatment of MTC when surgery cannot be performed.


Asunto(s)
Carcinoma Medular/diagnóstico por imagen , Carcinoma Medular/radioterapia , Ablación por Catéter/métodos , Neoplasias de la Tiroides/diagnóstico por imagen , Neoplasias de la Tiroides/radioterapia , Biopsia con Aguja Fina , Calcitonina/sangre , Femenino , Humanos , Persona de Mediana Edad , Cuello/diagnóstico por imagen , Glándula Tiroides/diagnóstico por imagen , Nódulo Tiroideo/diagnóstico por imagen , Resultado del Tratamiento , Ultrasonografía Intervencional
12.
Endocrinol Metab Clin North Am ; 37(2): 497-509, xi, 2008 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-18502339

RESUMEN

This article discusses the role of external beam radiotherapy (XRT) in the management of well-differentiated thyroid cancer (WDTC), medullary thyroid cancer, and anaplastic thyroid cancer. Although there are no randomized controlled studies on the use of XRT in thyroid cancer, evidence supports its use to treat gross disease after surgery or unresectable cancer and its use as an adjuvant after resection of a known high-risk disease in WDTC, and, to a lesser extent, in medullary thyroid cancer. The use of XRT for the palliation of symptomatic disease and recent advances in the technology of radiation delivery also will be discussed.


Asunto(s)
Carcinoma Papilar/radioterapia , Neoplasias de la Tiroides/radioterapia , Carcinoma/mortalidad , Carcinoma/patología , Carcinoma/radioterapia , Carcinoma Medular/mortalidad , Carcinoma Medular/patología , Carcinoma Medular/radioterapia , Carcinoma Papilar/mortalidad , Carcinoma Papilar/patología , Humanos , Metástasis de la Neoplasia , Cuidados Paliativos , Radioterapia Adyuvante , Radioterapia Conformacional , Análisis de Supervivencia , Neoplasias de la Tiroides/mortalidad , Neoplasias de la Tiroides/patología , Resultado del Tratamiento
13.
Biomed Pharmacother ; 62(3): 139-46, 2008 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-17892924

RESUMEN

Medullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor originating in the parafollicular cells (C cells) of the thyroid and secretes both calcitonin and carcino-embryonic antigen (CEA). Genetic and biochemical testing allow early pre-clinical identification of familial forms. Sporadic MTC usually presents as a solitary thyroid nodule; the diagnosis can be made preoperatively by fine-needle aspiration or by calcitonin assay, though it is usually established at the time of surgery. In the diagnostic assessment of MTC, nuclear medicine imaging provides its contribution mainly in the post-operative work-up to detect residual/recurrent tumor. For such purpose a number of radiopharmaceuticals, which take advantage of the specific expression of receptors (the somatostatin analogue (111)In-octreotide), hormone transporters (radiolabelled MIBG) or molecular targets (radiolabelled anti-CEA monoclonal antibodies) by MTC lesions are available; these tracers may be used also for the palliative treatment of advanced MTC. Interesting perspectives for MTC imaging are offered by PET radiopharmaceuticals.


Asunto(s)
Carcinoma Medular/diagnóstico por imagen , Carcinoma Medular/radioterapia , Medicina Nuclear , Radiofármacos/uso terapéutico , Neoplasias de la Tiroides/diagnóstico por imagen , Neoplasias de la Tiroides/radioterapia , 3-Yodobencilguanidina , Animales , Antígeno Carcinoembrionario/inmunología , Humanos , Radioisótopos de Yodo , Tomografía de Emisión de Positrones , Somatostatina/análogos & derivados , Somatostatina/farmacología , Tomografía Computarizada de Emisión de Fotón Único
14.
Clin Cancer Res ; 13(22 Pt 1): 6696-702, 2007 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-18006770

RESUMEN

PURPOSE: We aimed to explore the efficacy of (90)Yttrium-1,4,7,10-tetra-azacyclododecane N,N',N'',N-'''-tetraacetic acid ((90)Y-DOTA)-Tyr(3)-octreotide (TOC) therapy in advanced medullary thyroid cancer. EXPERIMENTAL DESIGN: In a phase II trial, we investigated the response, survival, and long-term safety profile of systemic [(90)Y-DOTA]-TOC treatment in metastasized medullary thyroid cancer. Adverse events were assessed according to the criteria of the National Cancer Institute. Survival analyses were done using multiple regression models. RESULTS: Thirty-one patients were enrolled. A median cumulative activity of 12.6 GBq (range, 1.7-29.6 GBq) of [(90)Y-DOTA]-TOC was administered. Response was found in nine patients (29.0%). Four patients (12.9%) developed hematologic toxicities and seven patients (22.6%) developed renal toxicities. Response to treatment was associated with longer survival from time of diagnosis (hazard ratio, 0.20; 95% confidence interval, 0.05-0.81; P = 0.02) and from time of first [(90)Y-DOTA]-TOC therapy (hazard ratio, 0.16; 95% confidence interval, 0.04-0.63; P = 0.009). The visual grade of scintigraphic tumor uptake was not associated with treatment response or survival. CONCLUSIONS: Response to [(90)Y-DOTA]-TOC therapy in metastasized medullary thyroid cancer is associated with a long-term survival benefit. Treatment should be considered independently from the result of the pretherapeutic scintigraphy.


Asunto(s)
Carcinoma Medular/radioterapia , Octreótido/análogos & derivados , Radiofármacos/uso terapéutico , Neoplasias de la Tiroides/radioterapia , Adulto , Anciano , Carcinoma Medular/mortalidad , Carcinoma Medular/secundario , Protocolos Clínicos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Octreótido/efectos adversos , Octreótido/uso terapéutico , Análisis de Supervivencia , Neoplasias de la Tiroides/mortalidad , Neoplasias de la Tiroides/patología
15.
Surg Oncol Clin N Am ; 17(1): 219-32, x, 2008 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-18177808

RESUMEN

The goal of this article is to review the various indications for the application of external beam radiotherapy in the management of thyroid cancer. This article includes a discussion of published literature to define risk variables that increase the risk of recurrence after surgery that might be mitigated by the use of radiation therapy. Clinical outcomes, recent technologic advances in treatment planning and radiation delivery, and potential morbidity associated with treatment are also reviewed.


Asunto(s)
Neoplasias de la Tiroides/radioterapia , Resultado del Tratamiento , Carcinoma/patología , Carcinoma/radioterapia , Carcinoma Medular/patología , Carcinoma Medular/radioterapia , Humanos , Radioterapia/efectos adversos , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/cirugía
16.
Radiat Prot Dosimetry ; 129(4): 372-80, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-17951242

RESUMEN

Chromosomal damage was investigated in lymphocytes of thyroid cancer patients after radioiodine treatment. An assay on micronuclei (MN) in binucleated cells was performed in blood samples of 25 patients 3 d after (131)I (3.7 GBq) was given. Statistical analysis does not show overdispersion of the MN distribution, thus considering the exposure to blood as being homogeneous (p < 0.05). A dose-protraction factor (G) of 0.1 was considered into the calculation of the blood dose to take into account the effect of the duration of exposure. The total MN count is a sum of the background distribution and the Poisson distribution induced by radiation exposure. A Bayesian approach was used to avoid inconsistencies when the total count was close to or lower than the background level. Estimated blood dose after 3 d of exposure was 0.73 Gy (0.197 mGy/MBq). The usefulness of the Bayesian method in analysing chromosomal damage when the count is low has been determined.


Asunto(s)
Teorema de Bayes , Aberraciones Cromosómicas/efectos de la radiación , Radioisótopos de Yodo/uso terapéutico , Radiometría/instrumentación , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/radioterapia , Adenocarcinoma Folicular/genética , Adenocarcinoma Folicular/radioterapia , Adolescente , Adulto , Anciano , Carcinoma Medular/genética , Carcinoma Medular/radioterapia , Carcinoma Papilar/genética , Carcinoma Papilar/radioterapia , Células Cultivadas , Niño , Relación Dosis-Respuesta en la Radiación , Femenino , Humanos , Linfocitos/efectos de la radiación , Masculino , Persona de Mediana Edad , Efectividad Biológica Relativa
17.
Hum Gene Ther ; 18(10): 916-24, 2007 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-17931047

RESUMEN

In contrast to follicular cell-derived thyroid cancer, medullary thyroid cancer (MTC) remains difficult to treat because of its unresponsiveness to radioiodine therapy, or to conventional chemo- and radiotherapy. We therefore examined the feasibility of radioiodine therapy of MTC after human sodium iodide symporter (hNIS) gene transfer, using the tumor-specific carcinoembryonic antigen (CEA) promoter for transcriptional targeting. NIS gene transfer was performed in vivo in human MTC cell (TT) xenografts, using adenoviral vectors carrying the NIS gene linked to the cytomegalovirus promoter (Ad5-CMV-NIS) or a CEA promoter fragment (Ad5-CEA-NIS). Functional NIS expression was confirmed by immunostaining as well as in vivo (123)I gamma-camera imaging followed by application of a therapeutic (131)I dose. TT cell xenografts in nude mice injected intratumorally with Ad5-CEA-NIS accumulated 7.5 +/- 1.2% ID/g (percentage injected dose per gram tumor tissue; 5 x 10(8) PFU) and 12 +/- 2.95% ID/g (1 x 10(9) PFU) with an average biological half-life of 6.1 +/- 0.8 and 23.6 +/- 3.7 hr, respectively, as compared with accumulation of 8.4 +/- 0.9% ID/g with a biological half-life of 12 +/- 8 hr after application of Ad5-CMV-NIS (5 x 10(8) PFU). After Ad5-CEA-NIS-mediated NIS gene transfer in TT cell xenografts administration of a therapeutic dose of 111 MBq (3 mCi) of (131)I resulted in a significant reduction of tumor growth associated with significantly lower calcitonin serum levels in treated mice as well as improved survival. We conclude that a therapeutic effect of (131)I was demonstrated in vivo in MTC cell xenografts after adenovirus-mediated induction of tumor-specific iodide accumulation by CEA promoter-directed hNIS expression.


Asunto(s)
Carcinoma Medular/radioterapia , Terapia Genética , Radioisótopos de Yodo/uso terapéutico , Simportadores/genética , Neoplasias de la Tiroides/radioterapia , Adenoviridae/genética , Animales , Antígeno Carcinoembrionario/genética , Antígeno Carcinoembrionario/metabolismo , Carcinoma Medular/genética , Línea Celular Tumoral , Vectores Genéticos , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Trasplante de Neoplasias , Regiones Promotoras Genéticas , Simportadores/metabolismo , Neoplasias de la Tiroides/genética , Transducción Genética
18.
Endocrinol Metab Clin North Am ; 36(3): 823-37, viii, 2007 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-17673130

RESUMEN

This article summarizes the clinical features and molecular pathogenesis of medullary thyroid cancer (MTC) and focuses on the current use of molecular, biochemical, and imaging disease markers as a basis for selection of appropriate therapy. Clinicians treating patients who have MTC face the following challenges: (1) distinguishing MTC as early as possible from benign nodular disease and differentiated thyroid cancer to choose the appropriate initial surgery, (2) managing low-level residual cancer in otherwise asymptomatic individuals, and (3) treating progressive metastatic disease. Early clinical trials using small molecules targeting Ret or vascular endothelial growth factor receptors suggest that such approaches could be effective and well tolerated. This article highlights early progress in targeted therapy of MTC and significant challenges in disease monitoring to appropriately select and evaluate patients being treated with these therapies.


Asunto(s)
Carcinoma Medular/diagnóstico , Carcinoma Medular/terapia , Neoplasias de la Tiroides/diagnóstico , Neoplasias de la Tiroides/terapia , Inhibidores de la Angiogénesis/uso terapéutico , Biomarcadores/sangre , Carcinoma Medular/genética , Carcinoma Medular/radioterapia , Diagnóstico por Imagen , Marcadores Genéticos , Humanos , Escisión del Ganglio Linfático , Proteínas Proto-Oncogénicas c-ret/antagonistas & inhibidores , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/radioterapia , Tiroidectomía
19.
Cancer Biother Radiopharm ; 22(5): 613-28, 2007 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-17979564

RESUMEN

UNLABELLED: Somatostatin and gastrin receptors are overexpressed in medullary thyroid carcinoma (MTC) cells; hence, both of them are potential targets for peptide receptor scintigraphy and radiotherapy. Therefore, the aim of our study was to assess the clinical value of two technetium-99m-labeled peptides, a new gastrin analog, the EDDA/HYNIC-(D)Glu-octagastrin and a somatostatin analog, EDDA/HYNIC-Tyr(3)-octreotide (EDDA/HYNIC-TOC) for scintigraphy in patients with MTC to detect recurrences and metastases and select patients for peptide receptor radiotherapy. MATERIAL AND METHODS: Thirty (30) patients, 20 females and 10 males, 22-83 years of age (mean, 52.7) with the diagnosis of MTC in different stages of the disease (preoperative, postsurgery, remission, recurrence, or metastatic disease) were included in this study. Before surgery, in all patients serum calcitonin concentrations were elevated. The diagnosis of MTC was confirmed in all cases by histopathology of the removed tumor and immunohistochemical staining giving positive reactions for calcitonin and chromogranin A. Imaging studies using (99m)Tc-EDDA/HYNIC-TOC and a new minigastrin analog, (99m)Tc-EDDA/HYNIC-(D)Glu-octagastrin, were performed in each patient and the results compared with each other and with other imaging methods. Scans of the whole body, head, neck, and chest were performed 2 and 4 hours after injections of the tracer, 500-600 MBq in each case, using a double-head Varicam (Elscint, Israel) gamma camera. RESULTS: (99m)Tc-EDDA/HYNIC-TOC detected somatostatin receptor-positive lesions in 20 patients with MTC, whereas (99m)Tc-EDDA/HYNIC-(D)Glu-octagastrin displayed gastrin receptors in 11 patients. In 9 cases, the scans were positive in both methods, although in 2 cases different pathologic foci were visualized. In 12 cases, only (99m)Tc-EDDA/HYNIC-TOC scintigraphy was positive, whereas in 3 other cases only (99m)Tc-EDDA/HYNIC-(D)Glu-octagastrin revealed pathologic lesions. CONCLUSIONS: Scintigraphy using (99m)Tc-HYNIC-TOC permits the visualization of somatostatin receptor-positive MTC in the majority of cases. The new gastrin analog, (99m)Tc-HYNIC-(D)Glu-octagastrin, is well tolerated, shows no renal retention, and in some cases of MTC, provides additional information on the expression of gastrin receptors. However, inferior quality of octagastrin scans indicates the need for further improvement of this radiopeptide.


Asunto(s)
Carcinoma Medular/diagnóstico , Gastrinas , Compuestos de Organotecnecio , Neoplasias de la Tiroides/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Animales , Carcinoma Medular/diagnóstico por imagen , Carcinoma Medular/radioterapia , Ácido Edético/análogos & derivados , Ácido Edético/química , Femenino , Gastrinas/química , Gastrinas/farmacocinética , Humanos , Hidrazinas/química , Radioisótopos de Indio/química , Masculino , Ratones , Ratones Endogámicos BALB C , Persona de Mediana Edad , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia/diagnóstico , Recurrencia Local de Neoplasia/diagnóstico por imagen , Recurrencia Local de Neoplasia/prevención & control , Ácidos Nicotínicos/química , Compuestos de Organotecnecio/síntesis química , Compuestos de Organotecnecio/farmacocinética , Cintigrafía/métodos , Sensibilidad y Especificidad , Glándula Tiroides/metabolismo , Glándula Tiroides/patología , Glándula Tiroides/efectos de la radiación , Neoplasias de la Tiroides/diagnóstico por imagen , Neoplasias de la Tiroides/radioterapia
20.
Gynecol Obstet Fertil ; 35(11): 1117-22, 2007 Nov.
Artículo en Francés | MEDLINE | ID: mdl-17977045

RESUMEN

OBJECTIVE: Typical medullary carcinoma of the breast is a rare histological form of breast carcinoma. It represents less than 5% of all breast cancer. It is known for its favourable prognosis. Considering the rarity of the series we could retrieve, we aimed at underlining the particularities of this pathology. PATIENTS AND METHODS: Retrospective study about 33 cases of typical medullary carcinoma managed at the Salah-Azaïz Institute during a period of six years between 1994 and 1999. RESULTS: The mean age was 47.5 years. The left breast was concerned in about 55% of cases. Mean tumoral size was 46mm. Sixty-one percent of our patients were treated by radical surgery. Seventy-three percent undergo radiotherapy, 57% chemotherapy and 42% hormonotherapy. The five-year free-disease survival was about 85%. DISCUSSION AND CONCLUSION: Typical medullary carcinoma of the breast is a rare histological form of breast carcinoma. Its treatment is similar to the other breast cancers. Our results agree with the different published studies and confirm its favourable prognosis.


Asunto(s)
Neoplasias de la Mama/patología , Carcinoma Medular/patología , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/cirugía , Carcinoma Medular/radioterapia , Carcinoma Medular/cirugía , Supervivencia sin Enfermedad , Femenino , Humanos , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos
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