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Although the overall prognosis for differentiated thyroid cancer (DTC) is excellent, a subset of patients will experience disease recurrence or may not respond to standard treatments. In recent years, DTC management has become more personalized in order to enhance treatment efficacy and avoid unnecessary interventions.In this context, major guidelines recommend post-surgery staging to assess the risk of disease persistence, recurrence, and mortality. Consequently, risk stratification becomes pivotal in determining the necessity of postoperative adjuvant therapy, which may include radioiodine therapy (RIT), the degree of TSH suppression, additional imaging studies, and the frequency of follow-up.However, the intermediate risk of recurrence is a highly heterogeneous category that encompasses various risk criteria, often combined, resulting in varying degrees of aggressiveness and a recurrence risk ranging from 5 to 20%. Furthermore, there is not enough long-term prognosis data for these patients. Unlike low- and high-risk DTC, the available literature is contradictory, and there is no consensus regarding adjuvant therapy.We aim to provide an overview of intermediate-risk differentiated thyroid cancer, focusing on criteria to consider when deciding on adjuvant therapy in the current context of personalized approach, including molecular analysis to enhance the accuracy of patient management.
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Radioisótopos do Iodo , Neoplasias da Glândula Tireoide , Humanos , Tireoidectomia , Resultado do TratamentoRESUMO
PURPOSE: This study aimed to evaluate neutrophil to lymphocyte ratio (NLR) as a laboratory biomarker in radioactive iodine-refractory (RAIR) locally advanced and/or metastatic differentiated thyroid cancer (DTC) and determine its correlation with overall survival (OS). METHODS: We retrospectively included 172 patients with locally advanced and/or metastatic RAIR DTC admitted between 1993 and 2021 at INCA. Age at diagnosis, histology, presence of distant metastasis (DM), DM site, neutrophil-to- lymphocyte ratio (NLR), imaging studies such as PET/CT results, progression free survival (PFS) and overall survival (OS) data were analyzed. NLR was calculated at the time of locally advanced and/or metastatic disease diagnosis and the cutoff value was 3. Survival curves were established using the Kaplan-Meier method. The confidence interval is 95%, and a p-value of less than 0.05 was considered statistically significant RESULTS: Out of 172 patients, 106 were locally advanced, and 150 presented DM at some point during follow-up. Regarding NLR data, 35 had NLR over 3 and 137 had NLR under 3. Higher NLR at was associated with shorter OS (6 vs. 10; p = 0.05) and with highest SUV on FDG PET-CT (15.9 vs. 7.7, p = 0.013). We found no association between higher NLR and age at diagnosis, DM or final status. CONCLUSION: NLR higher than 3 at the time of locally advanced and/or metastatic disease diagnosis is an independent fator for shorter OS in RAIR DTC patients. Noteworthy higher NLR was also associated with highest SUV on FDG PET-CT in this population.
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Adenocarcinoma , Neoplasias da Glândula Tireoide , Humanos , Neutrófilos , Radioisótopos do Iodo/uso terapêutico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Fluordesoxiglucose F18 , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/radioterapia , Neoplasias da Glândula Tireoide/patologia , Linfócitos/patologia , Prognóstico , Adenocarcinoma/patologiaRESUMO
Objective: The purpose of this study was to investigate the effect and influencing factors of postsurgical radioactive iodine (RAI) therapy for patients with low- and intermediate-risk differentiated thyroid cancer (DTC). Subjects and methods: A retrospective analysis of 423 low- and intermediaterisk DTC patients admitted to the Department of Nuclear Medicine, Sichuan Provincial People's Hospital from January 2005 to December 2020 was performed. All patients were treated with surgery, had a postoperative pathological diagnosis, and were treated with RAI, including 89 males and 334 females. Recurrence risk stratification: 143 cases were low-risk, and 280 cases were intermediaterisk. Results: The excellent response (ER) rate for low- and intermediate-risk were 93.7% and 78.2%, respectively (P < 0.05). There were significant differences in age, cumulative dose of [131I], and pretreatment stimulated-Tg (pre-Tg) levels between the low- and intermediate-risk groups (P < 0.05). There were significant differences in the cumulative dose of 131I and pre-Tg levels between ER and the non-ER group (P < 0.05). The area under the curve (AUC) values were 0.799 in the low-risk group, and 0.747 in the intermediate-risk group for the ROC curve by ER status of pre-Tg. The ER rate with RAI treatment decreased with an increase in pre-Tg levels. Conclusion: Pre-Tg was an important factor for RAI treatment decision-making and prognostic evaluation and differed between low-risk and intermediate-risk DTC. Aggressive RAI therapy was recommended for low-risk DTC with pre-Tg ≥ 20.0 ng/mL and in intermediate-risk group with pre-Tg ≥ 10.0 ng/mL.
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Adenocarcinoma , Neoplasias da Glândula Tireoide , Masculino , Feminino , Humanos , Neoplasias da Glândula Tireoide/patologia , Radioisótopos do Iodo/uso terapêutico , Tireoglobulina , Estudos Retrospectivos , Tireoidectomia , Fatores de RiscoRESUMO
ABSTRACT Objective: The purpose of this study was to investigate the effect and influencing factors of post-surgical radioactive iodine (RAI) therapy for patients with low- and intermediate-risk differentiated thyroid cancer (DTC). Subjects and methods: A retrospective analysis of 423 low- and intermediate-risk DTC patients admitted to the Department of Nuclear Medicine, Sichuan Provincial People's Hospital from January 2005 to December 2020 was performed. All patients were treated with surgery, had a postoperative pathological diagnosis, and were treated with RAI, including 89 males and 334 females. Recurrence risk stratification: 143 cases were low-risk, and 280 cases were intermediate-risk. Results: The excellent response (ER) rate for low- and intermediate-risk were 93.7% and 78.2%, respectively (P < 0.05). There were significant differences in age, cumulative dose of [131I], and pretreatment stimulated-Tg (pre-Tg) levels between the low- and intermediate-risk groups (P < 0.05). There were significant differences in the cumulative dose of 131I and pre-Tg levels between ER and the non-ER group (P < 0.05). The area under the curve (AUC) values were 0.799 in the low-risk group, and 0.747 in the intermediate-risk group for the ROC curve by ER status of pre-Tg. The ER rate with RAI treatment decreased with an increase in pre-Tg levels. Conclusion: Pre-Tg was an important factor for RAI treatment decision-making and prognostic evaluation and differed between low-risk and intermediate-risk DTC. Aggressive RAI therapy was recommended for low-risk DTC with pre-Tg ≥ 20.0 ng/mL and in intermediate-risk group with pre-Tg ≥ 10.0 ng/mL.
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ABSTRACT BACKGROUND: The efficacy of anti-thyroid drugs in conjunction with radioactive iodine therapy in the management of Graves' disease is still controversial. OBJECTIVE: To compare the efficacy of pretreatment with methimazole before the administration of radioactive iodine for the treatment of Graves' disease. DESIGN AND SETTING: A systematic review and meta-analysis was conducted at a teaching/tertiary hospital in Ibadan, Nigeria. METHODS: A systematic search of the PubMed, Embase, Cochrane Library, and Web of Science databases was performed from inception to December, 2021. RESULTS: Five studies with 297 participants were included. There was no difference in the risk of persistent hyperthyroidism when radioactive iodine was used in conjunction with methimazole compared with when radioactive iodine was used alone (relative risk: 1.02, 95% confidence interval, CI: 0.62-1.66; P = 0.95, I2 = 0%). Subgroup analysis based on the duration between discontinuation of methimazole and the administration of radioactive iodine showed a lower risk of persistent hyperthyroidism when methimazole was discontinued within 7 days before radioactive iodine use, although this did not reach statistical significance (risk ratio: 0.85, CI: 0.28-2.58). CONCLUSIONS: The use of methimazole before radioactive iodine administration was not associated with an increased risk of persistent hyperthyroidism. Concerns about medication toxicity and adverse effects should be considered when clinicians make decisions on combination therapies for the treatment of Graves' disease. PROSPERO REGISTRATION: CRD42020150013, https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=150013.
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The cumulative evidence over the past decades has shown that the incidence of differentiated thyroid carcinoma (DTC) has exponentially increased. Approximately 10% of patients with DTC exhibit recurrent or metastatic disease, and about two-thirds of the latter will be defined as refractory to radioactive iodine (RAIR) treatment. Since this condition implies 10-year survival rates less than 10% after detection, using available treatments, such as systemic and targeted therapies, have become increasingly relevant. The initiation of these treatments aims to reach stabilization, tumor volume reduction, and/or symptom improvement and it should be decided by highly specialized endocrinologists/oncologists on the basis of patient's features. Considering that despite enlarged progression-free survival was proven, multikinase inhibitors remain non-curative, their benefits last for a limited time and the side effects potentially cause harm and quality of life reduction. In this context, molecular testing of cancer cells provides a promising spectrum of targeted therapies that offer increased compatibility with individual patient needs by improving efficacy, progression free survival, overall survival and adverse events profile. This review article aims to provide a summary of the current therapeutic strategies in advanced RAIR-DTC, including approved target therapies as well as those for off-label use, RAI resensitization agents, and immunotherapy.
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Symptoms related to salivary gland damage are one of the most frustrating complications after radioactive iodine (131I) therapy. To the best of our knowledge, this is the first study that aimed to evaluate the prophylactic effect of Bethanechol on the radioiodine content of salivary gland. Fifty patients who were referred to 131I therapy were randomized into Bethanechol and placebo groups. Patients received Bethanechol or Placebo (25 mg, 2 times daily), starting 2 h after 131I therapy to 1-month. Both groups were compared at baseline, 10, 30 and 90 days after 131I therapy based on the following: symptoms related to salivary gland damage; unstimulated whole saliva (UWS) and quality of life using University of Washington Quality of Life 4 questionnaire. Bethanechol group presented significantly lower complaints of dry mouth on 10 (p = 0.047) and 30 (p = 0.003) days compared with placebo. Salivary gland pain and swelling were more frequent among placebo patients at 10 days (p = 0.047). Comparison of the two groups by UWS, no statistical difference was found. Placebo group presented worse score related to activity (p = 0.034), saliva (p = 0.05) and humor (p = 0.05) at 10 days; palate (p = 0.05) and saliva (p = 0.05) at 1 month. Interestingly, Bethanechol patients who received 131I dose > 125mCi, showed better xerostomia indices when compared to the Placebo with same dose. Bethanechol during 131I therapy was found to be effective in decreasing the acute salivary gland damage with impact on patients' quality of life.
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Neoplasias da Glândula Tireoide , Xerostomia , Betanecol/uso terapêutico , Humanos , Radioisótopos do Iodo/efeitos adversos , Qualidade de Vida , Glândulas Salivares , Neoplasias da Glândula Tireoide/complicações , Neoplasias da Glândula Tireoide/tratamento farmacológico , Xerostomia/epidemiologia , Xerostomia/etiologia , Xerostomia/prevenção & controleRESUMO
ABSTRACT Objective: The aim of this study was to describe the real-world experience multikinase inhibitors (MKI) in the treatment advanced differentiated thyroid carcinoma (DTC) refractory to radioactive iodine (RAIR) therapy. Subjects and methods: We reviewed the records of all patients with MKI-treated DTC from 2010 to 2018. Progression free survival (PFS), response rates (RR) and adverse events (AE) profiles were assessed. Clinical parameters were compared between groups with different outcomes (disease progression and death) to identify possible prognostic factors and benefit from treatment. Results: Forty-four patients received MKI for progressive RAIR DTC. Median PFS was 24 months (10.2-37.7) and median overall survival (OS) was 31 months. Best overall response was complete response in one patient (4.5%), partial response in nine (20.4%), stable disease in twenty-two (50%), and progressive disease (PD) in twelve (27.3%). Seventy-two point 7 percent patients had clinical benefit and AE were mild in most cases (82.7%). Progressive patients were more likely to have FDG positive target lesion than those who did not progress (p = 0.033) and higher maximum SUV on target lesions (p = 0.042). Presence of lung-only metastasis and lower thyroglobulin (Tg) during treatment was associated with stable disease (p = 0.015 and 0,049, respectively). Patients with shorter survival had larger primary tumor size (p = 0.015) and higher maximum SUV on target lesions (p = 0.023). Conclusion: Our findings demonstrate safety and effectiveness of MKI in patients with advanced RAIR DTC. We were able to identify as possible prognostic markers of better outcomes: absence of FDG uptake on target lesions, lower maximum SUV on PET-CT, presence of lung-only metastasis and lower Tg during treatment.
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Humanos , Neoplasias da Glândula Tireoide/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Antineoplásicos/uso terapêutico , Prognóstico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Radioisótopos do IodoRESUMO
Iodine is an essential constituent of thyroid hormone. Active iodide accumulation in the thyroid is mediated by the sodium iodide symporter (NIS), comprising the first step in thyroid hormone biosynthesis, which relies on the functional expression of NIS on the cell membrane. The retention of NIS expressed in differentiated thyroid cancer (DTC) cells allows further treatment with post-operative radioactive iodine (RAI) therapy. However, compared with normal thyroid tissue, differentiated thyroid tumors usually show a decrease in the active iodide conveyance and NIS is generally retained within the cells, indicating that posttranslational protein transfer to the plasma membrane is abnormal. In recent years, through in vitro studies and studies of patients with DTC, various methods have been tested to increase the transport rate of NIS to the cell membrane and increase the absorption of iodine. An in-depth understanding of the mechanism of NIS transport to the plasma membrane could lead to improvements in RAI therapy. Therefore, in this review, we discuss the current knowledge concerning the post-translational mechanisms that regulate NIS transport to the cell membrane and the current status of redifferentiation therapy for patients with RAI-refractory (RAIR)-DTC.
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Diferenciação Celular , Membrana Celular/efeitos da radiação , Radioisótopos do Iodo/uso terapêutico , Simportadores/metabolismo , Neoplasias da Glândula Tireoide/radioterapia , Animais , Membrana Celular/metabolismo , Humanos , Neoplasias da Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/patologiaRESUMO
INTRODUCCIÓN: el tiroides exhibe una gran avidez por el yodo radioactivo (I131) que al ser fijado por ésta glándula puede determinarse, desde afuera, aprovechando el hecho de que las radiaciones gamma atraviesan los tejidos blandos del cuello y pueden registrarse (Gammagrafía) a distancias apreciables. Desde 1962 Bolivia cuenta con esta tecnología, sin embargo, no cuenta con trabajos similares desde la declaración de país libre de enfermedades secundarias a la deficiencia de Yodo en 1997. El objetivo fue determinar valores de la captación tiroidea de I131 a las 24 horas en adultos jóvenes eutiroideos, residentes de gran altitud. MÉTODO: se realizó un estudio descriptivo transversal, en 76 sujetos obtenidos por intención y seleccionados mediante una entrevista clínica, examen físico dirigido y un consentimiento informado. El procedimiento fue ejecutado por personal calificado en el INAMEN siguiendo las recomendaciones de la OIEA. RESULTADOS: el valor de la captación tiroidea de I131 en 24 horas fue de 18,23 + 5,79% (rango 7,70 39,70). DISCUSIÓN: los expertos recomiendan establecer valores de referencia actualizados en cada región. Se han descrito variaciones de los valores normales influenciados por el sexo y edad; esta última, aparentemente por una hipofunción tiroidea inversamente proporcional con la edad. CONCLUSIÓN: el valor referencial encontrado en nuestro estudio es concordante con los establecidos en el extranjero, sin embargo, con una tendencia incrementada. Podría deberse a la secuencia cronológica de los estudios comparados en países que ya habían establecido políticas de yodación más tempranamente.
INTRODUCTION: the thyroid exhibits a great avidity for radioactive iodine (I131) which, when fixed by this gland, can be determined from the outside, taking advantage of the fact that gamma radiation passes through the soft tissues of the neck and can be registered (scintigraphy) at appreciable distances. Since 1962, Bolivia has had this technology, however, it does not have similar studies since the declaration of a country free of diseases secondary to iodine deficiency in 1997. The objective was to determine values of the thyroid uptake of I131 at 24 hours in euthyroid young adults, high altitude residents. METHOD: a descriptive cross-sectional study was carried out in 76 subjects obtained by intention and selected by means of a clinical interview, directed physical examination and informed consent. The procedure was carried out by qualified personnel at INAMEN, following IAEA recommendations. RESULTS: the value of the thyroid uptake of I131 in 24 hours was 18.23 + 5.79% (range 7.70 - 39.70). DISCUSSION: experts recommend establishing up-to-date reference values in each region. Variations in normal values influenced by sex and age have been described; the latter, apparently due to a thyroid hypofunction inversely proportional to age. CONCLUSION: the reference value found in our study is consistent with those established abroad, however, with an increased trend. It could be due to the chronological sequence of comparative studies in countries that had already established iodination policies earlier.
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Humanos , Masculino , Feminino , Adulto , Estudos Transversais , Iodo , Glândula Tireoide , Raios gama , Consentimento Livre e EsclarecidoRESUMO
OBJECTIVE: The intermediate-risk (IR) category includes tumors with different degrees of aggression. We aimed to identify the risk factors associated with unfavorable response to initial treatment and compare the effect of low/high radioactive iodine (RAI) therapy. METHODS: A total of 614 IR patients were selected from a database, during 1972-2015. All patients underwent total thyroidectomy and RAI therapy and were reclassified after 12-18 months into the favorable (complete/indeterminate) response group and the unfavorable (biochemical/incomplete structural) response group. A total of 92 patients were assessed for late response (mean: 9.19 ± 5.73 years). Age, gender, tumor size, histology, multifocality, vascular invasion, extrathyroidal extension, presence and number of lymph node metastasis, and stimulated thyroglobulin at ablation (sTg) were evaluated. RESULTS: Mean age at diagnosis was 41.47 ± 15.81 years, and 83.6% of the patients were female. Within 12-18 months after initial therapy, unfavorable response was detected in 41.2% of the patients and was associated, in multivariate analysis, with lymph node metastasis (p = 0.041; odds ratio [OR] = 1.9), presence of more than five metastatic lymph nodes (p = 0,017; OR = 2.6), and sTg > 10 ng/mL (p = 0.005; OR = 10.0). For patients with a longer follow-up, sTg >10 ng/mL was associated with unfavorable response (p = 0.002; OR = 6.8). A higher RAI dose was not related to better prognosis at the end of the follow-up. CONCLUSION: A sTg level of >10 ng/mL and lymph node metastasis were associated with an unfavorable response 12-18 months after initial treatment. A RAI dose below 150 mCi was proven sufficient to treat IR patients.
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Radioisótopos do Iodo , Neoplasias da Glândula Tireoide , Feminino , Humanos , Radioisótopos do Iodo/uso terapêutico , Masculino , Prognóstico , Estudos Retrospectivos , Tireoglobulina , Câncer Papilífero da Tireoide/cirurgia , Neoplasias da Glândula Tireoide/radioterapia , Neoplasias da Glândula Tireoide/cirurgia , TireoidectomiaRESUMO
OBJECTIVE: The aim of this study was to describe the real-world experience multikinase inhibitors (MKI) in the treatment advanced differentiated thyroid carcinoma (DTC) refractory to radioactive iodine (RAIR) therapy. METHODS: We reviewed the records of all patients with MKI-treated DTC from 2010 to 2018. Progression free survival (PFS), response rates (RR) and adverse events (AE) profiles were assessed. Clinical parameters were compared between groups with different outcomes (disease progression and death) to identify possible prognostic factors and benefit from treatment. RESULTS: Forty-four patients received MKI for progressive RAIR DTC. Median PFS was 24 months (10.2-37.7) and median overall survival (OS) was 31 months. Best overall response was complete response in one patient (4.5%), partial response in nine (20.4%), stable disease in twenty-two (50%), and progressive disease (PD) in twelve (27.3%). Seventy-two point 7 percent patients had clinical benefit and AE were mild in most cases (82.7%). Progressive patients were more likely to have FDG positive target lesion than those who did not progress (p = 0.033) and higher maximum SUV on target lesions (p = 0.042). Presence of lung-only metastasis and lower thyroglobulin (Tg) during treatment was associated with stable disease (p = 0.015 and 0,049, respectively). Patients with shorter survival had larger primary tumor size (p = 0.015) and higher maximum SUV on target lesions (p = 0.023). CONCLUSION: Our findings demonstrate safety and effectiveness of MKI in patients with advanced RAIR DTC. We were able to identify as possible prognostic markers of better outcomes: absence of FDG uptake on target lesions, lower maximum SUV on PET-CT, presence of lung-only metastasis and lower Tg during treatment.
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Antineoplásicos , Inibidores de Proteínas Quinases/uso terapêutico , Neoplasias da Glândula Tireoide , Antineoplásicos/uso terapêutico , Humanos , Radioisótopos do Iodo , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Prognóstico , Neoplasias da Glândula Tireoide/tratamento farmacológicoRESUMO
Las metástasis del carcinoma papilar de tiroides (CPT) generalmente son a nivel locorregional, la diseminación a distancia es poco habitual, sin embargo la invasión de tejidos blandos aunque inusual puede ocurrir, y afecta negativamente la supervivencia. El presente estudio describe una serie de casos de Metástasis Musculares de CPT. Se realizó un estudio transversal de un solo centro que evaluó diez pacientes con CPT con metástasis en músculo. La edad de los pacientes fue entre 46 a 77 años, siendo la edad promedio de 60 años, 7 de los cuales fueron de sexo masculino que corresponde al 70%, todos con antecedente de CPT con respuesta estructural incompleta, además de las metástasis en músculo presentaron afectación de tres o más órganos, con necesidad de varios tratamientos, cada paciente registró entre 1 a 8 cirugías, recibieron entre 100 a 780mCi de I131 (yodo radiactivo), ocho ameritaron radioterapia, todos tuvieron indicación de tratamiento con ITK, sin embargo solo cuatro pacientes tuvieron acceso a dicho medicamento. La mayoría de las metástasis del CPT en músculo fueron diagnosticadas en los estudios de imagen PET/ CT, después de la tiroidectomía el tiempo de su presentación fue muy variable entre 1 a 18 años, el número de músculos comprometidos se reporta entre uno a cuatro, siendo el glúteo (4 casos) el músculo metastásico más frecuente. La presencia de metástasis musculares empeora el pronóstico en nuestra serie de pacientes.
Metastases of thyroid papillary carcinoma (CPT) are generally at the locoregional level, the dissemination from a distance is unusual, however the invasion of soft tissues, although rare can occur, and it negatively affects survival. The present study describes several Muscular Metastases of CPT cases. A transversal study in one only center was performed and assessed ten patients CPT metastases in muscles.The patients age ranged from 46 to 77, being the average age of 60, and 7 of them were male, corresponding to the 70%, everyone with CPT records with an incomplete structural response. Besides muscular metastases they also presented issues with three or more organs, needing many treatments. Each patient registered between 1 to 8 surgeries, they received between 100 to 780mCi of I131. Eight required radiotherapies, everyone required treatment with ITK, however, just four patients had access to that medication. Most of the CPT metastases in muscles were diagnosed in PET/CT image studies, after the thyroidectomy, the time for its presentation was very variable between 1 to 18 years, the number of compromised muscles is reported between one to four, being the buttock (4 cases) the most frequently muscle with metastases. The presence of muscular metastases aggravates the prognosis in our series of patients.
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Humanos , Neoplasias da Glândula Tireoide/patologia , Carcinoma Papilar/secundário , Linfonodos/patologia , Músculos do Pescoço , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/sangue , Carcinoma Papilar/cirurgia , Carcinoma Papilar/sangue , Iodo , Linfonodos/cirurgia , Metástase NeoplásicaRESUMO
ABSTRACT Objective: The intermediate-risk (IR) category includes tumors with different degrees of aggression. We aimed to identify the risk factors associated with unfavorable response to initial treatment and compare the effect of low/high radioactive iodine (RAI) therapy. Subjects and methods: A total of 614 IR patients were selected from a database, during 1972-2015. All patients underwent total thyroidectomy and RAI therapy and were reclassified after 12-18 months into the favorable (complete/indeterminate) response group and the unfavorable (biochemical/incomplete structural) response group. A total of 92 patients were assessed for late response (mean: 9.19 ± 5.73 years). Age, gender, tumor size, histology, multifocality, vascular invasion, extrathyroidal extension, presence and number of lymph node metastasis, and stimulated thyroglobulin at ablation (sTg) were evaluated. Results: Mean age at diagnosis was 41.47 ± 15.81 years, and 83.6% of the patients were female. Within 12-18 months after initial therapy, unfavorable response was detected in 41.2% of the patients and was associated, in multivariate analysis, with lymph node metastasis (p = 0.041; odds ratio [OR] = 1.9), presence of more than five metastatic lymph nodes (p = 0,017; OR = 2.6), and sTg > 10 ng/mL (p = 0.005; OR = 10.0). For patients with a longer follow-up, sTg >10 ng/mL was associated with unfavorable response (p = 0.002; OR = 6.8). A higher RAI dose was not related to better prognosis at the end of the follow-up. Conclusion: A sTg level of >10 ng/mL and lymph node metastasis were associated with an unfavorable response 12-18 months after initial treatment. A RAI dose below 150 mCi was proven sufficient to treat IR patients.
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Humanos , Masculino , Feminino , Neoplasias da Glândula Tireoide/radioterapia , Neoplasias da Glândula Tireoide/ultraestrutura , Radioisótopos do Iodo/uso terapêutico , Prognóstico , Tireoglobulina , Tireoidectomia , Estudos Retrospectivos , Câncer Papilífero da Tireoide/cirurgiaRESUMO
Background: An important side effect of radioactive iodine (RAI) therapy in patients treated for papillary thyroid cancer (PTC) is chronic sialadenitis. Neck ultrasonography (US) easily recognizes radioiodine-induced salivary gland abnormalities. The objectives of this study were to determine the prevalence of US-detected sialadenitis caused by RAI and to identify the risk factors associated with this damage. Methods: This nonconcurrent cohort study includes all PTC-operated patients who were treated with RAI between 2007 and 2017 and were systematically evaluated with preoperative and follow-up neck US that included targeted exploration of the major salivary glands. Patients with pre-existing salivary gland diseases were excluded. The anatomical damage (diminished glandular volume, wavy contours, hypoechogenicity, and heterogeneity) was qualitatively assessed and compared with the preoperative study. RAI activity, sex, age, and preparation method were evaluated as risk factors using univariate and multivariate analyses with logistic regression. Results: Enrolled in this study were 570 patients who received a median RAI activity of 3700 MBq (100 mCi). On US, we found 143 patients (25.1%) with damage in at least one of their salivary glands: all had parotid damage (77 bilaterally) and 14 (9.8%) also had submandibular gland damage (7 of them bilaterally). The multivariate analysis indicated that the risk of sialadenitis was significantly (p < 0.01) correlated with both RAI activity and sex (14.1% of males vs. 28.5% of females). However, the main risk factor was RAI activity; no injury was detected in 156 patients who received 1110 MBq (30 mCi) and 1850 MBq (50 mCi) of RAI. In the groups of patients receiving 3700 MBq (100 mCi), 5550 MBq (150 mCi) and ≥7400 MBq (≥200 mCi), atrophy was found in 21%, 46.9%, and 77.7% of patients, respectively. Age and preparation method were not related to an increased risk of atrophy in this study. Conclusions: Chronic sialadenitis is common and affects approximately one fourth of patients who receive 3700 MBq (100 mCi) or higher RAI activity. The main risk factor for this injury is the total RAI activity administered. By using the lowest effective activity possible, irreversible anatomical damage in salivary glands can be minimized. US is an excellent tool to diagnose post-RAI atrophy.
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Radioisótopos do Iodo/efeitos adversos , Glândulas Salivares/diagnóstico por imagem , Glândulas Salivares/efeitos da radiação , Câncer Papilífero da Tireoide/diagnóstico por imagem , Câncer Papilífero da Tireoide/radioterapia , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/radioterapia , Ultrassonografia/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Atrofia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Pescoço/diagnóstico por imagem , Variações Dependentes do Observador , Glândula Parótida/diagnóstico por imagem , Qualidade de Vida , Radioterapia/efeitos adversos , Risco , Fatores de Risco , Glândulas Salivares/fisiopatologia , Glândula Submandibular/diagnóstico por imagem , Câncer Papilífero da Tireoide/cirurgia , Neoplasias da Glândula Tireoide/cirurgia , Adulto JovemRESUMO
PURPOSE: To describe the experience of our Division of Endocrinology with multikinase inhibitor (MKI) treatment in radioiodine-resistant differentiated thyroid cancer (DTC) patients. METHODS: Adults patients with a diagnosis of DTC treated with an MKI drug from March 2011 to October 2018 were registered into a retrospective database. Primary objectives were: the assessment of progression-free survival (PFS) and radiographic response evaluated according to RECIST v. 1.1. Adverse events (AEs) were evaluated by using Common Terminology Criteria for Adverse Events v. 5.0. RESULTS: Twenty-two patients were treated with MKIs (21 with sorafenib, one with lenvatinib as first-line treatment). Seven patients required a second-line therapy with lenvatinib and one patient required a third-line treatment with pazopanib. Median duration of treatment was 11.2 (4.8-79.6) months. Best responses with sorafenib were partial response (PR) in two patients (11%), stable disease (SD) >6 months in 13 patients (72%), and progressive disease (PD) in three patients (17%). Best responses with second-line lenvatinib were PR in one patient (33%) and SD in two patients (66%). Median PFS was 31.5 months. AEs were present in 19 (90%) patients under sorafenib. The most common AEs were hand-foot syndrome (HFS) (67%), diarrhea (52%), and hypertension (52%). Definitive withdrawal was necessary in only one patient (4.7%). CONCLUSIONS: Our study reflects the real-world clinical experience of an Endocrinology Division on the management of radioiodine-resistant DTC patients with sorafenib and lenvatinib, showing a beneficial therapeutic effect with acceptable tolerability.
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Antineoplásicos/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Neoplasias da Glândula Tireoide/tratamento farmacológico , Adulto , Idoso , Feminino , Humanos , Radioisótopos do Iodo/uso terapêutico , Masculino , Pessoa de Meia-Idade , Compostos de Fenilureia/uso terapêutico , Quinolinas/uso terapêutico , Estudos Retrospectivos , Sorafenibe/uso terapêuticoRESUMO
BACKGROUND: Recent studies suggest improved outcomes for children undergoing thyroidectomy at high-volume pediatric surgery centers. We present outcomes after thyroid surgery at a single center and advocate for referral to high-volume centers for multidisciplinary management of these children. METHODS: Medical records were reviewed for all pediatric patients undergoing thyroid surgery at a single institution from 2009 through 2017. Routine recurrent laryngeal nerve and parathyroid hormone monitoring was used. Lymph node dissections were performed in appropriately selected cancer patients. Data collection focused on pathologic diagnosis, surgical technique, and surgical complications, including postoperative hematoma, neurapraxia, permanent nerve damage, hypocalcemia, and transient and permanent hypoparathyroidism. RESULTS: From 2009 through 2017, 464 patients underwent thyroid surgery. Median age of the cohort was 15 years (range 2-24). Thirty-three percent were diagnosed with benign nodules (n=151), 36% with papillary or follicular thyroid cancer (n=168), 27% with Graves' disease (n=124), 3% with medullary thyroid cancer (n=14), and 1.5% underwent prophylactic thyroidectomy for MEN2a (n=7). Six patients required return to the OR for hematoma evacuation including 5 patients after surgery for Graves' disease (RR 8.7, 95% CI 1.06-71.85). In sixteen cases, concern about neurapraxia resulted in laryngoscopy, revealing eleven patients with vocal cord paresis. Two of these patients demonstrated a persistent deficit at 6 months postoperatively (0.4%). Thirty-seven percent of patients had transient hypoparathyroidism (n=137), and two patients had persistent hypoparathyroidism 6 months after total thyroidectomy (0.6%). There was no significant difference in either hypocalcemia or hypoparathyroidism after total thyroidectomy based on age or diagnosis. CONCLUSIONS: Characterizing outcomes for pediatric patients based on diagnosis will assist in preoperative counseling for patients and their families. This high-volume center reports low complication rates after pediatric thyroid surgery, highlighting that referral to high-volume centers should be considered for children and adolescents with thyroid disease requiring surgery. LEVEL OF EVIDENCE: Level IV.
Assuntos
Hospitais com Alto Volume de Atendimentos/estatística & dados numéricos , Hospitais Pediátricos/estatística & dados numéricos , Complicações Pós-Operatórias/epidemiologia , Doenças da Glândula Tireoide/cirurgia , Tireoidectomia/métodos , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Masculino , Philadelphia/epidemiologia , Estudos Retrospectivos , Adulto JovemRESUMO
Resumen Introducción: El riesgo de recurrencia en cáncer diferenciado de tiroides (CDT) se utiliza para determinar la frecuencia de las respuestas estructurales incompletas o excelentes con un valor predictivo positivo cercano al 30%. El riesgo dinámico, que evalúa la respuesta inicial al tratamiento demostró tener una proporción de varianza explicada de hasta el 80%. Por otro lado, en nuestro medio es fácil establecer la respuesta inicial, pero muchas veces es dificultoso determinar el riesgo de recurrencia desde donde partió el paciente. A esto hemos denominado "la silla rota" en pacientes con CDT. Materiales y métodos: Se realizó el análisis retrospectivo incluyendo 340 pacientes con los siguientes criterios:1) edad ≥18 años al momento del diagnóstico, 2) tratamiento inicial con tiroidectomía total y ablación con radioyodo, 3) seguimiento mínimo ≥3 años (excepto si ocurrió metástasis a distancia o muerte antes de ese tiempo), 4) datos anatomopatológicos y estudios complementarios suficientes para poder determinar tanto el riesgo de recurrencia como la respuesta inicial (evaluada en los primeros 6 meses a 2 años de seguimiento) y el estado al final del seguimiento (al momento de la última consulta). Objetivos: Describir la evolución de la respuesta inicial al final del seguimiento para demostrar que esta es la definición más importante, independientemente del riesgo de recurrencia al diagnóstico en pacientes con CDT. Resultados: El 36% de los pacientes presentó una respuesta excelente al tratamiento inicial (n=122) y de ellos, ninguno presentó evidencia estructural de enfermedad al final del seguimiento, independientemente del RR inicial. Conclusiones: La denominada "silla rota" parecería "repararse" correctamente cuando el paciente presenta una respuesta excelente al tratamiento, ya que esta se mantiene al final del seguimiento independientemente del RR inicial. La carencia de un correcto RR inicial no parecería ser imprescindible en pacientes con respuestas excelentes al tratamiento.
ABSTRACT Background: The risk of recurrence (RR) stratification system has been proposed as a useful tool for stablishing the frequency of the structural incomplete and excellent response-to-treatment in patients with differentiated thyroid cancer (DTC). However, the available information at diagnosis could be insufficient to accurately determine the initial RR. We called this situation "the broken chair". Although many studies have shown that the initial response to treatment usually predicts the final outcome, it is not clear if the final outcome could be different in the distinctive responses to treatment, if we analyze it together with the initial RR. Purpose: To investigate the outcomes of patients by comparing both situations: the initial RR and the initial response to treatment with the final outcome to establish if there was a different frequency of structural incomplete response at the end of follow-up. Methods: Retrospective review of 340 DTC patients followed up for at least 3 years after initial total thyroidectomy and radioactive iodine ablation (RAI). We assessed the initial response as the best response to therapy during the first 2 years, and the final response to therapy as the status at the end of follow-up, according to the definitions of the 2015 ATA guidelines. Conclusions: An excellent response to treatment during the first two years of follow-up can fix the "broken chair" in patients treated with DTC who received remnant ablation and it is independent of the initial RR. Results: None of the patients that achieved an initial excellent response to treatment (n=122, 36%), showed structural evidence of disease in the entire follow-up despite their initial RR.
Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Tempo de Reação/efeitos dos fármacos , Recidiva , Neoplasias da Glândula Tireoide/tratamento farmacológico , Medição de Risco/estatística & dados numéricos , Resultado do Tratamento , Medição de Risco/métodosRESUMO
OBJECTIVE: Bone metastases bring greater morbi-mortality to patients with differentiated thyroid carcinoma (DTC). Treatment was limited to radioactive iodine (RAI) and local approaches. Currently, bisphosphonates are included in the therapeutic arsenal. The aim of this study is to evaluate the impact of bone metastases and their treatment with zoledronic acid (ZA) and RAI therapy. METHODS: We retrospectively review 50 DTC patients with structurally evident bone metastases followed in a tertiary cancer center from 1994 to 2018. Clinical-pathologic characteristics, skeletal related events (SRE), and therapeutic approaches were recorded. RESULTS: Among the 50 patients analyzed, 22 underwent ZA adjuvant therapy and 28 did not. Mortality rate was 44%. Those patients presented SREs more frequently (90.9 vs. 67.9% the survival group, p = 0.05) and also had a greater number of bone lesions (40.9 vs. 10.7% had more than 6 metastatic sites, p = 0.03). The same group of patients was analyzed before and after therapy with ZA and the incidence of SRE decreased from 1.81 (0-8) before therapy to 0.29 (0-7) after therapy (p = 0.006). Comparing similar groups of 22 patients treated with ZA with 28 patients not treated, there was a trend of better overall survival (OS) in the group that received this drug (147 vs. 119 months, p = 0.06) and significantly improvement when bone metastases were RAI avid 155 (125-185) versus 120 (85-157) months, p < 0.01. Conclusion : ZA can successfully diminish the chance of having new SRE and possibly affect OS in DTC patients with bone metastases. The positive impact of RAI adjuvant treatment on OS is directly associated with RAI uptake.
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Resumen La tiroiditis es una enfermedad inflamatoria de la glándula tiroides, su etiología es habitualmente de tipo autoinmune o infecciosa sin embargo la exposición a agentes radioactivos terapéuticos como el yodo-131 (131-) también puede desencadenarla. La aplicación de yodo radiactivo tiende a ser un procedimiento por lo general inocuo y asintomático para el paciente sin embargo < 1% de las aplicaciones presentara un evento de inflamación del tejido tiroideo y aledaño conocido como tiroiditis por radiación secundaria a 131-. El diagnóstico de esta entidad es predominantemente clínico y por descarte de etiologías habituales, su tratamiento es controvertido y existen recomendaciones de expertos y guías de manejo sobre los medicamentos y dosis a utilizar. Su pronóstico es bueno y de corta duración, sin secuelas evidentes.
Abstract Thyroiditis is an inflammatory entity of the thyroid gland, the most common etiologies are autoimmune and infectious but the exposure to radioactive therapeutic such as 131- has not been reported as a cause. The use of -131 is usually a safe procedure with no common adverse effects nevertheless <1% of patients might present a thyroid gland and nearby soft tissue inflammatory process known as 131- secondary radiation thyroiditis. The diagnosis is clinical and after discarding other common etiologies. The optimal treatment is controversial with different agencies indicating different drugs and doses; the prognosis is good and with no long term consequences.