Dynamic risk allows us to adequately select patients with differentiated thyroid cancer who do not require radioiodine treatment

ABSTRACT Objective: The treatment of patients with differentiated thyroid cancer (DTC) was modified in the last decade towards a more individualized approach according to the risk of recurrence (RR). We compared the outcomes of patients with low and intermediate RR (LRR and IRR) who received or did not receive radioiodine remnant ablation (RRA) after assessing the dynamic risk. Materials and methods: We included 307 DTC patients with LRR and IRR submitted to total thyroidectomy. All patients were reclassified according to the dynamic risk stratification (low or high). Patients with high dynamic risk received RRA (141 patients). Results: LRR patients who received RRA presented a frequency of structural incomplete response (SIR) of 5% at the end of the follow-up, compared to 2% in those who did not receive it (p=0.353). IRR patients treated with RRA had a frequency of SIR of 22%, compared to 5% in patients without RRA (p=0.008). Conclusions: This study demonstrates the usefulness of dynamic risk assessment to decide RRA in a cohort with a long-term follow-up. The lower prevalence of SIR at the end of the follow-up in patients who did not receive RRA highlights the adequate selection of those who would not benefit from RRA, even with an intermediate risk of recurrence.

Prognostic factors for incomplete response in thyroid microcarcinoma: an analysis of initial response to therapy in 517 patients

ABSTRACT Objective: Although thyroid microcarcinoma (TMC) usually has a favorable prognosis, some patients present a higher risk of disease recurrence or persistence. Thus, we aimed at identifying possible risk factors associated with an incomplete response to therapy in TMC. Subjects and methods: This was a retrospective study of 517 patients with TMC treated with total thyroidectomy, with or without radioactive iodine (RAI) therapy, reclassified after 1.1 ± 0.4 years according to the response to treatment into "favorable" (excellent/indeterminate) or "unfavorable" (biochemical/structural incomplete) responses. We evaluated participants' age, sex, tumor size, histological variants, multifocality, presence of vascular/lymphatic/perineural invasion, extrathyroidal extension, metastatic lymph nodes (LN), and distant metastasis. The effect of RAI therapy on the response range was analyzed in a given subgroup. Results: The mean age observed was 46.4 ± 12.0 years, and 89.7% were female. We noted 97.5% with papillary carcinoma, 27.8% with multifocality and 11.2% with LN metastasis. Although the majority of patients had a low risk of recurrence/persistence (78%), 75% were submitted to RAI therapy. Incomplete response (20.7%) was associated with multifocality (p=0.041; OR=1.619) and metastatic LN (p=0.041; OR=1.868). These variables were strongly correlated (p=0.000; OR=3.283). No cut-off of tumor size was identified as a predictor of incomplete response by the receiver operating curve analysis. RAI treatment did not influence the response of patients with multifocality or LN metastasis. Conclusion: Multifocality and LN metastasis are independent risk factors for incomplete response in TMC patients and are strongly correlated. Additional RAI therapy was not associated with a more favorable response in these subgroups.

Intermediate-risk thyroid carcinoma: indicators of a poor prognosis

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.

Patterns of radioiodine use for differentiated thyroid carcinoma in Brazil: insights and a call for action from a 20-year database

ABSTRACT Objective: This study aimed to explore the patterns of radioactive iodine (RAI) use for differentiated thyroid cancer (DTC) in Brazil over the past 20 years. Materials and methods: A retrospective analysis of the DTC-related RAI prescriptions, from 2000 to 2018, retrieved from the Department of Informatics of the Unified Health System (Datasus) and National Supplementary Health Agency (ANS) database was performed. RAI activities prescriptions were re-classified as low (30-50 mCi), intermediate (100 mCi), or high activities (>100 mCi). Results: The number of DTC-related RAI prescriptions increased from 0.45 to 2.28/100,000 inhabitants from 2000 to 2015, declining onwards, closing 2018 at 1.87/100,000. In 2018, population-adjusted RAI prescriptions by state ranged from 0.07 to 4.74/100,000 inhabitants. Regarding RAI activities, in the 2000 to 2008 period, the proportion of high-activities among all RAI prescriptions increased from 51.2% to 74.1%. From 2009 onwards, there was a progressive reduction in high-activity prescriptions in the country, closing 2018 at 50.1%. In 2018, the practice of requesting high-activities varied from 16% to 82% between Brazilian states. Interestingly, variability of RAI use do not seem to be related to RAI referral center volume nor state socio-economic indicators. Conclusion: In recent years, there has been a trend towards the lower prescription of RAI, and a reduction of high-activity RAI prescriptions for DTC in Brazil. Also, significative inter-state and inter-institutional variability on RAI use was documented. These results suggest that actions to advance DTC healthcare quality surveillance should be prioritized.

Supervivencia prolongada luego de pequeñas dosis de terapia con radioyodo en metástasis cerebral de cáncer de tiroides / Long-term survival after small doses of radioiodine therapy for brain metastases of thyroid cancer

Resumen El cáncer diferenciado de tiroides generalmente se acompaña de una supervivencia a largo plazo. Sin embargo, en algunos casos pueden desarrollarse metástasis a distancia y, entre ellas, las localizaciones cerebrales son de mal pronóstico. El objetivo de esta presentación es comunicar el caso clínico de una mujer de 65 años que consultó por diplopía en la mirada vertical que había aparecido un mes antes. La resonancia magnética mostró una gran masa a nivel del cóndilo occipital. Se realizó el diagnóstico de tumor cerebral primario, por lo que fue operada dos veces con resección tumoral incompleta. El estudio histopatológico confirmó una lesión metastásica de carcinoma de tiroides. Se realizó una tiroidectomía total con resección de un cáncer papilar de la variante folicular. Luego, fue tratada con éxito con pequeñas cantidades repetitivas de yodo radiactivo para una dosis total acumulada de 325 mCi 131I, con una supervivencia a largo plazo.

Abstract Differentiated thyroid cancer is generally accompanied by a long term survival. However,in some cases distant metastases can develop and among them, brain localizations are of poor prognosis. The aim of this presentation is to communicate the clinical case of a 65 year-old woman who consulted for diplopia in vertical gaze which had appeared one month earlier. MRI showed a big mass at the level of the occipital condyle. Diagnosis of primary brain tumor was made so she was operated twice with incomplete tumor resection. The pathological study was confirmatory of a metastatic lesion of thyroid carcinoma. A total thyroidectomy with resection of a papillary cancer of the follicular variant was performed. Then, she was successfully treated with small repetitive radioiodine amounts for a total accumulated dose of 325 mCi 131I, with a long-term survival.

Administración de radioyodo en cáncer diferenciado de tiroides bajo régimen hospitalario: a propósito de la implementación del aislamiento de radioyodoterapia en un hospital regional / Administration of radioiodine in differentiated thyroid cancer under a hospital regime: about the implementation of radioiodotherapy isolation in a regional hospital

Resumen Introducción El cáncer diferenciado de tiroides (CDT) presenta un aumento a nivel mundial. El uso selectivo de terapia con radioyodo (RAI) es un pilar de su tratamiento. Su efecto terapéutico se debe a la radiación beta, mientras que la gamma hace que sea necesaria la hospitalización para limitar la exposición de terceros. Objetivo Describir la seguridad de la administración de altas dosis de RAI en pacientes con CDT. Materiales y Método Estudio retrospectivo descriptivo. Se incluyó a todos los pacientes con diagnóstico de CDT que requirieron hospitalización para administración de RAI ≥ 30 mCi en el Hospital Regional de Talca (HRT) entre agosto-diciembre de 2018. Resultados Durante el período descrito 10 pacientes recibieron RAI bajo régimen hospitalario. La mediana de dosis de RAI administrada fue de 100 mCi (rango: 50-150 mCi). Todos los pacientes fueron manejados con asilamiento estricto. El promedio de hospitalización fue 28 horas, siendo dados de alta al reportar una tasa de dosis absorbida < 70 µSv/h a 1 metro. Se entregaron instrucciones al alta para minimizar el riesgo de irradiación o contaminación a terceras personas. Conclusiones Nuestro protocolo de administración de RAI permite tratar de manera segura a pacientes con CDT disminuyendo la exposición a radiación de terceros. Las salas de asilamiento de radioyodoterapia, podrían dar cobertura al 100% de la demanda de terapia con RAI en CDT a nivel local.

Introduction Differentiated thyroid cancer (CDT) presents an increase in global levels. The selective use of radioiodine therapy (RAI) is a pillar of its treatment. Its therapeutic effect is due to beta radiation, while gamma makes hospitalization necessary to limit exposure. Aim To describe the safety treated with RAI inpatients and the functioning of the radioactive isolation rooms of our center. Materials and Method Retrospective descriptive study. All patients diagnosed with CDT who required RAI therapy under a hospital regimen at the Regional Hospital of Talca (HRT) between August-December 2018 were included. Results During the period described, 10 patients were treated. The median dose of RAI administered was 100 mCi (range: 50-150 mCi). The average of hospitalization was 28 hours, being discharged when reporting an absorbed dose rate < 70 μSv/h at 1 meter, giving the patient instructions, so that they follow to minimize the risk of irradiation or contamination of people in their environment. Conclusions Our RAI administration protocol allows patients with CDT to be treated safely. The radioactive isolation rooms could cover 100% of the demand for RAI therapy in CDT at the local level.

Variación de dosis de radioyodo en pacientes con cáncer diferenciado de tiroides post implementación de guías ATA 2015 / Variation of radioiodine dose in patients with differentiated thyroid cancer after implementation of the ATA 2015 guidelines

Introducción: El cáncer diferenciado de tiroides (CDT), es actualmente la neoplasia endocrina más frecuente. Su tratamiento estándar es la resolución quirúrgica, asociado a ablación con radioyodo (RI) según la clasificación propuesta por la American Thyroid Association (ATA). Las indicaciones y dosis de este último, han ido variando en los últimos años según avanzan las investigaciones en este ámbito. Objetivo: En el siguiente estudio se compararon las dosis de RI utilizadas previo y posterior a la implementación de las últimas guías de la ATA. Materiales y métodos: Estudio retrospectivo observacional de 70 pacientes con diagnóstico de CDT del Hospital Clínico de la Universidad de Chile entre 2012 y 2017. Se agruparon los pacientes en dos cohortes, los operados entre los años 2012-2015 y los 2016-2017 clasificándolos según riesgo ATA, TNM y riesgo de recurrencia. Se consignaron las dosis de RI utilizadas y se compararon entre las cohortes. Análisis estadístico: Mann Whithney. Resultados: Al comparar la dosis de RI entre ambas cohortes, según TNM y riesgo ATA, se obtuvo los siguientes resultados: los pacientes T1b de la cohorte 2012-2015 presentaron dosis de RI significativamente mayores que los de la cohorte 2016-2017; también se evidenció que en pacientes N0 hubo una diferencia estadísticamente significativa, mostrando una tendencia a disminuir la dosis de RI; además, en los pacientes de la cohorte 2012-2015 con riesgo ATA intermedio, se obtuvo que las dosis de RI fueron significativamente mayores que las utilizadas en la cohorte 2016-2017. Conclusión: Se concluye que las variaciones de las dosis de RI utilizadas en pacientes con CDT en un hospital universitario van acorde a las recomendaciones internacionales actuales, particularmente la publicación de la guía ATA 2015, aplicándose radioablación con menor dosis de RI. Dado este cambio, se ha evidenciado igualdad de efectos con dosis menores de RI y consecuentemente menos efectos adversos.

Introduction: Differentiated thyroid cancer (CDT) is currently the most frequent endocrine neoplasia. Its standard of care is surgical treatment, associated with radioiodine ablation (IR) according to the classification proposed by the American Thyroid Association (ATA). The indications and doses of the latter have changed in recent years as research in this area advances. Objective: In the following study, the doses of IR used before and after the implementation of the latest ATA guidelines were compared. Materials and methods: Retrospective observational study of 70 patients with a diagnosis of CDT from the Clinical Hospital of the University of Chile between 2012 and 2017. Patients were grouped into two cohorts, those surgically intervened between the years 2012-2015 and 2016-2017, classifying them according to ATA risk, TNM and recurrence risk. The IR doses used were reported and compared between the cohorts. Statistical analysis: Mann Whithney. Results: When comparing the IR dose between both cohorts, according to TNM and ATA risk, the following results were obtained: T1b patients in the 2012-2015 cohort had significantly higher IR doses than those in the 2016-2017 cohort; It was also evidenced that N0 patients showed a statistically significant tendency to decrease the IR dose; In addition, the 2012-2015 cohort with intermediate ATA risk, revealed IR doses significantly higher than those used in the 2016-2017 cohort. Conclusion: It is concluded that the variations in IR doses, used in patients with CDT in a university hospital, are in accordance with current international recommendations, particularly the publication of the ATA 2015 guidelines, applying radioablation with a lower dose of IR. Given this change, equality of effects has been evidenced with lower doses of IR and consequently fewer adverse effects.

Ultrasonography Echotexture as a surrogate for Sialadenitis secondary to 131I Radioiodine Therapy for differentiated Thyroid Cancer: a review and metaanalysis

To systematically review and analyze the medical literature to assess ultrasonography echotexture changes in thyroid cancer patients for the detection of chronic sialadenitis caused by radioiodine therapy. Methods: Sources were retrieved from PubMed, Scopus, EMBASE and LILACS through November 2018. All studies that assessed ultrasonographic features before 131I administration and at 12 months after 131I administration were selected. After data extraction, statistical analysis was performed by using Stata software. Results: From a total of 435 studies, 4 studies involving 665 patients were considered eligible, and echotexture heterogeneity was found with a significant difference. Conclusions: Ultrasound echotexture may detect chronic sialadenitis secondary to salivary radioiodine therapy.

Eficacia y seguridad de tirotropina recombinante para el tratamiento de pacientes adultos posoperados de cáncer de tiroides diferenciado que requieren terapia radioablativa y tienen contraindicación de suspensión del reemplazo hormonal con hormona tiroidea exógena / Efficacy and safety of recombinant thyrotropin for the treatment of postoperative adult patients with differentiated thyroid cancer who require radioablative therapy and have contraindication for suspension of exogenous thyroid hormone replacement

INTRODUCCIÓN: El presente dictamen expone la evaluación de la eficacia y seguridad de tirotropina recombinante en pacientes adultos posoperados de cáncer de tiroides diferenciado con contraindicación de suspensión del reemplazo hormonal con hormona tiroidea exógena y que requieren terapia radioablativa. El cáncer de tiroides es una neoplasia infrecuente (incidencia mundial alrededor de 15.0/100 000 varones y 22.0/100 000 mujeres); aunque se estima que entre el 70 % y 90 % de estos casos corresponde a un sobrediagnóstico. Se estima que la sobrevida a los 5 años es del 98.1 %, aproximadamente. En Perú, en el año 2017, se diagnosticaron 637 nuevos casos de cáncer de tiroides en el Instituto Nacional de Enfermedades Neoplásicas. El cáncer de tiroides que se forma a partir de las células epiteliales foliculares se denomina cáncer de tiroides diferenciado (CTD). TECNOLOGÍA SANITARIA DE INTERÉS: Tirotropina Recombinante Humana: La TSH es un estimulante específico de la tiroides, esencial para la función tiroidea, promoviendo la captación de yodo, la síntesis de tiroglobulina, y el crecimiento celular. Los CTD mantienen algunas características de la glándula tiroidea normal; entre ellas, la captación de yodo y la síntesis de tiroglobulina estimulada por la TSH. METODOLOGÍA: Se llevó a cabo una búsqueda sistemática de la literatura con respecto a la eficacia y seguridad de rhTSH en el tratamiento de pacientes adultos posoperados de CTD con contraindicación de THW y que requieren RAI. Se realizó tanto una búsqueda sistemática como una búsqueda manual en las páginas web de grupos dedicados a la investigación y educación en salud que elaboran guías de práctica clínica (GPC) y evaluaciones de tecnologías sanitarias (ETS). RESULTADOS: No se encontró evidencia que responda directamente al objetivo del presente dictamen preliminar La presente evaluación de tecnología sanitaria muestra la evidencia indirecta encontrada luego de una búsqueda sistemática, con respecto. a la eficacia y seguridad de rhTSH en términos de: sobrevida global, calidad de vida e incidencia de eventos adversos, en comparación con THW, para el tratamiento de pacientes adultos posoperados de CTD que requieren RAI. Al respecto, se identificaron tres guías de práctica clínica (GPC) elaboradas por la European Society for Medical Oncology (ESMO) en 2012, la American Thyroid Association (ATA) en 2015 y la Italian Society of Endocrinology (ISE) en 2016; dos evaluaciones de tecnologías sanitarias (ETS) elaboradas por El Ministerio de Salud Pública de Uruguay en 2011 y el Centro de colaboración del SUS: evaluación de tecnología & excelencia en salud (CCATES) en 2016; y, una revisión sistemática (RS) publicada en 2015. CONCLUSIONES: El equipo técnico del IETSI valoró los siguientes aspectos: i) El CTD es una enfermedad infrecuente y de buen pronóstico, pero que requiere de un tratamiento eficaz para mantener una adecuada calidad de vida, ii) Desde el punto de vista clínico, la evidencia disponible sugiere que rhTSH y THW presentan similar eficacia y seguridad como preparación para la RAI, en pacientes con CTD, iii) Dado que la población de interés del presente dictamen son pacientes con contraindicación de THW, es necesario ofrecer una alternativa que les permita recibir un tratamiento adecuado iv) La evidencia indirecta utilizada, sugiere que en pacientes con contraindicación de THW, el uso de rhTSH ofrecería resultados similares a los que se obtendrían con THW si no existiese dicha contraindicación. El Instituto de Evaluación de Tecnologías en Salud e Investigación ­ IETSI, aprueba el uso de rhTSH como parte del tratamiento de pacientes adultos posoperados de CTD que requieren RAI y tienen contraindicación de THW, según lo establecido en el Anexo N° 01. La vigencia del presente dictamen preliminar es de un año a partir de la fecha de publicación. Así, la continuación de dicha aprobación estará sujeta a la evaluación de los resultados obtenidos y de nueva evidencia que pueda surgir en el tiempo.

In properly selected patients with differentiated thyroid cancer, antithyroglobulin antibodies decline after thyroidectomy and their sole presence should not be an indication for radioiodine ablation

ABSTRACT Objective Our objective was to evaluate the trend of antithyroglobulin antibodies (TgAb) during follow-up of patients with differentiated thyroid cancer (DTC) treated without RAI, as well as their role in the risk of recurrence. Subjects and methods This was a prospective, descriptive study. A total of 152 consecutive patients with DTC treated in a single institution undergoing total thyroidectomy without RAI and followed for a median of 2.3 years (0.5-10.3) were divided in two groups: TgAb(-) (n = 111) and TgAb(+) (n = 41). Patients were classified according to AJCC 7th and 8th editions, as well as to their risk of recurrence and response to treatment categories. Results Both groups, TgAb(-) and TgAb(+), were similar regarding patient and tumor characteristics. At the end of follow-up, 90 (59.2%), 57 (37.5%), 3 (2%) and 2 (1.3%) patients achieved excellent, indeterminate, biochemically incomplete and structurally incomplete response, respectively. The risk of structural recurrence was similar in both groups (TgAb[-] 0.9% vs. TgAb[+] 2.4%, p = 0.46). In the TgAb(+) group, TgAb became negative in 10 (24.4%), decreased ≥ 50% without negativization in 25 (60.9%), decreased < 50% in 4 (9.8%) and remained stable or increased in 2 (4.9%) cases. The only incomplete structural response had increasing TgAb during follow-up. Conclusions In properly selected patients with DTC, TgAb concentration immediately after total thyroidectomy should not mandate RAI ablation, and their trend during follow-up may impact the risk of recurrence.

Clinical outcomes of low and intermediate risk differentiated thyroid cancer patients treated with 30mCi for ablation or without radioactive iodine therapy

ABSTRACT Objective To retrospectively evaluate the outcomes of patients with low and intermediate risk thyroid carcinoma treated with total thyroidectomy (TT) and who did not undergo radioiodine remnant ablation (RRA) and to compare them to patients receiving low dose of iodine (30 mCi). Subjects and methods A total of 189 differentiated thyroid cancer (DTC) patients treated with TT followed by 30mCi for RRA or not, followed in two referral centers in Brazil were analyzed. Results From the 189 patients, 68.8% was ATA low-risk, 30.6% intermediate and 0.6% high risk. Eighty-seven patients underwent RRA and 102 did not. The RRA groups tended to be younger and had a higher frequency of extra-thyroidal extension (ETE). RRA did not have and impact on response to initial therapy neither in low (p = 0.24) nor in intermediate risk patients (p = 0.66). It also had no impact on final outcome and most patients had no evidence of disease (NED) at final follow-up. Recurrence/persistence of disease was found in 1.2% of RRA group and 2% in patients treated only with TT (p = 0.59). Conclusions Our study shows that in low and intermediate-risk patients, RRA with 30 mCi seems to have no major advantage over patients who did not undergo RRA regarding response to initial therapy in each risk group and also in long term outcomes.

Papillary thyroid microcarcinoma: characteristics at presentation, and evaluation of clinical and histological features associated with a worse prognosis in a Latin American cohort

ABSTRACT Objective We aimed to describe the presentation of papillary microcarcinoma (PTMC) and identify the clinical and histological features associated with persistence/recurrence in a Latin American cohort. Subjects and methods Retrospective study of PTMC patients who underwent total thyroidectomy, with or without radioactive iodine (RAI), and who were followed for at least 2 years. Risk of recurrence was estimated with ATA 2009 and 2015 classifications, and risk of mortality with 7th and 8th AJCC/TNM systems. Clinical data obtained during follow-up were used to detect structural and biochemical persistence/recurrence. Results We included 209 patients, predominantly female (90%), 44.5 ± 12.6 years old, 183 (88%) received RAI (90.4 ± 44.2 mCi), followed-up for a median of 4.4 years (range 2.0-7.8). The 7th and 8th AJCC/TNM system classified 89% and 95.2% of the patients as stage I, respectively. ATA 2009 and ATA 2015 classified 70.8% and 78.5% of the patients as low risk, respectively. Fifteen (7%) patients had persistence/recurrence during follow-up. In multivariate analysis, only lymph node metastasis was associated with persistence/recurrence (coefficient beta 4.0, p = 0.016; 95% CI 1.3-12.9). There were no PTMC related deaths. Conclusions Our series found no mortality and low rate of persistence/recurrence associated with PTMC. Lymph node metastasis was the only feature associated with recurrence in multivariate analysis. The updated ATA 2015 and 8th AJCC/TNM systems classified more PTMCs than previous classifications as low risk of recurrence and mortality, respectively.

Thyroglobulin levels before radioactive iodine therapy and dynamic risk stratification after 1 year in patients with differentiated thyroid cancer

ABSTRACT Objectives: We sought to assess the relationship between stimulated thyroglobulin (sTg) before radioactive iodine therapy (RIT), and the dynamic risk stratification 1 year after treatment, and to establish the utility of the sTg as a predictor of response to therapy in these patients. A retrospective chart review of patients with differentiated thyroid cancer (DTC) who underwent RIT after surgery and were followed for at least 1 year, was carried out. Subjects and methods: Patients were classified according to the dynamic risk stratification 1 year after initial treatment. The sTg values before RIT were compared among the groups. ROC curve analysis was performed. Results: Fifty-six patients were enrolled (mean age 44.7 ± 14.4 years, 80.7% had papillary carcinoma). Patients with excellent response had sTg = 2.1 ± 3.3 ng/mL, those with indeterminate response had sTg = 8.2 ± 9.2 ng/mL and those with incomplete response had sTg = 22.4 ± 28.3 ng/mL before RIT (p = 0.01). There was a difference in sTg between excellent and incomplete response groups (p = 0.009) while no difference was found between indeterminate and either excellent or incomplete groups. The ROC curve showed an area under the curve of 0.779 assuming a sTg value of 3.75 ng/mL. Conclusion: Our study results suggest that the higher the sTg before RIT, the greater the likelihood of an incomplete response to initial treatment. A sTg cut-off of 3.75 ng/mL was found to be a good predictor of response to initial treatment in patients with DTC.

Radioactive iodine-refractory differentiated thyroid cancer: an uncommon but challenging situation

ABSTRACT Radioiodine (RAI)-refractory thyroid cancer is an uncommon entity, occurring with an estimated incidence of 4-5 cases/year/million people. RAI refractoriness is more frequent in older patients, in those with large metastases, in poorly differentiated thyroid cancer, and in those tumors with high 18-fluordeoxyglucose uptake on PET/CT. These patients have a 10-year survival rate of less than 10%. In recent years, new therapeutic agents with molecular targets have become available, with multikinase inhibitors (MKIs) being the most investigated drugs. Two of these compounds, sorafenib and lenvatinib, have shown significant objective response rates and have significantly improved the progression-free survival in the two largest published prospective trials on MKI use. However, no overall survival benefit has been achieved yet. This is probably related to the crossover that occurs in most patients who progress on placebo treatment to the open treatment of these studies. In consequence, the challenge is to correctly identify which patients will benefit from these treatments. It is also crucial to understand the appropriate timing to initiate MKI treatment and when to stop it. The purpose of this article is to define RAI refractoriness, to summarize which therapies are available for this condition, and to review how to select patients who are suitable for them.

Radioiodine-induced oxidative stress in patients with differentiated thyroid carcinoma and effect of supplementation with vitamins C and E and selenium (antioxidants)

ABSTRACT Objective The objective of this study, in addition to confirming that therapy with 131I causes oxidative stress, was to evaluate the effect of supplementation with vitamins C and E and selenium on this phenomenon by measuring plasma 8-epi-PGF2a, a marker of lipid peroxidation. Subjects and methods Forty patients with thyroid cancer submitted to thyroidectomy, who received 3.7 GBq 131I after levothyroxine withdrawal, were selected; 20 patients did not receive (control group) and 20 patients received (intervention group) daily supplementation consisting of 2000 mg vitamin C, 1000 mg vitamin E and 400 µg selenium for 21 days before 131I. Plasma 8-epi-PGF2a was measured immediately before and 2 and 7 days after 131I. Results A significant increase in plasma 8-epi-PGF2a after 131I was observed in the two groups. The concentrations of 8-epi-PGF2α were significantly higher in the control group before and 2 and 7 days after 131I. The percentage of patients with elevated 8-epi-PGF2α was also significantly higher in the control group before and after 131I. Furthermore, the increase (percent) in 8-epi-PGF2α was significantly greater in the control group (average of 112.3% versus 56.3%). Only two patients (10%) reported side effects during supplementation. Conclusions Ablation with 131I causes oxidative stress which can be minimized by the use of antioxidants.

Is radioactive iodine- 131 treatment related to the occurrence of non-synchronous second primary malignancy in patients with differentiated thyroid cancer?

Objective Much controversy relates to the risk of non-synchronous second primary malignancies (NSSPM) after radioactive iodine treatment (RAI-131) in differentiated thyroid cancer (DTC) patients. This study evaluated the relationship between RAI-131 and NSSPM in DTC survivors with long-term follow-up. Materials and methods Retrospective analysis of 413 DTC cases was performed; 252 received RAI-131 and 161 were treated with thyroidectomy alone. Exclusion criteria were: prior or synchronous non-thyroidal malignancies (within the first year), familial syndromes associated to multiple neoplasms, ionizing radiation exposure or second tumors with unknown histopathology. Results During a mean follow-up of 11.0 ± 7.5 years, 17 (4.1%) patients developed solid NSSPM. Patients with NSSPM were older than those without (p = 0.02). RAI-131 and I-131 cumulative activity were similar in patients with and without NSSPM (p = 0.18 and p = 0.78, respectively). Incidence of NSSPM was 5.2% in patients with RAI-131 treatment and 2.5% in those without RAI-131 (p = 0.18). Using multivariate analysis, RAI-131 was not significantly associated with NSSPM occurrence (p = 0.35); age was the only independent predictor (p = 0.04). Under log rank statistical analysis, after 10 years of follow-up, it was observed a tendency of lower NSSPM-free survival among patients that received RAI-131 treatment (0.96 vs . 0.87; p = 0.06), what was not affected by age at DTC diagnosis. Conclusion In our cohort of DTC survivors, with a long-term follow-up period, RAI-131 treatment and I-131 cumulative dose were not significantly associated with NSSPM occurrence. A tendency of premature NSSPM occurrence among patients treated with RAI-131 was observed, suggesting an anticipating oncogenic effect by interaction with other risk factors.

Obstrução de vias lacrimais em pacientes submetidos à radioiodoterapia / Lacrimal system obstruction in patients submitted to radioiodine therapy

A radioiodoterapia (RIT) constitui tratamento consagrado para carcinomas diferenciados de tireoide, sendo amplamente utilizada em todo o mundo, tendo-se em vista a incidência crescente desse tipo de neoplasia maligna. Embora efeitos adversos graves sejam infrequentes, são descritas complicações como xerostomia, sialoadenite e disfagia. O acometimento de olhos e anexos é pouco discutido, sendo relatadas xeroftalmia, ceratoconjuntivite e obstrução de vias lacrimais (OVL), notadamente após altas doses cumulativas do radiofármaco. A incidência de OVL e a eventual relação com outros sintomas oculares ou extraoculares não são bem estabelecidas. Neste estudo, buscamos determinar a frequência de obstrução de vias lacrimais (OVL) em pacientes submetidos à RIT, a existência de fatores preditores de OVL e a relação entre alterações de superfície ocular, xerostomia e alterações da mucosa nasal. Métodos: Foram avaliados pacientes com diagnóstico de carcinoma diferenciado de tireoide submetidos à RIT (Grupo 1) e não submetidos à RIT (Grupo 2) no período pré-operatório, pós-operatório e no 2º, 4º, 6º e 12º mês pós-cirurgia ou pós-RIT. Os pacientes foram submetidos a avaliações da superfície ocular e do filme lacrimal, sondagem e irrigação de vias lacrimais, quantificação da produção salivar e endoscopia nasal. As avaliações subjetivas de sintomas oculares, nasais e de xerostomia foram realizadas, respectivamente, por meio dos questionários OSDI, NOSE e Xerostomia Inventory. Resultados: O Grupo 1 (n=44, 88 olhos) apresentou 3 pacientes (04 olhos) com OVL, o que corresponde à incidência de 4,55% (4 eventos em 88 olhos) ou 6,8% (3 casos em 44 pacientes). O Grupo 2 (n=43, 86 olhos) não apresentou nenhum caso de OVL, fato que impossibilitou o cálculo da razão de chances (odds ratio). A avaliação objetiva da superfície ocular não apresentou diferenças significantes entre os grupos. Por outro lado, a avaliação endoscópica nasal revelou maior palidez de mucosa no Grupo...

Radioiodine therapy (RIT) is an established treatment for differentiated thyroid carcinomas and is widely used throughout the world, given the increasing incidence of this malignancy. Although serious adverse effects are infrequent, complications such as dry mouth, sialadenitis and dysphagia have been described. The involvement of the eyes and adnexa is not commonly discussed, despite dry eye, keratoconjunctivitis and lacrimal system obstruction (LSO) being reported, especially after high cumulative doses of this radiopharmaceutical. The incidence of LSO and any relationship with other ocular or extraocular symptoms are not well established. The study objectives were to determine the frequency of lacrimal system obstruction (LSO) in patients undergoing RIT, the existence of predictive factors of LSO and the relationship between ocular surface changes, xerostomia and changes in nasal mucosa. Patients and Methods: Patients with differentiated thyroid carcinoma undergoing (Group 1) and not undergoing (Group 2) RIT were evaluated in the preoperative and postoperative periods and 2, 4, 6 and 12 months post-surgery or post-RIT. Patients underwent ocular surface and tear film evaluation, lacrimal system probing and irrigation, quantification of salivary production and nasal endoscopy. The subjective evaluations of ocular symptoms, nasal symptons and xerostomia were done, respectively, through the OSDI, NOSE and Xerostomia Inventory questionnaires. Results: Group 1 (n = 44, 88 Eyes) had 3 patients (4 eyes) with LSO, corresponding to an incidence of 4.55% (4 events in 88 eyes) or 6.8% (3 cases in 44 patients). Group 2 (n = 43.86 eyes) did not present any cases of LSO, that makes it impossible to calculate the odds ratio. Objective assessment of ocular surface did not show significant differences between groups. On the other hand, nasal endoscopy revealed larger mucosa pallor in Group 1 in the 2nd month (OR: 3.61; 95% CI: 1.44 to 9.09; p < 0.01),...

Gerenciamento do cuidado de enfermagem na radioiodoterapia para câncer diferenciado de tireoide: (re)configuração de estratégias de ação

O estudo teve como foco a elaboração de estratégias de ação para a gerência docuidado de enfermagem na Radioiodoterapia a partir da perspectiva de clientes portadores decâncer diferenciado de tireoide. Os objetivos foram: Conhecer a percepção dos clientes acercadas ações desenvolvidas pela equipe de enfermagem na Radioiodoterapia; Elaborar com osclientes estratégias que atendam suas necessidades de ajuda; e discutir desafios epossibilidades para implementação das estratégias elaboradas visando a (re) configuração dogerenciamento do cuidado de enfermagem na Radioiodoterapia. Para nortear o estudo foiutilizado como referencial teórico-filosófico o pensamento complexo formulado pelosociólogo Edgar Morin, em especial a noção de ecologia da ação, além de princípios acerca daRelação de Ajuda na Totalidade da Prática da Enfermagem propostos pela EnfermeiraProfessora Doutora Vilma de Carvalho. Trata-se de uma Pesquisa Convergente Assistencial,desenvolvida num processo interativo e participativo em uma Unidade de Radioiodoterapia daseção de Medicina Nuclear de Instituto Centro de Referência para Tratamento de AltaComplexidade em Oncologia no município do Rio de Janeiro, Brasil. Para a produção dosdados adotou-se a noção de pequeno grupo considerado como um sistema vivo formado porindivíduos-sujeitos humanos, possuidores de linguagem, cultura e consciência no processo deprodução e organização social...

The study focused on the development of action strategies for the management ofnursing care in Radioiodine therapy from the perspective of clients with differentiated thyroidcancer. The objectives were: To understand the customer perception about the actionsdeveloped by the nursing team in Radioiodine therapy; To elaborate with customers strategiesthat meet their need for help; and to discuss challenges and opportunities for implementationof developed strategies to (re) configurate the nursing care management in Radioiodinetherapy. To guide the study was used as a theoretical-philosophical framework complexthinking formulated by the sociologist Edgar Morin, especially the notion of ecology ofaction, and principles about the Helping Relationship in Totality of Nursing Practice proposedby the Nurse Professor Doctor Vilma de Carvalho. This is a Convergent Care Research,developed on an interactive and participatory process in a unit of Radioiodine therapytreatment of the Nuclear Medicine section of the Institute of Reference for High Complexityin Oncology in the city of Rio de Janeiro, Brazil. For compiling the data we adopted theconcept of small group regarded as a living system composed of human-subject individuals,language holders, culture and consciousness in the process of production and socialorganization...

El estudio se enfocó en la elaboración de estrategias de acción para la gerencia delcuidado de enfermería en la Radioyodoterapia, a partir de la perspectiva de clientes portadoresde cáncer diferenciado de tiroides. Los objetivos fueron: conocer la percepción de los clientesacerca de las acciones desarrolladas por el equipo de enfermería en la Radioyodoterapia;elaborar con los clientes estrategias que atiendan sus necesidades de ayuda y, por último,discutir desafíos y posibilidades para implementación de las estrategias elaboradas,contemplando la (re) configuración del gerenciamiento del cuidado de enfermería en laRadioyodoterapia. Para orientar el estudio fue utilizado como referencial teórico-filosófico elpensamiento complejo formulado por el sociólogo Edgar Morin, en especial la noción deecología de la acción, además de principios acerca de la Relación de Ayuda en la Totalidad dela Práctica de la Enfermería propuestos por la Enfermera Profesora Doctora Vilma deCarvalho. Se trata de una Investigación Convergente Asistencial, desarrollada en un procesointeractivo y participativo en una Unidad de Radioyodoterapia de la sección de MedicinaNuclear de Instituto Centro de Referencia para Tratamiento de Alta Complejidad enOncología en el municipio de Río de Janeiro, Brasil. Para la producción de los datos se adoptóla noción de pequeño grupo, considerado como un sistema vivo formado por individuossujetoshumanos, poseedores de lenguaje, cultura y conciencia en el proceso de producción yorganización social...

Comparación de la eficacia de dos dosis de radioyodo para la ablación del remanente tiroideo en el cáncer diferenciado de tiroides con metástasis ganglionar locorregional / Comparison of efficacy of two doses of radioiodine for thyroid remnant ablation in differentiated thyroid cancer with locoregional lymph node metastasis

Determinar la eficacia de dos dosis de radioyodo para la ablación del remanente tiroideo en pacientes con cáncer diferenciado de tiroides (CDT) que presentan metástasis ganglionar locorregional. Metodología. El estudio fue de diseño experimental, tipo muestreo aleatorio simple. La muestra estuvo conformada por 40 pacientes con el diagnóstico de CDT, con evidencia de metástasis ganglionar locorregional. Los pacientes fueron inscritos y aleatorizados en dos grupos, el grupo experimental (3 700 MBq I-131) y el grupo control (5 550 MBq I-131). En relación al presente estudio, la medición de la eficacia fue un rastreo corporal total con I-131 negativo, porcentaje de captación a las 24 horas menor de 0,5 % y tiroglobulina sérica menor de 2 ng/mL. Resultados. Cuando se definió el éxito la ablación, solo con el rastreo corporal con I-131 negativo no se encontraron diferencias entre el grupo de estudio (100 %, P = 0,31) y el grupo control (94,4 %, para un P > 0,05). Cuando se consideró el rastreo corporal total con I-131 más el valor de corte de la tiroglobulina sérica < 2 ng/mL, si hubo diferencia significativa en la tasa de éxito de la ablación entre el grupo de estudio y el grupo control (P = 0,006). Conclusión. La eficacia de la ablación del remanente tiroideo usando dosis de 3 700 MBq es similar a la de 5 550 MBq de radioyodo en pacientes con cáncer diferenciado de tiroides que presentan metástasis ganglionar locorregional...

To determine the efficacy of two doses of radioiodine for thyroid remnant ablation in patients with differentiated thyroid cancer presenting locoregional lymph node metastases. Methodology. The experimental study design was simple random sampling type. The sample consisted of 40 patients with a diagnosis of differentiated thyroid cancer with evidence of locoregional lymph node metastases. Patients were enrolled and randomized into two groups, the experimental group (3 700 MBq I-131) and control group (5 550 MBq I-131). In relation to our study measuring the effectiveness was a total body scan with I-131 negative percentage uptake at 24 hours < 0,5 % and serum thyroglobulin < 2 ng/mL. Results. When success was defined ablation, only with the body scintigraphy with I-131 negative, no differences between the study group (100 %, P = 0,31) and the control group (94.4 %, for a P > 0,05). When the whole body scan was considered to I-131 over the cutoff value of serum thyroglobulin < 2 ng/mL, if there was significant difference in the success rate of ablation between the study group and the control group (P = 0,006). Conclusion. The effectiveness of remaining thyroid ablation using 3 700 MBq dose is similar to 5 550 MBq of radioactive iodine in patients with differentiated thyroid cancer lymph node metastasis presenting locoregional...

Incidencia de patología salival sintomática aleada en pacientes tratados con yodo radioactivo por cáncer diferenciado de tiroides / Incidence of sympthomatic salivary disease in patients with differentiated thyroid cancer treated with radioactive iodine

Background: The radioactive iodine therapy for differentiated thyroid cancer can produce severe and frequent salivary symptoms, during the treatment or later. Aim: To analyze the incidence, severity and charactheristics of the salivary signs and symptoms in these patients. Patients and Method: Retrospective and descriptive analisis of 106 patients with confirmed diagnosis of differentiated thyroid cancer, treated with surgery and radioactive iodine, that completed a telephonic survey for the evaluation of salivary symptoms. Results: 26 (24.52 percent) patients presented with salivary symptoms or signs after the radioactive iodine therapy (mean 5 months). The average doses of I 131 was 128,5 mCi. Xerostomy, pain, xeroftalmy, inflammation, sialoadenitis and dysgeusia, were the most frequent clinical symptoms. Conclusions: After radioactive iodine therapy the salivary symptoms and signs incidence is high. We conclude that the indication for this treatment must be selective, but in accordance with the oncological risk of each patient.

Introducción: El tratamiento con yodo radioactivo en el tratamiento del cáncer diferenciado de tiroides puede originar síntomas alejados de origen salival. Éstos pueden llegar a ser intensos y frecuentes. Objetivo: Conocer la incidencia, características e intensidad de dichos síntomas. Material y Método: Revisión retrospectiva y análisis descriptivo de 106 pacientes con diagnóstico definitivo y anatomopatológico de cáncer diferenciado de tiroides, tratados con yodo radioactivo, que contestaron una encuesta telefónica especialmente diseñada para evaluación de patología salival. Resultados: Veintiséis (24,52 por ciento) pacientes presentaron y consultaron por síntomas y/o signos alejados (promedio 5 meses) de la terapia ablativa, de origen salival. La dosis promedio fue de 128,5 mCi de I 131. Los síntomas más frecuentes fueron xerostomía, dolor, xeroftalmia, inflamación, sialoadenitis y alteración del gusto. Discusión: La incidencia de signos y síntomas salivales alejados en pacientes tratados con I 131 es alta y justificaría a nuestro juicio su indicación selectiva, de acuerdo a los riesgos de recurrencia tumoral de cada paciente.