Impacto do TNM-8 e do rastreio corporal total pós-dose de radioiodo no manejo de pacientes com carcinoma diferenciado de tireoide

O carcinoma diferenciado de tireoide (CDT) inclui os subtipos papilar (CPT) e folicular (CFT) e é responsável pela maioria das neoplasias malignas tireoidianas. Aproximadamente 85% dos CDT são CPT, atingindo principalmente mulheres, nas faixas etárias entre 40-59 anos. O CDT é geralmente um tumor indolente, usualmente diagnosticado em estágio I e com excelente prognóstico. O manejo do CDT tem mudado nos últimos anos, em janeiro de 2018 foi incorporado à prática clínica a oitava edição do sistema de estadiamento do American Joint Committee on Cancer - Tumor, node, metastasis (AJCC/TNM-8) que traz duas principais mudanças com relação à antiga classificação (sétima edição do tumor, linfonodos e metástases - TNM-7): o corte de idade ao diagnóstico passa dos 45 anos para os 55 anos e os critérios de classificação de T3 e T4. Essa atualização objetiva melhorar a predição de doença e sobrevida dos pacientes, separando os pacientes em risco de persistência e/ou recorrência de doença em estágios mais avançados do TNM. Com objetivo de avaliar o impacto da mudança do TNM-7 para o TNM-8 em uma população brasileira de CDT fizemos uma análise comparativa das classificações e dos desfechos relacionados à doença que se encontra no artigo intitulado "Impact of the update TNM staging criteria on prediction of persistent disease in a differentiated thyroid carcinoma cohort". Comparamos as classificações do TNM-7 e do TNM-8 em uma coorte de pacientes brasileiros, do sul do país, com carcinoma diferenciado de tireoide. Foram incluídos no trabalho 419 pacientes, quando comparadas às distribuições dos pacientes dentro das classificações notamos que as diferenças entre o TNM-7 e o TNM-8 são estatisticamente significativas e levaram os pacientes, com o TNM-8, a 37% de reclassificações para estágios de menor risco de mortalidade relacionada à doença. Mais da metade (56%) das reclassificações foi atribuída a mudança do corte de idade ao diagnóstico para 55 anos. Com a classificação TNM-8 os pacientes de menor risco foram alocados em estágios mais baixos, sugerindo que o novo sistema é melhor em distribuir os pacientes de acordo com suas categorias de risco. Durante o seguimento mediano de 4,4 anos, os achados referentes à resposta ao tratamento são coerentes com essa interpretação. Evidenciando assim que o TNM-8 é melhor em estratificar os pacientes com CDT, alocando os pacientes dentro das categorias de risco correspondentes, o que leva ao tratamento mais adequado, menos agressivo, sem expô-los a tratamentos desnecessários e excessivos. Corroborando com condutas mais conservadoras no manejo dos pacientes com CDT, o consenso Americano no Manejo de Pacientes Adultos com CDT publicado em dezembro de 2015 deixa de indicar tratamento com radioiodo (RIT) aos pacientes de baixo risco. Para todos os outros pacientes que recebem tratamento RIT, a realização do exame de rastreamento corporal total (RCT) após a dose de iodo é mandatória. Diante da incerteza dos benefícios da realização do RCT e dos potenciais risco do exame, faziase necessária uma releitura da sua utilidade para os pacientes com CDT que receberam RAI. No artigo intitulado "Reappraising the Diagnostic Accuracy of Post-Treatment Whole-Body Scan for Differentiated Thyroid Carcinoma" usamos a mesma coorte de pacientes para avaliar a acurácia diagnóstica do RCT, onde foram avaliados 268 pacientes após sua primeira dose de RAI. Foram revisadas todas as imagens de RCT e os pacientes com diagnóstico documentado de metástases à distância ou captação à distância no RCT foram revisados independentemente por dois especialistas em carcinoma de tireoide. Vinte e nove pacientes possuíam metástases à distância, destes 20 apresentaram captação à distância no RCT (verdadeiro-positivos) e 9 não apresentaram captação à distância (falso-negativos). Vinte e oito pacientes apresentaram captação à distância ao RCT, 9 deles falso-positivos. Estratificando o RCT de acordo com a classificação de risco da American Thyroid Association (ATA) notamos que para pacientes de risco baixo e intermediario o exame apresenta baixa sensibilidade no diagnóstico de metástáse à distância. Quando excluídos os pacientes de baixo risco, que atualmente não tem indicação de tratamento com RIT, a performance do exame mostrou-se ainda pior. No entanto, para o grupo de alto risco da ATA, o RCT foi melhor em predizer presença de metástase à distância, com boa sensibilidade, especificidade e valor preditivo positivo (82%, 100% e 100%, respectivamente), com significância estatística. Em resumo, em pacientes com baixa probabilidade pré-teste o exame deve ser reconsiderado, já para os pacientes de alto risco da ATA nos quais a probabilidade pré-teste é alta, o RCT se mostra uma ferramenta útil para diagnóstico de metástases à distância.Differentiated thyroid carcinoma (DTC) includes the papillary (PTC) and follicular (FTC) subtypes and is responsible for most thyroid malignancies. Approximately 85% of DTC are PTC, afflicting mainly women aged 40-59 years. DTC is usually an indolent tumor, diagnosed in stage I and with excellent prognosis. The management of DTC has changed in recent years. Released in January 2018, the eighth edition of the American Joint Committee on Cancer - Tumor, node, metastasis (AJCC/TNM-8) staging system included two main changes from the previous classification (the seventh edition, TNM-7): the age range at diagnosis of 45 years to 55 years old and the classification criteria for T3 and T4. These updates aim to improve disease prediction and survival of patients, separating patients at risk of persistence and/or recurrence of disease in more advanced stages of TNM. In order to evaluate the impact of the change from TNM-7 to TNM-8 in a Brazilian population of DTC, we performed a comparative analysis of the classifications and outcomes related to the disease found in the article titled Impact of the update TNM staging criteria on prediction of persistent disease in a differentiated thyroid carcinoma cohort. We compared the TNM-7 and TNM-8 classifications in a cohort of 419 Brazilian DTC patients from the south of the country. The differences in the distributions of patients between TNM-7 and TNM-8 were statistically significant and led to 37% of patients classified under TNM-8 being moved to stages with a lower risk of mortality related to the disease. More than half (56%) of the reclassifications were attributed to changing the age cut-off to 55 years. With the TNM-8 classification, the lowest risk patients were placed in lower stages, suggesting that the new system is better at distributing patients according to their risk categories. During the median follow-up of 4.4 years, findings regarding treatment response were consistent with this interpretation and showed that TNM-8 is better at stratifying patients with DTC, which leads to more appropriate and less aggressive treatment, thereby not exposing them to unnecessary or excessive treatments. Corroborating the more conservative management of DTC patients, the U.S. consensus given in the Management of Adult Patients with DTC published in December 2018 no longer indicates treatment with radioiodine (RAI) for low-risk patients. For all other patients receiving RAI treatment, a whole-body scan (WBS) following the iodine dose is mandatory. Given the uncertainty of the benefits of WBS and the potential risk of the test, a rereading of its usefulness was necessary for patients with DTC who received RAI. In the article entitled Reappraising the Diagnostic Accuracy of Post- Treatment Whole-Body Scan for Differentiated Thyroid Carcinoma, we used the same cohort of patients to assess the diagnostic accuracy of the WBS, where 268 patients were evaluated after their first dose of RAI. All WBS images were reviewed and the patients with documented diagnosis of distant metastases or remote uptake in the WBS were independently reviewed by two specialists in thyroid carcinoma. Twenty-nine patients had distant metastases, of which 20 had remote uptake in the WBS (true-positive) and 9 had no distant uptake (false-negative). Twenty-eight patients presented remote uptake in the WBS, nine of them false-positive. Stratifying the WBS according to the American Thyroid Association (ATA) risk classification, we note that for low-risk and intermediate-risk patients, the test presents low sensitivity in the diagnosis of distant metastases. When low-risk patients, who currently do not have an indication for RAI treatment, were excluded, the performance of the exam was even worse. However, for the high-risk ATA group, WBS was better at predicting presence of distant metastases with statistically significant sensitivity, specificity, and positive predictive value (82%, 100%, and 100%, respectively). In summary, for patients with a low pre-test probability the exam should be reconsidered, whereas for high-risk patients in whom the pre-test probability is high, the WBS is a useful tool for the diagnosis of distant metastases

Impact of the updated TNM staging criteria on prediction of persistent disease in a differentiated thyroid carcinoma cohort

Objective: The 8th TNM system edition (TNM-8) released in 2018 presents significant changes when compared to the 7th edition (TNM-7). The aim of this study was to assess the impact of changing the TNM staging criteria on the outcomes in a Brazilian cohort of differentiated thyroid carcinoma (DTC). Subjects and methods: DTC patients, attending a tertiary, University-based hospital, were classified by TNM-7 and TNM-8. Prediction of disease outcomes status of the two systems was compared in a retrospective cohort study design. Results: Four hundred and nineteen DTC patients were evaluated, comprised by 82% (345/419) women, with mean age at diagnosis of 46.4 ± 15.6 years, 89% (372/419) papillary thyroid carcinoma, with a median tumor size of 2.3 cm (P25-P75, 1.3-3.5). One hundred and sixty patients (38%) had lymph node metastases and 47 (11%) distant metastases at diagnosis. Using the TNM-7 criteria, 236 (56%) patients were classified as Stage I, 50 (12%) as Stage II, 75 (18%) as Stage III and 58 (14%) as Stage IV. When evaluated by the TNM-8, 339 (81%) patients were classified as Stage I, 64 (15%) as Stage II, 2 (0.5%) as Stage III and 14(3%) as Stage IV. After a median followup of 4.4years (P25-P75 2.6-6.6), the rate of incomplete biochemical and/or structural response was 54% vs. 92% (P = 0.004) and incomplete structural response was 42% vs. 86% (P = 0.009) for patients classified as stage IV by TNM-7 vs TNM-8, respectively. Only 4 (1%) disease-related deaths were recorded. Conclusions: In our cohort, 37% of DTC patients were down staged with the application of TNM-8 (vs. TNM-7). Additionally, TNM-8 seems to better stratify the risk of structural incomplete response at follow-up

Neoadjuvant multikinase inhibitor in patients with locally advanced unresectable thyroid carcinoma

Background: Papillary thyroid carcinoma (PTC) is the most common and less aggressive thyroid cancer, but some patients may display locally advanced disease. Therapeutic options are limited in these cases, particularly for those patients with unresectable tumors. Neoadjuvant therapy is not part of the recommended work up. Methods: Report a case of an unresectable grossly locally invasive PTC successfully managed with neoadjuvant therapy and provide a systematic review (SR) using the terms “Neoadjuvant therapy” AND “Thyroid carcinoma.” Results: A 32-year-old man with a 7.8 cm (in the largest dimension) PTC was referred to total thyroidectomy, but tumor resection was not feasible due to extensive local invasion (trachea, esophagus, and adjacent structures). Sorafenib, a multikinase inhibitor (MKI), was initiated; a 70% tumor reduction was observed after 6 months, allowing new surgical intervention and complete resection. Radioactive iodine (RAI) was administered as adjuvant therapy, and whole body scan (WBS) shows uptake on thyroid bed. One-year post-surgery the patient is asymptomatic with a status of disease defined as an incomplete biochemical response. The SR retrieved 123 studies on neoadjuvant therapy use in thyroid carcinoma; of them, 6 were extracted: 4 case reports and 2 observational studies. MKIs were used as neoadjuvant therapy in three clinical cases with 70–84% of tumor reduction allowing surgery. Conclusion: Our findings, along with other reports, suggest that MKIs is an effective neoadjuvant therapy and should be considered as a therapeutic strategy for unresectable grossly locally invasive thyroid carcinomas

Global disparities in surgeons’ workloads, academic engagement and rest periods: the on-calL shIft fOr geNEral SurgeonS (LIONESS) study

: The workload of general surgeons is multifaceted, encompassing not only surgical procedures but also a myriad of other responsibilities. From April to May 2023, we conducted a CHERRIES-compliant internet-based survey analyzing clinical practice, academic engagement, and post-on-call rest. The questionnaire featured six sections with 35 questions. Statistical analysis used Chi-square tests, ANOVA, and logistic regression (SPSS® v. 28). The survey received a total of 1.046 responses (65.4%). Over 78.0% of responders came from Europe, 65.1% came from a general surgery unit; 92.8% of European and 87.5% of North American respondents were involved in research, compared to 71.7% in Africa. Europe led in publishing research studies (6.6 ± 8.6 yearly). Teaching involvement was high in North America (100%) and Africa (91.7%). Surgeons reported an average of 6.7 ± 4.9 on-call shifts per month, with European and North American surgeons experiencing 6.5 ± 4.9 and 7.8 ± 4.1 on-calls monthly, respectively. African surgeons had the highest on-call frequency (8.7 ± 6.1). Post-on-call, only 35.1% of respondents received a day off. Europeans were most likely (40%) to have a day off, while African surgeons were least likely (6.7%). On the adjusted multivariable analysis HDI (Human Development Index) (aOR 1.993) hospital capacity > 400 beds (aOR 2.423), working in a specialty surgery unit (aOR 2.087), and making the on-call in-house (aOR 5.446), significantly predicted the likelihood of having a day off after an on-call shift. Our study revealed critical insights into the disparities in workload, access to research, and professional opportunities for surgeons across different continents, underscored by the HDI

Impacto do TNM-8 e do rastreio corporal total pós-dose de radioiodo no manejo de pacientes com carcinoma diferenciado de tireoide

O carcinoma diferenciado de tireoide (CDT) inclui os subtipos papilar (CPT) e folicular (CFT) e é responsável pela maioria das neoplasias malignas tireoidianas. Aproximadamente 85% dos CDT são CPT, atingindo principalmente mulheres, nas faixas etárias entre 40-59 anos. O CDT é geralmente um tumor indolente, usualmente diagnosticado em estágio I e com excelente prognóstico. O manejo do CDT tem mudado nos últimos anos, em janeiro de 2018 foi incorporado à prática clínica a oitava edição do sistema de estadiamento do American Joint Committee on Cancer - Tumor, node, metastasis (AJCC/TNM-8) que traz duas principais mudanças com relação à antiga classificação (sétima edição do tumor, linfonodos e metástases - TNM-7): o corte de idade ao diagnóstico passa dos 45 anos para os 55 anos e os critérios de classificação de T3 e T4. Essa atualização objetiva melhorar a predição de doença e sobrevida dos pacientes, separando os pacientes em risco de persistência e/ou recorrência de doença em estágios mais avançados do TNM. Com objetivo de avaliar o impacto da mudança do TNM-7 para o TNM-8 em uma população brasileira de CDT fizemos uma análise comparativa das classificações e dos desfechos relacionados à doença que se encontra no artigo intitulado "Impact of the update TNM staging criteria on prediction of persistent disease in a differentiated thyroid carcinoma cohort". Comparamos as classificações do TNM-7 e do TNM-8 em uma coorte de pacientes brasileiros, do sul do país, com carcinoma diferenciado de tireoide. Foram incluídos no trabalho 419 pacientes, quando comparadas às distribuições dos pacientes dentro das classificações notamos que as diferenças entre o TNM-7 e o TNM-8 são estatisticamente significativas e levaram os pacientes, com o TNM-8, a 37% de reclassificações para estágios de menor risco de mortalidade relacionada à doença. Mais da metade (56%) das reclassificações foi atribuída a mudança do corte de idade ao diagnóstico para 55 anos. Com a classificação TNM-8 os pacientes de menor risco foram alocados em estágios mais baixos, sugerindo que o novo sistema é melhor em distribuir os pacientes de acordo com suas categorias de risco. Durante o seguimento mediano de 4,4 anos, os achados referentes à resposta ao tratamento são coerentes com essa interpretação. Evidenciando assim que o TNM-8 é melhor em estratificar os pacientes com CDT, alocando os pacientes dentro das categorias de risco correspondentes, o que leva ao tratamento mais adequado, menos agressivo, sem expô-los a tratamentos desnecessários e excessivos. Corroborando com condutas mais conservadoras no manejo dos pacientes com CDT, o consenso Americano no Manejo de Pacientes Adultos com CDT publicado em dezembro de 2015 deixa de indicar tratamento com radioiodo (RIT) aos pacientes de baixo risco. Para todos os outros pacientes que recebem tratamento RIT, a realização do exame de rastreamento corporal total (RCT) após a dose de iodo é mandatória. Diante da incerteza dos benefícios da realização do RCT e dos potenciais risco do exame, faziase necessária uma releitura da sua utilidade para os pacientes com CDT que receberam RAI. No artigo intitulado "Reappraising the Diagnostic Accuracy of Post-Treatment Whole-Body Scan for Differentiated Thyroid Carcinoma" usamos a mesma coorte de pacientes para avaliar a acurácia diagnóstica do RCT, onde foram avaliados 268 pacientes após sua primeira dose de RAI. Foram revisadas todas as imagens de RCT e os pacientes com diagnóstico documentado de metástases à distância ou captação à distância no RCT foram revisados independentemente por dois especialistas em carcinoma de tireoide. Vinte e nove pacientes possuíam metástases à distância, destes 20 apresentaram captação à distância no RCT (verdadeiro-positivos) e 9 não apresentaram captação à distância (falso-negativos). Vinte e oito pacientes apresentaram captação à distância ao RCT, 9 deles falso-positivos. Estratificando o RCT de acordo com a classificação de risco da American Thyroid Association (ATA) notamos que para pacientes de risco baixo e intermediario o exame apresenta baixa sensibilidade no diagnóstico de metástáse à distância. Quando excluídos os pacientes de baixo risco, que atualmente não tem indicação de tratamento com RIT, a performance do exame mostrou-se ainda pior. No entanto, para o grupo de alto risco da ATA, o RCT foi melhor em predizer presença de metástase à distância, com boa sensibilidade, especificidade e valor preditivo positivo (82%, 100% e 100%, respectivamente), com significância estatística. Em resumo, em pacientes com baixa probabilidade pré-teste o exame deve ser reconsiderado, já para os pacientes de alto risco da ATA nos quais a probabilidade pré-teste é alta, o RCT se mostra uma ferramenta útil para diagnóstico de metástases à distância.Differentiated thyroid carcinoma (DTC) includes the papillary (PTC) and follicular (FTC) subtypes and is responsible for most thyroid malignancies. Approximately 85% of DTC are PTC, afflicting mainly women aged 40-59 years. DTC is usually an indolent tumor, diagnosed in stage I and with excellent prognosis. The management of DTC has changed in recent years. Released in January 2018, the eighth edition of the American Joint Committee on Cancer - Tumor, node, metastasis (AJCC/TNM-8) staging system included two main changes from the previous classification (the seventh edition, TNM-7): the age range at diagnosis of 45 years to 55 years old and the classification criteria for T3 and T4. These updates aim to improve disease prediction and survival of patients, separating patients at risk of persistence and/or recurrence of disease in more advanced stages of TNM. In order to evaluate the impact of the change from TNM-7 to TNM-8 in a Brazilian population of DTC, we performed a comparative analysis of the classifications and outcomes related to the disease found in the article titled Impact of the update TNM staging criteria on prediction of persistent disease in a differentiated thyroid carcinoma cohort. We compared the TNM-7 and TNM-8 classifications in a cohort of 419 Brazilian DTC patients from the south of the country. The differences in the distributions of patients between TNM-7 and TNM-8 were statistically significant and led to 37% of patients classified under TNM-8 being moved to stages with a lower risk of mortality related to the disease. More than half (56%) of the reclassifications were attributed to changing the age cut-off to 55 years. With the TNM-8 classification, the lowest risk patients were placed in lower stages, suggesting that the new system is better at distributing patients according to their risk categories. During the median follow-up of 4.4 years, findings regarding treatment response were consistent with this interpretation and showed that TNM-8 is better at stratifying patients with DTC, which leads to more appropriate and less aggressive treatment, thereby not exposing them to unnecessary or excessive treatments. Corroborating the more conservative management of DTC patients, the U.S. consensus given in the Management of Adult Patients with DTC published in December 2018 no longer indicates treatment with radioiodine (RAI) for low-risk patients. For all other patients receiving RAI treatment, a whole-body scan (WBS) following the iodine dose is mandatory. Given the uncertainty of the benefits of WBS and the potential risk of the test, a rereading of its usefulness was necessary for patients with DTC who received RAI. In the article entitled Reappraising the Diagnostic Accuracy of Post- Treatment Whole-Body Scan for Differentiated Thyroid Carcinoma, we used the same cohort of patients to assess the diagnostic accuracy of the WBS, where 268 patients were evaluated after their first dose of RAI. All WBS images were reviewed and the patients with documented diagnosis of distant metastases or remote uptake in the WBS were independently reviewed by two specialists in thyroid carcinoma. Twenty-nine patients had distant metastases, of which 20 had remote uptake in the WBS (true-positive) and 9 had no distant uptake (false-negative). Twenty-eight patients presented remote uptake in the WBS, nine of them false-positive. Stratifying the WBS according to the American Thyroid Association (ATA) risk classification, we note that for low-risk and intermediate-risk patients, the test presents low sensitivity in the diagnosis of distant metastases. When low-risk patients, who currently do not have an indication for RAI treatment, were excluded, the performance of the exam was even worse. However, for the high-risk ATA group, WBS was better at predicting presence of distant metastases with statistically significant sensitivity, specificity, and positive predictive value (82%, 100%, and 100%, respectively). In summary, for patients with a low pre-test probability the exam should be reconsidered, whereas for high-risk patients in whom the pre-test probability is high, the WBS is a useful tool for the diagnosis of distant metastases