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.

Riesgo dinámico en cáncer diferenciado de tiroides: comparación entre pacientes ablacionados con aquellos no ablacionados de bajo riesgo y riesgo intermedio de recurrencia

RESUMEN El enfoque actual de los pacientes con carcinoma diferenciado de tiroides (CDT) es individualizado de acuerdo al riesgo de recurrencia (RR) de la enfermedad. La clasificación estática del RR inicial podría mejorarse al aplicar el denominado riesgo dinámico, que resulta de adicionar al RR, los hallazgos que surgen durante el seguimiento. Los objetivos de este trabajo fueron comparar pacientes ablacionados de bajo RR y riesgo intermedio estático que recibieron ablación inmediatamente luego de la cirugía vs. los no ablacionados de bajo riesgo dinámico. Secundariamente, comparar la población de pacientes ablacionados de bajo riesgo estático vs. los no ablacionados de bajo riesgo dinámico. Se incluyeron 412 pacientes, 309 ablacionados (Grupo 1: G1), y 103 no ablacionados (Grupo 2: G2). El G1 también incluyó a 29 pacientes que fueron ablacionados al observar el riesgo dinámico (Tg bajo terapia hormonal > 5 ng/ml). La frecuencia de respuesta estructural incompleta (REI) al inicio y al final del seguimiento fue mayor en el grupo de pacientes ablacionados de bajo RR y riesgo intermedio estático comparados con los no ablacionados de bajo riesgo dinámico (11,3% vs 0,9%: p=<0,001). La frecuencia de respuesta excelente al final del seguimiento fue mayor en los no ablacionados de bajo riesgo dinámico vs. ablacionados de bajo RR y riesgo intermedio estático (72,8% vs 62,1%: p=0,058). En conclusión, los pacientes ablacionados de bajo RR y riesgo intermedio presentaron una mayor frecuencia de REI que los no ablacionados adecuadamente seleccionados, al tener en cuenta el RR inicial. En cambio, al comparar pacientes ablacionados de bajo RR estático vs. no ablacionados de bajo riesgo dinámico, la REI fue similar. Estos resultados avalan la conducta de no ablacionar a aquellos pacientes de riesgo intermedio de recurrencia que presentan en el seguimiento un bajo riesgo dinámico.

ABSTRACT The current approach of patients with differentiated thyroid carcinoma (DTC) is individualized according to the risk of recurrence (RR) of the disease. The static classification of the initial RR could be improved by applying the dynamic risk of recurrence to decide remnant ablation. The dynamic risk definition arise from the findings obtained during the initial follow-up. The aim of this manuscript is to compare the response to treatment in patients with low and intermediate static RR in whom the decision for radioiodine remnant ablation (RRA) was performed immediately after surgery with those non-ablated patients with low dynamic RR. Secondary, to compare the responses to treatment in ablated patients with low static RR compared with those non-ablated low dynamic RR. We included 412 patients, they were divided in two groups Group 1 (G1): n=309 ablated patients and Group 2 (G2): n=103 non-ablated patients. G1 also included 29 patients who received remnant ablation considering the dynamic risk (Tg levels > 5 ng/ml). The initial structural incomplete response (SIR) was greater in G1 compared with G2 (11.3% vs 0.9%: p = <0.001). The frequency of an excellent response at the end of follow-up was similar in G2 compared with low initial RR of G1 (72.8% vs. 62.1%: p = 0.058). In conclusion, low and intermediate static RR ablated patients had a higher frequency of SIR compared with non-ablated patients in the dynamic risk assessment. In contrast, the frequency of SIR was similar when ablated patients of low static RR were compared with those non-ablated patients of low dynamic risk. These results show how the dynamic RR helps to move those intermediate RR patients on the low RR decreasing the need for RRA.

La respuesta excelente al tratamiento en pacientes con cáncer diferenciado de tiroides se mantiene a lo largo del seguimiento independientemente del riesgo de recurrencia inicial / Excellent response to treatment in patients with differentiated thyroid cancer is maintained throughout follow-up regardless of the risk of initial recurrence

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.

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.

Riesgo dinámico en pacientes con cáncer diferenciado de tiroides no ablacionados / Dynamic risk assessment in patients with differentiated thyroid cancer without remnant ablation

En la actualidad, el enfoque terapéutico y el seguimiento de los pacientes con carcinoma diferenciado de tiroides (CDT) es individualizado de acuerdo con el riesgo de recurrencia de la enfermedad, con una menor tendencia a ablacionar a pacientes de bajo riesgo de recurrencia. Por otro lado, la evaluación de las respuestas al tratamiento se validó en pacientes tratados con tiroidectomía total (TT) y ablación con radioyodo (RAI), pero son escasos los estudios en pacientes no ablacionados. Los objetivos de este estudio fueron describir las características de una población de pacientes con CDT no ablacionados y validar las respuestas al tratamiento durante el seguimiento. Se incluyó a 88 pacientes con un seguimiento mínimo de 12 meses. El 87,6% eran mujeres y la edad promedio en el momento del diagnóstico fue de 47,5 años. Basados en el Consenso Intersocietario Argentino, el 97,7% de la cohorte fue clasificada como de bajo riesgo y el 2,3% como de riesgo intermedio de recurrencia. Los pacientes presentaron una respuesta inicial excelente en el 73% de los casos, con un estado sin evidencia de enfermedad al final del seguimiento en el 85,5%. Una minoría de los pacientes (1%) presentó una respuesta inicial estructural incompleta, la cual fue similar al final del seguimiento (1%). Por otro lado, el 26% de los pacientes presentó una respuesta inicial indeterminada, aunque solo el 13,5% permaneció con esta respuesta al final del seguimiento. Nuestros datos validan las respuestas al tratamiento en pacientes con CDT que recibieron TT no ablacionados como una herramienta efectiva para la estratificación del riesgo dinámico. Los pacientes apropiadamente seleccionados tratados sin RAI tienen un excelente pronóstico, con una baja frecuencia de respuesta estructural incompleta en el seguimiento, inclusive menor que la de los pacientes de bajo riesgo ablacionados.

The therapeutic approach and the follow-up of patients with differentiated thyroid cancer (DTC) is currently individualised according to the risk of recurrence, with a lower tendency to perform remnant ablation (RA) in patients with low risk of recurrence. While response to therapy assessment has been validated for DTC patients treated by total thyroidectomy (TT) and RA, it has not been widely confirmed in patients treated with TT without RA. The aims of this study were to describe the characteristics of the population of patients treated with TT without RA, and to validate the response to therapy. The study included 88 patients followed-up for at least 12 months after surgery. In the entire cohort, 87.9% were female and the mean age was 47.5 years old. Based on the Argentine Intersociety Consensus, 97.7% and 2.3% were classified as low risk and intermediate risk of recurrence, respectively. Patients had an initial excellent response to treatment in 73% of cases, with a disease-free status at the end of follow-up of 85.5%. A minority of patients (1%) presented with an initial structural incomplete response, which was similar at the end of follow-up (1%). On the other hand, 26% of the patients had an initial indeterminate response, although only 13.5% remained with this response at the end of follow-up. These results validate the responses to treatment in DTC patients treated with TT without RA as an effective tool for the dynamic risk stratification. Patients appropriately selected who did not receive RA have an excellent outcome, with a low frequency of structural incomplete response, even lower than that observed in low risk ablated patients.