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.

High- vs. low-dose radio-iodine therapy for initial thyroid remnant ablation in post-thyroidectomized patients with non-metastatic differentiated thyroid cancer: A meta-analysis

@#The use of high- or low-dose radio-iodine therapy (RAIT) for initial thyroid remnant ablation in post-thyroidectomised patients diagnosed with differentiated thyroid cancer (DTC) with no distant metastases has long been a subject of much debate. Meta-analyses and systematic reviews have been previously made using both randomised control trials (RCTs) and observational studies without due regard to differences in study design. Hence, amore focused meta-analysis of available RCTs alone was conducted to determine the presence of a compelling difference between the initial remnant ablation success rates of high- and low-dose RAIT in post-thyroidectomised DTC patient without distant demtastases. An extensive search of PubMed and Cochrane Central register of RCTs (up to August 2013) was performed by two reviewers, which was completed by hand search of referencesfrom releveangt articles and review papers published from 1996 to 2012. The two reviewers independtly selected eligible studies, with disagreement resolved by consensus. The inclusion criteria were as follows: (a) randomised controlled trials, (b) post-thyroidectomised adult subjects diagnosed with well differentiated thyroid cancer and no evidence of distant metastases, and (c) subject randomisation into 30-50 mCi or 100 mCi 131I treatment groups. Studies were exluded if (a) the full text of the study is not available, (b) the study is in another language other than English, and (c) if the data on relative risk was not available or could not be derived from the study. Of eight published RCTs on radio-iodine therapy as of August 2013, only 5 were eligible for this meta-analysis; namely those by JOhansen et al. (1991), Bal et al. (1996), Zaman et al. (2006), Maenpaa et al. (2008) and Caglar et al. (2012). The same two reviewers independenty extracted data from the full text of the selected five studies. Two-by-two tables comparing frequencies of successful and failed remnant ablation using low-dose (30-60 mCi) and high-dise (100 mCi) RAIT were derived from the published results of the included studies, and the weighted and pooled relative risks for successful remnant ablation were computed via the Mantel-Haenszel method using a fixed effects model (cx = 5%). Subgroup analyses were performed based on different definitions of a successful remnant ablation. The pooled relative risk (-0.03) was statistically insignificant (p=0.54) and had poor precision (95% confidence interval of {-0.12,0.06}) even when adjustments to the varied definitions of a successful ablation were performed. Thus, using available RCTs that compare high- and low-dose RAIT for remnant ablation of DTC, there is an apparent trend favoring higher success rates using high-dose RAIT. However, the lack of well designed RCTs precludes recommending high-dose initial RAI ablation, and encourages the present practice of individualized.

Pathological N1b Node Metastasis Itself Can Be Still a Valid Prognostic Factor in PTC after High Dose RAI Therapy

BACKGROUND AND OBJECTIVES: The aim of this study was to determine whether pathologically proven central or lateral lymph node (LN) metastasis (pN1a or pN1b) could affect ablation success and recurrence after high-dose radioactive iodine (RAI) ablation. We also sought to identify the risk factors for long-term recurrence in patients with papillary thyroid carcinoma (PTC). MATERIALS AND METHODS: A total of 277 patients with pN1 disease who had undergone high-dose RAI ablation (5.55 GBq) between 2000 and 2006 were included in this retrospective study. We compared the ablation success rate and the recurrence rate between patients with pN1a and pN1b disease. Univariate and multivariate analyses were performed to identify the risk factors for recurrence. RESULTS: The median duration of follow-up was 10.2 years. The overall ablation success rate was 64%, and the ablation success rate in the pN1b group (49%) was lower than in the pN1a group (74%). The overall recurrence rate was 23%, and the recurrence rate in the pN1b group (30%) was higher than in pN1a group (18%). A higher ratio of metastatic LNs, a higher level of pre-ablation thyroglobulin, and ablation failure were significant risk factors for recurrence by multivariate analysis. CONCLUSION: Patients with pN1b disease experienced a lower ablation success rate and a higher recurrence rate than patients with pN1a disease. However, a higher ratio of metastatic LNs, a higher level of pre-ablation thyroglobulin, and ablation failure were stronger risk factors than the pathological N stage for long term recurrence in patients with node-positive PTC.

Pathological N1b Node Metastasis Itself Can Be Still a Valid Prognostic Factor in PTC after High Dose RAI Therapy

BACKGROUND AND OBJECTIVES: The aim of this study was to determine whether pathologically proven central or lateral lymph node (LN) metastasis (pN1a or pN1b) could affect ablation success and recurrence after high-dose radioactive iodine (RAI) ablation. We also sought to identify the risk factors for long-term recurrence in patients with papillary thyroid carcinoma (PTC). MATERIALS AND METHODS: A total of 277 patients with pN1 disease who had undergone high-dose RAI ablation (5.55 GBq) between 2000 and 2006 were included in this retrospective study. We compared the ablation success rate and the recurrence rate between patients with pN1a and pN1b disease. Univariate and multivariate analyses were performed to identify the risk factors for recurrence. RESULTS: The median duration of follow-up was 10.2 years. The overall ablation success rate was 64%, and the ablation success rate in the pN1b group (49%) was lower than in the pN1a group (74%). The overall recurrence rate was 23%, and the recurrence rate in the pN1b group (30%) was higher than in pN1a group (18%). A higher ratio of metastatic LNs, a higher level of pre-ablation thyroglobulin, and ablation failure were significant risk factors for recurrence by multivariate analysis. CONCLUSION: Patients with pN1b disease experienced a lower ablation success rate and a higher recurrence rate than patients with pN1a disease. However, a higher ratio of metastatic LNs, a higher level of pre-ablation thyroglobulin, and ablation failure were stronger risk factors than the pathological N stage for long term recurrence in patients with node-positive PTC.