Publication: Valoración de la persistencia, recidiva y supervivencia de los pacientes con carcinoma medular de tiroides esporádico y familiar
Authors
Ros Madrid, Inmaculada
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Escuela Internacional de Doctorado
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Febrero Sánchez, Beatriz ; Rodríguez González, José Manuel
Publisher
Universidad de Murcia
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DOI
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info:eu-repo/semantics/doctoralThesis
Description
Abstract
Introducción
El carcinoma medular de tiroides (CMT) es un tumor agresivo que representa solamente el 2-4% de los carcinomas de tiroides. Se caracteriza por afectación ganglionar precoz y riesgo de metástasis a distancia, con una reducción en la supervivencia global (SG) frente a la población general. Los objetivos de este trabajo son evaluar en pacientes con CMT: 1) variables que favorecen la afectación ganglionar al diagnóstico; 2) variables influyentes en la aparición de metástasis a distancia; 3) supervivencia libre de enfermedad estructural (SLEE) y factores relacionados; y, 4) tiempo de SG y factores influyentes.
Metodología
Se realizó un estudio observacional retrospectivo en pacientes con CMT confirmado histológicamente de origen esporádico como familiar (síndrome MEN-2). Se realizó un análisis descriptivo y comparativo univariante (Chi-cuadrado, test de Mann Whitney y Kruskal Wallis), así como un análisis multivariante de regresión logística. Se efectuó un análisis del rendimiento diagnóstico de distintas variables para predecir la afectación ganglionar y enfermedad estructural mediante curvas ROC. Las diferencias en la SLEE y SG en función de las variables se analizaron mediante curvas de Kaplan-Meier y el test de log-rank.
Resultados
Se analizaron 146 pacientes. El 75% (n=109) presentó CMT familiar, 106 pacientes síndrome MEN2A y 3 síndrome MEN2B; el resto fueron casos esporádicos. A los 6 meses, el 35% (n=51) estaba curado, el 45% (n=66) presentó persistencia bioquímica, el 11% (n=16) persistencia estructural y en el 9% (n=14) no fue valorado. De los 66 pacientes con persistencia bioquímica a los 6 meses, el 65% normalizó sus niveles de calcitonina (Ct). Al final del seguimiento, el 24% (n=33) presentó enfermedad estructural, con una SLEE (mediana) de 179.5 meses.
La afectación ganglionar se vio relacionada con: mayor edad, CMT esporádico, niveles de Ct y CEA preoperatorios, tamaño tumoral, invasión vascular, estadio III-IV, y tasa de duplicación de Ct. La edad fue la única variable significativa en el análisis multivariante (OR 0.093).
La afectación metastásica se vio afectada por: edad, Ct, heredabilidad, afectación ganglionar y estadio. Tras el análisis multivariante, únicamente la LNR (lymph node ratio, proporción de ganglios linfáticos metastásicos/ total de ganglios extirpados) fue significativa (OR 29.124).
La SLEE a los 10 y 20 años fue del 80% y 72%, y las variables influyentes fueron: mayor edad, CMT esporádico, Ct prequirúrgica, tamaño tumoral, estadio T y N, estadio global, afectación ganglionar lateral, LNR, invasión vascular, invasión linfática, necrosis tumoral, y la Ct a los 6-12 meses. En el análisis multivariante se mantuvieron como significativas la LNR, la Ct a los 6-12 meses de la cirugía y el estadio T.
La SG a los 10 y 20 años fue del 92% y 85%. El empeoramiento de la SG se relacionó con: la edad, CMT esporádico, CEA, presentar HP, tratamiento paliativo, recibir TT junto a LCB y LLU, presentar complicaciones, estadio T, estadio N, afectación ganglionar, afectación ganglionar ipsilateral, presentar metástasis al diagnóstico, estadio III-IV, número de adenopatías patológicas, LNR, tamaño tumoral, Ki67, Ct>150pg/ml a los 6-12 meses, SLE, metástasis durante el seguimiento y fallecer por CMT. En el análisis multivariante, permanecieron la edad, LNR y la presencia de metástasis al diagnóstico.
Conclusiones
La afectación ganglionar al diagnóstico está relacionada con la edad. La variable más relevante en la aparición de metástasis a distancia es la LNR. La SLEE a los 10-20 años es del 80% y 72%, y las variables que más repercutieron en la misma son el incremento de la LNR, la Ct a los 6-12 meses de la cirugía y el estadio T (TNM). Las variables más influyentes en la SG son la edad al diagnóstico, la LNR y la presencia de metástasis al diagnóstico.
Introduction Medullary thyroid carcinoma (MTC) is an aggressive tumor that accounts for only 2-4% of thyroid carcinomas. It is characterized by early lymph node involvement and a high risk of distant metastases, leading to reduced overall survival (OS) compared with the general population. The aims of this study were to evaluate in patients with MTC: (1) variables associated with lymph node involvement at diagnosis; (2) factors influencing the development of distant metastases; (3) structural disease-free survival (SDFS) and related predictors; and (4) OS and its determinants. Methods We conducted a retrospective observational study in patients with histologically confirmed MTC of both sporadic and hereditary origin (MEN2 syndrome). Descriptive and univariate analyses were performed (Chi-square, Mann-Whitney, and Kruskal-Wallis tests), as well as multivariate logistic regression. The diagnostic performance of several variables for predicting lymph node involvement and structural disease was assessed using ROC curves. Differences in SDFS and OS according to clinical and pathological variables were analyzed with Kaplan-Meier curves and the log-rank test. Results A total of 146 patients were included. Familial MTC accounted for 75% (n=109): 106 MEN2A and 3 MEN2B; the remaining cases were sporadic. At 6 months, 35% (n=51) were cured, 45% (n=66) had biochemical persistence, 11% (n=16) structural persistence, and 9% (n=14) were not evaluated. Among the 66 patients with biochemical persistence at 6 months, 65% normalized calcitonin (Ct) levels without reintervention. At the end of follow-up, 24% (n=33) had structural disease, with a median SDFS of 179.5 months. Lymph node involvement was associated with older age, sporadic MTC, higher preoperative Ct and CEA, larger tumor size, vascular invasion, advanced stage (III-IV) and Ct doubling time. In multivariate analysisi, only age remained significant (OR 0.093). Distant metastases were associated with age, Ct, hereditary status, lymph node involvement and stage. After multivariate analysis, only lumph node ratio (LNR; metastatic/excised lymph nodes) remained significant (OR 29.124). SDFS rates at 10 and 20 years were 80% and 72%, respectively. Predictive factors included olver age, sporadic MTC, preoperative Ct, tumor size, T and N stage, overall stage, lateral lymph node involvement, LNR, vascular invasion, lymphatic invasion, tumor necrosis and Ct at 6-12 months. In multivariate analysis, LNR, Ct at 6-12 months, ant T stage remained significant. OS rates at 10 and 20 years were 92% and 85%. Worse OS was associated with age, sporadic MTC, elevated CEA, hyperparathyrodism, palliative treatment, combined therapy with central and lateral lymphadenectomy, surgical complications, T and N stage, lymph node involvement (ipsilateral or overall), metastases at diagnosis, advanced stage (III-IV), number of pathological lymph nodes, LNR, tumor size, Ki67, Ct>150pg/mL at 6-12 months, SDFS, distant metastases during follow-up, and death due to MTC. In multivariate analysis, age at diagnosis, LNR and metastases at diagnosis remained significant. Conclusions Lymph node involvement at diagnosis was associated with age. The most relevant predictor of distant metastases was the LNR, which also proved to be a key prognostic factor for both SDFS and OS. SDFS rates at 10 and 20 years were 80% and 72%, and were most strongly influenced by LNR, Ct levels at 6-12months, and T stage. OS was mainly determined by age at diagnosis, LNR, and the presence of metastases at diagnosis
Introduction Medullary thyroid carcinoma (MTC) is an aggressive tumor that accounts for only 2-4% of thyroid carcinomas. It is characterized by early lymph node involvement and a high risk of distant metastases, leading to reduced overall survival (OS) compared with the general population. The aims of this study were to evaluate in patients with MTC: (1) variables associated with lymph node involvement at diagnosis; (2) factors influencing the development of distant metastases; (3) structural disease-free survival (SDFS) and related predictors; and (4) OS and its determinants. Methods We conducted a retrospective observational study in patients with histologically confirmed MTC of both sporadic and hereditary origin (MEN2 syndrome). Descriptive and univariate analyses were performed (Chi-square, Mann-Whitney, and Kruskal-Wallis tests), as well as multivariate logistic regression. The diagnostic performance of several variables for predicting lymph node involvement and structural disease was assessed using ROC curves. Differences in SDFS and OS according to clinical and pathological variables were analyzed with Kaplan-Meier curves and the log-rank test. Results A total of 146 patients were included. Familial MTC accounted for 75% (n=109): 106 MEN2A and 3 MEN2B; the remaining cases were sporadic. At 6 months, 35% (n=51) were cured, 45% (n=66) had biochemical persistence, 11% (n=16) structural persistence, and 9% (n=14) were not evaluated. Among the 66 patients with biochemical persistence at 6 months, 65% normalized calcitonin (Ct) levels without reintervention. At the end of follow-up, 24% (n=33) had structural disease, with a median SDFS of 179.5 months. Lymph node involvement was associated with older age, sporadic MTC, higher preoperative Ct and CEA, larger tumor size, vascular invasion, advanced stage (III-IV) and Ct doubling time. In multivariate analysisi, only age remained significant (OR 0.093). Distant metastases were associated with age, Ct, hereditary status, lymph node involvement and stage. After multivariate analysis, only lumph node ratio (LNR; metastatic/excised lymph nodes) remained significant (OR 29.124). SDFS rates at 10 and 20 years were 80% and 72%, respectively. Predictive factors included olver age, sporadic MTC, preoperative Ct, tumor size, T and N stage, overall stage, lateral lymph node involvement, LNR, vascular invasion, lymphatic invasion, tumor necrosis and Ct at 6-12 months. In multivariate analysis, LNR, Ct at 6-12 months, ant T stage remained significant. OS rates at 10 and 20 years were 92% and 85%. Worse OS was associated with age, sporadic MTC, elevated CEA, hyperparathyrodism, palliative treatment, combined therapy with central and lateral lymphadenectomy, surgical complications, T and N stage, lymph node involvement (ipsilateral or overall), metastases at diagnosis, advanced stage (III-IV), number of pathological lymph nodes, LNR, tumor size, Ki67, Ct>150pg/mL at 6-12 months, SDFS, distant metastases during follow-up, and death due to MTC. In multivariate analysis, age at diagnosis, LNR and metastases at diagnosis remained significant. Conclusions Lymph node involvement at diagnosis was associated with age. The most relevant predictor of distant metastases was the LNR, which also proved to be a key prognostic factor for both SDFS and OS. SDFS rates at 10 and 20 years were 80% and 72%, and were most strongly influenced by LNR, Ct levels at 6-12months, and T stage. OS was mainly determined by age at diagnosis, LNR, and the presence of metastases at diagnosis
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