viernes, 19 de julio de 2019

Tratamiento del sarcoma de tejido blando infantil (PDQ®) 5/6 –Versión para profesionales de salud - Instituto Nacional Del Cáncer

Tratamiento del sarcoma de tejido blando infantil (PDQ®)–Versión para profesionales de salud - Instituto Nacional Del Cáncer



Instituto Nacional Del Cáncer



Tratamiento del sarcoma de tejido blando infantil (PDQ®)–Versión para profesionales de salud


Tumores vasculares

Los tumores vasculares varían desde los hemangiomas, que siempre se consideran benignos, hasta los angiosarcomas, que son muy malignos.[289] Los tumores vasculares malignos incluyen los siguientes subtipos:

Hemangioendotelioma epitelioide

Incidencia y desenlace
En 1982, Weiss y Enzinger describieron por primera vez este tumor de tejido blando. Los hemangioendoteliomas epitelioides a veces se presentan a una edad más temprana, pero la incidencia máxima se ubica en la cuarta y quinta décadas de vida. Los tumores pueden tener una evolución poco activa o de gran malignidad; la supervivencia general a 5 años es de 73 %. Hay informes de casos de pacientes con lesiones múltiples que no recibieron tratamiento y que presentaron una evolución muy benigna comparada con la de otros pacientes con una evolución muy maligna. Si bien algunos patólogos han tratado de estratificar a los pacientes para evaluar los riesgos y ajustar el tratamiento, se necesita llevar a cabo más investigación sobre este tema.[290-296]
La presencia de efusiones, un tamaño tumoral mayor de 3 cm y un índice mitótico alto (>3 mitosis/50 campos de gran aumento) se han relacionado con desenlaces desfavorables.[292]
Características histopatológicas y moleculares
Se encontró la fusión génica WWTR1-CAMTA1 en un gran porcentaje de pacientes; con menos frecuencia, se notificó la fusión génica YAP1-TFE3.[290] No es posible dirigir el efecto de los medicamentos actuales de forma directa a estas fusiones. Se ha descrito monoclonalidad en las lesiones hepáticas múltiples, lo que indicaría un proceso metastásico.
Desde el punto de vista histológico, estas lesiones se caracterizan como lesiones epitelioides dispuestas en nidos, hebras y trabéculas, con pocos espacios vasculares. Las características que quizá se relacionen con un comportamiento clínico muy maligno incluyen atipia celular, una o más mitosis por 10 campos de gran aumento, un incremento en la proporción de células fusiformes, necrosis focal y formación ósea metaplásica.[292]
El número de pacientes pediátricos notificados en la bibliografía es limitado.
Cuadro clínico inicial y evaluación diagnóstica
Los sitios comunes de compromiso son: solo el hígado (21 %), hígado y pulmón (18 %), solo el pulmón (12 %) y solo el hueso (14 %).[292,297,298] El cuadro clínico inicial depende del sitio comprometido, como sigue:
  • Hígado: los nódulos hepáticos exhiben vascularización central en la ecografía, mejor contraste de las lesiones en la tomografía computarizada, además de señal T1 baja y señal T2 moderada en las imágenes por resonancia magnética.
  • Pulmón: el hemangioendotelioma epitelioide pulmonar a veces es un hallazgo asintomático en una radiografía de tórax o se relaciona con dolor pleural, hemoptisis, anemia y fibrosis.
  • Hueso: las metástasis óseas a veces se relacionan con una fractura patológica. En las radiografías, hay lesiones osteolíticas bien definidas, múltiples o solitarias.
  • Tejido blando: 30 % de los casos con compromiso de tejido blando se vinculan con metástasis y, cuando están presentes, tienen una evolución muy maligna con escasa respuesta a la quimioterapia.
  • Piel: las lesiones cutáneas se presentan en forma sobresaliente y nodular, o en placas calientes de color marrón rojizo.
Tratamiento del hemangioendotelioma epitelioide
Las opciones de tratamiento del hemangioendotelioma epitelioide son las siguientes:
  1. Observación.
  2. Cirugía.
  3. Inmunoterapia.
  4. Terapia dirigida.
  5. Quimioterapia.
Para los casos de poca malignidad, se justifica la observación. Para los casos más malignos, se han utilizado múltiples medicamentos, como interferón, talidomida, sorafenib, pazopanib y rapamicina.[299] Los casos más malignos se tratan con quimioterapia como la que se utiliza para el angiosarcoma. La cirugía se utiliza siempre que sea posible. El trasplante de hígado se ha utilizado para lesiones hepáticas muy malignas, con metástasis o sin estas.[292,300-303]
Los pacientes o las familias que deseen una terapia adicional dirigida a la enfermedad deberían considerar la participación en ensayos sobre abordajes terapéuticos novedosos ya que con ninguno de los fármacos tradicionales se ha demostrado una actividad clínicamente significativa.
Independientemente de si se decide continuar con una terapia dirigida a la enfermedad en el momento de la progresión, el objetivo principal del tratamiento sigue siendo el cuidado paliativo. Esto garantiza que se aumenta al máximo la calidad de vida mientras se intenta reducir la tensión relacionada con la enfermedad terminal.
Opciones de tratamiento en evaluación clínica para el hemangioendotelioma epitelioide
La información en inglés sobre los ensayos clínicos patrocinados por el Instituto Nacional del Cáncer (NCI) se encuentra en el portal de Internet del NCI. Para obtener información en inglés sobre ensayos clínicos patrocinados por otras organizaciones, consultar el portal de Internet ClinicalTrials.gov.
A continuación se presentan ejemplos de ensayos clínicos nacionales o institucionales en curso:
  1. NCT03148275 (Trametinib in Treating Patients with Epithelioid Hemangioendothelioma That Is Metastatic, Locally Advanced, or Cannot Be Removed by Surgery): este es un ensayo de fase II en el que se evalúa la eficacia de trametinib, con desenlaces notificados por los pacientes como objetivos secundarios.
  2. NCT01532687 (Gemcitabine Hydrochloride With or Without Pazopanib Hydrochloride in Treating Patients With Refractory Soft Tissue Sarcoma): en este ensayo aleatorizado de fase II se estudia qué tan eficaz es el clorhidrato de gemcitabina con el clorhidrato de pazopanib, o sin este, para tratar a los pacientes con sarcoma de tejido blanco resistente al tratamiento.
Ensayos clínicos en curso
Realizar una búsqueda avanzada en inglés de los ensayos clínicos sobre cáncer auspiciados por el NCI que ahora aceptan pacientes. La búsqueda se puede simplificar por ubicación del ensayo, tipo de tratamiento, nombre del fármaco y otros criterios. También se dispone de información general sobre los ensayos clínicos.

Angiosarcoma de tejido blando

Incidencia
El angiosarcoma es un tumor vascular poco frecuente (representa 2 % de los sarcomas) y de gran malignidad que puede surgir en cualquier parte del cuerpo, pero es más común en el tejido blando. Se calcula que la incidencia del angiosarcoma es de 2 casos por millón de personas; en los Estados Unidos, cada año afecta a alrededor de 600 personas que suelen tener entre 60 y 70 años.[304]
Los angiosarcomas son muy infrecuentes en los niños y no está claro si la fisiopatología de este tumor es diferente en la población pediátrica. Se notificaron casos en recién nacidos y lactantes mayores que presentaron al inicio lesiones cutáneas y hepáticas múltiples, algunas de las cuales expresan GLUT1.[305-308] La mayoría de los angiosarcomas comprometen la piel y el tejido blando superficial, aunque también afectan el hígado, el bazo y el pulmón; con poca frecuencia afectan el hueso.
Factores de riesgo
Los factores de riesgo establecidos incluyen los siguientes:[309]
  • Exposición al cloruro de vinilo.
  • Exposición a la radiación.
  • Linfedema crónico por cualquier causa, incluso el síndrome de Stewart-Treves.
Características histopatológicas y moleculares
Los angiosarcomas son tumores mayormente aneuploides. Los escasos casos de angiosarcoma que surgen de lesiones benignas, como los hemangiomas, siguen una vía distintiva que se necesita investigar. En el angiosarcoma inducido por radiación se observa amplificación de MYC. Las mutaciones KDR-VEGFR2 y las amplificaciones de FLT4-VEGFR3 se han observado con una frecuencia de menos de 50 %.[309]
Es posible que el diagnóstico histopatológico sea muy difícil porque a veces hay áreas de atipia variada. La característica común es una red irregular de canales en un modelo de disección a lo largo de haces de colágeno dérmico. Hay variación de forma celular, tamaño celular, mitosis, múltiples capas de endotelio y formación papilar. También puede haber células epitelioides. La necrosis y la hemorragia son comunes. Los tumores se tiñen para analizar el factor VIII, el CD31 y el CD34. Algunas lesiones hepáticas se parecen a los hemangiomas infantiles y tienen expresión focal de GLUT1. La nomenclatura de estas lesiones hepáticas ha sido difícil y confusa con el uso de la terminología de 1971 (por ejemplo, hemangioendotelioma tipo I: hemangioma infantil; hemangioendotelioma tipo II: angiosarcoma de grado bajo; hemangioendotelioma de tipo III: angiosarcoma de grado alto).[306]
Tratamiento del angiosarcoma del tejido blando
Las opciones de tratamiento del angiosarcoma de tejido blando son las siguientes:
  1. Cirugía (enfermedad localizada).
  2. Radioterapia (enfermedad cutánea localizada en adultos).
  3. Cirugía, quimioterapia y radioterapia (enfermedad metastásica).
La enfermedad localizada se cura mediante cirugía radical. La resección quirúrgica completa parece ser fundamental para los angiosarcomas y los linfangiosarcomas pese a las pruebas de que el tumor se encoge en algunos pacientes tratados con terapia local o sistémica.[307,310-312] En una revisión de 222 pacientes (mediana de edad de 62 años; intervalo de edad de 15–90 años), se observó una tasa de supervivencia general específica para la enfermedad (SEE) de 38 % a los 5 años. La SEE a 5 años fue de 44 % en 138 pacientes con tumores localizados resecados, pero solo de 16 % en 43 pacientes con metástasis en el momento del diagnóstico.[312] Hay poca información sobre el uso del trasplante de hígado para el angiosarcoma localizado.[313][Grado de comprobación: 3iiA]
Es posible tratar con radioterapia la enfermedad localizada, en especial el angiosarcoma cutáneo. La mayoría de los casos notificados son de adultos.[314]
El tratamiento multimodal con cirugía, quimioterapia sistémica y radioterapia se utiliza para la enfermedad metastásica, a pesar de que rara vez es curativo.[315] El objetivo del tratamiento del angiosarcoma metastásico es el control de la enfermedad, con tasas de supervivencia sin progresión publicadas de 3 a 7 meses [316] y una mediana de supervivencia general (SG) de 14 a 18 meses.[317] Tanto en adultos como en niños, se notifican tasas de SG a 5 años de 20 a 35 %.[307,308,318]
En un niño con diagnóstico de angiosarcoma secundario a una transformación maligna de un hemangioma infantil, se notificó una respuesta al tratamiento con bevacizumab, un anticuerpo monoclonal contra el factor de crecimiento endotelial vascular, combinado con quimioterapia sistémica.[305,315] En un informe de ocho casos de angiosarcoma de hígado en niños se resaltó el uso indebido del término hemangioendotelioma así como la importancia del diagnóstico y tratamiento tempranos de estos tumores.[319]
Los inhibidores biológicos de la angiogénesis han mostrado actividad en adultos con angiosarcoma.[306,318]
Los pacientes o las familias que deseen una terapia adicional dirigida a la enfermedad deberían considerar la participación en ensayos sobre abordajes terapéuticos novedosos ya que con ninguno de los fármacos tradicionales se ha demostrado una actividad clínicamente significativa.
Independientemente de si se decide continuar con una terapia dirigida a la enfermedad en el momento de la progresión, el objetivo principal del tratamiento sigue siendo el cuidado paliativo. Esto garantiza que se aumenta al máximo la calidad de vida mientras se intenta reducir la tensión relacionada con la enfermedad terminal.
Opciones de tratamiento en evaluación clínica para el angiosarcoma de tejido blando
La información en inglés sobre los ensayos clínicos patrocinados por el Instituto Nacional del Cáncer (NCI) se encuentra en el portal de Internet del NCI. Para obtener información en inglés sobre ensayos clínicos patrocinados por otras organizaciones, consultar el portal de Internet ClinicalTrials.gov.
A continuación se presenta un ejemplo de ensayo clínico nacional o institucional en curso:
  1. NCT01532687 (Gemcitabine Hydrochloride With or Without Pazopanib Hydrochloride in Treating Patients With Refractory Soft Tissue Sarcoma): En este ensayo aleatorizado de fase II se estudia qué tan eficaz es el clorhidrato de gemcitabina con el clorhidrato de pazopanib, o sin este, para tratar a los pacientes con sarcoma de tejido blanco resistente al tratamiento.
Ensayos clínicos en curso
Realizar una búsqueda avanzada en inglés de los ensayos clínicos sobre cáncer auspiciados por el NCI que ahora aceptan pacientes. La búsqueda se puede simplificar por ubicación del ensayo, tipo de tratamiento, nombre del fármaco y otros criterios. También se dispone de información general sobre los ensayos clínicos.

Ensayos clínicos en curso

Realizar una búsqueda avanzada en inglés de los ensayos clínicos sobre cáncer auspiciados por el NCI que ahora aceptan pacientes. La búsqueda se puede simplificar por ubicación del ensayo, tipo de tratamiento, nombre del fármaco y otros criterios. También se dispone de información general sobre los ensayos clínicos.
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