Nueva técnica predice cuáles pacientes con melanoma están en riesgo de metástasis

Agencia Latina de Noticias Medicina y Salud Pública | Salud y Oncología

Para la mayoría de los pacientes, el melanoma comienza con una mancha pequeña y pigmentada en la piel que notan que comienza a cambiar. Muchos melanomas primarios se pueden curar con la extirpación de esta lesión, pero el melanoma también puede recurrir y diseminarse. Un análisis de la lesión extirpada puede ofrecer alguna información sobre la probabilidad de que el cáncer regrese.

Hoy en día, las lesiones se analizan de manera muy similar a como se hacían hace 100 años. A pesar de los avances en el diagnóstico molecular de otras formas de cáncer, el análisis de una lesión de cáncer de piel es sorprendentemente simplista. Se considera el grosor de la lesión (los pacientes con melanomas más delgados tienden a tener un mejor resultado) y las características microscópicas, como las ulceraciones, y se asigna una etapa T de 1 a 4.

En un artículo publicado en Nature Cancer, los investigadores del Hospital Brigham and Women’s, en colaboración con colegas internacionales, presentan una nueva técnica cuantitativa que aprovecha la secuenciación del ADN para hacer predicciones más sofisticadas y precisas sobre qué melanomas primarios tienen más probabilidades de reaparecer y extenderse.

“Hace tan sólo 10 años, el panorama para el melanoma metastásico era desalentador, pero ahora tenemos tratamientos para ofrecer a los pacientes con enfermedad metastásica y también podemos aplicar estos tratamientos cuando la enfermedad primaria no ha hecho metástasis”,

dijo el autor correspondiente Thomas Kupper, MD, jefe del Departamento de Dermatología en el Brigham.

Debido al advenimiento de estos nuevos tratamientos de inmunoterapia, es importante tener una idea clara de qué pacientes tienen probabilidades de progresar para que podamos adaptar el tratamiento en consecuencia“, agregó.

Inhibidores de los puntos de control inmunológicos

Los inhibidores de los puntos de control inmunológicos, que pueden despertar las células T para montar una respuesta inmunológica contra las células cancerosas, han cambiado radicalmente los resultados y las opciones disponibles para los pacientes cuyo cáncer de piel se ha extendido. En algunos pacientes, pueden provocar respuestas dramáticas, incluyendo la remisión a largo plazo, esencialmente curando al paciente. Pero la identificación de los pacientes con mayor riesgo de progresión de la enfermedad sigue siendo una necesidad insatisfecha.Le puede interesar:   Científicos demostraron que el COVID-19 no fue creado en un laboratorio

Para abordar esto, Kupper y sus colegas buscaron determinar si ciertas características mensurables de las células T podrían predecir la reincidencia en pacientes cuyo melanoma primario había sido extirpado y estaban libres de la enfermedad.

Los melanomas T1 (<1mm) raramente hacen metástasis, por lo que estudiaron los melanomas primarios T2 (1-2mm), T3 (2-4mm) y T4 (>4mm). El equipo de investigación se enfrentó a un obstáculo único en la adquisición de suficientes muestras para llevar a cabo un estudio robusto. A diferencia de la mayoría de los tumores, que son extirpados por un cirujano en un hospital, las lesiones de la piel pueden ser removidas en prácticas privadas y clínicas ambulatorias, lo que significa que los especímenes no se concentran en los entornos hospitalarios.

Además, las muestras deben conservarse durante varios años después de la extirpación, lo que retrasa su disponibilidad para los estudios de investigación. Para recoger suficientes muestras, los investigadores del Brigham colaboraron con sus colegas del Instituto del Melanoma de Australia y el Hospital Universitario de Zealand en Dinamarca para compartir recursos. El análisis actual incluye más de 300 muestras de pacientes de todos estos sitios.

Detalles del estudio en melanoma primario

El equipo comparó muestras de pacientes cuyo melanoma primario progresó a enfermedad metastásica con pacientes cuyo melanoma primario no lo hizo. Utilizaron la secuenciación de ADN de alto rendimiento, realizada por Adaptive Biotechnologies, para analizar el repertorio de células T de los tumores.

Los investigadores encontraron que de todas las variables identificadas, la fracción de células T (TCFr; o proporción de células en la lesión que eran células T) era un poderoso predictor independiente de qué pacientes progresarían.Le puede interesar:   Desordenes metabólicos generarían graves complicaciones ante el COVID-19

Aún para los pacientes cuyo espesor de la lesión (T) era el mismo, la TCFr pudo predecir cuáles pacientes tenían más probabilidad de tener enfermedad metastásica.

Los pacientes con una TCFr inferior al 20 por ciento tenían más riesgo de progresión de la enfermedad que los pacientes con una TCFr superior al 20 por ciento. Por ejemplo, para los pacientes con melanoma T3 (2-4mm de grosor), cinco años después de que se les extirpara la lesión primaria, el 51 por ciento de los que tenían una TCFr menor experimentaron una recurrencia, en comparación con el 24 por ciento de los que tenían una TCFr mayor.

Disponibilidad de la prueba

La prueba utilizada en este trabajo está disponible comercialmente para uso de investigación solamente y no está actualmente disponible en la clínica. Los autores también señalan que el estudio actual es retrospectivo, ya que examina muestras de pacientes cuyos resultados ya se conocen. Se necesitarán estudios prospectivos de pacientes cuyos resultados aún se desconocen para validar aún más la prueba. Si se lleva a la clínica, Kupper y sus colegas prevén que la prueba podría fortalecer los modelos de predicción actuales y mejorar la atención al paciente.

“Esta es una prueba simple y elegante. Es cuantitativa en lugar de subjetiva, y podría ser capaz de añadir valor a las predicciones sobre la progresión de la enfermedad“, dijo Kupper. “En el futuro, tal prueba podría ayudarnos a adaptar el tratamiento; los pacientes con alta TCFr pueden beneficiarse aún más de la terapia de inhibidores de punto de control, mientras que los pacientes con baja TCFr pueden necesitar una intervención adicional“.

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