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Análisis sistemático de la variabilidad de los puntos finales biológicos e implicaciones para el modelado

Isabella Colizzi^1,2, Mathilde Toschini^1,2, Antony J Lomax^1,2

¹Center for Proton Therapy, Paul Scherrer Institut, 5232 Villigen, PSI, Switzerland.

Physics and imaging in radiation oncology

|February 16, 2026

Resumen

La radioterapia de dosis ultra alta (UHDR), o FLASH, muestra una gran promesa, pero los datos preclínicos varían ampliamente. La estandarización de los puntos finales es crucial para desarrollar modelos predictivos y avanzar en las aplicaciones de la radioterapia FLASH.

Área de la Ciencia:

Oncología de Radiación
Investigación Preclínica
Modelado Cuantitativo

Sus antecedentes:

La radioterapia de dosis ultra alta (UHDR), conocida como FLASH, ofrece potencial para mejorar el ahorro de tejido normal y el control tumoral.
Existe una heterogeneidad significativa en los experimentos preclínicos FLASH, lo que dificulta las comparaciones entre estudios y el desarrollo de modelos predictivos.

Objetivo del estudio:

Identificar la variabilidad en los puntos finales y las metodologías dentro de la investigación preclínica de radioterapia FLASH.
Aclarar las inconsistencias y las lagunas de conocimiento esenciales para el modelado cuantitativo futuro.
Guiar la estandarización de los puntos finales biológicos y los enfoques experimentales en los estudios FLASH.

Principales métodos:

Revisión sistemática de experimentos preclínicos in vivo con protones y electrones FLASH en ratones de 1966 a 2024.
Análisis cualitativo y cuantitativo de los puntos finales comúnmente reportados, incluida la relación de células de cripta, la supervivencia, la descamación y las pruebas cognitivas.
Análisis de regresión logística para evaluar los parámetros que influyen en el efecto FLASH en un subconjunto de puntos finales comparables.

Principales resultados:

Se revisaron cincuenta artículos, lo que reveló una heterogeneidad sustancial en la selección, el momento y la metodología de los puntos finales.
Un número limitado de puntos finales (cuatro) fueron adecuados para el análisis entre estudios debido a diferencias metodológicas.
El análisis de regresión logística se vio limitado por la colinealidad de los parámetros, lo que indica heterogeneidad experimental y falta de armonización.

Conclusiones:

Existe una necesidad urgente de puntos finales y metodologías biológicas estandarizadas en la investigación preclínica FLASH.
Cuantificar la variabilidad e identificar puntos finales comparables en los datos FLASH es fundamental para la modelización futura.
Este trabajo proporciona orientación para integrar la evidencia biológica con enfoques cuantitativos para la planificación del tratamiento en radioterapia FLASH.

Palabras clave:

Puntos finales FLASH Efecto FLASH Directrices Metaanálisis Modelado Estudios preclínicos UHDR

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