Heavy Ion FLASH

Descripción del proyecto

Ampliar las fronteras de la radioterapia para tratar el cáncer

El glioblastoma y otros tumores altamente resistentes siguen siendo en gran medida intratables con radioterapia convencional, ya que incluso las terapias de partículas más avanzadas están limitadas por el daño al tejido sano. El equipo del proyecto HI-FLASH, financiado por el CEI, tiene como objetivo aprovechar el efecto FLASH, descubierto recientemente, mediante el cual la irradiación con dosis ultra altas preserva el tejido normal al tiempo que destruye los tumores. En el proyecto, pionero en GSI, se utilizarán iones más pesados que el carbono, incluido el neón, en modelos preclínicos, empleando moduladores impresos en 3D para un tratamiento preciso. Al comparar la supervivencia, la toxicidad y el control tumoral entre dosis convencionales y dosis ultra altas, en HI-FLASH se busca ampliar la ventana terapéutica, transformando potencialmente las opciones de tratamiento para pacientes que padecen los cánceres más mortales y resistentes a la terapia.

Objetivo

Charged particle therapy is generally acknowledged as the most advanced type of radiotherapy (RT). Particle therapy patients are treated either with high-energy protons or 12C-ions, but there is a general agreement that heavier ions would be highly beneficial in treating extremely resistant, hypoxic and lethal tumors, such as glioblastoma (GBM). Unfortunately, the use of very heavy ions is constrained by their excessive normal tissue toxicity.
A way to enable very heavy ion therapy with acceptable toxicities is to make use of the recently discovered FLASH effect. This effect occurs when ultra-high dose-rate (UHDR) electrons or protons are used and results in significantly sparing the normal tissues whilst maintaining tumour control. Although the molecular mechanism is still unclear, the FLASH effect considerably broadens the therapeutic window and has proven to be a game-changer in radiotherapy. While my group at GSI has pioneered the first demonstration of the FLASH effect with high-energy carbon ions, UHDR use of even heavier ions can be safe and very effective for very resistant tumor.
GSI is the only facility world-wide where the FLASH effect can be explored with ions heavier than carbon. In fact, the GSI synchrotron can accelerate all ions for H to U up to very high energy and intensity, and my group has developed a unique technology to perform 3D conformal UHDR irradiation using 3D-printed range modulators. We will perform UHDR irradiation experiments with 20Ne-ions using a GBM rat model and will compare survival, toxicity and tumour control with the same ion at conventional dose-rate and with UHDR protons as a reference. If successful, HI-FLASH will pave the way for the use of heavy ions in cancer treatment, improving outcomes for patients with highly resistant and lethal tumors like GBM.