Speaker
Descrizione
The THE Project (Spoke 1, WP1.5) provided a structured translational framework for the
clinical implementation of low-energy electron FLASH radiotherapy, integrating dosimetric
protocol development, treatment planning adaptation, device upgrade, and preclinical
validation. Beyond technical feasibility, the project generated key insights into trial design
and patient selection for first-in-human FLASH applications.
A central lesson was that technological optimization—beam monitoring, applicator
refinement, collimation systems, and positioning solutions—is a prerequisite but not
sufficient condition for clinical translation. Early-phase trials must prioritize
reproducibility, strict dosimetric control, and minimization of technical variability to ensure
safety and scientific credibility.
Patient selection emerged as equally critical. Early FLASH trials require highly restricted
and homogeneous populations, limited confounding variables, and simple, measurable
endpoints. T1 non-melanoma skin cancers were selected as an ideal model due to their
accessibility, geometric definition, and suitability for precise high-dose irradiation with low
energy electrons. The skin provides a controlled in vivo environment to assess toxicity, local
control, and oxygen-dependent radiobiological mechanisms central to the FLASH effect.
Accordingly, the primary endpoint focused on skin toxicity up to six months, with
hierarchical evaluation of local control.
Overall, the THE Project underscores that the credibility of FLASH radiotherapy will depend
on rigorous early trial design, conservative indication selection, and multidisciplinary
integration, ensuring safety, reproducibility, and robust clinical translation.
