Advanced electron sources for novel radiotherapy applications

Radiotherapy is a cornerstone in cancer treatment, with continuous innovations focused on improving precision and reducing side effects on healthy tissues. Among the most promising developments is ultra-high dose rate (UHDR) radiotherapy, also known as FLASH radiotherapy. This technique delivers radiation doses in extremely short time frames, typically under 100 ms, offering the unique potential to selectively spare normal tissues while preserving effective tumor control. Precise and conformal dose delivery remains one of the main challenges in the context of FLASH radiotherapy. Wide beam irradiation has already demonstrated the ability to trigger the FLASH effect and to spare healthy tissues across various animal models; however, its poor dose conformity prevents clinical translation. A promising alternative is the pencil-beam approach, which still requires validation to assess whether the FLASH effect can be reliably reproduced under this configuration. In this work, we propose a comparative study between wide beam and pencil beam irradiation protocols for the Glioblastoma tumor. Treatment plans for mice, based on Monte Carlo simulations, were developed to optimize dose distributions in the tumor and surrounding healthy tissues, enabling a rigorous evaluation for pencil beam scanning. To support this research, a dedicated FLASH Linac and a versatile beam delivery line are currently being developed at Sapienza University. Demonstrating that pencil-beam irradiation can induce the same healthy tissue sparing observed with wide-beam exposure would provide a clinically feasible pathway for FLASH-RT, combining conformal dose delivery with the ultrashort timescales required to induce the FLASH effect. • Linear accelerator at Sapienza. • Pencil beam and wide beam irradiation modality. • Treatment planning and Monte-Carlo simulation.