Radiobiology Contributions and Perspectives in Hadron Therapy, With a Focus on Carbon Ions: Report From the Workshop Hadron Therapy for Life, Caen, March 2025

The "Hadrontherapy for Life" symposium in Caen, France, highlighted that a new era of radiobiology is fundamental for advancing particle therapy to the next level. A radiobiology capable of integrating molecular biology and omics technologies is needed to deeply analyze treatment responses and underlying mechanisms. Key challenges discussed at the symposium included tumor hypoxia, which remains only partially mitigated by high-LET radiation, and the specificity of carbon ions, or more broadly, high-LET particles, considered as "new drugs" capable of providing systemic benefits beyond local tumor control, including their potential to promote immunogenicity. Moreover, emerging modalities, such as Ultra High Dose Rate irradiation and spatial fractionated beams, were also discussed, with consensus that all require dedicated and coordinated radiobiological investigations. Infrastructure presentations highlighted the international capabilities of leading centers in Europe and Asia, emphasizing the importance of integrating radiobiology into clinical programs, advancing multi-ion experimentation, and adopting innovative experimental models, such as organoids and/or 3D cell cultures. Participants also stressed the need for greater access to animal experimentation facilities, which are essential for accelerating progress in the field. Furthermore, the meeting underscored translational endpoints such as biomarker development, a hot topic in current radiotherapy. The C400 accelerator enables Caen to incorporate radiobiology from its very inception, establishing a European hub for collaborative research. Round-table discussions emphasized the importance of harmonized protocols, dedicated in vivo irradiation rooms, international training programs with exchange of students and researchers, and comprehensive patient biobanking. In summary, the symposium reinforced the essential role of radiobiology in advancing hadron therapy (HT), providing strategic directions for translational research, infrastructure development, and international collaborations to accelerate personalized and effective particle therapy.