Clinical White Paper From the "Hadrontherapy for Life" Symposium-Clinical Expansion of Carbon Ion Facilities Worldwide.

Background: Carbon ion radiotherapy (CIRT) combines the physical precision of charged particles with high-linear energy transfer (LET) biological effectiveness, enabling superior control of radioresistant or anatomically complex tumors. Initially developed in Japan, CIRT is slowly expanding globally with increasing institutional and clinical maturity. Objective: To summarize current clinical evidence, operational strategies, and expansion plans for carbon ion facilities worldwide, as discussed during the "Hadrontherapy-for-Life" symposium held in Caen, France (March 2025). Methods: This white paper compiles presentations and institutional reports from major CIRT centers in Japan (QST, Gunma), Europe (HIT, CNAO, MedAustron, Cyclhad), and other emerging sites. Data sources include institutional registries, peer-reviewed studies, and national frameworks for hadrontherapy development. Results: Over 50,000 patients have received CIRT worldwide. Japan remains the leading contributor through the J-CROS network, emphasizing registry-based research, hypofractionation, and treatment of mobile tumors. European centers adopt translational programs aimed at further exploiting biological properties of carbon and helium ions. Major barriers include heterogeneous dose-modeling (local effect model vs modified microdosimetric kinetic model), limited image guidance, lack of standardized indications, and funding disparities. Ongoing efforts emphasize registry harmonization, pragmatic trials, and cost-effectiveness modeling. New multi-ion facilities such as Cyclhad (Caen) aim to propose multi-ion therapy, increase the level of evidence for clinical use, and promote research. Conclusions: CIRT is transitioning from pioneering programs to a coordinated global network. Collaborative initiatives and shared data platforms are essential to establish evidence-based indications, optimize biological modeling, and ensure economic sustainability. The "Hadrontherapy-for-Life" initiative calls for a strategic step toward internationally standardized, clinically integrated heavy-ion therapy.