Global Landscape of Clinical Studies Open to Enrollment in Carbon Ion Radiotherapy: A PTCOG Review.

Background: Radiotherapy with high linear energy transfer (LET) has shown promise for improving cancer outcomes. Carbon ion radiotherapy (CIRT) combines charged-particle dose conformality with enhanced biological effectiveness. However, clinical development remains constrained by limited center availability, modest trial accrual, and few randomized studies. We reviewed the global landscape of CIRT studies open to enrollment to identify current priorities and gaps. Methods: This Particle Therapy Cooperative Group (PTCOG)-sanctioned project, conducted within the CIRT Guidelines Subcommittee, identified studies through registry review and institutional verification. ClinicalTrials.gov and the Japan Registry of Clinical Trials were searched from December 2025 through February 2026. We included interventional CIRT trials and prospective registries open to new enrollment and excluded studies not open to enrollment, retrospective cohorts, proton-only studies, and preclinical studies. Results: Thirty-six studies were identified: 35 interventional trials in 6 countries and 1 North American registry-based comparative-effectiveness study. Japan had the largest share, followed by Germany, China, Italy, Austria, and France. Three centers (SPHIC, QST, and HIT) accounted for 21 of 36 studies. The portfolio included 7 phase I, 23 phase II, 5 phase III, and 1 registry study. Pancreatic cancer and sarcoma-related tumors each accounted for 7 studies; head and neck cancers, 5; prostate and breast cancers, 3 each; glioblastoma, lung cancer, and gynecologic malignancies, 2 each; and mucosal melanoma, mixed solid tumors, kidney cancer, esophageal cancer, and hepatocellular carcinoma, 1 each. Most studies were conducted at a single institution and emphasized feasibility, toxicity, local control, progression-free survival, or overall survival. Conclusions: This expert-verified inventory shows that CIRT studies open to enrollment remain concentrated by center, disease site, and phase. Future progress may depend more on shared outcome definitions, transparent biological dose reporting, and registry-enabled or multicenter comparative designs than on additional isolated single-institution studies.