Vision and implementation for the first U.S. carbon ion therapy center part I: Clinical rationale and the need for CIRT in the United States

Carbon ion radiotherapy (CIRT) has evolved into an established clinical modality over the past three decades. Owing to its unique physical and biological characteristics, CIRT has demonstrated favorable outcomes for selected malignancies characterized by radioresistance, proximity to critical organs, locally advanced disease requiring safe dose escalation, and recurrent tumors requiring re-irradiation. This review summarizes the physical and radiobiological rationale for CIRT, the evolution of international clinical practice and the clinical relative biological effectiveness models and dose prescription systems currently used in Asia and Europe. We discuss the differences between the modified microdosimetric kinetic model and Local Effect Model frameworks and their implications for interpreting and applying international clinical experience. We also describe the biological dose calculation framework adopted by Mayo Clinic Florida (MCF) to integrate established international CIRT experience into the first U.S. program. Published estimates of CIRT eligibility and need in the United States are reviewed to provide context for the anticipated U.S. patient population. This population includes many clinically complex disease sites characterized by proximity to critical organs, respiratory motion, anatomical variation, and the potential need for adaptive treatment. These clinical characteristics define important requirements for the first U.S. CIRT program and provide the foundation for the design philosophy and technical implementation described in the companion Part II article.