Carbon ion radiotherapy and radiation-induced lung injury: clinical evidence, mechanistic insights, and future directions.

Carbon ion radiotherapy (CIRT), owing to its unique physical dose distribution and high linear energy transfer (high-LET) characteristics, has shown remarkable advantages in the treatment of thoracic tumors in recent years. Compared with photon and proton radiotherapy, CIRT not only offers a higher relative biological effectiveness, enabling efficient eradication of hypoxic and radioresistant tumor cells, but also significantly reduces the radiation dose to surrounding normal lung tissue while maintaining excellent local control, thereby lowering the risk of radiation-induced lung injury (RILI). Clinical evidence indicates that CIRT demonstrates favorable tolerability and a lower incidence of radiation pneumonitis across various patient groups. Mechanistic evidence further suggests that the reduced risk of RILI with CIRT may arise from a combination of factors, including superior dose distribution and distinct high-LET radiobiological effects that induce complex DNA damage in tumor cells. In addition, carbon ion irradiation may influence key biological processes involved in lung injury, such as oxidative stress responses, inflammatory signaling, and profibrotic pathways, including TGF-β activation. Although current findings are largely derived from limited clinical cases and preclinical studies, they collectively highlight the potential of CIRT as an optimal approach to achieve effective tumor control while mitigating RILI. Future multicenter prospective studies and international collaborations are urgently needed to further clarify the protective effects and clinical value of CIRT, together with technological advances in beam delivery and adaptive treatment planning, as well as continued exploration of its integration with immunotherapy.