Clinical indications and future directions of carbon-ion radiotherapy: a narrative review

Carbon-ion radiotherapy (CIRT) offers superior dose distributions and greater biological effectiveness than conventional photon-based radiotherapy (RT). Due to its higher linear energy transfer and relative biological effectiveness, CIRT is particularly effective against radioresistant tumors and those located near critical organs. Since the first dedicated CIRT facility was established in Japan in 1994, CIRT has demonstrated remarkable efficacy against various malignancies, including head and neck tumors, skull base and upper cervical spine tumors, non-small-cell lung cancer (NSCLC), hepatocellular carcinoma (HCC), pancreatic cancer, prostate cancer, and bone and soft tissue sarcomas. This narrative review provides a comprehensive overview of the current status of CIRT, highlighting its clinical indications and future directions. According to clinical studies, CIRT achieves high local control rates with manageable toxicity across multiple cancer types. For instance, in head and neck tumors (e.g., adenoid cystic carcinoma and mucosal melanoma), CIRT has achieved local control rates exceeding 80%. In early-stage NSCLC, CIRT has resulted in local control rates over 90% with minimal toxicity. Moreover, CIRT has shown promise in treating challenging cases of HCC and pancreatic cancer, where conventional therapies are limited. Nonetheless, the global adoption of CIRT remains limited due to high costs and complexity. Future directions include conducting randomized controlled trials to establish high-level evidence, integrating new technologies such as ultrahigh-dose-rate (FLASH) therapy, and expanding CIRT facilities globally with strategic planning and cost-effectiveness analyses. If these challenges are addressed, CIRT is poised to play a transformative role in cancer treatment, improving survival rates and the quality of life.