The Role of Carbon Ion Therapy in the Changing Oncology Landscape-A Narrative Review of the Literature and the Decade of Carbon Ion Experience at the Italian National Center for Oncological Hadrontherapy

Simple Summary Carbon ion radiotherapy offers ballistic and radiobiological advantages over conventional photon-based radiotherapy, making it an effective option in case of rare, radioresistant, and difficult-to-treat tumours. The current narrative review aims to critically report the state-of-the-art application of carbon ion radiotherapy in oncological settings, highlighting the clinical activity on carbon ion radiotherapy at the National Center for Oncological Hadrontherapy (CNAO). CNAO is the only Italian facility, and one of four located in Europe using both protons and carbon ions for oncological treatments. Proton and CIRT became fully operational at CNAO starting in 2011 and November 2012, respectively. After an initial ramp-up period, CNAO has progressively honed its clinical, technical, and dosimetric skills and contributed to increasing knowledge on the efficacy, feasibility, and safety of CIRT in selected tumour types, demonstrating the mild rate of toxicities also in case of re-irradiation and tolerance in case of association with systemic treatments.Abstract Background: Currently, 13 Asian and European facilities deliver carbon ion radiotherapy (CIRT) for preclinical and clinical activity, and, to date, 55 clinical studies including CIRT for adult and paediatric solid neoplasms have been registered. The National Center for Oncological Hadrontherapy (CNAO) is the only Italian facility able to accelerate both protons and carbon ions for oncological treatment and research. Methods: To summarise and critically evaluate state-of-the-art knowledge on the application of carbon ion radiotherapy in oncological settings, the authors conducted a literature search till December 2022 in the following electronic databases: PubMed, Web of Science, MEDLINE, Google Scholar, and Cochrane. The results of 68 studies are reported using a narrative approach, highlighting CNAO's clinical activity over the last 10 years of CIRT. Results: The ballistic and radiobiological hallmarks of CIRT make it an effective option in several rare, radioresistant, and difficult-to-treat tumours. CNAO has made a significant contribution to the advancement of knowledge on CIRT delivery in selected tumour types. Conclusions: After an initial ramp-up period, CNAO has progressively honed its clinical, technical, and dosimetric skills. Growing engagement with national and international networks and research groups for complex cancers has led to increasingly targeted patient selection for CIRT and lowered barriers to facility access.