Review on carbon ion minibeam radiotherapy: Dosimetry, dynamic phantoms and radiobiology.

Carbon ion minibeam radiotherapy (CIMRT) is an emerging technique that intends to combine the biological and physical advantages of carbon ions with the normal-tissue sparing potential of spatially fractionated dose delivery. The increased linear energy transfer (LET) and higher relative biological effectiveness (RBE) of carbon ions compared with photons and protons, together with the immunomodulatory effects reported for carbon ion therapy and the biological responses observed after minibeam irradiation for photons and protons, suggest the potential for enhanced tumor control while preserving normal tissue during CIMRT. Given the poor prognosis associated with tumors such as pancreatic cancer, CIMRT may offer an option to increase therapeutic efficacy for these kinds of tumors. However, the clinical translation of CIMRT remains challenging due to unresolved questions in beam physics, dosimetry, radiation biology, and treatment robustness. A comprehensive understanding of carbon-ion-specific biological effects in spatially fractionated fields is required, and accurate dosimetric methods must be developed to characterize steep peak-to-valley dose gradients in high-LET environments. Furthermore, geometric and anthropomorphic phantoms are needed for treatment validation, and the influence of organ motion on the minibeam pattern should be systematically investigated. This review summarizes the current progress in CIMRT from four key perspectives: (i) physical and biological aspects, including the particularities of carbon-ion RBE and the biological responses to minibeam irradiation; (ii) dosimetric approaches for high-LET spatially fractionated fields; (iii) development of anthropomorphic and motion-capable phantoms; and (iv) the impact of organ motion and motion mitigation strategies. By highlighting recent advances and remaining challenges, this review provides a framework for future CIMRT development. It evaluates the requirements for its long-term transition from an experimental technique toward a clinical treatment modality.