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Multi-ion radiotherapy has been suggested as a new way to treat cancer, combining the radiological advantages of lighter and heavier ions in a single treatment to improve plan robustness and increase LETd in the target. To succeed, multi-ion radiotherapy requires a treatment planning system capable of computing dose for and optimising multi-ion treatment plans. In this project, prototypical multi-ion radiotherapy treatment planning support has been implemented in the RayStation treatment planning system. The existing dose engine for helium and carbon ion beams has been extended to support protons, oxygen and neon ions, and support has been added for dose computation and plan optimisation for any combination of these ion species. The implemented functionality has been evaluated in two phantom cases and a patient case. Multi-ion treatment plans have been shown to outperform carbon ion treatment plans in terms of simultaneously providing plan robustness, uniform RBE-weighted dose and high LETd. In the patient case, the multi-ion plan displayed significant improvements in the ability to "paint" high LETd in the target. Clinical studies are required to determine to what extent this new modality increases treatment quality in practice.

Multi-ion radiotherapy has been suggested as a new way to treat cancer, combining the radiological advantages of lighter and heavier ions in a single treatment to improve plan robustness and increase LETd in the target. To succeed, multi-ion radiotherapy requires a treatment planning system capable of computing dose for and optimising multi-ion treatment plans. In this project, prototypical multi-ion radiotherapy treatment planning support has been implemented in the RayStation treatment planning system. The existing dose engine for helium and carbon ion beams has been extended to support protons, oxygen and neon ions, and support has been added for dose computation and plan optimisation for any combination of these ion species. The implemented functionality has been evaluated in two phantom cases and a patient case. Multi-ion treatment plans have been shown to outperform carbon ion treatment plans in terms of simultaneously providing plan robustness, uniform RBE-weighted dose and high LETd. In the patient case, the multi-ion plan displayed significant improvements in the ability to "paint" high LETd in the target. Clinical studies are required to determine to what extent this new modality increases treatment quality in practice.

PURPOSE: The Union of Light Ion Centers in Europe (ULICE) program addressed the need for uniting scientific results for carbon-ion radiation therapy obtained by several institutions worldwide in different fields of excellence, and translating them into a real benefit to the community. Particularly, the concepts for dose/volume parameters developed in photon radiotherapy cannot be extrapolated to high linear energy transfer particles. METHODS AND MATERIALS: The ULICE-WP2 taskforce included radiation oncologists involved in carbon-ion radiation therapy and International Commission on Radiation Units and Measurements, radiation biologists, expert physicists in the fields of carbon-ion radiation therapy, microdosimetry, biological modeling and image-guided radiotherapy. Consensual reports emerged from multiple discussions within both the restricted group and the wider ULICE community. Public deliverables were produced and disseminated to the European Commission. RESULTS: Here we highlight the disparity in practices between treating centers, then address the main topics to finally elaborate specific recommendations. Although it appears relatively simple to add geometrical margins around the clinical target volume to obtain the planning target volume as performed in photon radiotherapy, this procedure is not appropriate for carbon-ion radiation therapy. Due to the variation of the radiation quality in depth, there is no generic relative biological effectiveness value for carbon-ions outside of an isolated point, for a given fractionation and specific experimental conditions. Absorbed dose and "equieffective dose" for specified conditions must always be reported. CONCLUSIONS: This work contributed to the development of standard operating procedures for carbon-ion radiation therapy clinical trials. These procedures are now being applied, particularly in the first phase III international, multicenter trial (PHRC Étoile)., [Concepts et terminologie des paramètres de dose et volumes proposés en hadronthérapie par ions carbone] OBJECTIF DE L'ÉTUDE : Le programme Union of Light Ion Centers in Europe (ULICE) s’est proposé d’harmoniser et de favoriser la diffusion internationale des procédures et résultats de l’hadronthérapie par ions carbone. En particulier, les concepts pour les paramètres de volume et de dose recommandés en radiothérapie externe ou protonthérapie ne peuvent pas être extrapolés aux particules de transfert d’énergie linéique élevé. MATÉRIELS ET MÉTHODES : Le groupe de travail ULICE-WP2 comprenait des radiothérapeutes impliqués dans l’hadronthérapie par ions carbone et l’International Commission on Radiation Units and Measurements (ICRU), des biologistes, des physiciens experts en hadronthérapie, microdosimétrie, modélisation biologique et radiothérapie guidée par image. Des rapports consensuels ont émergé de discussions multiples, tant dans le groupe restreint que dans la communauté élargie d’ULICE. Les livrables publics ont été produits et diffusés auprès de la Commission européenne. RÉSULTATS : Nous avons mis en évidence une disparité des pratiques de prescription et spécification de la dose et des volumes entre les centres de traitement par ions carbone. Nous avons ensuite discuté des concepts fondamentaux qui s’appliquent à ces paramètres en hadronthérapie par ions carbone. Nous avons ensuite élaboré des recommandations spécifiques. Bien qu’il semble relativement simple d’ajouter des marges géométriques autour du volume cible anatomoclinique pour obtenir le volume cible prévisionnel en radiothérapie externe, cette procédure n’est pas appropriée pour l’hadronthérapie par ions carbone. En raison de la variation de la qualité du rayonnement en profondeur, il n’y a pas de valeur générique d’efficacité biologique relative pour les ions carbone en dehors d’un point isolé, pour un fractionnement donné et des conditions expérimentales spécifiques. La dose absorbée et la « dos

The Union of Light Ion Centers in Europe (ULICE) program addressed the need for uniting scientific results for carbon-ion radiation therapy obtained by several institutions worldwide in different fields of excellence, and translating them into a real benefit to the community. Particularly, the concepts for dose/volume parameters developed in photon radiotherapy cannot be extrapolated to high linear energy transfer particles. The ULICE-WP2 taskforce included radiation oncologists involved in carbon-ion radiation therapy and International Commission on Radiation Units and Measurements, radiation biologists, expert physicists in the fields of carbon-ion radiation therapy, microdosimetry, biological modeling and image-guided radiotherapy. Consensual reports emerged from multiple discussions within both the restricted group and the wider ULICE community. Public deliverables were produced and disseminated to the European Commission. Here we highlight the disparity in practices between treating centers, then address the main topics to finally elaborate specific recommendations. Although it appears relatively simple to add geometrical margins around the clinical target volume to obtain the planning target volume as performed in photon radiotherapy, this procedure is not appropriate for carbon-ion radiation therapy. Due to the variation of the radiation quality in depth, there is no generic relative biological effectiveness value for carbon-ions outside of an isolated point, for a given fractionation and specific experimental conditions. Absorbed dose and "equieffective dose" for specified conditions must always be reported. This work contributed to the development of standard operating procedures for carbon-ion radiation therapy clinical trials. These procedures are now being applied, particularly in the first phase III international, multicenter trial (PHRC Étoile).