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The specific advantages of ion beams for application in tumor therapy are attributed to their different macroscopic and microscopic energy deposition pattern as compared to conventional photon radiation. On the macroscopic scale, the dose profile with a Bragg peak at the highest depths and small lateral scattering allow a better conformation of the dose to the tumor. On the microscopic scale, the localized energy deposition around the trajectory of the particles leads to an enhanced biological effectiveness, typically expressed in terms of clinically significant relative biological effectiveness (RBE). Experimental investigations reveal complex dependencies of RBE on many physical and biological parameters, as e.g. ion species, dose, position in the field, and cell or tissue type. In order to complement the experimental work, different approaches are used for the characterization of the specific physical and biological properties of ion beams. In a set of two papers, which are linked by activities within a European HORIZON 2020 project about nuclear science and application (ENSAR2), we describe recent developments in two fields playing a key role in characterizing the increased biological effectiveness. These comprise the biophysical modeling of RBE and the microdosimetric measurements in complex radiation fields. This second paper focuses on microdosimeters and on the importance of providing the instrumental measurement of the spectra of the imparted energy. The relevance of microdosimetric quantities, complementary to the absorbed dose is emphasized. This parts provides an overview of the microdosimetric concepts and the recent experimental developments in the field of microdosimetry applied to ion beam therapy. Finally, a non-exhaustive, dedicated section in included to emphasize the relevance of Monte Carlo simulations as tool for the design of the microdosimetric detectors and for the interpretation of the experimental results. For the two distinctive clinical

The specific advantages of ion beams for application in tumor therapy are attributed to their different macroscopic and microscopic energy deposition pattern as compared to conventional photon radiation. On the macroscopic scale, the dose profile with a Bragg peak at the highest depths and small lateral scattering allow a better conformation of the dose to the tumor. On the microscopic scale, the localized energy deposition around the trajectory of the particles leads to an enhanced biological effectiveness, typically expressed in terms of clinically significant relative biological effectiveness (RBE). Experimental investigations reveal complex dependencies of RBE on many physical and biological parameters, as e.g. ion species, dose, position in the field, and cell or tissue type. In order to complement the experimental work, different approaches are used for the characterization of the specific physical and biological properties of ion beams. In a set of two papers, which are linked by activities within a European HORIZON 2020 project about nuclear science and application (ENSAR2), we describe recent developments in two fields playing a key role in characterizing the increased biological effectiveness. These comprise the biophysical modeling of RBE and the microdosimetric measurements in complex radiation fields. This second paper focuses on microdosimeters and on the importance of providing the instrumental measurement of the spectra of the imparted energy. The relevance of microdosimetric quantities, complementary to the absorbed dose is emphasized. This parts provides an overview of the microdosimetric concepts and the recent experimental developments in the field of microdosimetry applied to ion beam therapy. Finally, a non-exhaustive, dedicated section in included to emphasize the relevance of Monte Carlo simulations as tool for the design of the microdosimetric detectors and for the interpretation of the experimental results. For the two distinctive clinical

The specific advantages of ion beams for application in tumor therapy are attributed to their different macroscopic and microscopic energy deposition pattern as compared to conventional photon radiation. On the macroscopic scale, the inverted dose profile with a Bragg peak and small lateral scattering allow a better conformation of the dose to the tumor. On the microscopic scale, the localized energy deposition around the trajectory of the particles leads to an enhanced biological effectiveness, typically expressed in terms of the relative biological effectiveness (RBE). Experimental investigations reveal complex dependencies of RBE on many physical and biological parameters, as e.g., ion species, dose, position in the field and cell or tissue type. In order to complement the experimental work, different approaches are used for the characterization of the specific physical and biological properties of ion beams. In a set of two papers, which are linked by activities within a European HORIZON 2020 project about nuclear science and application (ENSAR2), we describe recent developments in two fields playing a key role in characterizing the increased biological effectiveness. These comprise the biophysical modeling of RBE and the microdosimetric measurements in complex radiation fields. This first paper gives a brief introduction into these fields and then focuses on aspects of biophysical modeling of RBE, specifically on semi-empirical approaches that are currently used in treatment planning for ion beam therapy. It summarizes the status and recent developments of the Local Effect Model (LEM) and its conceptual framework and shows examples of model validation using recent experimental data. The model is compared to other approaches, e.g., to the Microdosimetric-Kinetic Model (MKM), that builds the bridge to the experimental microdosimetric work. © Copyright © 2020 Scholz, Friedrich, Magrin, Colautti, Ristić-Fira and Petrović.

The specific advantages of ion beams for application in tumor therapy are attributed to their different macroscopic and microscopic energy deposition pattern as compared to conventional photon radiation. On the macroscopic scale, the dose profile with a Bragg peak at the highest depths and small lateral scattering allow a better conformation of the dose to the tumor. On the microscopic scale, the localized energy deposition around the trajectory of the particles leads to an enhanced biological effectiveness, typically expressed in terms of clinically significant relative biological effectiveness (RBE). Experimental investigations reveal complex dependencies of RBE on many physical and biological parameters, as e.g. ion species, dose, position in the field, and cell or tissue type. In order to complement the experimental work, different approaches are used for the characterization of the specific physical and biological properties of ion beams. In a set of two papers, which are linked by activities within a European HORIZON 2020 project about nuclear science and application (ENSAR2), we describe recent developments in two fields playing a key role in characterizing the increased biological effectiveness. These comprise the biophysical modeling of RBE and the microdosimetric measurements in complex radiation fields. This second paper focuses on microdosimeters and on the importance of providing the instrumental measurement of the spectra of the imparted energy. The relevance of microdosimetric quantities, complementary to the absorbed dose is emphasized. This parts provides an overview of the microdosimetric concepts and the recent experimental developments in the field of microdosimetry applied to ion beam therapy. Finally, a non-exhaustive, dedicated section in included to emphasize the relevance of Monte Carlo simulations as tool for the design of the microdosimetric detectors and for the interpretation of the experimental results. For the two distinctive clinical

The specific advantages of ion beams for application in tumor therapy are attributed to their different macroscopic and microscopic energy deposition pattern as compared to conventional photon radiation. On the macroscopic scale, the dose profile with a Bragg peak at the highest depths and small lateral scattering allow a better conformation of the dose to the tumor. On the microscopic scale, the localized energy deposition around the trajectory of the particles leads to an enhanced biological effectiveness, typically expressed in terms of clinically significant relative biological effectiveness (RBE). Experimental investigations reveal complex dependencies of RBE on many physical and biological parameters, as e.g. ion species, dose, position in the field, and cell or tissue type. In order to complement the experimental work, different approaches are used for the characterization of the specific physical and biological properties of ion beams. In a set of two papers, which are linked by activities within a European HORIZON 2020 project about nuclear science and application (ENSAR2), we describe recent developments in two fields playing a key role in characterizing the increased biological effectiveness. These comprise the biophysical modeling of RBE and the microdosimetric measurements in complex radiation fields. This second paper focuses on microdosimeters and on the importance of providing the instrumental measurement of the spectra of the imparted energy. The relevance of microdosimetric quantities, complementary to the absorbed dose is emphasized. This parts provides an overview of the microdosimetric concepts and the recent experimental developments in the field of microdosimetry applied to ion beam therapy. Finally, a non-exhaustive, dedicated section in included to emphasize the relevance of Monte Carlo simulations as tool for the design of the microdosimetric detectors and for the interpretation of the experimental results. For the two distinctive clinical

The specific advantages of ion beams for application in tumor therapy are attributed to their different macroscopic and microscopic energy deposition pattern as compared to conventional photon radiation. On the macroscopic scale, the dose profile with a Bragg peak at the highest depths and small lateral scattering allow a better conformation of the dose to the tumor. On the microscopic scale, the localized energy deposition around the trajectory of the particles leads to an enhanced biological effectiveness, typically expressed in terms of clinically significant relative biological effectiveness (RBE). Experimental investigations reveal complex dependencies of RBE on many physical and biological parameters, as e.g. ion species, dose, position in the field, and cell or tissue type. In order to complement the experimental work, different approaches are used for the characterization of the specific physical and biological properties of ion beams. In a set of two papers, which are linked by activities within a European HORIZON 2020 project about nuclear science and application (ENSAR2), we describe recent developments in two fields playing a key role in characterizing the increased biological effectiveness. These comprise the biophysical modeling of RBE and the microdosimetric measurements in complex radiation fields. This second paper focuses on microdosimeters and on the importance of providing the instrumental measurement of the spectra of the imparted energy. The relevance of microdosimetric quantities, complementary to the absorbed dose is emphasized. This parts provides an overview of the microdosimetric concepts and the recent experimental developments in the field of microdosimetry applied to ion beam therapy. Finally, a non-exhaustive, dedicated section in included to emphasize the relevance of Monte Carlo simulations as tool for the design of the microdosimetric detectors and for the interpretation of the experimental results. For the two distinctive clinical

The specific advantages of ion beams for application in tumor therapy are attributed to their different macroscopic and microscopic energy deposition pattern as compared to conventional photon radiation. On the macroscopic scale, the inverted dose profile with a Bragg peak and small lateral scattering allow a better conformation of the dose to the tumor. On the microscopic scale, the localized energy deposition around the trajectory of the particles leads to an enhanced biological effectiveness, typically expressed in terms of the relative biological effectiveness (RBE). Experimental investigations reveal complex dependencies of RBE on many physical and biological parameters, as e.g., ion species, dose, position in the field and cell or tissue type. In order to complement the experimental work, different approaches are used for the characterization of the specific physical and biological properties of ion beams. In a set of two papers, which are linked by activities within a European HORIZON 2020 project about nuclear science and application (ENSAR2), we describe recent developments in two fields playing a key role in characterizing the increased biological effectiveness. These comprise the biophysical modeling of RBE and the microdosimetric measurements in complex radiation fields. This first paper gives a brief introduction into these fields and then focuses on aspects of biophysical modeling of RBE, specifically on semi-empirical approaches that are currently used in treatment planning for ion beam therapy. It summarizes the status and recent developments of the Local Effect Model (LEM) and its conceptual framework and shows examples of model validation using recent experimental data. The model is compared to other approaches, e.g., to the Microdosimetric-Kinetic Model (MKM), that builds the bridge to the experimental microdosimetric work. © Copyright © 2020 Scholz, Friedrich, Magrin, Colautti, Ristić-Fira and Petrović.

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