Elsevier

Cancer/Radiothérapie

Volume 22, Issue 8, December 2018, Pages 802-809
Cancer/Radiothérapie

Review
Concepts and terms for dose/volume parameters in carbon-ion radiotherapy: Conclusions of the ULICE taskforceConcepts et terminologie des paramètres de dose et volumes proposés en hadronthérapie par ions carbone

https://doi.org/10.1016/j.canrad.2017.11.016Get rights and content

Abstract

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).

Résumé

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 « dose isoefficace » pour des conditions spécifiées doivent toujours être signalées.

Conclusions

Ce travail a contribué à l’élaboration de procédures standard pour la génération d’essais cliniques en l’hadronthérapie par ions carbone. Ces procédures sont désormais appliquées notamment dans le premier essai international multicentrique de phase III (programme hospitalier de recherche clinique Étoile).

Introduction

Advanced photon irradiation techniques offer a relevant but not yet fully optimized ballistic and/or radiobiological solution for 10 to 12% of human tumors characterized by their high-risk of local failure due to radio-unresponsiveness, hypoxia, or a critical location among sensitive healthy tissues [1], [2]. Carbon-ions are densely ionizing particles with a high relative biological effectiveness, a lower oxygen enhancement ratio and higher level of physical selectivity compared to photons, justifying the use of hypofractionation [3], [4].

Carbon-ion radiation therapy is available in very few centers worldwide. The first dedicated center for large-scale treatment opened in Japan in 1994, with five centers now active. Four European facilities are operational, two in Germany [Heidelberg (HIT) and Marburg (MIT)], Pavia (CNAO) in Italy, and Wiener-Neustadt (MedAustron) in Austria. Several carbon-ion radiation therapy projects are under consideration in the USA, following pioneering work at Berkeley [5]. Treating centers are equipped with two kinds of dose delivery systems, each of which has its own ballistic properties [6]. To date, more than 15,000 patients have been treated worldwide with carbon-ion radiation therapy, mainly in phase I and II trials [7], [8], [9], [10].

Due to the high technical and financial investments required to expand carbon-ion radiation therapy practice, phase III studies comparing carbon-ions to protons or photons have been requested by the authorities but will be difficult to develop due to the rarity of eligible tumors and available centers [11], [12]. Large-scale collaborations are required but are problematic for two historical reasons. Firstly, initial treatment facilities were established in academic and research environments, each developing their own technology and engineering. Secondly, various clinical research philosophies have been adopted; while Japanese centers have studied a broad spectrum of indications with dose escalation trials, hypo fractionated and passive beam shaping, the German facilities have treated small patient sets, developing fully active beam scanning, and a specific mapping of relative biological effectiveness-weighted dose. Consequently, prescribing, recording and reporting treatments differ significantly between centers, hampering comparability of treatments.

Section snippets

The ULICE project

The European CIRT scientific community has grown significantly over the last decade through multidisciplinary large-scale collaborations such as ENLIGHT [13]. The program entitled Union of Light Ion Centers in Europe (ULICE) was a 5-year framework program 7 capacities (FP7) project initiated in 2009 to address the need for greater access to carbon-ion radiation therapy facilities for particle therapy research (grant #228436). The program was established by 20 leading European research

Planning target volume

The planning target volume (PTV) is a geometrical concept introduced for treatment planning, dose prescription, dose volume reporting and evaluation. In ICRU report 62, it was recommended that for external beam photon radiotherapy, internal and set-up margins be added quadratically [7]. The concept of PTV is particularly complex in regard to carbon-ion radiation therapy and this procedure appears inadequate due to the physical properties of the particles and the resulting higher heterogeneity

Recommendations

In the absence of specific recommendations from the ICRU, we propose here consensual, and when necessary, original concepts to better define and understand the biological dose and its determinants. We address three main areas: (1) quantities and units, (2) volume concepts, and (3) recommendations for reporting.

The PTV issue

In the present state of knowledge and techniques, established concepts are well suited to treat immobile or immobilized tumours in a stationary environment.

The effects of different beam arrangements on the target expansions necessary to ensure a predefined level of plan robustness have recently been investigated. A non-isotropical expansion rule based on the concept of weighted margins according to the probability of the presence of the target has been proposed [42]. Irrespective of the

Conclusions

Through international cooperation, the carbon-ion radiation therapy community needs to coordinate therapy planning and delivery in such a way that clinical results can be collected in the framework of multicenter prospective trials. Efforts must be made to develop procedures, which will produce readily comparable results, with reliable and verifiable dosimetry reporting. ULICE's commitment was primarily to transnational exchanges and multilateral access to promote such collaboration. In this

Funding

ULICE programme, FP7, European Union, grant #228436

Disclosure of interest

The authors declare that they have no competing interest.

Acknowledgements

English language was verified by Angloscribe.

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