A step towards international prospective trials in carbon ion radiotherapy: investigation of factors influencing dose di

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A step towards international prospective trials in carbon ion radiotherapy: investigation of factors influencing dose distribution in the facilities in operation based on a case of skull base chordoma G. Vogin1,2* , A. Wambersie3,4, M. Koto5, T. Ohno6, M. Uhl7, P. Fossati8,9, J. Balosso10,11,12 and on behalf of ULICE WP2 working group

Abstract Background: Carbon ion radiotherapy (CIRT) has been delivered to more than 20,000 patients worldwide. International trials have been recommended in order to emphasize the actual benefits. The ULICE program (Union of Light Ion Centers in Europe) addressed the need for harmonization of CIRT practices. A comparative knowledge of the sources and magnitudes of uncertainties altering dose distribution and clinical effects during the whole CIRT procedure is required in that aim. Methods: As part of ULICE WP2 task group, we sent a centrally reviewed questionnaire exploring candidate sources of uncertainties in dose deposition to the ten CIRT facilities in operation by February 2017. We aimed to explore native beam characterization, immobilization, anatomic data acquisition, target volumes and organs at risks delineation, treatment planning, dose delivery, quality assurance prior and during treatment. The responders had to consider the clinical case of a clival chordoma eligible for postoperative CIRT according to their clinical practice. With the results, our task group discussed ways to harmonize CIRT practices. Results: We received 5 surveys from facilities that have treated 77% of the patients worldwide per November 2017. We pointed out the singularity of the facilities and beam delivery systems, a divergent definition of target volumes, the multiplicity of TPS and equieffective dose calculation approximations. Conclusion: Multiple uncertainties affect equieffective dose definition, deposition and calculation in CIRT. Although it is not possible to harmonize all the steps of the CIRT planning between the centers, our working group proposed counter-measures addressing the improvable limitations. Keywords: Carbon ion radiotherapy, Equieffective dose, Clinical trials methodology, Chordoma

* Correspondence: [email protected] 1 Department of Radiation Oncology, Institut de Cancérologie de Lorraine, 6 avenue de bourgogne - CS 30519, 54519 Nancy, Vandoeuvre-les-Nancy Cedex, France 2 UMR 7365 CNRS-UL, IMoPA, Nancy, Vandoeuvre-les-Nancy Cedex, France Full list of author information is available at the end of the article © The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the d