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      Estimation of the risk for radiation-induced liver disease following photon- or proton-beam radiosurgery of liver metastases

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          Abstract

          Background

          Radiotherapy of liver metastases is commonly being performed with photon-beam based stereotactic body radiation therapy (SBRT). The high risk for radiation-induced liver disease (RILD) is a limiting factor in these treatments. The use of proton-beam based SBRT could potentially improve the sparing of the healthy part of the liver. The aim of this study was to use estimations of normal tissue complication probability (NTCP) to identify liver-metastases patients that could benefit from being treated with intensity-modulated proton therapy (IMPT), based on the reduction of the risk for RILD.

          Methods

          Ten liver metastases patients, previously treated with photon-beam based SBRT, were retrospectively planned with IMPT. A CTV-based robust optimisation (accounting for setup and range uncertainties), combined with a PTV-based conventional optimisation, was performed. A robustness criterion was defined for the CTV (V 95% > 98% for at least 10 of the 12 simulated scenarios). The NTCP was estimated for different endpoints using the Lyman-Kutcher-Burman model. The ΔNTCP ( NTCP IMPT  −  NTCP SBRT ) for RILD was registered for each patient. The patients for which the NTCP (RILD) < 5% were also identified. A generic relative biological effectiveness of 1.1 was assumed for the proton beams.

          Results

          For all patients, the objectives set for the PTV and the robustness criterion set for the CTV were fulfilled with the IMPT plans. An improved sparing of the healthy part of the liver, right kidney, lungs, spinal cord and the skin was achieved with the IMPT plans, compared to the SBRT plans. Mean liver doses larger than the threshold value of 32 Gy led to NTCP values for RILD exceeding 5% (7 patients with SBRT and 3 patients with the IMPT plans). ΔNTCP values (RILD) ranging between − 98% and − 17% (7 patients) and between 0 and 2% (3 patients), were calculated.

          Conclusions

          In this study, liver metastases patients that could benefit from being treated with IMPT, based on the NTCP reductions, were identified. The clinical implementation of such a model-based approach to select liver metastases patients to proton therapy needs to be made with caution while considering the uncertainties involved in the NTCP estimations.

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          Most cited references30

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          Use of normal tissue complication probability models in the clinic.

          The Quantitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) review summarizes the currently available three-dimensional dose/volume/outcome data to update and refine the normal tissue dose/volume tolerance guidelines provided by the classic Emami et al. paper published in 1991. A "clinician's view" on using the QUANTEC information in a responsible manner is presented along with a description of the most commonly used normal tissue complication probability (NTCP) models. A summary of organ-specific dose/volume/outcome data, based on the QUANTEC reviews, is included. Copyright 2010 Elsevier Inc. All rights reserved.
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            Radiotherapy combination opportunities leveraging immunity for the next oncology practice.

            Approximately one-half of patients with newly diagnosed cancer and many patients with persistent or recurrent tumors receive radiotherapy (RT), with the explicit goal of eliminating tumors through direct killing. The current RT dose and schedule regimens have been empirically developed. Although early clinical studies revealed that RT could provoke important responses not only at the site of treatment but also on remote, nonirradiated tumor deposits-the so-called "abscopal effect"- the underlying mechanisms were poorly understood and were not therapeutically exploited. Recent work has elucidated the immune mechanisms underlying these effects and has paved the way for developing combinations of RT with immune therapy. In the wake of recent therapeutic breakthroughs in the field of immunotherapy, rational combinations of immunotherapy with RT could profoundly change the standard of care for many tumor types in the next decade. Thus, a deep understanding of the immunologic effects of RT is urgently needed to design the next generation of therapeutic combinations. Here, the authors review the immune mechanisms of tumor radiation and summarize the preclinical and clinical evidence on immunotherapy-RT combinations. Furthermore, a framework is provided for the practicing clinician and the clinician investigator to guide the development of novel combinations to more rapidly advance this important field. CA Cancer J Clin 2017;67:65-85. © 2016 American Cancer Society.
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              Selection of patients for radiotherapy with protons aiming at reduction of side effects: the model-based approach.

              Most new radiation techniques, have been introduced primarily to reduce the dose to normal tissues in order to prevent radiation-induced side effects. Radiotherapy with protons is such a radiation technique that due to its superior beam properties compared to photons enables better sparing of normal tissues. This paper describes a stepwise methodology to select patients for proton therapy when the primary aim is to reduce side effects. This method has been accepted by the Dutch health authorities to select patients for proton therapy. In addition, an alternative method is described in case randomised controlled trials are considered not appropriate. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
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                Author and article information

                Contributors
                +46-8-585 800 00 , gracinda.mondlane@ki.se
                ana.ureba@ki.se
                michael.gubanski@karolinska.se
                pehr.lind@ki.se
                albert.siegbahn@ki.se
                Journal
                Radiat Oncol
                Radiat Oncol
                Radiation Oncology (London, England)
                BioMed Central (London )
                1748-717X
                22 October 2018
                22 October 2018
                2018
                : 13
                : 206
                Affiliations
                [1 ]ISNI 0000 0004 1936 9377, GRID grid.10548.38, Department of Physics – Medical Radiation Physics, , Stockholm University, ; Stockholm, Sweden
                [2 ]GRID grid.8295.6, Department of Physics, , Universidade Eduardo Mondlane, ; Maputo, Mozambique
                [3 ]ISNI 0000 0004 1937 0626, GRID grid.4714.6, Department of Oncology and Pathology, , Karolinska Institutet, ; Stockholm, Sweden
                [4 ]ISNI 0000 0000 9241 5705, GRID grid.24381.3c, Department of Oncology and Pathology, , Karolinska University Hospital, ; Stockholm, Sweden
                [5 ]Department of Oncology, Södersjukhuset, Stockholm, Sweden
                Author information
                http://orcid.org/0000-0002-9904-7217
                Article
                1151
                10.1186/s13014-018-1151-6
                6196431
                30348194
                5668fc9f-85b3-4fe4-adc5-1552fbfd8560
                © The Author(s). 2018

                Open AccessThis 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 data made available in this article, unless otherwise stated.

                History
                : 21 May 2018
                : 4 October 2018
                Categories
                Research
                Custom metadata
                © The Author(s) 2018

                Oncology & Radiotherapy
                rild,liver metastases,sbrt,impt,patient selection
                Oncology & Radiotherapy
                rild, liver metastases, sbrt, impt, patient selection

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