Verdiana Trappetti1, Cristian Fernandez-Palomo1, Lloyd Smyth2, Mitzi Klein3, David Haberthür1, Duncan Butler3, Micah Barnes4, Nahoko Shintani1, Michael de Veer5, Jean A Laissue1, Marie C Vozenin6, Valentin Djonov7. 1. Institute of Anatomy, University of Bern, Switzerland. 2. Department of Obstetrics and Gynaecology, University of Melbourne, Royal Women's Hospital, Melbourne, Australia. 3. Imaging and Medical Beamline, Australian Nuclear Science and Technology Organisation, Australian Synchrotron, Clayton, Australia. 4. Imaging and Medical Beamline, Australian Nuclear Science and Technology Organisation, Australian Synchrotron, Clayton, Australia; Department of Physical Sciences, Peter MacCallum Cancer Centre, Melbourne, Australia. 5. Monash Biomedical Imaging, Monash University, Clayton, Australia. 6. Department of Radiation Oncology/CHUV, Lausanne University Hospital and University of Lausanne, Switzerland. 7. Institute of Anatomy, University of Bern, Switzerland. Electronic address: valentin.djonov@ana.unibe.ch.
Abstract
PURPOSE: In the past 3 decades, synchrotron microbeam radiation therapy (S-MRT) has been shown to achieve both good tumor control and normal tissue sparing in a range of preclinical animal models. However, the use of S-MRT for the treatment of lung tumors has not yet been investigated. This study is the first to evaluate the therapeutic efficacy of S-MRT for the treatment of lung carcinoma, using a new syngeneic and orthotopic mouse model. METHODS AND MATERIALS: Lewis Lung carcinoma-bearing mice were irradiated with 2 cross-fired arrays of S-MRT or synchrotron broad-beam (S-BB) radiation therapy. S-MRT consisted of 17 microbeams with a width of 50 µm and center-to-center spacing of 400 µm. Each microbeam delivered a peak entrance dose of 400 Gy whereas S-BB delivered a homogeneous entrance dose of 5.16 Gy (corresponding to the S-MRT valley dose). RESULTS: Both treatments prolonged the survival of mice relative to the untreated controls. However, mice in the S-MRT group developed severe pulmonary edema around the irradiated carcinomas and did not have improved survival relative to the S-BB group. Subsequent postmortem examination of tumor size revealed that the mice in the S-MRT group had notably smaller tumor volume compared with the S-BB group, despite the presence of edema. Mice that were sham-implanted did not display any decline in health after S-MRT, experiencing only mild and transient edema between 4 days and 3 months postirradiation which disappeared after 4 months. Finally, a parallel study investigating the lungs of healthy mice showed the complete absence of radiation-induced pulmonary fibrosis 6 months after S-MRT. CONCLUSIONS: S-MRT is a promising tool for the treatment of lung carcinoma, reducing tumor size compared with mice treated with S-BB and sparing healthy lungs from pulmonary fibrosis. Future experiments should focus on optimizing S-MRT parameters to minimize pulmonary edema and maximize the therapeutic ratio.
PURPOSE: In the past 3 decades, synchrotron microbeam radiation therapy (S-MRT) has been shown to achieve both good tumor control and normal tissue sparing in a range of preclinical animal models. However, the use of S-MRT for the treatment of lung tumors has not yet been investigated. This study is the first to evaluate the therapeutic efficacy of S-MRT for the treatment of lung carcinoma, using a new syngeneic and orthotopic mouse model. METHODS AND MATERIALS: Lewis Lung carcinoma-bearing mice were irradiated with 2 cross-fired arrays of S-MRT or synchrotron broad-beam (S-BB) radiation therapy. S-MRT consisted of 17 microbeams with a width of 50 µm and center-to-center spacing of 400 µm. Each microbeam delivered a peak entrance dose of 400 Gy whereas S-BB delivered a homogeneous entrance dose of 5.16 Gy (corresponding to the S-MRT valley dose). RESULTS: Both treatments prolonged the survival of mice relative to the untreated controls. However, mice in the S-MRT group developed severe pulmonary edema around the irradiated carcinomas and did not have improved survival relative to the S-BB group. Subsequent postmortem examination of tumor size revealed that the mice in the S-MRT group had notably smaller tumor volume compared with the S-BB group, despite the presence of edema. Mice that were sham-implanted did not display any decline in health after S-MRT, experiencing only mild and transient edema between 4 days and 3 months postirradiation which disappeared after 4 months. Finally, a parallel study investigating the lungs of healthy mice showed the complete absence of radiation-induced pulmonary fibrosis 6 months after S-MRT. CONCLUSIONS: S-MRT is a promising tool for the treatment of lung carcinoma, reducing tumor size compared with mice treated with S-BB and sparing healthy lungs from pulmonary fibrosis. Future experiments should focus on optimizing S-MRT parameters to minimize pulmonary edema and maximize the therapeutic ratio.
Authors: M J Barnes; J Paino; L R Day; D Butler; D Häusermann; D Pelliccia; J C Crosbie Journal: J Synchrotron Radiat Date: 2022-06-07 Impact factor: 2.557
Authors: Elisabeth Schültke; Michael Lerch; Timo Kirschstein; Falko Lange; Katrin Porath; Stefan Fiedler; Jeremy Davis; Jason Paino; Elette Engels; Micah Barnes; Mitzi Klein; Christopher Hall; Daniel Häusermann; Guido Hildebrandt Journal: J Synchrotron Radiat Date: 2022-05-18 Impact factor: 2.557
Authors: Felix Jaekel; Elke Bräuer-Krisch; Stefan Bartzsch; Jean Laissue; Hans Blattmann; Marten Scholz; Julia Soloviova; Guido Hildebrandt; Elisabeth Schültke Journal: Int J Mol Sci Date: 2022-07-28 Impact factor: 6.208
Authors: Munir A Al-Zeer; Franziska Prehn; Stefan Fiedler; Ulrich Lienert; Michael Krisch; Johanna Berg; Jens Kurreck; Guido Hildebrandt; Elisabeth Schültke Journal: Int J Mol Sci Date: 2022-09-01 Impact factor: 6.208