Synchrotron Microbeam Radiation Therapy for the Treatment of Lung Carcinoma: A Preclinical Study

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.