Synchrotron Microbeam Radiotherapy for the treatment of lung carcinoma: a pre-clinical study

Trappetti, Verdiana; Fernandez Palomo, Cristian; Smyth, Lloyd; Klein, Mitzi; Haberthür, David; Butler, Duncan; Barnes, Micah; Shintani, Nahoko; de Veer, Michael; Laissue, Jean A.; Vozenin, Marie C.; Djonov, Valentin (2021). Synchrotron Microbeam Radiotherapy for the treatment of lung carcinoma: a pre-clinical study. International journal of radiation oncology, biology, physics, 111(5), pp. 1276-1288. Elsevier 10.1016/j.ijrobp.2021.07.1717

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# Purpose
In the last three decades, Synchrotron Microbeam Radiation Therapy (S-MRT) has been shown to achieve both good tumour control and normal tissue sparing in a range of pre-clinical animal models. However, the use of S-MRT for the treatment of lung tumours 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 two cross-fired arrays of S-MRT or Synchrotron Broad-Beam (S-BB) radiotherapy. S-MRT consisted of 17 microbeams with a width of 50 µm and centre-to-centre spacing of 400 µm. Each microbeam delivered a peak entrance dose of 400 Gy while 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 (CTR). However, mice in the S-MRT group developed severe pulmonary oedema around the irradiated carcinomas and did not have improved survival relative to the S-BB group. Subsequent post-mortem examination of tumour size revealed that the mice in the S-MRT group had notably smaller tumour volume compared to the S-BB group, despite the presence of oedema. Mice that were sham-implanted did not display any decline in health following S-MRT, experiencing only mild and transient oedema between 4 days and 3 months post-irradiation 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 tumour size compared to mice treated with S-BB and sparing healthy lungs from pulmonary fibrosis. Future experiments should focus on optimising S-MRT parameters to minimise pulmonary oedema and maximise the therapeutic ratio.

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