Synchrotron Microbeam Radiation Therapy for the Treatment of Lung Carcinoma: A Preclinical Study
Autor: | Verdiana Trappetti, Jean A. Laissue, Nahoko Shintani, Lloyd M. L. Smyth, David Haberthür, Cristian Fernandez-Palomo, Valentin Djonov, Duncan Butler, Micah Barnes, Michael John de Veer, Marie C. Vozenin, Mitzi Klein |
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Rok vydání: | 2021 |
Předmět: |
Cancer Research
Lung Neoplasms Pulmonary Fibrosis medicine.medical_treatment 610 Medicine & health Pulmonary Edema 030218 nuclear medicine & medical imaging Mice 03 medical and health sciences 0302 clinical medicine Therapeutic index Microbeam radiation therapy Pulmonary fibrosis Transient oedema medicine Carcinoma Animals Radiology Nuclear Medicine and imaging Lung Radiation business.industry Parallel study medicine.disease 3. Good health Radiation therapy medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis Nuclear medicine business Synchrotrons |
Zdroj: | 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 |
ISSN: | 0360-3016 |
Popis: | 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. |
Databáze: | OpenAIRE |
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