Ultra-high dose-rate proton FLASH improves tumor control.
Radiother Oncol
; 186: 109741, 2023 09.
Article
em En
| MEDLINE
| ID: mdl-37315577
ABSTRACT
BACKGROUND AND PURPOSE:
Proton radiotherapy (PRT) offers potential benefits over other radiation modalities, including photon and electron radiotherapy. Increasing the rate at which proton radiation is delivered may provide a therapeutic advantage. Here, we compared the efficacy of conventional proton therapy (CONVpr) to ultrahigh dose-rate proton therapy, FLASHpr, in a mouse model of non-small cell lung cancers (NSCLC). MATERIALS ANDMETHODS:
Mice bearing orthotopic lung tumors received thoracic radiation therapy using CONVpr (<0.05 Gy/s) and FLASHpr (>60 Gy/s) dose rates.RESULTS:
Compared to CONVpr, FLASHpr was more effective in reducing tumor burden and decreasing tumor cell proliferation. Furthermore, FLASHpr was more efficient in increasing the infiltration of cytotoxic CD8+ T-lymphocytes inside the tumor while simultaneously reducing the percentage of immunosuppressive regulatory T-cells (Tregs) among T-lymphocytes. Also, compared to CONVpr, FLASHpr was more effective in decreasing pro-tumorigenic M2-like macrophages in lung tumors, while increasing infiltration of anti-tumor M1-like macrophages. Finally, FLASHpr treatment reduced expression of checkpoint inhibitors in lung tumors, indicating reduced immune tolerance.CONCLUSIONS:
Our results suggest that FLASH dose-rate proton delivery modulates the immune system to improve tumor control and might thus be a promising new alternative to conventional dose rates for NSCLC treatment.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Carcinoma Pulmonar de Células não Pequenas
/
Terapia com Prótons
/
Neoplasias Pulmonares
Limite:
Animals
Idioma:
En
Revista:
Radiother Oncol
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Estados Unidos