Oxygen supplementation in anesthesia can block FLASH effect and anti-tumor immunity in conventional proton therapy

• Published in: Communications medicine 2023-12, Vol.3 (1), p.183-183, Article 183
• Main Authors: Iturri, Lorea, Bertho, Annaïg, Lamirault, Charlotte, Brisebard, Elise, Juchaux, Marjorie, Gilbert, Cristèle, Espenon, Julie, Sébrié, Catherine, Jourdain, Laurène, de Marzi, Ludovic, Pouzoulet, Frédéric, Muret, Jane, Verrelle, Pierre, Prezado, Yolanda
• Format: Article
• Language: English
• Subjects: 13/1; 13/31; 13/51; 14; 14/34; 14/5; 14/63; 59/57; 631/250/580; 631/67/1059/485; 631/67/1922; 692/308/3187; 692/4028/67/2332; Brain cancer; Childrens health; Cognition & reasoning; Cognitive ability; Dosimetry; General anesthesia; Immunity (Disease); Investigations; Life Sciences; Medicine; Medicine & Public Health; Neurogenesis; Oncology; Pediatrics; Radiation therapy; Toxicity; Tumors
• ISSN: 2730-664X; 2730-664X
• DOI: 10.1038/s43856-023-00411-9

Background Radiation-induced neurocognitive dysfunction is a major adverse effect of brain radiation therapy and has specific relevance in pediatric oncology, where serious cognitive deficits have been reported in survivors of pediatric brain tumors. Moreover, many pediatric patients receive proton therapy under general anesthesia or sedation to guarantee precise ballistics with a high oxygen content for safety. The present study addresses the relevant question of the potential effect of supplemental oxygen administered during anesthesia on normal tissue toxicity and investigates the anti-tumor immune response generated following conventional and FLASH proton therapy. Methods Rats (Fischer 344) were cranially irradiated with a single high dose of proton therapy (15 Gy or 25 Gy) using FLASH dose rate proton irradiation (257 ± 2 Gy/s) or conventional dose rate proton irradiation (4 ± 0.02 Gy/s), and the toxicities in the normal tissue were examined by histological, cytometric and behavioral analysis. Glioblastoma-bearing rats were irradiated in the same manner and tumor-infiltrating leukocytes were quantified by flow cytometry. Results Our findings indicate that supplemental oxygen has an adverse impact on both functional and anatomical evaluations of normal brain following conventional and FLASH proton therapy. In addition, oxygen supplementation in anesthesia is particularly detrimental for anti-tumor immune response by preventing a strong immune cell infiltration into tumoral tissues following conventional proton therapy. Conclusions These results demonstrate the need to further optimize anesthesia protocols used in radiotherapy with the goal of preserving normal tissues and achieving tumor control, specifically in combination with immunotherapy agents. Plain Language Summary Proton therapy is a type of precise radiotherapy that can have reduced side effects. Children undergoing proton therapy are often given a general anesthetic, supplemented with high oxygen levels as a measure of safety. However, the consequences of modifying the oxygen concentration in the treatment have not been studied. In this study, we evaluated the consequences of adding oxygen in the anesthesia in a model of brain tumor after conventional proton therapy and a new radiotherapy technique, FLASH proton therapy. We observed that oxygen supplementation can cause more brain damage in FLASH proton therapy and block anti-tumor immune cell infiltration into the tumor in conventional prot