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Proton FLASH radiotherapy ameliorates radiation-induced salivary gland dysfunction and oral mucositis and increases survival in a mouse model of head and neck cancer
Molecular Cancer Therapeutics ( IF 5.7 ) Pub Date : 2024-04-09 , DOI: 10.1158/1535-7163.mct-23-0663
Priyanka Chowdhury 1 , Anastasia Velalopoulou 2 , Ioannis I. Verginadis 3 , George Morcos 1 , Phoebe E. Loo 4 , Michele M. Kim 5 , Seyyedeh Azar Oliaei Motlagh 1 , Khayrullo Shoniyozov 6 , Eric S. Diffenderfer 5 , Emilio A. Ocampo 7 , Mary Putt 3 , Charles-Antoine Assenmacher 8 , Enrico Radaelli 3 , Jiawei Lu 1 , Ling Qin 3 , Hengxi Liu 1 , Nektaria Maria Leli 3 , Swati Girdhani 9 , Nicolas Denef 9 , Francois Vander Stappen 9 , Keith A. Cengel 3 , Theresa M. Busch 3 , James M. Metz 3 , Lei Dong 3 , Alexander Lin 5 , Constantinos Koumenis 1
Affiliation  

Head and neck cancer radiotherapy often damages salivary glands and oral mucosa, severely negatively impacting patients’ quality of life. The ability of FLASH- Proton Radiation therapy (F-PRT) to decrease normal tissue toxicity while maintaining tumor control compared to Standard Proton Radiation therapy (S-PRT) has been previously demonstrated for several tissues. However, its potential in ameliorating radiation-induced salivary gland dysfunction and oral mucositis and controlling orthotopic head and neck tumor growth has not been reported. The head and neck area of C57BL/6 mice was irradiated with a single dose of RT (ranging from 14-18 Gy) or a fractionated dose of 8 Gy x 3 of F-PRT (128 Gy/s) or S-PRT (0.95 Gy/s). Following irradiation, the mice were studied for radiation-induced xerostomia by measuring their salivary flow. Oral mucositis was analyzed by histopathological examination. To determine the ability of F-PRT to control orthotopic head and neck tumors, tongue tumors were generated in the mice and then irradiated with either F-PRT or S-PRT. Mice treated with either a single dose or fractionated dose of F-PRT showed significantly improved survival than those irradiated with S-PRT. F-PRT-treated mice showed improvement in their salivary flow. S-PRT-irradiated mice demonstrated increased fibrosis in their tongue epithelium. F-PRT significantly increased the overall survival of the mice with orthotopic tumors compared to the S-PRT-treated mice. The demonstration that F-PRT decreases radiation-induced normal tissue toxicity without compromising tumor control, suggests that this modality could be useful for the clinical management of head and neck cancer patients.

中文翻译:

质子闪光放射治疗可改善放射引起的唾液腺功能障碍和口腔粘膜炎,并提高头颈癌小鼠模型的存活率

头颈癌放射治疗经常损伤唾液腺和口腔粘膜,严重影响患者的生活质量。与标准质子放射治疗 (S-PRT) 相比,FLASH-质子放射治疗 (F-PRT) 先前已在多种组织中得到证实,能够降低正常组织毒性,同时保持肿瘤控制。然而,其在改善辐射引起的唾液腺功能障碍和口腔粘膜炎以及控制原位头颈肿瘤生长方面的潜力尚未见报道。 C57BL/6小鼠的头颈部区域接受单剂量RT(范围为14-18 Gy)或分次剂量8 Gy x 3的F-PRT(128 Gy/s)或S-PRT( 0.95 戈瑞/秒)。辐射后,通过测量小鼠的唾液流量来研究小鼠的辐射引起的口干症。通过组织病理学检查分析口腔粘膜炎。为了确定 F-PRT 控制原位头颈肿瘤的能力,在小鼠体内产生舌肿瘤,然后用 F-PRT 或 S-PRT 进行照射。与接受 S-PRT 照射的小鼠相比,接受单剂量或分次剂量 F-PRT 治疗的小鼠的存活率显着提高。 F-PRT 治疗的小鼠的唾液流量有所改善。 S-PRT 照射的小鼠的舌上皮纤维化增加。与 S-PRT 治疗的小鼠相比,F-PRT 显着增加了原位肿瘤小鼠的总体存活率。 F-PRT 可以降低辐射引起的正常组织毒性而不影响肿瘤控制,这表明这种方法可用于头颈癌患者的临床管理。
更新日期:2024-04-09
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